"Diabetes Special" u Editorial u Diabetes & Mahabhart u Guest Editorial:Diabetes Dangal u Hypoglycemia Prevention & Management u Fasts in Haryana u Insulin Injection Technique u Haryanavi Diet u Outdoor Management of Ketosis u Chasing Euglycemia u Fasts & Ramadan u Diabetic Nephropathy u Bionic Pancreas u Diabetic Retinopathy u Renal Nutcracker Syndrome

Haryana Medical Journal Chief Editor : • Dr. Ashok Taneja March 2017, Vol. 40, Issue No. 1 Guest Editor : • Dr. Sanjay Kalra • Dr. Sameer Aggarwal

Editorial Board : Editorial Chief Editor Dr Ashok K.Taneja Gurgaon Dear Friends and Collegues Associate Editor : Dr Kapil Midha-Gurgaon Welcome to the HMJ renaissance. Dr V K Gupta-Hisar HMJ is back. Back from the void. After a long Jt. Editor : Dr Rajesh Kakkar-Gurgaon hiatus of several years, now in your hands in a Advt. Editor : new Avatar. Dr Anil Hans- Gurgaon Members : Welcome back folks! and we come back with the promise; " HMJ Dr Arun Narula-Rohtak is now here to stay". Not going anywhere now. This new lease of Dr Devender Sangwan-Rohtak life is long. Very Long! Dr Kamla Singh-Panchkula Dr Kavita Lekhi-Panchkula Just to remind you , my dear friends and comrades. We are an Dr Manoj Aggarwal-Ambala indexed journal. I reiterate and emphasize this. " We are an Dr Narender Taneja-Bhiwani Dr Narottam Goel-Palwal indexed journal". All articles published in this journal have Dr Nidhi Sanduja-Fatehabad lasting value. We know that this is important and even more so Dr Pawan Goel-Rewari for residents; who wish to publish their research Dr Pawan Gupta-Bahadurgarh Dr Raj K.Sharma-Narnaul We welcome original research articles and reviews and case Dr R L Arya-Shahbad reports. We also invite yours suggestions to make this journal Dr R P Jindal-Panipat Dr Rohtas Yadav-PGIMS,Rohtak more relevant in today's scenario. Dr Rajan Gupta-Tohana The first issue ;ie the one in your hands is focussed on diabetes Dr Rajiv Aggarwal-Ambala City Dr Rajiv Gupta-Karnal and its myriad manifestations. Dr Rajiv Gupta-Ambala Cantt My dear IMA collegues, Dr Ramesh Batra-Sonepat Dr Shailesh Tomar-Sirsa Our profession is increasingly under siege. Both from the Dr Surat Yadav-Mahendergarh patients and the authorities. Attacks on doctors continue Dr Surender Mehta-Kurukshetra Dr Suresh Arora-Faridabad unchecked throughout the country, and this coupled with a Dr Suresh Jain-Jind lackadaisical response of the administration is making our Dr Vijay Arya-Kaithal survival almost untenable. Newer and tougher regulations ; President IMA : DR A P Setia-Hisar without a single thought about the ground realities and the Secretary IMA : situations under which most doctors practice, are heart Dr Ajay Mahajan-Hisar breaking and morale busting. President Elect : Dr Munish Prabhakar-Gurgaon What can we do about? The answer pals! is actually as clear as Advisors : daylight. We Prosper together. Together we carry a big punch to Dr Anil Goel-Faridabad do almost anything. We must stand together for the common Dr Dhruv Chaudhary-Rohtak Dr H K Aggarwal-Rohtak good and take a tough and united stand. It is actually much Dr P D Pahwa-Gurgaon easier to achieve this than to suffer heartless misconceived and Dr P S Gehlot-Khanpur Med.College impossible to comply regulations. Dr Pankaj Mutneja-Panipat Dr R P Gupta-Gurgaon HMJ thus dear friends is also your mouthpiece; and will work to Dr Rajan Sharma-Yamunanagar promote unity amongst the fraternity. Dr Ramesh Goel-Gurgaon Dr S K Dhatarwal-PGIMS Rohtak Welcome you once more and thanking you for your support Dr S L Verma-Rohtak Dr S P Yadav-Gurgaon Dr Sansar Sharma-Nuh Medical College your truly Dr Satish Chugh-Kalanaur Dr Ashok Taneja Dr Satish Gulati-Rohtak Dr Suresh Singhal-PGIMS Rohtak Editor HMJ Dr V K Katyal-PGIMS Rohtak Dr Ved Beniwal-Sirsa E-mail : [email protected]

IMA IMA President Secretary

Dear IMA Members, Dear Friends, Namaskar ! It gives me immense It is a matter of immense pleasure to address all the pride that the mouthpiece of IMA Haryana esteemed members of IMA Haryana is seeing the light of the day after a break of through this medium of Haryana Medical few years. Journal. With the efforts of Dr Ashok Taneja, the reprinting of our association The icing on the cake is its latest journal after a gap of two years is indexation. commendable, and I hope a harbinger of The editorial team of HMJ, led by dynamic the good things to come up this year. IMA leader Dr.Ashok Taneja has made persistent and pains taking efforts for the The first month in itself has been quite revival as well as indexation of Haryana hectic for the association with the Medical Journal. observation of the “National Solidarity Day” and “Say No to NEXT” campaign. I am It would be a source of authentic, scientific overwhelmed by the unity shown and the and practical knowledge for the medical response that we have received from all the professionals. members. I am sure that under the My best wishes to the editorial team for the guidance of the seniors and enthusiasm of success of the venture. all the worthy members, we will be able to My special thanks to the Guest editors for establish an unprecedented rapport in the accepting the invite and making the current association. issue a masterpiece. The email of the association this year is [email protected]. You can Long live IMA ! share your views and branch activities with us on this. We are also in the process of putting up our own website this year. With regards, Hoping for the cooperation and blessings of Dr. A. P. Setia all the members throughout the year! State President, Jai IMA! IMA Haryana Dr. Ajay Mahajan Honorary State Secretary

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 01 Guest Editorial THE DIABETES DANGAL: HARYANA IN ACTION

Sanjay Kalra Arun Kumar Sameer Aggarwal Department of Endocrinology Department of Community Medicine Department of Medicine Bharti Hospital, Karnal SHKM Government Medical College, Pt BDS PGIMS, Rohtak Nalhar, Mewat

DIABETES been spared the worst of the diabetes As the diabetes epidemic spreads across the pandemic. The lowest prevalence of globe, it spares no country or state. India, and dysglycemia is found in women of Kurukshetra Haryana, too, face a heavy burden of diabetes (2.9%), Mahendragarh (2.8%), Hisar (3.0%) and its associated complications. The and Jind (3.1%), as well as men from Sirsa epidemiological trends in our part of the world (1.6%), Jind (3.5%), rural Sonipat (2.2%), and are such that apart from being a diabetes urban areas of Hisar (2.6%), Yamunanagar capital, diabetes is now being considered an (3.4%), and Karnal (3.7%). (2). endemic, rather than epidemic, condition (1). OUR CULTURE, OUR STRENGTH DYSGLYCEMIA IN HARYANA Haryana’s lifestyle has much to contribute Data from the National Family Health Survey-4 towards prevention and management of suggests that overweight and diabetes are diabetes. Focus on simple diet, regular physical highly prevalent in Haryana. A district-wise activity, and religiosity is the hall mark of our breakdown reveals a heterogeneous spread of state. These virtues can be highlighted to these conditions across the state. Districts persons living with diabetes and their care which are urbanized, industrialized, or home to givers. We call ourselves the state of ‘milk and migrant populations, report a greater yoghurt’ (jit doodh dahi ka khaana) (3). This prevalence of metabolic dysfunction. The epithet should be popularized, to encourage highest prevalence of high glucose values in consumption of milk, yoghurt and buttermilk, women aged 15 to 49 years is seen in urban and as opposed to butter, ghee or cream (malai). rural areas of Panipat (12.2% and 8.6% Reliance of traditional cuisine on locally respectively), Faridabad (6.4%), Rewari sourced, fresh foodstuffs, including coarse (6.6%) and Gurgaon (6.5%). In men, the order grains and green leafy vegetables, should be is: Rewari (11.4%; rural=13.7%), Faridabad reinforced as a healthy habit. (9.4%), Panipat (9%; urban=11.8%) and In our state, we encourage respect for rules and Gurgaon (9.5%) (2). Haryana, therefore, has regulations, and obedience to elders. This become the Dangal of Diabetes today. characteristic can be utilized to promote No stranger to challenges and obstacles, proactive health-seeking behavior and Haryana has weathered much larger wars and acceptance of modern diagnostic, therapeutic battles in the past, including those of and monitoring strategies. Religious teaching Kurukshetra and Panipat. Culture of Haryana, can be used to create a positive attitudes is such that people are able to survive against towards health care (4). Yoga too is a useful all odds. Even today, rural districts, which still intervention, which enjoys widespread follow the traditional Haryanvi way of life, have acceptance in Haryana. This can be promoted Haryana Medical Journal - March 2017, Vol. 40, Issue 01 02 as a primordial health preventive strategy (5). REFERENCES The robust social scaffolding which exists in 1. K a l ra S , Ku m a r A , J a r hya n P, Haryana, such as strong community Unnikrishnan AG. Endemic or epidemic? interaction in chaupals and panchayats, Measuring the endemicity index of diabetes. facilitates community-based campaigns to Indian journal of endocrinology and promote healthy lifestyle. metabolism. 2015 Jan 1;19(1):5. Our successes on the sports field, and off it (on 2. Key findings from NFHS-4. Available at: Bollywood movie screens) act as positive http://rchiips.org/nfhs/HR.shtml. Last motivation for the community at large. accessed on 7 January 7, 2017 Dissemination and discussion of these facts creates a diabetes-friendly social environment, 3. A b o u t H a r y a n a . Av a i l a b l e a t : which facilitates acceptance and adherence of http://haryanatourism.gov.in/showpage.aspx modern medical therapy. The advantages of ?contentid=5049. Last accessed on 7 January 7, sports can be extrapolated to physical activity, 2017 yoga and folk dance. Our energetic dances, such 4. Jawad F, Kalra S. Ramadan and diabetes: as jhoomer and bhangra, must be encouraged Holistic trial design. J Pak Med Assoc. at mass level (5). 2016;66(7):791. This approach must be tempered with an 5. Unnikrishnan AG, Kalra S, Garg MK. understanding of our shortcomings as well. Preventing obesity in India: Weighing the Emphasis must be laid on avoidance of tobacco options. Indian J Endocrinol Metab 2012 ; in all forms (6), and on limiting intake of ghee. 16:4-6. The reasons for this should be explained in an 6. Kalra S, Gupta Y. Cardiovascular risk empathic, yet non-judgmental manner (7). management in diabetes in primary care. J Pak CULTURAL COMPETENCE Med Assoc 2015;605:1. These suggestions should be integrated in 7. Kalra S, Sridhar GR, Balhara YP, Sahay RK, daily practice by all medical, in a patient Bantwal G, Baruah MP, et al. National centered manner (8) specialties. Health care recommendations: Psychosocial management workers from paramedical professions should of diabetes in India. Indian journal of be encouraged to use culture and a religion as a means of motivation for patients. Such a e n d o c r i n o l o g y a n d m e t a b o l i s m . campaign can be successful only if all health 2013;17(3):376. care professionals strive to achieve cultural 8. Kalra S, Megallaa MH, Jawad F. Patient- and linguistic competence (9), relevant to the centered care in diabetology: From eminence- population they serve. These skills are as based, to evidence-based, to end user-based important as required in addition to medicine. Indian journal of endocrinology and knowledge related to the biomedical domain of metabolism. 2012;16(6):871. health. They strengthen, and support, our 9. Bhutani J, Bhutani S, Kumar J. Achieving ability to translate theoretical or research- patient centered care: Communication and based information into practically useful, cultural competence. Indian journal of clinically appropriate knowledge. e n d o c r i n o l o g y a n d m e t a b o l i s m . SUMMARY 2013;17(1):187. The Haryana Medical Journal has taken a major Disclaimer: Authors have taken reasonable step towards this by releasing a thematic issue care to ensure that figures written from the on diabetes. Let us take this as our first move, in references are correct but does not warrant the Dangal of Diabetes, to wrestle with, and this to be the case and accept no liability for defeat, the diabetes epidemic, in Haryana and any errors or omissions. beyond. Haryana Medical Journal - March 2017, Vol. 40, Issue 01 03 Fasts in Haryana : Glycemic Management

Rajneesh Mittal Endocrinologist, Yamunanagar

Introduction Thus, the individual becomes dependent upon Fasting is the willing abstinence from all or alternate sources of energy, augmenting some food, drink or both, for a period of time. It glycogenolysis and gluconeogenesis. It leads to is considered a method of attaining control increased levels of glucagon, catecholamines over one’s desires and senses for spiritual gain. and increased fatty acid release from Fasting is known as “Upavaasa” in Sanskrit. adipocytes. Oxidation of fatty acids generates “Upa” means near and “vaasa” means to stay, ketones that can be used as fuel by skeletal and that is, “to stay near the Lord”. cardiac muscle, liver, kidney, and adipose tissue. In the state of Haryana, majority of the In normal individuals, the glucose levels are residents are Hindus. Hindu tradition is full of maintained in the physiological range by different type of fasts, which vary according to maintaining balance between insulin and the geographical region and subsects. The fasts counter regulatory hormones. In Diabetics, may be once a week, once a fortnight however, insulin secretion is already disturbed. (Ekadashi) or on festivals like Navratri, Karva Therefore, if fasting for prolonged time, they chauth etc. Women in the state of Haryana can have dysglycemia and ketogenesis, celebrate the Teej festival to appease the depending upon the extent of insulin Goddess Parvati to bless them with a blissful resistance and/or deficiency. Hyperglycemia married life. This fast is especially rigorous can even result in diabetic ketoacidosis with no food or water for a full 24 hours. especially if the patient decreases medication. Intake during fasts differs – Bingeing on high-fat, high-carbohydrate foods, 1. In few fasts, no water or food is allowed after completion of the fast promotes for a specific time period eg till moonrise in hyperglycemia. karva chauth Patients taking oral hypoglycaemic agents are 2. In some, the person may eat once in the susceptible to hypoglycaemia during fasting. In day with water allowed during the rest of the addition, abstinence from all liquids day eg weekly fasts predisposes to dehydration, dyselectrolytemia, hypotension, and thrombosis. 3. In some, the person has to avoid cereals Approach to glycemic management during like the Navratri fasts Fasting in Diabetics is different than a healthy Fasting is associated with one’s religious person as both insulin action and secretion are beliefs and not fasting can often lead to a sense reduced, even after 24 hours, leading to poor of guilt. Therefore, though it is a personal glucose tolerance and fluctuating blood decision, patients should discuss with their glucose levels - “starvation diabetes”. , doctor for safer fasting experience. Basic physiology of glucose homeostasis The incidence of complications depends on the during fasting risk factors present in the individual at the time During fasting, insulin secretion decreases. of fasting (Table 1)

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 04 General considerations: The treating physician must discuss with the patient prior to fasting regarding how long he will fast, what exactly he would eat including sublingual foods, and freedom to break the fast in case of any problem. Symptoms of hypoglycemia and dehydration must be explained to the patient in detail. Patient should avoid fasting if he has additional health problems. Management plan for each individual needs to be individualized as each patient has different response to drug therapy and fasts. First and foremost, the patient needs more frequent monitoring of blood glucose levels, especially type1 diabetics and type 2 diabetics that require insulin. Fasts should be broken if patient’s glucose levels are either below 70mg/dl or above 300 mg/dl3. Diet during fast should be as near to “balanced diet” as possible. Patients should avoid calorie rich foods like sweets (sabudana kheer etc) which are commonly eaten during fasts like Navratri. Instead, they should restrict to fruits and milk. The physician should help patient do carbohydrate counting. For reference the commonly used foods are mentioned in table 2. Excessive physical activity should be avoided for the fear of hypoglycaemia, though routine physical activity may be maintained.

Table 2 Dietary values of commonly eaten foods during fasts (compared to wheat and rice)

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 05 Pharmacotherapy: The choice of oral antidiabetic drugs should be individualized. Generally risk of hypoglycaemia is lower with the drugs that increase insulin sensitivity than the ones which increase insulin secretion. The large number of currently available agents allows innumerable permutation and combinations. In selective cases, changing the time of administration of the dose may also be helpful. In case the fast allows for three meals with avoidance of cereal, same therapy may be continued. Metformin can safely be continued as it has minimal chances of causing hypoglycemia. Glitazones take 2-4 weeks to show full therapeutic effect, hence cannot be quickly substituted for agents associated with hypoglycaemia during periods of fasting. Sulfonylureas, though unsuitable for use

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 06 during fasting, because of the inherent risk of Dose timing Drug Modification hypoglycaemia, can be cautiously used in patients with good health profile. Short-acting insulin secretagogues like Repaglinide and Nateglinide could be alternatives to sulfonylureas because of much shorter duration of action. One study in patients with type 2 diabetes who fasted showed that use of Dose timing Drug Modification Repaglinide was associated with less hypoglycemia compared with Glibenclamide . Incretin based therapies like GLP1 analogues and DPP4 inhibitors can safely be used during fasts because of lesser risk of hypoglycaemia, and can be given after breaking the fast instead of daytime. If the patient tends to take carbohydrate rich preparations or heavy meal after full day of fasting, alpha-glucosidase inhibitors like Acarbose, Miglitol, and Voglibose can safely be used. Newer oral drugs like SGLT2 inhibitors like Canagliflozin, Dapagliflozin and Empagliflozin are also safe if patient takes adequate fluids the whole day. The approach to patients with type 2 diabetes who administer insulin is similar to type 1 diabetes, except that the incidence of hypoglycemia is less. There is some evidence suggesting that use of a rapid acting insulin analogue instead of regular human insulin before meals is associated with less hypoglycemia and smaller postprandial glucose excursions. Prior to fasting, patients on insulin should receive adequate training and education, particularly with respect to self- Dose timing Drug Modification management and insulin dose adjustment. Changes in therapy depend on the type of fast. For people who keep fasts occasionally, during NPH festivals, drugs should be modified prior to the fast (table 3) Degludec, glargine, detemir

Table 3 - Adjustment of drugs for fasts kept Premixed 25:75 / 30:70 / 50:50 occasionally e.g. Karva chauth, Teej Insulin

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 07 For people who keep regular fasts such as on specific days of the week or ekadashi, single nighttime dose is preferred to thrice a day or basal bolus regimens. Other changes are mentioned in table 4 Table 4 - Adjustment of drugs for fasts kept regularly8

Drug Modification

DISCUSSION If an individual with Diabetes decides to fast, he should have a detailed discussion with the treating physician regarding the complications and means to prevent them. Dose of drugs causing hypoglycemia can either be decreased on the morning of the fast, or skipped that day, or substituted with newer drugs that cause less hypoglycaemia. In case the person is already taking drugs not associated with hypoglycaemia, no change is required during fast. CONCLUSION Physicians treating Diabetes need to have a compassionate outlook and balance the patient’s physical as well as spiritual needs. Fasting in Hinduism is a purification process, hence, an individualized and systematic approach is required to take care of patients who want to fast. More research is necessary in this area, so that all are free to practice their beliefs in a safe and healthy manner.

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 08 References Björkman O, Eriksson LS. Influence of a 60-hour fast on insulin-mediated splanchnic and peripheral glucose metabolism in humans. J Clin Invest. 1985 Jul;76(1):87-92 Morse WI, Mahabir R. Changes in glucose tolerance and plasma free fatty acids aftre fasting in obesity. Diabetes. 1964 May-Jun;13:286-90. Al-Arouj M, Assaad-Khalil S, Buse J, Fahdil I, Fahmy M, Hafez S, Hassanein M, Ibrahim MA, Kendall D, Kishawi S, Al-Madani A, Nakhi AB, Tayeb K, Thomas A.Recommendations for management of diabetes during Ramadan: update 2010. Diabetes Care. 2010 Aug;33(8):1895-902 Gopalan C, Rama Shastri BV, Balasubramanian SC. Nutritive value of Indian foods. Hyderabad: National Institute of Nutrition, ICMR, Offset Press; 2011 Retnakaran R, Zinman B. Thiazolidinediones and clinical outcomes in type 2 diabetes. Lancet. 2009 Jun 20;373(9681):2088-90. Mafauzy M. Repaglinide versus glibenclamide treatment of Type 2 diabetes during Ramadan fasting. Diabetes Res Clin Pract. 2002 Oct;58(1):45-53. Mattoo V, Milicevic Z, Malone JK, Schwarzenhofer M, Ekangaki A, Levitt LK, Liong LH, Rais N, Tounsi H; Ramadan Study Group.. A comparison of insulin lispro Mix25 and human insulin 30/70 in the treatment of type 2 diabetes during Ramadan. Diabetes Res Clin Pract. 2003 Feb;59(2):137-43 Kalra S, Bajaj S, Gupta Y, Agarwal P, Singh SK, Julka S, Chawla R, Agrawal N. Fasts, feasts and festivals in diabetes-1: Glycemic management during Hindufasts. Indian J Endocrinol Metab. 2015 Mar- Apr;19(2):198-203.

IMA HARYANA ANNUAL FUNCTION - ROHTAK Annual Conference of IMA Haryana State for year 2016 was held on 20th November 2016 at Sitara Garden, Rohtak. The event was hosted by IMA Rohtak City branch. About 325 IMA members from all over Haryana attended the conference. Sh. Manish Grover, Co-Operative Minister Haryana and Dr. kamal Gupta, CPS Haryana inaugurated the conference. Hony Secretary General Elect IMA HQ Dr. R.N. Tandon also graced the occasion as Guest of Honour. Scientific lectures concerning various specialities were delivered by renowned speakers from Delhi & NCR. Eminent doctors from various cities of Haryana were invited to chair the sessions. Panel discussion on today's burning issue of "Growing Violence against Medical Professionals" was appreciated by all delegates. Panel Moderator Dr. PK Kohli sought views of expert penalist from Health department, medical field, police department, social activist & legal profession. Panelists detailed the causes of this menace & suggested the ways to minimize such incidences. All Past Presidents of IMA Haryana State were facilitated by the host branch organising team. Souvenir was also released on this occasion. More than a dozen stalls were put up by Corporate hospitals, Pharma companies & Surgical equipment concerns. Apart from enjoying delicious snacks, food & fellowship. Each delegate was given conference kit bag. The successful conference was the result of hard work put up by Org. Chairman Dr. S.L. Verma, Org. Secretary Dr. R.K. Chowdhary, Host branch President Dr. Sunil Sethi, branch Secretary Dr. J.P. Arora, conference treasurer Dr. Satish Gulati, then host branch President Elect Dr. Ramesh Chitkara, dedicated members of host branch & above all the whole hearted support of honourable office bearers of IMA Haryana State.

Dr. R.K. Chowdhary, Org. Secretary, Annual Conference 2016, IMA Haryana.

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 09 HARYANVI DIET, HEALTHY DIET Meenu Chaudhary Rohit Sharma Bharti Kalra Dept of Dietetics Dept of Diabetes Education Dept of Gynecology Bharti Hospital, Karnal Bharti Hospital, Karnal Bharti Hospital, Karnal

ABSTRACT DISHES Our state Haryana is blessed with abundance of The traditional dishes of Haryana are prepared milk & curd. Other than these dairy products using the foods listed above. Some dishes of Haryanvi cuisine includes a wide variety of Haryana are listed in Table 4. Haryana has foodstuffs. In this article, we review the foods retained simplicity in its cuisine. In earlier times people of Haryana preferred to have that are part of Haryanvi diet, and describe how nutritious and healthy roti made from a flour of to use them in a healthy manner. wheat, gram barley and bajra. They consumed KEYWORDS: balanced diet, carbohydrate, bajra khichri as evening meal. They use butter fat, health, Haryana, protein liberally in their daily diet. The traditional butter is called “nooni ghee” or “tindi ghee”. FOOD GROUPS Lassi, raita, thandai, curd are popular drinks, of Diet is an integral part and determinant of the state. Rice is eaten occasionally in the form health, especially metabolic health (1). of rajma chawal, mithe chawal, kheer. Haryanvi diet contain different food groups. The nutrient values of some of these dishes are Cereals and millets are the staple diets of shown in Table 5. A traditional rural Haryanvi Haryana. The major cereals and millets are lifestyle is concordant with a 2+2 meal pattern. consumed in Haryana are pearl millets (bajra), Two examples are given in Table 6. wheat (genhu), barley (joon) and rice (chawal) SUMMARY (Table 1).Rice is eaten occasionally. Jowar We have highlighted the nutrient composition (sorghum) and ragi (finger millets) are and value of foods used in Haryanvi diet. All consumed in small amounts in specific areas. health care providers, who serve the citizens of Jowar roti, made with sorghum flour, is eaten as Haryana, should be aware of these facts. a nutritious chapatti. Ragi is cooked as porridge and eaten as an evening meal. These grains are REFERENCES the main and cheapest source of energy. 1. Willet WC. Diet and health: what should Vegetables are an important part of a healthy we eat?. Science(Washington). 1994 Apr diet. People of Haryana consume vegetables 22;264(5158):532-7. such as spinach, fenugreek (Methi), bathua 2. Nagla M. Leisure, food and health: leaves, mustard leaves, amaranthus (cholai) Practices and attitudes of rural and urban and hara chholiya. (Table 2). People of Haryana people in India. World Leisure Journal. 2005 consume large amounts of homemade butter Jan 1;47(1):24-31. and ghee (3). In Haryana Murrah buffalo and 3. Rani P, Sangwan V. Food Intake of Rural the Hariana cow‘s milk are preferred. Lassi and School Going Boys and Girls of Haryana, India: curd are other popular drinks in the state. A Comparative Study. International Journal of Other foods which are frequently used in the Advanced Research in Management and Social state are listed in Table 3. Sciences. 2016;5(1):75-88

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 10 Table 1: CEREALS

Table 2: VEGETABLES

Table 3: OTHER FOODS

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 11 Table 4: TRADITIONAL FOODS OF HARYANA

Table 6: HARYANVI DIET PLAN

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 12 Table 5: NUTRIENT COMPOSITION OF HARYANVI DISHES

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 13 Chasing the Euglycemia in Diabetes: Primum-Non-Nocere Short running Title: Chasing the Euglycemia in Diabetes Authors: Rajiv Singla DM (Endocrinology) Yashdeep Gupta DM (Endocrinology) Consultant & Head, Assistant Professor (Endocrinology), Department of Endocrinology and Diabetes, Department of Medicine, Govt Medical College, Saket City Hospital, Delhi Sector 32, Chandigarh Madhusudhan Solanki MD Tenzin Choedon Consultant, Department of Psychiatry, Diabetes Educator, Saket City Hospital, Delhi Max Smart Superspeciality Hospital, Delhi

Abstract Case Patient centric approach in diabetes 48 year old female, well-educated and management is the need of hour. A blind chase belonging to upper middle socio-economic to bring down blood glucose levels and strata presented with history of Diabetes glycated hemoglobin, without analyzing the Mellitus for last 8 years. She was started on underlying pathophysiology can bring d o u b l e o r a l h y p o g l y c e m i c a g e n t s iatrogenic misery to patient’s life. This (Sulfonylureas and Metformin) at diagnosis in manuscript presents the case of a forty eight view of markedly raised blood glucose levels year old lady who lost her academic career as (blood glucose fasting ~ 17 mmol/l). Patient well as prime years of her life due to avoidable did make life-style modifications, but her complications of therapeutic misadventures glycemic control was never optimal. Dose of for treatment of her diabetes. We also propose oral hypoglycemic agents was gradually a hypothesis to explain persistent maximized and subsequently insulin was hyperglycemia despite over-treatment in this added two year later in view of uncontrolled case. glycemic status. Patient’s family was very Introduction positive about compliance of patient to diet and medications. But, her glycemic control has Primum-non-nocere: first do no harm is the always been poor with last HbA1c of 12.1% basic principle on which modern allopathy is (109 mmol/mol) and FBG of 16.2 mmo/l. Her practiced or should be practiced. In field of endocrinology and diabetes, numerous trials general condition gradually worsened and she have been done to prove the benefit of intensive started getting nervous all the time and would glycemic control. Though there is some feel jittery without any stress. She had to leave evidence that intensive glycemic control when her job as she had always been in poor health done early in course of disease and in since diagnosis of diabetes. She was diagnosed motivated people may have long lasting to have depression in view of her symptoms benefit, hypoglycemia is consistently increased and has been taking treatment for it for last in frequency and severity in intensively treated four years. She had no history suggestive of any patients. Hypoglycemia is well known to m i c r o v a s c u l a r o r m a c r o v a s c u l a r inversely affect cardiovascular disease and complications. She had been admitted three increase mortality. So, proper selection of times in last two years for glycemic control and patient for intensive management and each admission resulted in escalation of dose of stepwise approach to treatment is of utmost insulin. Her current medication included 4 mg importance. This case is a prototype for what Glimipride, 2 gm Metformin, 100 mg Sitagliptin can go wrong if basic principles of medicine are and 60 units of premix insulin. She had flouted. presented with an urgent request for Haryana Medical Journal - March 2017, Vol. 40, Issue 01 14 admission as she was not able to stand, was India. Patients in western countries are feeling dizzy and had sinking feeling. She had generally detected early in course of disease no evidence of infection or cardiac illness. Her due to universal availability of health services. dietary compliance was good but she did not In contrast, in developing countries people like to take her medication as, according to her, generally come in contact with healthcare it makes her sick. Her random BG at system relatively late. So, algorithms given by presentation was 27.8 mmol/l, but workup for various societies in west may not be applicable diabetic ketoacidosis was negative. On to our group of patients (2). This patient should examination, systemic examination was have been offered a life style modification with normal including vitals. But she looked visibly or without metformin as first intervention, tense and tremulous. Her co-morbidities irrespective of her HbA1c value. She would included Hypothyroidism (euthyroid on have been managed with metformin during all treatment), depression (on multiple drugs, but these years as proven by the fact that she has worsened over the years) and she had maintained her HbA1c just on metformin gained 10 kg weight over 5 years. In view of during follow-up of one year. The fact that she weight gain, her dislike for anti-diabetic was gaining weight despite being uncontrolled medication, worsening psychiatry issues and diabetic for so many years made us suspect tremulousness, it was decided to decrease her underlying hypoglycaemia as real culprit for medication. Her glimipride was stopped and her condition. Moreover, her statement that insulin dose was decreased to half (Table 1). anti-diabetic medication makes her sick Her symptoms as well as glycemic control further strengthened our conviction. improved markedly over next 3 days (Table 1). Her drugs were tapered to only Metformin 1 Another aspect that has been brought to fore by gm BD and insulin stopped altogher. She this case is lack of literature on this kind of markedly improved and stated that she has patients. It is commonly accepted fact in never felt better in last 8 years (Table 2). Need e n d o c r i n o l o g y p r a c t i c e t h a t a n y for anti-depressants decreased (Table 2). She hypoglycaemia can result in paradoxical maintained good glycemia control with FBG 5- hyperglycaemia as a result of counter- 7 mmol/l and PPBG 7.5-8.5 mmol/l till last regulatory hormones. But the duration for follow up and her HbA1c dropped to 6.8% (51 which this exaggerated response would persist mmol/mol) over next twelve months. is not known. Moreover, but happens to this Discussion exaggerated metabolic response in case of repeated hypoglycaemia has also not been American diabetes association and European elucidated, contrary to our well established association for study of diabetes, in their knowledge about hypoglycemia associated landmark position statement emphasized the autonomic failure. value of individualization of diabetic therapy for every patient (1). This emphasized that fact We propose a hypothesis explaining persistent that we should not be treating lab reports to hyperglycemia in-spite of over-medication some arbitrary targets, but it’s the quality of life (Figure 1). Persistent hyperglycemia may be of patient, according to their own choices, that result of combination of exaggrated couter- should matter most. In this case, as it regulatory hormones and insulin receptor eventually turned out, patient was being over- d o w n r e g u l a t i o n s e c o n d a r y t o treated all this time and most of her problems hyperinsulinemia. were iatrogenic rather than diabetes related. In an editorial, published in journal “Diabetes” This case also brings out the difference in in 1960, Michael Somogyi observed that patient-healthcare system interaction in “Anyone who is unaware of the paradoxical fact western countries vs. developing countries like that hypoglycemia begets hyperglycemia will

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 15 be prompted to combat the hypoglycemia- Association for the Study of Diabetes (EASD). induced glycosuric tide by stepping up the Diabetes Care. 2012 Jun;35(6):1364-79. insulin dosage. A vicious cycle leading to higher 2. Garber AJ, Abrahamson MJ, Barzilay JI et and higher insulin dosage ensues; the severity al. AACE comprehensive diabetes management of diabetes progressively increases and can algorithm 2013. Endocr Pract. 2013 Mar- advance to an extremely unstable state” (3). Apr;19(2):327-36. This is exactly what seems to have happened in 3. Somogyi M. Exacerbation of diabetes by this case. Hypoglycemia is well known to be an excess insulin action. Diabetes. 1960 Jul- independent predictor of increased mortality Aug;9:328-30. in patients with diabetes in all major diabetes 4. Bonds DE, Miller ME, Bergenstal RM, et trials (4,5). Authors would like to emphasize al. The association between symptomatic, the importance of patient centric approach for severe hypoglycaemia and mortality in type 2 diabetes management through this case. diabetes: retrospective epidemiological References analysis of the ACCORD study. BMJ 1. Inzucchi SE, Bergenstal RM, Buse JB, 2010;340:b4909 Diamant Metal. Management of hyperglycemia 5. Duckworth W, Abraira C, Moritz T et al. in type 2 diabetes: a patient-centered Glucose control and vascular complications in approach: position statement of the American veterans with type 2 diabetes. N Engl J Med. Diabetes Association (ADA) and the European 2009 Jan 8;360(2):129-39.

Table 1: Pattern of fall in Blood Glucose in immediate period post intervention Haryana Medical Journal - March 2017, Vol. 40, Issue 01 16 Table 2: Change in clinical parameters before and after treatment

Figure 1: Possible mechanisms linking persistent hyperglycemia with over-medication Corresponding Author: Rajiv Singla, 1704, Gyanshakti Apartments, Plot 7, Sector 6, Dwarka, New Delhi 110075 Phone: +919968277369 Email: [email protected]

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 17 Review Article :- DIABETIC NEPHROPATHY: The Future Sameer Aggarwal*, Nityanand ** *Associate Professor : **Senior Professor & Head, Deptt. of Medicine, PGIMS Rohtak, India email : [email protected]

Introduction/ Epidemiology filtration rate (eGFR) is a calculated estimate of Diabetic nephropathy is a clinical syndrome the glomerular filtration rate and is therefore characterized by the following : also referred to as the calculated GFR. eGFR has come into use over the last decade because it is • Persistent albuminuria (>300 mg/d or easy to calculate and is a convenient substitute >200 μg/min) that is confirmed on at least 2 for the measured GFR which is not to easy to occasions 3-6 months apart determine and requires measurement of • Progressive decline in the glomerular clearance of substances such as inulin, filtration rate (GFR) creatinine, radioisotope (Tc-DTPA, Cr-EDTA) • Elevated arterial blood pressure and radiocontrast agents (iothalamate, iohexol) from the plasma. Many of the Asian Prevalence of diabetic kidney disease is rising countries have now validated eGFR equations worldwide, even while prevalence of some specifically for their respective populations. other diabetes complications is showing a Although efforts to develop an equation for the downward trend. (1) Indian population are continuing, we do not as The overall burden for people with diabetic yet have such an equation The commonest nephropathy is extremely high because of the method used for calculating the eGFR depends strong associations of diabetic nephropathy on the abbreviated MDRD (Modification of Diet and cardiovascular disease (CVD) with End in Renal Disease) equation. Stage Renal Disease. The Indian Council of The other widely used equations for Medical Research India Diabetes Study (ICMR- calculating eGFR are the Cockroft-Gault, CKD- INDIAB study) showed that India had 62.4 Epi. The formulae are given in table 1 with million people with diabetes in 2011. These serum creatinine expressed in mg/dl. (4) numbers are projected to increase to 101.2 Table 1 million by 2030. (2) With rising prevalence of Diabetes in India, prevalence of Chronic Kidney Disease is expected to rise. Abbreviated GFR(ml/min/1.73 m²)= 186 x (S.Cr in Between 1997 and 2013, median years of life MDRD µmol/l × 0.011312) -1.154 × (age)- 0.203 × (0.742 if female) × (1.212 if lost worldwide to chronic kidney disease African/American Black) increased by 90%, compared with a 67% increase for years of life lost to diabetes .(3) Cockroft- CCr (ml/min) = (140-age) x lean body weight (kg) x0.85 (if female) / 72xS.cr Work-up Gault (mg/dl) Identifying and monitoring diabetic nephropathy primarily involves two diagnostic CKD-Epi GFR (ml/min)= 166 x (Cr/0.7)-0.329 x modalities: assessment of kidney function in (0.993)Age terms of estimated glomerular filtration rate (eGFR) and estimation of kidney damage in terms of albuminuria. Estimated glomerular

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 18 New-Biomarkers Preliminary results from the ARTS-DN trial Interestingly significant glomerular damage s u g g e s t t h a t o r a l f i n e r e n o n e has already occurred by the time albuminuria (mineralocorticoid receptor antagonist) is apparent. (5,6). Therefore several new reduces urinary albumin-to-creatinine ratio, a biomarkers are being investigated to surrogate parameter of renal impairment.(11) overcome the limitations of current diagnostic Recent evidence showed that lack of a vitamin tools for diabetic nephropathy. Investigators D receptor resulted in an increase in RAAS have recently focused on tubular damage activity and significant proteinuria . The renal markers as biomarkers of the development and protective effects of 1,25(OH)2D3 and its progression of diabetic nephropathy analogs might involve suppression of renin particularly non-albumin proteinuria (NAP) gene transcription as well as high glucose- markers like α-1 microglobulin, β-2 induced angiotensinogen production. A recent macroglobulin, immunoglobulin G, cystatin C, large, randomized controlled trial showed that transferrin, nephrin, metalloproteinase-9, and paricalcitol reduced albuminuria in patients tissue inhibitor of metalloproteinases-1. (7) with type 2 diabetic nephropathy. An ongoing While we wait for these modalities to make the trial is evaluating whether direct VDR long journey from the research laboratory to activation can reduce the human RAAS in the clinic, we must make full use of available diabetes compared with the effect of an ACE resources inhibitor and whether this mechanism can translate to clinically relevant endpoints of Present / Future Treatment Possibilities diabetic nephropathy. The outcomes of this Limited treatment options are available for trial will have important implications for the prevention and treatment of Diabetic r e c o m m e n d a t i o n o f v i t a m i n D Nephropathy. Renal protection is observed supplementation for the primary prevention of with renin-angiotensin-aldosterone system kidney complications in diabetes (12,13) (RAAS) pathway blockade, but the residual risk Trials assessing renal outcomes of SGLT2 of progression to severe disease or death is still inhibitors (such as canaglifozin and high. Several therapeutic strategies have been e m p a g l i f l o z i n ) h a v e s h o w n t h e s e suggested to improve this risk, including low- hypoglycaemic drugs to prevent progression of protein diets, dual or triple blockade of the diabetic kidney disease. (14,15). SGLT2 RAAS, statins, erythropoietin, sulodexide, inhibitors reduce sodium reabsorption in the bardoxolone, and carbon absorption.(8,9) p rox i m a l t u b u l e , c a u s i n g , t h ro u g h However, none of these approaches has been tubuloglomerular feedback, afferent arteriole shown to be effective. Emerging data shows va s o c o n s t r i c t i o n a n d re d u c t i o n i n that many pathways beyond hypertension hyperfiltration. In the EMPA-REG OUTCOME underlie the pathophysiology of diabetic trial analyses of the secondary renal outcomes kidney disease. These additional pathways ,compared with those receiving placebo, have been the basis for several new therapeutic patients receiving empagliflozin experienced a approaches. Endothelin receptor antagonists 39% reduction in the risk of new or worsening (such as atrasentan) and inhibitors of the nephropathy (defined as a UACR >300 mg/g, inflammatory response (eg, JAK–STAT doubling of serum creatinine with an eGFR of inhibitors, or chemokine receptor blockers ) 45 mL/min/1.73 m2 or less, initiation of renal a re u n d e rg o i n g c l i n i c a l t r i a l s . ( 1 0 ) replacement therapy, or death due to renal Mineralocorticoid receptor antagonists, which disease). When the composite outcome of have shown good outcomes in heart failure, are doubling of serum creatinine, initiation of renal being tested as a treatment for diabetic kidney replacement therapy, or death due to renal disease. disease was considered, the relative risk

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 19 reduction in the empagliflozin group was even 5. Barratt J, Topham P. Urine proteomics: more pronounced (46%). These data provide the present and future of measuring urinary strong support for a nephroprotective effect of protein components in disease. CMAJ. SGLT2 inhibitors. 2007;177:361–368 Renal replacement therapy is a massive burden 6. Cooper ME. Pathogenesis, prevention, on healthcare systems. Low-cost systems for and treatment of diabetic nephropathy. Lancet dialysis are being explored 1998; 352:213. 7. Kamijo-Ikemori A, Sugaya T, Kimura K. Combination treatment targeting several Novel urinary biomarkers in early diabetic pathophysiological pathways simultaneously kidney disease. Curr Diab Rep. 2014;14:513 might be needed and combination treatment 8. Pergola PE, Raskin P, Toto RD. might need to be personalised. However Bardoxolone methyl and kidney function in dealing with heterogeneity of diabetic kidney CKD with type 2 diabetes. N Engl J Med 2011; disease pathophysiology is difficult. 365:327. Identification of biomarkers for risk 9. Heerspink HL, Greene T, Lewis JB, . prediction, prognosis, and treatment response Effects of sulodexide in patients with type 2 should be a key area of research in the coming diabetes and persistent albuminuria. Nephrol years Dial Transplant 2008; 23:1946. Development of effective and affordable drugs 10. Kohan DE, Pritchett Y, Molitch M, . for prevetion and treatment are essential to Addition of atrasentan to renin-angiotensin prevent diabetic kidney disease from system blockade reduces albuminuria in becoming the next global epidemic. diabetic nephropathy. J Am Soc Nephrol 2011; 22:763. References 11. Bakris GL, Agarwal R, Chan JC, Cooper 1. .Gregg EW, Li Y, Wang J, Burrows NR. MEEffect of Finerenone on Albuminuria in Changes in Diabetes-Related Complications Patients With Diabetic Nephropathy: A in the United States, 1990–2010. N Engl J Med Randomized Clinical Trial. JAMA. 2015 Sep 2014;370:1514-23 1;314(9):884-94. 2. Anjana RM, Pradeepa R, Deepa M, Datta 12. De Zeeuw D, Agarwal R, Amdahl M, M. Prevalence of diabetes and prediabetes A u d h y a P. Selective vitamin D receptor (impaired fasting glucoseand/or impaired activation with paricalcitol for reduction of glucose tolerance) in urban and rural India: albuminuria in patients with type 2 diabetes Phase I results of the Indian Council of Medical (VITAL study): a randomised controlled trial. Research-INdia DIABetes (ICMR-INDIAB) Lancet 2010;376:1543–1551. study. Diabetologia 2011;54:3022-7 13. Brown JM, Secinaro K, Williams JS, Vaidya A. Evaluating hormonal mechanisms of vitamin 3. GBD 2013 Mortality and Causes of Death D receptor agonist therapy in diabetic kidney Collaborators*. Global, regional, and national disease: the VALIDATE-D study. BMC Endocr age–sex specifi c all-cause and cause-specifi c Disord 2013;13:33. mortality for 240 causes of death, 1990–2013: 14. Lambers-Heerspink HJ, Desai M, Jardine a systematic analysis for the Global Burden of M, Balis D. Canagliflozin slows progression of Disease Study 2013. Lancet. 2015 Jan renal function decline independent of glycemic 10;385(9963):117-71 effects. J Am Soc Nephrol 2016; 28;2016. 4. Waad-Allah S, Mula-Abed, Khalid Al 15. Wanner C, Inzucchi SE, Lachin JM, Rasadi, Dawood AR.Estimated Glomerular Fitchett D. Investigators E-RO. Empagliflozin Filtration Rate (eGFR): A Serum Creatinine- and progression of kidney disease in type 2 Based Test for the Detection of Chronic Kidney diabetes [published online ahead of print June Disease and its Impact on Clinical Practice. 14, 2016]. N Engl J Med doi:10.1056/ Oman Med J. 2012 Mar; 27(2): 108–113 NEJMoa1515920

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 20 Diabetic Retinopathy-A Brief Review of Current Practice. Dr Kapil Midha, Dr Divya Taneja, Dr Ashok Taneja Reprint Requests to Dr Kapil Kumar Midha Midha Eye Centre, D N Colony, [near fire station] New Railway Road Gurgaon. Email: [email protected]

Prevalance. disease, whereas those with Type 2 diabetes The prevalence of diabetes, is increasing all should have a prompt examination at the time over the world and so is that of diabetic of diagnosis and at least yearly examinations retinopathy. thereafter. Prevalence in India. Tight control of diabetes and keeping the BP as normal as possible lowers the risk of Prevalence of Diabetic Retinopathy in India is retinopathy development and progression. approx 20% of the diabetic population. There lies the need of keeping near normal I n v e s t O p h t h a l m o l V i s S c i . 2 0 0 5 HbA1C levels, serum lipids and BP. Jul;46(7):2328-33. Diabetic women , who become pregnant should Prevalence of diabetic retinopathy in urban be examined early during pregnancy to look India: the Chennai Urban Rural Epidemiology for any diabetic retinopathy. Study (CURES) eye study, I. Risk Factors Singh R, Ramasamy K, Abraham C, Gupta V, Duration of diabetes is the biggest risk factor. Gupta A. Diabetic retinopathy: An update. Type 1- 25% after 5yrs and almost 60% at 10 Indian J Ophthalmol [serial online] 2008 [cited and 80% at 15yrs, have retinopathy. 2015 Feb 13];56:179-88. 50% of type 1 young adult patients, developed A v a i l a b l e f r o m : proliferative diabetic retinopathy after 20ys http://www.ijo.in/text.asp?2008/56/3/179/ according to the Wisconsin Epidemiologic 40355 Study of Diabetic Retinopathy (WESDR) study. Vision Loss in Diabetic Retinopathy Can be Type 2 patients-24 to 40 % at 5yrs, and 50 to 80 Severe % at 20yrs . PDR in upto 25% in patients with After 10 years of onset of DM, blindness (visual diabetes of 25yrs. acuity of 20/200 or less in the better eye) was 1.8, 4.0 and 4.8% in type 1, insulin-treated type Major International Trials and Studies on 2 and non-insulin-treated type 2 patients, Diabetic Retinopathy. respectively. In these three groups of patients, the 10-year incidence visual impairment (loss Over the past many year; there has been a lot of of 15 letters on a scale of 0-70 letters) was 9.4, clinical research on this disease, which has 37.2 and 23.9%, respectively. given us the know how on the prevelance, risk factors, natural disease progression, and .Moss SE, Klein R, Klein BE. Ten-year incidence guidelines for management. This article is of visual loss in a diabetic population. mainly based on these major studies. Ophthalmology 1994;101:1061-70. • Diabetes Control and Complications Awareness and Screening Trial (DCCT)[1,2,3] People with Type 1 diabetes should have • Follow-up study to the DCCT titled annual screenings for diabetic retinopathy Epidemiology of Diabetes Interventions and beginning 5 years after the onset of their Complications (EDIC)4.5.6.7.8 Haryana Medical Journal - March 2017, Vol. 40, Issue 01 21 • Diabetic Retinopathy Study (DRS)9.10 neovascularisation on the retina. NVD [new • Early Treatment Diabetic Retinopathy vessels on disc] and NVE[new vessels Study (ETDRS)11.12 elsewhere]. • Diabetic Retinopathy Vitrectomy Study The vessels may bleed and cause vitreous Hge. (DRVS)13 New vessels can undergo fibrosis and cause epiretinal membranes, vitreo retinal traction • Wisconsin Epidemiologic Study of and even retinal detachment. Diabetic Retinopathy (WESDR)14 • Diabetic Retinopathy Clinical Research In extreme cases new vessels can even develop Network (DRCR.net) Protocol I study15 in the angle of the eye and cause neovascular glaucoma. Stages of Diabetic Retinopathy PDR cases should receive prompt PRP and Diabetic retinopathy progresses over a period intravitreal VEGF Injections should be of time; from mild to more severe stages ;if it considered. goes unmanaged. Additional Diagnostic Tests: • NPDR: ie non proliferative stage of diabetic retinopathy • Color and red-free fundus photography • Microaneurysms • Optical coherence tomography (OCT) • Intraretinal hemorrhages • Fluorescein angiography (FA) • Cotton wool spots • Ultrasonography • Venous Dilatation Optical Coherence Tomography • Retinal edema and lipid deposits[hard • High resolution imaging of the retina. exudates] • Excellent test for monitoring diabetic • All are retinal vascular abnormalities macular edema. • CSME: or clinically significant macular • In clinical practice today decisions are edema often based on OCT : for eg whether to give or • Retinal thickening and/or hard exudates repeat anti vegf injections. involving the macular centre or threatening to involve it. Requires prompt treatment to prevent vision loss. Fundus Flourescein Angiography • Before the coming of OCT , it was the Severe NPDR mainstay investigation. Still very useful. • Retinal ischemia due to gradual closure • Differentiate DME from other macular of retinal vessels; causing pathology, • Venous abnormalities • Identify macular capillary nonperfusion- for vision loss unresponsive to therapy • IRMA • Detect untreated areas after previous • Extensive leakage from retinal vessels PRP –more and more hemorrgages and exudation. S u c h p a t i e n t s a r e r e c o m m e n d e d Ultrasonography PRP{panretinal-scatter- photocoagulation Useful For assessment of retinal status in the Proliferative Diabetic Retinopathy presence of a vitreous hemorrhage or other media opacity As the disease progresses unchecked, increasing retinal ischemia causes Importance of early detection of DR. Haryana Medical Journal - March 2017, Vol. 40, Issue 01 22 Clinical Trials have clearly shown that we can OCT is a great diagnostic tool for properly prevent severe visual loss due to DR in a vast evaluating DME. majority of patients by proper treatment Retinal Laser and Intravitreal anti-vegf agents Effective Screening by an Ophthalmologist is are effective treatment modalities for DME. therefore very important. A close partnership Multiple studies and now more in favour of between the treating Physician and antivegf agents. Ophthalmologist is highly recommended. Severe NPDR Available Management Strategies ETDRS recommends: Anti-VEGF s in Diabetic Retinopathy. Anti-VEGF therapy is now the frontline panretinal photocoagulation not required for therapy in diabetic Macular edema along with eyes with mild or moderate NPDR, but focal laser treatment. Many clinical trial maintain close follow up. When retinopathy is support this Paradigm. For eg READ-2 study, more severe,--consider panretinal DRCR protocol. photocoagulation. Prompt PRP recommended when the eye reaches the high-risk Anti vegfs with either prompt or deferred laser proliferative stage. photocoagulation is now considered better for DME than laser alone. The goal of laser surgery is to reduce the risk of vision loss. Laser Photocoagulation DRS and ETDRS studies have defined effective High Risk PDR: defined as laser treatment protocols for Diabetic • New vessels on the optic disc >25% to Retinopathy. However anti-vegf therapy is 33% disc area now the mainstay for diabetic macular edema. • New vessels on the optic disc associated Treatment Protocols: with pre-retinal or vitreous haemorrhage Early NPDR • Retinal new vessels with vitreous or pre- Annual Follow up and tight control of Diabetes retinal haemorrhage recommended PRP is strongly indicated in such patients to Moderate NPDR: Follow up within one yr reduce the risk of sever visual loss. {DRS and because disease progression is common. The ETDRS}. PRP usually induces regression of new risk of Diabetic Macular Edema in moderate vessels. NPDR is approx 23%. OCT imaging of the macula is helpful in suspected cases . Unresponsive High-Risk PDR NPDR with Diabetic Macular Edema severe vitreous or preretinal hemorrhage, - Early Treatment Diabetic Retinopathy Study PRP not possible.-vitrectomy indicated. defines CSME[clinically significant macular Vitreous surgery is also indicated in patients edema]: • with macula-threatening traction retinal Thickening of the retina at or within 500 µm of detachment , the center of the macula. • combined traction-rhegmatogenous Hard exudates at or within 500 µm of the center retinal detachment, of the macula, when associated with adjacent retinal thickening. • Patients with vitreous hemorrhage and rubeosis iridis need prompt vitrectomy and A zone or zones of retinal thickening one disc intraoperative PRP. area or larger, where any portion of the thickening is within one disc diameter of the Recommendations from major studies on center of the macula Diabetic Retinopathy.

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 23 • DIABETIC RETINOPATHY STUDY • Diabetic Retinopathy Vitrectomy Study (1972-1979) Research Group. Early vitrectomy for severe (DRS) investigates the value of laser vitreous hemorrhage in diabetic retinopathy: photocoagulation surgery for patients with four-year results of a randomized trial-- severe NPDR and PDR. Diabetic Retinopathy Vitrectomy Study report 5. Arch Ophthalmol 1990;108:958-64. Diabetic Retinopathy Study Research Group. Indications for photocoagulation treatment of • Diabetic Retinopathy Vitrectomy Study diabetic retinopathy: Diabetic Retinopathy Research Group. Early vitrectomy for severe Study report number 14. Int Ophthalmol Clin vitreous hemorrhage in diabetic retinopathy: 1987;27:239-53. two-year results of a randomized trial-- • WISCONSIN EPIDEMIOLOGIC STUDY Diabetic Retinopathy Vitrectomy Study report OF DIABETIC RETINOPATHY (1979) 2. Arch Ophthalmol 1985;103:1644-52. (WESDR) studies the incidence of • Diabetic Retinopathy Vitrectomy Study complications associated with diabetes (eye Research Group. Early vitrectomy for severe complications such as diabetic retinopathy and proliferative diabetic retinopathy in eyes with visual loss, kidney complications such as useful vision: results of a randomized trial-- diabetic nephropathy, and amputations), Diabetic Retinopathy Vitrectomy Study report assesses risk factors (such as poor glycemic 3. Ophthalmology 1988;95:1307-20. control, smoking, and high blood pressure) • Diabetic Retinopathy Vitrectomy Study that may contribute to the development of Research Group. Early vitrectomy for severe these complications. proliferative diabetic retinopathy in eyes with • Klein R, Klein BE, Moss SE, Cruickshanks useful vision: clinical application of results of a KJ. The Wisconsin Epidemiologic Study of randomized trial--Diabetic Retinopathy diabetic retinopathy. XIV. Ten-year incidence Vitrectomy Study report 4. Ophthalmology and progression of diabetic retinopathy. Arch 1988;95:1321-34. Ophthalmol 1994;112:1217-28. • DIABETIC RETINOPATHY CLINICAL • EARLY TREATMENT DIABETIC RESEARCH NETWORK (DRCR.Net) (2002- RETINOPATHY STUDY (1985-1990) PRESENT) (ETDRS) evaluates the value of -- a collaborative study including over 100 photocoagulation for patients with NPDR or participating sites in the US and funded by PDR without high-risk characteristics. National eye institute. It is dedicated to • Early Treatment Diabetic Retinopathy facilitating multicenter clinical research of Study Research Group. Photocoagulation for diabetic retinopathy, diabetic macular edema, diabetic macular edema: Early Treatment and associated conditions . Diabetic Retinopathy Study report number 1. Under its umbrella; multiple clinical trials have Arch Ophthalmol 1985;103:1796-806. been carried out to assess,the role of anti-VEGF, • Early Treatment Diabetic Retinopathy laser treatment, and corticosteroids in diabetic Study Research Group. Early photocoagulation macular edema. for diabetic retinopathy: ETDRS report number • Elman MJ, Qin H, Aiello LP, et al, Diabetic 9. Ophthalmology 1991;98:766-85. Retinopathy Clinical Research Network. • D I A B E T I C R E T I N O P A T H Y Intravitreal ranibizumab for diabetic macular VITRECTOMY STUDY (1983-1987) edema with prompt versus deferred laser (DRVS) --role of vitrectomy in managing eyes treatment: three-year randomized trial results. with very severe PDR. Ophthalmology 2012;119:2312-8.

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 24 • RANIBIZUMAB FOR EDEMA OF THE 4-Diabetes Control and Complications MACULA IN DIABETES (READ-2) Trial/Epidemiology of Diabetes Interventions • Nguyen QD, Shah SM, Khwaja AA, et al, and Complications Research Group. READ-2 Study Group. Two-year outcomes of Retinopathy and nephropathy in patients with the ranibizumab for edema of the mAcula in type 1 diabetes four years after a trial of diabetes (READ-2) study. Ophthalmology intensive therapy. N Engl J Med 2000;342:381- 2010;117:2146-51. 9. • BEVACIZUMAB OR LASER THERAPY 5-Writing Team for the Diabetes Control and (BOLT) STUDY Complications Trial/Epidemiology of Diabetes Interventions and Complications Research • Rajendram R, Fraser-Bell S, Kaines A, et Group. Effect of intensive therapy on the al. A 2-year prospective randomized controlled microvascular complications of type 1 diabetes trial of intravitreal bevacizumab or laser mellitus. JAMA 2002;287:2563-9 therapy (BOLT) in the management of diabetic 6-4Lyons TJ, Jenkins AJ, Zheng D, et al. Diabetic macular edema: 24-month data: report 3. Arch retinopathy and serum lipoprotein subclasses Ophthalmol 2012;130:972-9. in the DCCT/EDIC cohort. Invest Ophthalmol Vis Sci 2004;45:910-8. STUDY OF RANIBIZUMAB INJECTION IN 7-Epidemiology of Diabetes Interventions and SUBJECTS WITH CSDME WITH CENTER Complications (EDIC) Research Group. INVOLVEMENT SECONDARY TO DIABETES Epidemiology of Diabetes Interventions and MELLITUS (RISE AND RIDE) C o m p l i c a t i o n s ( E D I C ) : d e s i g n , Nguyen QD, Brown DM, Marcus DM, et al. implementation, and preliminary results of a Ranibizumab for diabetic macular edema: long-term follow-up of the Diabetes Control results from 2 phase III randomized trials: RISE and Complications Trial cohort. Diabetes Care and RIDE. Ophthalmology 2012;119:789-801. 1999;22:99-111. References: 8-Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions 1-Diabetes Control and Complications Trial and Complications (DCCT/EDIC) Research Research Group. The relationship of glycemic Group. Modern-day clinical course of type 1 exposure (HbA1c) to the risk of development diabetes mellitus after 30 years' duration: the and progression of retinopathy in the Diabetes Diabetes Control and Complications Control and Complications Trial. Diabetes Trial/Epidemiology of Diabetes Interventions 1995;44:968-83. a n d C o m p l i c a t i o n s a n d P i t t s b u r g h 2-Diabetes Control and Complications Trial Epidemiology of Diabetes Complications Research Group. The effect of intensive experience (1983-2005). Arch Intern Med treatment of diabetes on the development and 2009;169:1307-16. progression of long-term complications in 9-Diabetic Retinopathy Study Research Group. insulin-dependent diabetes mellitus. N Engl J Indications for photocoagulation treatment of Med 1993;329:977-86. diabetic retinopathy: Diabetic Retinopathy 3-Diabetes Control and Complications Trial Study report number 14. Int Ophthalmol Clin Research Group. The effect of intensive 1987;27:239-53. diabetes treatment on the progression of 10-Diabetic Retinopathy Study Research diabetic retinopathy in insulin-dependent Group. Photocoagulation treatment of diabetes mellitus: the Diabetes Control and proliferative diabetic retinopathy: the second Complications Trial. Arch Ophthalmol report of Diabetic Retinopathy Study findings. 1995;113:36-51. Ophthalmology 1978;85:82-106.

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 25 11-Early Treatment Diabetic Retinopathy four-year results of a randomized trial-- Study Research Group. Grading diabetic Diabetic Retinopathy Vitrectomy Study report retinopathy from stereoscopic color fundus 5. Arch Ophthalmol 1990;108:958-64. photographs--an extension of the modified 14-Klein R, Klein BE, Moss SE, Cruickshanks KJ. Airlie House classification: ETDRS report The Wisconsin Epidemiologic Study of diabetic number 10. Ophthalmology 1991;98:786-806. retinopathy. XIV. Ten-year incidence and 12-Early Treatment Diabetic Retinopathy progression of diabetic retinopathy. Arch Study Research Group. Photocoagulation for Ophthalmol 1994;112:1217-28. diabetic macular edema: Early Treatment 15-Elman MJ, Qin H, Aiello LP, et al, Diabetic Diabetic Retinopathy Study report number 1. Retinopathy Clinical Research Network. Arch Ophthalmol 1985;103:1796-806. Intravitreal ranibizumab for diabetic macular 13-Diabetic Retinopathy Vitrectomy Study edema with prompt versus deferred laser Research Group. Early vitrectomy for severe treatment: three-year randomized trial results. vitreous hemorrhage in diabetic retinopathy: Ophthalmology 2012;119:2312-8.

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 26 Diabetes & Mahabharata

Dheeraj Kapoor Ruchi Kapoor Senior Consultant Senior Consultant & Head Endocrinology Lab Medicine, Oncquest Diagnostics Artemis Hospitals , Gurugram New Delhi

ABSTRACT – DIABETES IN MAHABHARATA We try to correlate the episode where in the battle is about to start – This article highlights the possibility of diabetes in some characters of Mahabharata As Arjun says this to Lord Krishna - which was not mentioned in an overt manner सीदन्ति मम गात्राणि मुखं च परिशुष्यति । but subtle pointers did exist. वेपथुश्च शरीरे मे रोमहर्षश्च जायते ॥ १ - २९ ॥ The Mahabharata is a compendium of the My limbs weaken and give way , associated stories of the Kuru Vansh and the battle that they fought. The characters are My mouth is dry, burning chosen for the possible reference to My body trembles and tingles with goose-flesh. dysglycemia. We hope that this article will not only open a । new insight into the existence of diabetes from गाण्डीवंस्रंसतेहस्तात्त्वक्चैवपरिदह्यते ancient times but will also encourage the न च शक्नोम्यवस्थातुं भ्रमतीव च मे मनः ॥ १ - ३० ॥ readers to learn about our ancient mythology The Ganḍ ̣iva slips resistless from my hand; and culture. My skin burns, I cannot stand; Keywords – My mind is restless, unable to be still. India, Diabetes, Mahabharata, Lord Krishna, Arjun, Bhishma. The Mahabharata, one of the longest epics ever At the outset it seems to be just a case of simple written, was authored by the sage Ved Vyasa. It anxiety and actually nothing more than that may mean different things to different subsets But , seeing from the vision of an of people, classified as per age, education and endocrinologist (just as Arjun saw the EYE of most importantly spirituality the bird on the tree),could Arjun have had diabetes; a dysglycaemia which initially went On the other extreme, it may just be another unnoticed because of the rigorous regime that book for some. the warriors followed,which has now been Let us however look at it from an entirely worsened by anxiety. Anxiety which may cause different perspective; the perspective of cortisol and catecholamine surge and worsen diabetes. the sugars, the hormone surge may lead to ketosis which would actually worsen weakness It has been aptly written that “Whatever is here and may cause pain and cramps in the legs may be found elsewhere, whatever is not, leading to the legs giving way. The dry mouth is cannot be found anywhere else.” This fact, one of the hallmarks of poor glycemic control encouraged me to look for the possibility of and may fit well with the existing disease. The searching for diabetes in the various characters burning in the limbs and weakness and the of the epic, by trying to pick up subtle hints and inability to stand could have been due to acute knitting them up together.(1,2) h y p e r g l y c e m i c n e u r o p a t h y , a Haryana Medical Journal - March 2017, Vol. 40, Issue 01 27 condition which is known to improve when an not counter and was looted; he could not recall optimal glycemic control is achieved. the mantras which he had learnt in his earlier Alternatively the above condition can also be days. Was it dementia due to recurrent infarcts explained by starvation ketosis. In this case, the secondary to uncontrolled diabetes, or was it impending war with own brethren could have Alzheimer’s Disease(Type 3 Diabetes),(7)we led to loss of appetite and starvation and shall never know therefore the features of hypoglycemia and Lord Krishna, the eighth incarnation of Lord ketosis, like generalized weakness, sweating Vishnu was extremely fond of butter, ghee, milk and the legs trembling. products and sweets. He probably had diabetes but even as time passed by, he could not control The trembling of the body could have been due his diet and could not overcome his urge to to anxiety, glycemic issues or it could have been have sweets. He died of a wound in his thyrotoxicosis which is actually causing foot,caused by an arrow. Interestingly, the foot tremors, sweating which (in the subsequent is a non vital organ; and so to die from an arrow shloka) leads to the slipping of the Gandiva and due to a foot injury and a subsequent ulcer that burning in the whole body. The legs giving way never healed , raises the possibility of a non could have been due to proximal weakness, a healing diabetic foot or gangrene which may sign which could also have affected the upper have led to sepsis and eventual septicemia. extremities and resulted in the inability to hold Ashwathama,the son of Acharya Drona was a the Gandiva properly. But more importantly very heavy character , who again had a liking from the point of view of the present context, for ghee and sweets. Once the ‘Mani’ on his thyrotoxicosis could also have led to the forehead was ripped off by Lord Krishna,the worsening of sugars.(4) wound on his forehead never healed.(2) Could The tremulousness of the body, along with the this non healing wound be because of sensation of heat and flushing may be a subtle uncontrolled diabetes. pointer towards a neuroendocrine tumor The notorious character of Shakuni , who had (most commonly a pheochromocytoma) which stabbed himself in the thigh,to remind himself will produce all the above symptoms of the revenge against the kuruvansh had particularly an extreme nervousness resulting developed a non healing wound (2)which from excessive catecholamines and also with could also be the result of dysglycaemia given weakness of the lower limbs and sweatiness of the fact that such personalities consumed the palms. Pheochromocytoma, again, more more of Rajasik and Tamasik Bhojan as often than not will worsen glycemic control. (5) compared to their Satvik counterparts. However one must realize that Arjun had won a Bheem ,the big burly Pandav has been believed to have acromegaly,but given his polyphagia it battle for King Viraat just 6 months back, at a is quite possible that he had secondary time when he had no symptoms. It is therefore diabetes(6) difficult to prove or disprove whether he actually had diabetes or not but even if he had Pitamah Bhishma,the most revered amongst any of the above mentioned diseases they were the kuruvansh used to have intractable pain in not of a long standing at the time of the start of the legs and was believed to be suffering from neuropathy(6). Given the dietary advices that the battle.(3) Bhishma has mentioned in his archives it may In the twilight of his life when Arjun was be plausible that this neuropathy was diabetic returning from Dwarka(3) with those who had in origin and he was practicing diet control and survived the destruction of Dwarka,he was lifestyle modification in a bid to control his attacked by a band of thieves whom he could sugars(8)

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 28 This article was in no way intended to make fun 3. MAHABHARATA retold by C. Rajagopalachari of my ancient heritage and my religion,that me 4. The Relationship between Type 2 Diabetes and you are extremely proud of,but was written Mellitus and Related Thyroid Diseases J with a view to paint an entirely fresh canvas Diabetes Res. 2013; 2013: 390534 from the perspective of an endocrinologist and to drive home the point that diabetes has 5. Diabetes as a marker of pheochromocytoma existed from time immemorial and if it is in hypertensive patients. J Hypertens. 2003 handled with discipline it will have a minimal Sep;21(9):1703-7. impact on our lives,just as it could not come in 6. The endocrine quiz Indian J Endocrinol way of valor of our ancient warriors and idols. Metab. 2014 May-Jun; 18(3): 304–306. 7 . A l z h e i m e r ' s D i s e a s e I s Ty p e 3 REFERENCES Diabetes–Evidence Reviewed J Diabetes Sci 1. Krishnamacharya NM. The Mahabharata. Technol. 2008 Nov; 2(6): 1101–1113. Tirupati: Tirumala Tirupati Devasthanams; 2012. 8. The Mahabharata of Krishna-Dwaipayana 2. Bhagavad Gita As It Is Original by Vyasa translated by Kisari Mohan Ganguli Prabhupada [published between 1883 and 1896]

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Haryana Medical Journal - March 2017, Vol. 40, Issue 01 29 Hypoglycemia Prevention and Management -A Pragmatic Approach

Aastha Chawla Rajeev Chawla Shalini Jaggi S P Govt Medical College Bikaner1 North Delhi Diabetes Centre2 & Dr Mohan’s Diabetes Centre 3 New Delhi

Abstract: Hyperglycemia in diabetes leads to severe Hypoglycemia is characterized by a reduction debilitating microvascular and macrovascular complications. The results of Diabetes Control in blood glucose levels to an extent where the and Complications Trial (DCCT) led to wide- patient generally manifests autonomic or spread adoption of intense glycemic control neuroglycopenic symptoms resulting from the measures for the management of diabetes. A counter-regulatory hormones which are number of clinical studies have demonstrated secreted by the body in response to the fall in an association between intense glycemic blood glucose levels to correct it as a control and iatrogenic hypoglycemia in type 1 physiological defense mechanism. Due to the and type 2 diabetes.1,2 The incidence is greater morbidity and potential mortality associated in type 1 diabetes as compared to type 2 with it, hypoglycemia is recognized as the diabetes.3 Thus, hypoglycemia presents a strongest barrier to intensive glycemic control clinical barrier against the beneficial effects of in both type 1 as well as type 2 diabetes, more tight glycemic control. Optimization of these two factors has become an important and so in chronic type 1 diabetics with integral part of diabetes management. hypoglycemia unawareness due to autonomic dysfunction. Iatrogenic hypoglycemia is a Epidemiological Aspects common presentation in patients on insulin or The Action to Control Cardiovascular Risk in oral hypoglycemic agents especially Diabetes (ACCORD) Study Group reported a sulfonylureas and meglitinides. Early significantly high incidence of hypoglycemia recognition and appropriate correction as well (requiring any assistance) in patients receiving as prevention of hypoglycemia are essential intense glycemic treatment as compared to components of diabetes management. those on standard treatment (16.2% vs 5.1%, p < 0.001).1 Numerous other studies have Key words ; Iatrogenic Hypoglycemia, reported similar findings. In regular clinical Counter regulatory Hormones , adrenergic settings, asymptomatic and moderate or neuroglycopenic symptoms hypoglycemic episodes have a low probability Hypoglycemia is a common side effect of of detection in the absence of routine glucose treatment with insulin and oral hypoglycemic monitoring. Estimates indicate that patients on intense glycemic control may suffer at least agents, especially sulphonylureas, and is a one episode of severe hypoglycemia every major factor preventing near normoglycemia year. It has been estimated that 2–4% of deaths in patients with type 1 and type 2 diabetes. of people with T1DM are caused by Iatrogenic hypoglycemia often causes physical hypoglycemia.4-8 As a barrier to effective and psychosocial morbidity and sometimes glycemic control and with a serious potential to causes death (the ‘dead-in-bed’ syndrome may impair psychological and social well-being, be due to cardiac arrhythmias secondary to iatrogenic hypoglycemia is associated with nocturnal hypoglycemia) serious medical and economic burden.

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 30 Risk Factors and Pathogenesis Table 1 Common symptoms of hypoglycemia in patients with diabetes The pathogenesis of iatrogenic hypoglycemia results from the interplay of insulin excess and Autonomic Neuroglycopenic Malaise blunting of key physiological and behavioral • Sweating • Confusion • Nausea defenses (Figure 1).9 Conventionally, relative • Pounding heart • Drowsiness • Headache • Tremor • Speech difficulty or absolute insulin excess is the sole risk • Hunger • Atypical behavior determinant for iatrogenic hypoglycemia, • Visual disturbances during glycemic control. However, the results • Circumoralparasthesia

of DCCT trial indicated that these risk factors account only for a minority of episodes of severe iatrogenic hypoglycemia (Table 2).10,11

Consequences of Hypoglycemia Consequences of hypoglycemia in diabetes Table 2 Common Causes of Hypoglycemia

• Obstacle to achieving normoglycemia q W r o n g u s a g e o f • Disabling symptoms insulin/hypoglycemic medications • Sudden death syndrome q Fasting/dieting • Cognitive impairment in children q Alcohol abuse • Major source of anxiety in patients q Strenuous exercise in the previous 24 Symptoms of hypoglycemia hours (Table 1) can be classified as ‘autonomic’, q Use of pentamidine, quinine, or caused by activation of the sympathetic or nonselective beta-blocker drugs q parasympathetic nervous system, or Critical illnesses such as sepsis, or hepatic, or renal, or cardiac failure ‘neuroglycopenic’ caused by the effects of q glucose deprivation on the brain. Non-specific History of severe hypoglycemia symptoms of malaise such as headache and q Hypoglycemia unawareness nausea may also be present. Autonomic symptoms may be prominent in patients with a Management short duration of diabetes, but diminish with Management of iatrogenic hypoglycemia increasing duration of diabetes. Episodes of includes two components: treatment of asymptomatic hypoglycemia are common in hypoglycemia and risk minimization optimized to adequate glycemic control. The patients with type 1 diabetes; plasma glucose Global Partnership for Effective Diabetes may be 2.8-3.3 mmol/l in 10% of patients. M a n a g e m e n t p r o v i d e s p r a c t i c a l

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 31 recommendations to help improve the care of One milligram of glucagon raises the blood patients with type 1 and type 2 diabetes.2 glucose levels similar to 1 ampoule of D50W, These recommendations are summarized in with the onset of action being 10–20 minutes, box1.2 In essence, the recommendations seek and peak response 30–60 minutes. Other to blunt iatrogenic hypoglycemia through treatment strategies include adjustment of improved patient awareness and patient insulin/oral hypoglycemic agents. Regimen education programs along with stringent adjustments include use of insulin analogues patient monitoring. Patient education and bedtime treatments. In case of alcohol programs must include the following abuse, thiamine is also given. aspects:12,13 General principles for optimizing glycemic q Symptoms of hypoglycemia. control and minimizing the risk of q Physiologic factors that come into play: hypoglycemia include: knowledge of the inter-relationship of physical • Patient education activity, diet, and insulin. • Flexible insulin and treatment regimens q The duration and action of the • Frequent self-monitoring of blood medications they are on. glucose q P r e v e n t i o n a n d t r e a t m e n t o f hypoglycemia episodes. • Individualized glycemic targets q Frequent self-monitoring of blood • Ongoing professional advice and support glucose levels. Figure 2. Algorithm for management of q Importance of adhering to treatment acute hypoglycemia in patients with regimens. diabetes q Need to document hypoglycemic episodes and to contact doctor in case of frequent/unexpected episodes. • Oral glucose (20-30 g) · IV glucose (30-50 ml of Treatment • Oral sucrose 50% solution) Most mild or moderate episodes of • Glucagon 1 mg SC or IM hypoglycemia can be self-treated relatively easily by ingesting fast-acting carbohydrates such as glucose tablets, glucose gels, or food (juices, soft drinks, or a meal). The suggested • Check blood glucose after 15-20 min amount of carbohydrate to be ingested is about • Confirm recovery 15 g. However, when the symptoms are severe parenteral glucose may be required. One to three ampoules of 50% dextrose in water Recovery No Recovery (D50W) should be administered intravenously. In infants and younger children,10% dextrose IV glucose (5% or 10%) water should be given, as D50W can lead to venous sclerosis, resulting in rebound hypoglycemia. About 1–2 mg of glucagon can • Identify cause be administered either intra-muscularly or • Re-educate subcutaneously, in cases where I.V. access • Take measures to avoid hypoglycemia cannot be rapidly obtained.14

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 32 5. The effect of intensive treatment of Cautions diabetes on the development and progression • Oral glucose gels may be ineffective of long-term complications in insulin- • Glucagon may lose its effect with dependent diabetes mellitus. The Diabetes repeated use Control and Complications Trial Research • Glucagon is contraindicated in Group.N Engl J Med. 1993;329:977-86. sulphonylurea induced hypoglycemia 6. Akram K, Pedersen-Bjergaard U, • Sulphonylurea induced hypoglycemia Carstensen B, Borch-Johnsen K, Thorsteinsson may be very prolonged B. Frequency and risk factors of severe hypoglycemia in insulin-treated Type 2 Clinical Pearls diabetes: a cross-sectional survey. Diabet Med. 2006;23:750-6. • Asymptomatic and moderate episodes of hypoglycemia have a low probability of 7. Saudek CD, Duckworth WC, Giobbie- detection because of lack of glucose Hurder A, et al. Implantable insulin pump vs monitoring. multiple-dose insulin for non-insulin- • Absolute insulin excess is the sole risk dependent diabetes mellitus: a randomized determinant for iatrogenic hypoglycemia, clinical trial. Department of Veterans Affairs during glycemic control. Implantable Insulin Pump Study Group. JAMA. • Hypoglycemia is better prevented than 1996;276:1322-7. treated 8. Cryer PE, Davis SN, Shamoon H. References Hypoglycemia in diabetes. Diabetes Care. 1. Gerstein HC, Miller ME, Byington RP, et al. 2003;26:1902-12. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545-59. 9. Cryer PE. Mechanisms of 2. Aschner P, Horton E, Leiter LA, et al. sympathoadrenal failure and hypoglycemia in Practical steps to improving the management diabetes.J Clin Invest. 2006;116:1470-3. of type 1 diabetes: recommendations from the 10. Epidemiology of severe hypoglycemia in Global Partnership for Effective Diabetes the diabetes control and complications trial. Management. Int J ClinPract. 64:305-15. The DCCT Research Group.Am J Med. 3. Donnelly LA, Morris AD, Frier BM, et al. 1991;90:450-9. Frequency and predictors of hypoglycemia in 11. McAulay V, Deary IJ, Frier BM. Symptoms Type 1 and insulin-treated Type 2 diabetes: a of hypoglycemia in people with diabetes. population-based study. Diabet Med. Diabet Med. 2001;18:690-705. 2005;22:749-55. 4. Pedersen-Bjergaard U, Pramming S, Heller 12. Davis S, Alonso MD. Hypoglycemia as a SR, et al. Severe hypoglycemia in 1076 adult barrier to glycemic control.J Diabetes patients with type 1 diabetes: influence of risk Complications. 2004;18:60-8. markers and selection. Diabetes Metab Res Rev. 13. Gabriely I, Shamoon H. Hypoglycemia in 2004;20:479-86. diabetes: common, often unrecognized. Cleve In infants and younger children,10% dextrose Clin J Med. 2004;71:335-42 water should be given, as D50W can lead to venous sclerosis, resulting in rebound 14. Collier A, Steedman DJ, Patrick AW, et al. hypoglycemia. About 1–2 mg of glucagon can Comparison of intravenous glucagon and be administered either intra-muscularly or dextrose in treatment of severe hypoglycemia subcutaneously, in cases where I.V. access in an accident and emergency department. cannot be rapidly obtained.14 Diabetes Care. 1987;10:712-5. Haryana Medical Journal - March 2017, Vol. 40, Issue 01 33 Outdoor Management of Ketosis in Diabetes Dr.Robin Maskey Additional Professor Internal Medicine B.P.Koirala Institute of Health Sciences Dharan Nepal Definition Other causes can be the result of being on a low Ketosis is a state the body goes into if it needs to carb diet. A low level of carbohydrate will lead break down body fat for energy. The state is to low levels of insulin, and therefore the body marked by raised levels of ketones in the blood will produce ketones which do not rely on as fuel.1Ketones which are not used for fuel are insulin to get into and fuel the body’s cells. excreted out of the body via the kidneys and the A further cause of ketosis, less relevant to urine. people with diabetes, is a result of excessive Is ketosis the same as ketoacidosis? alcohol consumption. There is often confusion as to the difference Is ketosis dangerous? between ketosis and ketoacidosis. The NHS describes ketosis as a potentially Ketosis is the state whereby the body is serious condition, whereas a number of producing ketones. In ketosis, the level of popular diets cite ketosis as being an essential ketones in the blood can be anything between part of weight loss. normal to very high. Ketosis is described as being potentially Diabetic ketoacidosis, also known as DKA, only dangerous as very high level of ketones can describes the state in which the level of ketones make the blood acidic, a state known as is either high or very high. In ketoacidosis, the ketoacidosis, which can lead to serious illness amount of ketones in the blood is sufficient to in a relatively short space of time. turn the blood acidic, which is a dangerous Diabetes Management General Principles 2 medical state. (Monitoring/ Insulin/ Hydration): When does ketosis occur? 2 1. More frequent BG and ketone (urine or Ketones are produced by the liver from free blood) Monitoring fatty acids that are mobilized as an alternative energy source when there is a lack of glucose 2. DONOT STOP INSULIN for intracellular metabolism. 3. Monitor and maintain salt and water Starvation ketones are produced when the BG balance - Hydration is low. 4. Treat the underlying precipitating illness Ketones are also produced when insulin is 5. Sick day guidelines including insulin lacking to initiate the transport of glucose from adjustment should be taught soon after the bloodstream into the cell. diagnosis and reviewed at least annually with Ketones accumulate because of increased patients and family members with a goal of lipolysis, increased ketogenesis and decreased minimizing and/or avoiding DKA and similarly ketone body utilization due to low insulin minimizing and/or avoiding illness associated hypoglycemia. Haryana Medical Journal - March 2017, Vol. 40, Issue 01 34 1. Monitoring: • Monitoring BOHB may also have the a. Blood Glucose monitoring: potential to help prevent late hypoglycemia from overtreatment with insulin based upon • Frequent BG monitoring facilitates the persistence of ketonuria at the same time optimal management during illness (with adult the ketonemia is improving. supervision especially in adolescents) • Blood BOHB monitoring may be • BG should be monitored at least every 3 – especially useful in very young children or 4 h including through the night and sometimes when urine specimens are difficult to obtain. every 1–2 h • 2. Never stop insulin b. Ketone bodies monitoring: • Treatment: Urinary ketone tests (liquid or test strips for A. Elevated BG with an absence or only small acetone and AcAc levels) or, when available, amount of ketones (ketosis) : 6.7,8 blood ketone tests (for BOHB), help to guide • Give 5 – 10% of the total daily dose (TDD) of sick day management. insulin (∼0.05 – 0.1 U/kg) as short or rapid- Blood ketone testing (measuring BOHB) a c t i n g i n s u l i n s u b c u t a n e o u s l y o r provides additional information to urine intramuscularly and repeat this same dose ketone testing: every 2 – 4 h according to BG response and • Blood BOHB >0.5 mmol/L is abnormal in clinical condition. TDD of insulin is the sum of children with diabetes. 3 all long, intermediate and short/rapid-acting insulins usually taken. • Adult studies have shown that the time delay after a pump stop to diagnosis of ketosis is • Insulin doses may need to be increased significantly longer for ketonuria than for considerably in children who are in the partial remission phase, often up to 1 U/kg . plasma ketonemia and that a urinary ketone test can remain positive more than 24h after • Blood ketones are preferred over urine resolution of an episode of ketoacidosis in over ketones when available and affordable, and the half of patients studied. 4 use during illness can reduce emergency room visits and hospitalizations . • There may be dissociation between urine • Strive for a BG between 4 and 10mmol/L ketone (AcAc) and blood BOHB concentrations (70–180 mg/dL) and blood ketones below 0.6 which may be increased to levels consistent mmol/L when the child is ill . with DKA when a urine ketone test is negative or shows only trace or small ketonuria. • The insulin dose often needs to be decreased when there is gastroenteritis, but Home measurement of blood BOHB should not be lowered to the extent that concentrations in children and adolescents ketones are produced. enables earlier identification and treatment of • B. Elevated BG with moderate or high ketosis, when compared to urine ketone amount of ketones (ketosis) : testing, and decreases diabetes-related hospital visits (both emergency department • If there is hyperglycemia and more visits and hospitalizations). 5 marked ketonuria (moderate to high), usual recommendations are to give an additional 10 – • During resolution of ketosis, blood BOHB 20% of TDD (approximately not more than 0.1 normalizes sooner than urine ketones. U/kg) as short-/rapid-acting insulin. This dose

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 35 should be repeated every 2–4h; based upon Special Recommendation for patient on Insulin frequent glucose and ketone results response Pump: 9 to the supplemental dose, clinical status and Patients on pumps use only rapid- or short- hydration status. acting insulin and do not have any injected Additional doses of short/rapid-acting insulin depot of long-acting insulin. With pumps DKA are required with careful monitoring to reduce can develop rapidly with either interruption of BG, prevent ketoacidosis, and avoid hospital insulin delivery or intercurrent illness to which admission . there is no increased insulin response. • Both rapid-acting insulin analogs as well as Episodes of hyperglycemia must be taken very older, more traditional short acting insulin seriously especially if associated with positive (synthetic or animal-origin) can be used to urine and/or blood ketones. If the BG level is 14 provide supplemental insulin during sick days mmol/L (250 mg/dL) or above in an insulin depending upon availability and cost. pump patient, the following steps should be • The dose and frequency of injection will taken: depend on the level and duration of hyperglycemia as well as the severity of ketosis. • Immediately check for problems with the Such supplemental doses are usually given pump or delivery system and change the subcutaneously but may also be given infusion set, tubing and reservoir of insulin. intramuscularly with healthcare professional Kinks in the catheter, air in the infusion line, advice. disconnected catheters especially at the 3. Hydration: 6.7.8 insertion site or insertion site irritation all get identified when patient and family members Hyperglycemia, fever, excessive glycosuria, and ketonuria all contribute to increased fluid are instructed to first change the infusion set losses. Sick day cabinets should contain and second, give an immediate injection by supplies as above to prevent dehydration. syringe or pen to be certain that insulin is being Liquids for hydration should contain salt and delivered. water and not just plain water especially if • Check for ketones in the blood or urine : In there are ongoing losses associated with case of ketosis, extra insulin should always be vomiting or diarrhea. Eg: Chicken soup or clear given with a pen or syringe, not with the pump broths. (as malfunction may be the cause of ketosis). If appetite is decreased or the BG is falling • To overcome insulin resistance, the basal below 10mmol/L (180 mg/dL), sugar- rate may be increased from 120% to 150% containing fluids should be considered to according to BG and ketone results and, at the d e c r e a s e s t a r v a t i o n k e t o s i s ( e . g . , same time, correction boluses also may need to sports/electrolyte drinks, pediatric electrolyte be increased by 10–20% during the period of mixtures, diluted fruit drinks, colas, ginger ale, illness. etc. References Especially in young children with diabetes, intravenous fluids may be required if nausea, 1. Brink S, Joel D, Laffel L, Lee WWR, Olsen B, vomiting or diarrhea are persistent and Phelan H, Hanas R. Sick day management in associated with ongoing weight loss in order to c h i l d r e n a n d a d o l e s c e n t s w i t h prevent cardiovascular collapse, hypotension, diabetes.Pediatric Diabetes 2014: 15 (Suppl. coma, and death. 20): 193–202.

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 36 2. Laffel L. Ketone bodies: a review of 6. Brink SJ. Diabetic ketoacidosis: prevention, physiology, pathophysiology and application of treatment and complications in children and monitoring to diabetes. Diabetes Metab Res adolescents. Diabetes Nutr Metab 1999: 12: Rev 1999: 15: 412–426. 122 – 135. 3. Guerci B, Tubiana-Rufi N, Bauduceau B, 7. Walker M, Marshall SM, Alberti KG. Clinical Bresson R, Cuperlier A, Delcroix C. Advantages aspects of diabetic ketoacidosis. Diabetes to using capillary blood beta-hydroxybutyrate Metab Rev 1989: 5: 651–663. determination for the detection and treatment of diabetic ketosis. Diabetes Metab 2005: 31: 8. Haymond MW, Schreiner B. Mini-dose 401–406. glucagon rescue for hypoglycemia in children with type 1 diabetes. Diabetes Care 2001: 24: 4. Guerci B, Benichou M, Floriot M, Bohme P, 643 – 645.Hartley M, Thomsett MJ, Cotterill Fougnot S, Franck P. Accuracy of an AM. Mini-dose glucagon rescue for mild electrochemical sensor for measuring capillary blood ketones by fingerstick samples during hypoglycaemia in children with type 1 metabolic deterioration after continuous diabetes: the Brisbane experience. J Paediatr subcutaneous insulin infusion interruption in Child Health 2006: 42: 108 – 111. type 1 diabetic patients. Diabetes Care 1995: 9.Walsh J, Roberts R. Pumping Insulin: 18: 137 – 138. Everything You Need for Success on a Smart 5. Klocker AA, Phelan H, Twigg SM, Craig ME. Insulin Pump. 4th edn. San Diego, CA: Torrey Blood ß-hydroxybutyrate vs urine acetoacetate Pines, 2006.Kaufman FR. Insulin Pumps and testing for the prevention and management of Continuous Glucose Monitoring. 1st edn. ketoacidosis in Type 1 diabetes: a systematic Alexandria VA: American Diabetes Association, review. Diabetes Med 2013: 30: 818 – 824. 2012.

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 37 FASTS AND RAMADAN Sandeep Chaudhary Consultant Endocrinology Department of Endocrinology, ADK Hospital Male’ Maldives

Abstract Fasting is advised for all healthy Muslims who Ramadan” is a holy month for Muslims. More have reached puberty during this month. Each than 50 million individuals with diabetes fast period of fasting may last for up to 20 hours during Ramadan. Physiological changes which (from just before dawn to just after sunset) occur during fasting and medication being depending on the season and geographic taken to treat diabetes can be associated with location. the development of complications like Physiology of Ramadan Fasting hypoglycemia, hyperglycemia, dehydration Fasting during Ramadan leads to number of and DKA. Ensuring the optimal care of diabetic physiological changes in homeostatic and patients who fast during Ramadan is crucial. It endocrine processes of the body. There is a is possible through pre-Ramadan assessment sudden shift in meal timing, as well as in sleep and risk stratification followed by and wakefulness patterns with the onset of individualized patient’s education, dietary Ramadan. The time between meals during advice and drug modification. Ramadan is much longer because no food or Keywords: Ramadan, Type1DM, Type T2DM, drink is taken during the hours of daylight. Iftar, Suhoor, Risk stratification During fasting, circulating glucose levels fall and insulin secretion is suppressed. Reduction INTRODUCTION in glucose leads to gluconeogenesis and The prevalence of diabetes has been increasing glycogenolysis due to increase in glucagon and throughout the world. In 2015 there were catecholamines secretion. When glycogen approximately 415 million people with stores are depleted and insulin levels are low, diabetes globally [1]. Estimates suggest that fatty acids are oxidized to generate ketones there are 148 million Muslims with diabetes bodies which are used as fuel by many worldwide. “Ramadan” is a holy month for organs[3]. Muslims. Fasting during Ramadan is one of the In individuals with diabetes, these five pillars of Islam. It is a religious obligation physiological changes and the type of for all healthy adult Muslims all over the world medication being taken to treat diabetes can be including Haryana and neighboring states in associated with the development of India. In Haryana it is particularly observed in Mewat district which has over 70 percent c o m p l i c a t i o n s l i k e h y p o g l y c e m i a , Muslim population. The population-based hyperglycemia, dehydration and acute Epidemiology of Diabetes and Ramadan metabolic complications such as diabetic (EPIDIAR) study conducted in 13 Islamic ketoacidosis (DKA), thrombosis. countries showed that about 43% and 79% Pre-Ramadan Assessment and Risk respectively of Muslims with type 1 and type 2 Stratification of Individuals with Diabetes diabetes mellitus (T2DM) fast during Ramadan Various studies have shown that fasting may be meaning that more than 50 million individuals associated with high rate of acute with diabetes fast during Ramadan [2]. complications. The EPIDIAR study which Haryana Medical Journal - March 2017, Vol. 40, Issue 01 38 included more than 12,000 persons with • History of hypoglycaemia unawareness diabetes who fasted during Ramadan showed a • Poorly controlled T1DM high rate of acute complications. Rate of severe • Acute illness hypoglycemia was increased 4.7 fold in T1DM and 7.5 fold in T2DM during Ramadan • Pregnancy in pre-existing diabetes, or compared with before Ramadan [2]. Similarly GDM treated with insulin or SUs rate of hyperglycemia with or without diabetic • Chronic dialysis or CKD stage 4 & 5 ketoacidosis was increased 5.0-fold in patients • Advanced macrovascular complications with T2DM[2]. • Old age with ill health All diabetic individuals who wish to fast should undergo pre-ramadan assessment and risk stratification at least 2 to 3 months before Category 2: High risk Ramadan [4].Factors which should be • T2DM with sustained poor glycaemic considered when quantifying the risk are[5]: control • Type of diabetes • Well-controlled T1DM • Clinical examination including BP and • Well-controlled T2DM on MDI or mixed weight insulin • Present glycemic status • Pregnant T2DM or GDM controlled by • Present medications diet only or metformin • Assessment of complications and other • CKD stage 3 co morbid conditions • Stable macrovascular complications • Individual hypoglycemic risk • People with diabetes performing intense • Possibility of dehydration and physical labour electrolyte imbalance • Treatment with drugs that may affect • Social and working circumstances of the cognitive function individual • History of previous Ramadan experience Category3 : Moderate risk • Well-controlled patients treated with American Diabetes Association (ADA) short-acting insulin secretagogues such as recommendations for management of diabetes repaglinide or nateglinide. during Ramadan has categorised people with diabetes into four risk groups – very high risk, Category 4 : Low risk high risk, moderate risk and low risk[5]. • Well-controlled patients treated with diet alone, metformin, or a thiazolidinedione Category 1 : Very high risk who are otherwise healthy. • History of Severe hypoglycaemia/ DKA/ Very high risk / High risk categories patients Hyperosmolar hyperglycaemic coma within 3 should not fast because probability of harm is months prior to Ramadan high. However, Patients who insist on fasting • History of recurrent hypoglycaemia must be respected and they should be made

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 39 aware of the risks associated with fasting, and in educational programmes that that pricking of techniques to decrease this risk. They should the skin for blood glucose testing does not be followed by a qualified Diabetes team. They invalidate the Ramadan fast [10]. should be educated regarding regular checking Fluids and dietary advice provided during of their blood glucose (SMBG), preparedness to education programme also helps in reducing break the fast in case of hypo- or the likelihood of complications associated with hyperglycaemia . They should stop fasting if the consumption of large, carbohydrate-heavy hypo- or hyperglycaemia occurs frequently or meals, and sugary drinks due to fasting and there is worsening of other related medical feasting nature of Ramadan. conditions Ramadan Nutrition Plan

Special populations Unhealthy nutrition habits that commonly develop during Ramadan include: T1DM : People with T1DM are generally advised against fasting because of the risks of 1. Eating particularly large meals at iftar of severe complications. However, many of them highly processed carbohydrates and sugar/ can fast safely if they have good glycemic desserts or having large and frequent snacks control and hypoglycaemic awareness and between the two main meals, resulting in complies with their individual management severe hyperglycaemia and weight gain plan under medical supervision [6] 2 Eating suhoor early may result in The elderly: They should not be categorised as hypoglycaemia before iftar, or consumption of high risk based on a specific age but rather on large portions of high glycaemic index (GI) health status and their social circumstances carbohydrates at suhoor, which can lead to [7]. postprandial hyperglycaemia[11]. Patients should be encouraged to take a Pregnancy : Vast majority of women with balanced meal with carbohydrates (low GI T2DM during pregnancy are treated with preferred) comprising around 45–50%; insulin, metformin or glibenclamide. They are protein comprising 20–30%; and fat at high risk of hypoglycaemia if fasting. comprising <35% of the total calorie intake . Similarly hyperglycaemia is also associated Saturated fat should be limited to <10% of the with increased risk for both mother and baby. total daily caloric intake. It is also Therefore pregnant women with pre-existing recommended to proportionally distribute diabetes or GDM should be advised against daily caloric intake between suhoor and iftar fasting [8]. with iftar comprising around 40–50% , suhoor 30–40% and snack between meals (one or two, Ramadan-focused diabetes education if necessary) 10–20% of the total calorie intake [12] . Patient education is mainstay of the diabetes management during Ramadan. It can be Medication adjustments during fasting provided by physicians, dieticians or community workers in group sessions or one- Metformin to-one consultations focusing on information There are no randomised controlled trials on on risks, glucose monitoring, nutrition, metformin use in patients with T2DM during exercise and medication.[9] It should be Ramadan. Metformin is considered safe strongly emphasized because the likelihood of hypoglycaemia is low.

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 40 Changes to Metformin dosing during Ramadan Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) Pre-Ramadan dosing Suggested modifications during Ramadan When used as monotherapy the risk of severe hypoglycaemia is low with GLP-1 RA. However • No dose modification Once daily dosing required hypoglycemia can occur when used with SUs, • Take at Iftar or insulin. Number of studies have shown that

• N O d o s e m o d i f i c a t i o n liraglutide is safe and effective in reducing Twice daily dosing required weight and HbA1c when used as an add-on • Take at Iftar and suhoor treatment to metformin during Ramadan [16,17,18]. There is paucity of data on use of Three times daily • Morning dose to be taken at dosing Suhoor newer GLP-1 RAs (lixisenatide, dulaglutide and • Combine afternoon dose with albiglutide) during Ramadan. iftar dose Short-acting insulin secretagogues • N O d o s e m o d i f i c a t i o n Prolonged released The short duration of action of repaglinide and metformin required • Take at iftar nateglinide make them attractive for use during Ramadan as risk of hypoglycaemia is Alpha-glucosidase inhibitors low .Studies have also shown low incidence of No dose adjustment is needed during Ramadan hypoglycemia during Ramadan[19.20] .The as the risk of hypoglycaemia is low. dose should be reduced or redistributed to two Thiazolidinediones doses during Ramadan to be before iftar and TZD does not require any dose adjustment suhoor. during Ramadan and doses can be taken with Sulphonylureas iftar or suhoor[13]. This class of drugs are associated with a higher Sodium-glucose co-transporter-2 (SGLT2) risk of hypoglycaemia compared with other inhibitors OADs due to their prolonged action. However, SGLT2 inhibitors are associated with an this risk varies across medications within this increased risk of dehydration in vulnerable class due to differing receptor interactions, patients during Ramadan .Therefore the binding affinities and durations of action. elderly, patients with renal impairment, Changes to SU dosing during Ramadan hypotensive individuals, those at risk of dehydration or those taking diuretics should Pre-Ramadan Suggested modification Dosing during Ramadan not be treated with SGLT2 inhibitors. No dose · Take at iftar adjustment is required and the dose should be Once-daily dosing · In patients with well controlled BG levels the dose taken at iftar[14]. may be reduced Dipeptidyl peptidase-4 (DPP-4) inhibitors · Iftar dose remains the same Twice-daily dosing · In patients with well A recent meta-analysis of 16 RCTs and 13 controlled BG levels, the observational studies in patients with T2DM suhoor dose should be reduced who fasted during Ramadan has shown that, Older drugs in the · Older drugs(e.g. DPP-4 inhibitors were associated with the class glibenclamide) carry a lowest incidence and rate of hypoglycaemic higher risk of hyperglycemia and should be avoided events as compared to SUs [15] . No dose · Second generation SUs adjustment is required during Ramadan. should be used preferably

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 41 Insulin treatment for T2DM Insulin use during prolonged fasting is associated with an increased risk of hypoglycaemia in both T1DM and T2DM . The data regarding the optimal insulin type or regimen for patients with T2DM during Ramadan is scarce. Various studies done during Ramadan indicate that it may be safe to fast while on insulin, however treatment must be appropriately individualized. Advantages like less hypoglycaemia and smaller postprandial glucose excursions makes insulin analogues more preferable over regular human insulin [21]. CONCLUSION It is possible to optimize the care of a diabetic individual during Ramadan through prior risk stratification, patient’s education and drug modification. References 1. International Diabetes Federation. IDF Diabetes Atlas (Seventh Edition). 2015; A v a i l a b l e a t : h t t p : / / www.diabetesatlas.org/resources/2015- atlas.html. Accessed 09 February 2016. Changes to premixed insulin doing during 2. Salti I, Benard E, Detournay B, et al. A Ramadan population-based study of diabetes and its characteristics during the fasting month of Ramadan in 13 countries: results of the epidemiology of diabetes and Ramadan 1422/2001 (EPIDIAR) study. Diabetes Care 2004;27:2306-11. 3. Ali Riza Uysal; Erdogan, Murat Faik; Sahin, Gunay; Kamel, Nuri; Gurbuz Erdogan Adults with T1DM Clinical and metabolic effects of fasting in 41 type 2 diabetic patients during Ramadan. The decision by an individual with T1DM to fast Diabetes Care 1998 Nov; 21(11): 2033-2034 during Ramadan must be respected . There is some evidence to suggest that, as long as they . Mir Iftikhar Bashir, Md Faruque Pathan, are otherwise stable and healthy, they can do so Syed Abbas Raza, Jamal Ahmad, A. K. Azad safely[22]. However, strict medical supervision Khan,Osama Ishtiaq, Rakesh K. Sahay, Aisha and focused education on how to control their Sheikh, Abdul Hamid: Role of oral glycaemic levels is essential hypoglycemic agents in the management of

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 42 type 2 diabetes mellitus during Ramadan 14. Wan Juani WS, Najma K, Subashini R, et Indian Journal of Endocrinology and al. Switching from sulphonylurea to an SGLT2 Metabolism / Jul-Aug 2012 / Vol 16 | Issue 4 inhibitor in the fasting month of Ramadan is associated with a reduction in hypoglycaemia. 5. Al-Arouj M, Assaad-Khalil S, Buse J, et al. D i a b e t e s O b e s M e t a b 2 0 1 6 D O I : Recommendations for management of 10.1111/dom.12649. diabetes during Ramadan: Update 2010. Diabetes Care 2010;33:1895-902. 15. Lee SW, Lee JY, Tan CS, et al. Strategies to make Ramadan fasting safer in type 2 diabetics: 6. Mohsin F, Azad K, Zabeen B, et al. Should A systematic review and network meta- Type 1 diabetics fast in Ramadan. J Pak Med analysis of randomized controlled trials and Assoc 2015;65:S26-9. observational studies. Medicine (Baltimore) 7. Azzoug S, Mahgoun S, and Chentli F. 2016;95:e2457. Diabetes mellitus and Ramadan in elderly 16. Bravis V, Hui E, Salih S, et al. A patients. J Pak Med Assoc 2015;65:S33-6. comparative analysis of exenatide and 8. Bajaj S, Khan A, Fathima FN, et al. South gliclazide during the month of Ramadan. Asian consensus statement on women’s health Diabet Med 2010;27:130. and Ramadan. Indian J Endocrinol Metab 17. Brady E, Davies M, Gray L, et al. A 2012;16:508-11. randomized controlled trial comparing the 9. Bravis V, Hui E, Salih S, et al. Ramadan GLP-1 receptor agonist liraglutide to a Education and Awareness in Diabetes (READ) sulphonylurea as add on to metformin in programme for Muslims with Type 2 diabetes patients with established type 2 diabetes during Ramadan: The Treat 4 Ramadan Trial. who fast during Ramadan. Diabet Med Diabetes Obes Metabol 2014;16:527-36. 2010;27:327-31. 18. Khalifa A, El Rashid A, and Bashier A. 10. Masood SN, Sheikh MA, Masood Y, et al. Safety and efficacy of liraglutide as an add-on Beliefs of people with diabetes about skin prick therapy to pre-existing anti-diabetic regimens during Ramadan fasting. Diabetes Care during Ramadan, a prospective observational 2014;37:e68-9. trial. J Diabetes Metab 2015;6:590 11. Evert AB, Boucher JL, Cypress M, et al. 19. Anwar A, Azmi K, Hamidon B, et al. An Nutrition therapy recommendations for the open label comparative study of glimepiride management of adults with diabetes. Diabetes versus repaglinide in type 2 diabetes mellitus Care 2014;37 Suppl 1:S120-43. Muslim subjects during the month of Ramadan. 12. Diabetes and Ramadan Practicle Med J Malaysia 2006;61:28-35. guidelines International Diabetes Federation 20. Mafauzy M. Repaglinide versus a n d D A R i n t e r n a t i o n a l A l l i a n c e . glibenclamide treatment of Type 2 diabetes https://www.idf.org/sites/default/files/IDF- during Ramadan fasting. Diabetes Res Clin DAR-Practical-Guidelines-Final-Low.pdf Pract 2002;58:45-53. 13. Vasan S, Thomas N, Bharani AM, et al. A 21. Grunberger G. Insulin analogs—Are they double-blind, randomized, multicenter study worth it? Yes! Diabetes Care 2014;37:1767-70. evaluating the effects of pioglitazone in fasting 22. Mohsin F, Azad K, Zabeen B, et al. Should Muslim subjects during Ramadan. Int J Type 1 diabetics fast in Ramadan. J Pak Med Diabetes Dev Ctries 2006;26:70-6. Assoc 2015;65:S26-9.

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 43 Insulin Injection Technique Sanjay Kalra Saurabh Arora *Department of Endocrinology, Bharti Hospital, Karnal **Senior resident , Department of Endocrinology and Metabolism Banaras Hindu University, Varanasi

Abstract Storage and Shipping Insulin therapy remains the best treatment for Prior to opening, insulin vials and pens should diabetes even after ninety years of use. Correct be refrigerated at temperature of 4-8°C and not injection technique is a crucial aspect of to be frozen. If it becomes frozen, it should be diabetes management. Insulin therapy relies discarded and never used again. Insulin should on correct injection technique for optimal be stored in a cool and dark place at room effect. How and where you inject is as temperature (15-25°C) and discarded 30 days important as what you inject. Faulty injection after initial use. If the vial is stored in technique compromise dosage accuracy and its refrigerator, it should be taken out and kept at effectiveness, thus highlighting the pressing room temperature for atleast 30 minutes need for effective patient education. before injecting. Travel-surface Introduction In case the environmental temperature >30°C, A dramatic increase in prevalence of diabetes insulin needs to be stored in a flask with ice, or has been documented in recent years. The in a handbag or in a proper container. Do not number of people with diabetes has risen from store insulin in the glove compartment of the 108 million in 1980 to 422 million in 2014.1 car. According to current studies, 67 million Travel-air indians are affected with diabetes. Prevalence of diabetes in indians is expected to reach 87 Adequate injection supply is to be ensured. million by 2030.2 Insulin therapy is the Travelling to a place with time zone difference cornerstone of management of Type I diabetes of > 2 hours may necessitate a change of mellitus and insulin requiring type II diabetes injection schedule. Insulin should never be mellitus. Recent studies demonstrated that the kept in the baggage hold of the plane to avoid exposure to extremely low temperatures. use of shorter needles is equally effective in achieving glycemic control as compared to Device selection and use longer needles, without increasing the number The prescription for subcutaneous insulin of leakage events. A study done by Grassi G et al therapy must include the choice of injection showed that switching to 4 mm needle leads to device, needle length and gauge, and the type of improved glycemic control, greater satisfaction insulin syringe to be used. with therapy and lower insulin requirements Syringe and vial compatibility after only a three months period.3 The It is important to ensure that patient injects objective of this article is to address various correct insulin strength with appropriate issues and complications encountered with insulin syringe. Both U-40 and U-100 insulin insulin injection therapy. concentrations are available in India. The

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 44 patient should be made understand that U-100 • The injection site should be inspected at vials should be used with U-100 insulin syringe every visit or atleast 6 months. and U-40 vials with U-40 insulin syringes only. • Systemic rotation of injection sites to Insulin syringes are available in three different reduce risk of lipohypertrophy and optimizes needle lengths i.e. 6mm, 8mm and 12.7 mm. insulin absorption. The most effective Insulin syringe with three different gauge sizes technique is to divide injection site into 31, 30 and 29 are available in India. quadrants (abdomen) or halves (thighs, Pens and Pen needles buttocks and arms) and use one quadrant or Insulin pens have an attached insulin cartridge half for one week. Move to another quadrant or rather than using a syringe and separated vial. half next week either in clockwise or an The pens come in two basic forms: disposable anticlockwise direction. ( d i s c a r d e d o n c e e m p t i e d ) a n d • Avoid reusing needles. reusable(cartridge can be reloaded). Pen Injection Technique needles are available in four different sizes i.e. Syringe and vial 4, 5, 6 and 8mm and are of 32, 31 and 30 gauge. Risk of intramuscular injection is alleviated A syringe is most commonly used injecting with use of shorter needles. Shorter length device in India. While injecting insulin, needles has also been shown to improve following points to be taken into consideration: patient compliance to insulin injection therapy. a) Insulin vial is taken out of refrigerator 30 Injection site minutes prior to the injection to ensure that insulin is at room temperature. Insulin absorption varies significantly from different sites. Insulin is rapidly absorbed from b) If insulin is cloudy, make sure that it is abdomen, followed by the arms and then the uniformly mixed by rolling the vial between thighs. The rate of absorption is slowest from palms. buttocks. It is recommended not to change sites c) The top of the vial to be cleaned with frequently because of different rates of alcohol. An amount of air equal to the desired absorption.4 dose of insulin has to be drawn up into the Seven- step injection site care process syringe and injected into the vial to avoid creating vacuum. Invert the vial and pull the • Inspection and palpation of the injection plunger back to the number of units needed to site is to be done before injection to look for inject. If air bubbles are visualized in the wounds, bruises or lipohypertrophy. syringe, pull the plunger gently to withdraw • If the injection site shows any evidence of several more units of insulin and reinject the inflammation, infection or lipohypertrophy, a bubbles into the vial. If bubbles do not different site should be chosen. disappear with above mentioned technique, • Injection should be administered at a slowly push insulin back into the vial and again clean site using hygienic measures. pull the plunger very slowly to the desired • If the injection site is found unclean, it number of units. This procedure is to be should be cleansed either with cotton balls repeated until no air bubbles are seen. dipped in water or with alcohol swabs. d) Select the correct injection site and clean Cleansing to be done in circular fashion it with an alcohol swab as described in the starting from centre and moving outwards. seven step injection site care process.

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 45 e) Lift the skin fold with thumb and index Insulin injection- meal time interval finger and push the needle at the desired angle Insulin injection- meal time gap has been based on needle length and other factors. A 45° shown to be a significant factor determining angle with pinch up technique is appropriate proper insulin action and good glycemic for areas with less fat and a 90° angle is used for control. areas of body with more fat. Insulin delivery to • Rapid acting insulins (lispro, aspart and be ensured by pushing the plunger and glusiline) can be administered before or counting till 10 before withdrawing the needle immediately after a meal. out of the body. • Short acting (regular) insulin needs to be Mixing Insulins injected 30 minutes before meal. While mixing the insulin, correct sequence • Intermediate- NPH and long acting insulin (detemir and glargine) should be needs to be followed. Regular insulin should be injected at the same time everyday regardless filled first followed by NPH insulin. Reversal of of timings of meals. this sequence can lead to impurities in regular • Ultra- long acting insulin (degludec) can insulin vials. Mixing of insulin can alter the be injected at any time of day, irrespective of pharmacokinetics of individual insulin the timings of meals or timing of previous day’s components. injection. • Mixing of rapid acting insulin (lispro, Special Populations aspart and glusiline) and NPH can result in • Pregnancy:- slight decrease in the absorption rate. Insulin is the mainstay of therapy and is However, clinical trials have shown similar required in about 10-20% of all pregnant postprandial response with this combination. women with diabetes. Abdomen is the • Glargine is not to be mixed with any other preferred site for insulin injection in type of insulin because of its acidic pH and pregnancy. No change is required in the site of solubility.5 insulin administration during 1st trimester of Pens pregnancy. In the 2nd trimester, insulin should be injected over lateral parts of the abdomen, While using premixed or NPH insulin, make staying away from fetus. Insulin can be injected sure that insulin has been resuspended by over abdomen in 3rd trimester provided the rolling the pen. In preparation for injection, the skin fold is raised properly. Patient may also insulin pen should be primed with two units of prefer to use thigh or upper arm for insulin insulin. This is then discarded and the actual injection in the 3rd trimester. dose dialed in. After inserting the needle into • Dermatological disease:- the skin, injection button is pushed to deliver Insulin should not be administered at the site of the desired dose of insulin. It is advised to active infection or inflammation, such as skin dispose off the needle immediately after and soft tissue infections and psoriasis. Avoid injection in order to prevent the air entry into administering injection into keloids or scars. the cartridge as well as leakage of the Insulin may be safely injected into stable medication. vitiligo and acanthosis nigricans.

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 46 • Immunocompromised individuals:- advent of smaller needles). Apart from these Risk of hypoglycaemia is increased in functional consequences, needle reuse also immunocompromised patients, especially increases the risk of injection pain, injection suffering from HIV or hepatitis. Health care site irritation or damage and the risk of needle workers and those handling these materials breaking off and remaining in the tissue.8 are at high risk of transmission of blood borne Needle reuse has also been implicated in the pathogens (HIV and Hepatitis). Therefore, development of lipohypertrophy and reuse of needles and syringes is strictly occasionally may be associated with bleeding prohibited in this group of individuals. and bruising at local site. • Surgical diseases:- Injection through clothing Patients having surgical wounds over abdomen Many patients inject through clothing, should use different quadrant for insulin especially when they are in a hurry or in a injection. Appropriate aseptic precautions are public place. In a Canadian survey, > 7% of to be taken before insulin injection. Patient patients were found to inject through with history of recent abdominal surgery may clothing.9 use thigh or upper arm for injection. This practice must be strongly discouraged as 1) The needle can become infected Errors with insulin injection and associated 2) Loss of lubrication can cause injection consequences site pain Lack of rotation of injection sites 3) Clothing fibres can enter and irritate the Rotation of the injection site is necessary to skin10 prevent the development of lipohypertrophy- the most common cutaneous complication of Needle stick injuries insulin therapy, occurring in almost 50% of Needle stick injuries pose a significant risk of patients with diabetes.6 Lipohypertrophy has transmitting blood borne infection to health been shown to decrease the insulin absorption care workers. Education and training on safe by upto 25%. A multicentre study conducted in needle practices are mandatory to reduce the Spain enrolled 430 insulin injection users and incidence of needle stick injuries. found that almost 64% of patients had lipohypertrophy and the strongest protective Trypanophobia (Belenophobia) factor against lipohypertrophy was the correct Trypanophobia is defined as extreme fear of rotation of injection sites. Infrequently , medical procedures involving injections or localized amyloidosis can occur at the site of needles. Needle phobia may be associated with repeated insulin injection in patients with one or more of the following factors:- insulin requiring diabetes.7 The nature of • Lack of confidence in handling the amyloid in insulin associated amyloidosis is demands of insulin therapy considered to be amyloid insulin type(A INS). • Perceived loss of control over his/her life Reuse of needles • Perception that initiation of insulin Reuse of needles may be associated with loss of therapy is equivalent to personal failure sterility and damage to the needle tip by bending or breakage (particularly since the • Anxiety related to injection use

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 47 • Belief that the disease process has control. Journal of Clinical Translational become much worse Endocrinology. 2014;148:145–50. Injection device disposal 4. Bantle JP, Weber MS, Rao SM, et al., JAMA, As per NACO guidelines, used syringes or 1990;263(13):1802–6. needles to be discarded in a puncture proof 5. Deckert T. Intermediate-acting insulin box, labelled as “biohazard” and are handed preparations: NPH and lente. Diabetes Care. over to waste management department. Use of 1980;3:623–6. needle clipping devices is recommended for 32. Dimitriadis G, Gerich J. Importance of the safe removal of insulin syringe needle and timing of preprandial subcutaneous insulin pen needles. administration in the management of diabetes Conclusion mellitus. Diabetes care 1985;6:374-377 . Results from multiple surveys have shown that 6. Vardar B, Kizilci S. Incidence of despite improvement in insulin injection lipohypertrophy in diabetic patients and a technique over recent years, many aspects of study of influencing factors. Diabetes Res Clin the technique are not being performed Pract. 2007;77(2):231-236. optimally, exposing patients to unnecessary 7. Dische FE, Wernstedt C, Westermark GT, risks of hypoglycemia and uncontrolled Westermark P, Pepys MB, Rennie JA, et al. HbA1C. Such findings highlight the importance Insulin as an amyloid-fibril protein at sites of of patient education on correct insulin injection technique. Diabetes education , repeated insulin injections in a diabetic especially in terms of proper injection patient. Diabetologia. 1988;31:158–61. technique , requires lot of time and effort. 8. Misnikova IV, Dreval AV, Gubkina VA, Without it, however, the right type of insulin at Rusanova EV. The risks of repeated use of the right dose might not necessarily give the insulin pen needles in patients with diabetes right results. mellitus. J Diabetol. 2011;1:1-5. References 9. Berard L, Cameron B. Injection technique 1. Global report on diabetes . World Health practices in a population of Canadians with organisation, Geneva,2016 . d i a b e t e s : r e s u l t s f r o m a r e c e n t patient/diabetes educator survey. Can J 2. Shaw JE, Sicree RA, Zimmet PZ. Global Diabetes. 2015;39(2):146-151. estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 10. Kalra S, Balhara YP, Baruah MP, . Forum for 2010;87:4–14. injection techniques, India: the first Indian 3. Grassi G, Scuntero P, Trepiccioni R, Marubbi F, recommendations for best practice in insulin Strayss K. Optimizing insulin injection injection technique. Indian J Endocrinol technique and its effect on blood glucose Metab.2012;16(6):876-885.

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 48 THE SCIENCE AND EMOTIONS BEHIND BIONIC PANCREAS Jothydev Kesavadev MD,FRCP(London,Glasg), FACP(USA),FRSSDI Jothydev’s Diabetes Research Centres, Trivandrum & Kochi [email protected], www.jothydev.net

ABSTRACT deficient insulin production and subsequent, Technological advancements during the past huge glycemic fluctuations. By default, these few decades have contributed significantly individuals thus require daily administration towards improving the standard of diabetes of insulin to maintain their glycemic status 1. care. New generation insulin pumps and the Despite careful planning, maintaining optimal ongoing clinical trials exploring the glycemic targets is almost impossible in T1DM possibilities of completely closing the loop, 2. When subjected to Continuous Glucose bring promises to subjects with diabetes to Monitoring (CGM), even those T1DM patients lead a near normal life. An ideal closed loop with acceptable HbA1c values have been system combines continuous glucose shown to be prone to unacceptable episodes of monitoring with a computer-based algorithm l i fe t h re a te n i n g hy p o glyc e m i a a n d to automatically dictate insulin delivery via an hyperglycemia. Destruction of β-cells also insulin pump and would be able to determine results in secondary abnormalities in glucagon the insulin requirement in real time, regardless and incretins which can contribute towards of the situation, and deliver proper insulin metabolic instability and extreme glycemic dosage with minimal patient involvement. variability. Upon disease progression, patients These systems have turned out to be a realistic also tend to develop hypoglycemia option particularly for T1DM patients to u n a wa re n e s s a n d d e f e c t s i n t h e i r acheive their glycemic goals. ‘Bionic pancreas’ (now better known as ‘iLet’) is a novel kind of counterregulatory defences. Hence, intensive closed loop system and unlike other systems insulin therapy can result in severe that are programmed to deliver only insulin, hypoglycemia as well as hinder the effective comprises: a dual chambered pump (one for and safe control of hyperglycemia 3. delivering insulin and other for glucagon) with Closed Loop Systems to Tackle T1DM a built-in algorithm and a continuous glucose Technological innovations to tackle T1DM aim monitor (CGM) and aids in completely at achieving a near physiological delivery of automated glycemic control. The current insulin, elimination of hypoglycemia, painless article provides a brief overview of Bionic frequent glucose monitoring and ultimately a Pancreas starting from its conceptualization to multi-hormonal closed loop system. Such its invention and the ongoing efforts by the team towards attaining an FDA approval for the concerns have been overcome to a large extent device by this year. with the advent of Continuous Subcutaneous Insulin Infusion (CSII) systems (4-7) Open Keywords: Bionic pancreas, Closed loop loop systems that makes use of real-time CGMs system, Diabetes, Glycemic control, Type 1 in combination with CSII further simplified the diabetes process with even more accuracy and efficacy. INTRODUCTION Nonetheless, patients still need to frequently T1DM challenge review their glucose values and take into Type 1 diabetes (T1DM) is characterised by account diet and physical activities when destruction of pancreatic β-cells resulting in making treatment decisions (8). Haryana Medical Journal - March 2017, Vol. 40, Issue 01 49 onstant efforts are going on to achieve most physicians were not yet persuaded automated insulin delivery in the form of a whether the device was suitable for use with closed loop system. An ideal closed loop system very young children. Dr Damiano envisioned of consists of 3 specific components- a drug developing a bionic pancreas which forms a infusion system (with 1 or 2 hormones), a trio of connected devices: a continuous glucose continuous glucose monitor (CGM), and a sensor, a dual insulin and glucagon pump and a control algorithm, which makes automated small computer, which could be built into the dosing decisions about when and how much of pump and would determine how much insulin the hormone(s) to administer. Many research or glucagon to administer. He has been working groups are working hard to achieve an ideal for over a decade to materialise this dream of closed loop system and some of them have developing an artificial, or bionic, pancreas shown promising results. When compared to a that can literally transform the lives of so many standard pump therapy, most of them were like David. His long-term goal has been to get found to be advantageous in terms of increased the bionic pancreas FDA approval to enter the time spent within glucose targets, and/or market before his son goes off to college in reduced hypoglycemia and/or better overnight 2017. (14. ) blood glucose control (9-13) ii. iLet BIONIC PANCREAS "Bionic pancreas" originally refers specifically to a dual-chambered investigational device that comprises two pumps: one for delivering insulin and another for glucagon, a CGM, and a control algorithm built into an iPhone app. This device is the first and only of its kind to integrate glucagon delivery and makes therapeutic decisions every 5 minutes. i. History and Early Concept “ B i o n i c P a n c r e a s ” w a s o r i g i n a l l y conceptualised and developed by Dr Edward iLet – Fully integrated and automated Damiano, a professor in Biomedical bihormonal bionic pancreas Engineering at Boston University. The Bionic Pancreas platform that was developed inspiration behind Damiano in developing the in the academic research setting was taken device was when his son David was diagnosed over by “Beta Bionics” – a “public benefit with T1DM at just 11 months of age. Dr corporation” (with Dr. Damiano as the CEO) Damiano and his wife Toby Milgrome a and integrated it into a single medical device practising paediatrician, were extremely (the iLet, with reference to the pancreatic islets worried about any hypoglycemic episode that of Langerhans), with an aim to obtain FDA might sweep in, particularly at a time when approval to bring it to people with type 1 David’s blood glucose levels were not being diabetes. It looks like a thick iPhone, with two monitored, such as while sleeping. Ever since ports on the end for the tiny drug delivery tubes the diagnosis, both the parents had been so (one for insulin and other for glucagon). iLet concerned that they would check the blood requires minimal patient input and can be glucose levels of young David several times at initiated simply by providing data on the night to ward off any unlikely events as well as patient’s body weight and the device took all possible precautionary measures. They essentially takes over, whereas other peers still put their son on an insulin pump even when require the user to count carbs, take an insulin

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 50 bolus before meals, and program their insulin This closed loop device guided by advanced doses (15.) Some of the remarkable features of algorithms was found to reduce- i) on average, iLet include (16 ) time spent with low blood sugars, ii) on average, mean blood sugars and iii) inter- subject variability in blood sugar control 11, • Automates both insulin and glucagon (17-21). Preliminary research also point outs delivery that automated glucose control (by employing • Requires only body mass to initialize and insulin only, glucagon only or bihormonal comes online immediately (no run-in period) configuration as required) may also find utility • Determines all dosages autonomously in managing other conditions such as T2DM, • Accounts for outstanding insulin in both hypoglycemia in T1DM patients managing the subcutaneous depot and blood in its their own insulin therapy, post-bariatric algorithm hypoglycemia and congenital hyperinsulinism (22). Active efforts are going on to develop a • Suspends insulin dosing based on the more stable glucagon analogue for use with the glucose level trend to prevent hypoglycemia iLet, as the current formulation requires daily • Administers micro-doses of glucagon reconstitution. iLet in its single chamber mode pre-emptively to prevent hypoglycemia (insulin-only) is thus expected to come into the • Updates and stores a high-resolution market in 2018 and its bihormonal version a “basal-rate” profile for insulin delivery while later in 2019 26. • Allows optional user-initiated (but CONCLUSION system-calculated) meal-announcements Despite the latest advancements in medicine, • Allows the user to temporarily raise the T1DM is still a difficult puzzle both for the glucose target for added safety during certain patient and the physician. Continuous glucose activities monitoring systems and CSII systems have • Allows the user to trigger a glucagon already proven its advantages in managing this microburst before temporarily disconnecting chronic disease. With the development of from the device completely closed loop systems type 1 patients • Distributes insulin doses more optimally will be in future, able to lead a normal life which than under usual care had been a dream for several decades! . Bionic pancreas can definitely be considered as the • Proven to be safe and effective in children biggest advancement in the management of and adults type 1 diabetes and real benefits of this novel • Operates as a fully-integrated, fully- technology will become more evident only automated medical device platform with no after its FDA approval and widespread use. smartphone or tablet needed REFERENCES • Consists of a unique dual-cannula 1. Organization WH. Part 1: Diagnosis and infusion set, which prohibits inadvertent cross- classification of diabetes mellitus. Geneva: channelling of insulin and glucagon Wo r l d H e a l t h O r g a n i z a t i o n ; 1 9 9 9 . WHO/NCD/NCS/99.2. iii. Clinical trials 2. Kesavadev J, Sadikot SM, Saboo B, et al. Safety and efficacy of Bionic Pancreas have Challenges in Type 1 diabetes management in been demonstrated in a series of clinical trials South East Asia: Descriptive situational involving T1DM adults, adolescents and assessment. Indian Journal of Endocrinology preadolescents in different real life settings. and Metabolism. 2014;18(5):600.

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 51 3. McCall A, Farhy L. Treating type 1 13. Nimri R, Muller I, Atlas E, et al. MD-Logic diabetes: from strategies for insulin delivery to overnight control for 6 weeks of home use in dual hormonal control. Minerva Endocrinol. patients with type 1 diabetes: randomized 2013;38(2):145. c r o s s o v e r t r i a l . D i a b e t e s C a r e . 4. Kesavadev J, Das AK, Unnikrishnan R, et 2014;37(11):3025-3032. al. Use of insulin pumps in India: suggested 14. Jahnke A. A diabetic child spurs a race for guidelines based on experience and cultural a bionic pancreas. Summer 2013 BOSTONIA differences. Diabetes technology & [http://www.bu.edu/bostonia/summer13/da therapeutics. 2010;12(10):823-831. miano/. Accessed 24 January, 2017. 5. Kesavadev J, Jain SM, Muruganathan A, et 15. Tucker ME. Coming Soon: 'Artificial al. Consensus evidence-based guidelines for Pancreas' Options for Diabetes. Medscape use of insulin pump therapy in the M e d i c a l N e w s , C o n f e r e n c e N e w s management of diabetes as per Indian clinical [http://www.medscape.com/viewarticle/865 practice. The Journal of the Association of 060. Accessed 23 January, 2017. Physicians of India. 2014;62(7 Suppl):34-41. 16. Mapes M. ENDO 2016 Preview: Bringing 6. Weissberg-Benchell J, Antisdel-Lomaglio the Bionic Pancreas to the Presidential Plenary. J, Seshadri R. Insulin pump therapy a meta- F e b 2 0 1 6 ; analysis. Diabetes Care. 2003;26(4):1079- http://endocrinenews.endocrine.org / endo- 1087. 2016-preview-bringing-the-bionic-pancreas- 7. Morrison G, Weston P. The role of to-the-presidential-plenary/. Accessed 25 01 continuous subcutaneous insulin infusion in 17, 2017. the management of diabetes. Journal of 17. Betabionics clinical results. 23 January Diabetes Nursing. 2013;17(1):32-37. 2017; http://www.betabionics.org/clinical- 8. Kropff J, DeVries JH. Continuous glucose results. monitoring, future products, and update on 18. Russell SJ, El-Khatib FH, Nathan DM, et al. worldwide artificial pancreas projects. Blood glucose control in type 1 diabetes with a Diabetes technology & therapeutics. bihormonal bionic endocrine pancreas. 2016;18(S2):S2-53-S52-63. Diabetes Care. 2012;35(11):2148-2155. 9. Weinstock RS. Closing the loop: Another 19. Russell SJ, El-Khatib FH, Sinha M, et al. step forward: Am Diabetes Assoc; 2011. Outpatient glycemic control with a bionic 10. Castle JR, Engle JM, El Youssef J, et al. pancreas in type 1 diabetes. N Engl J Med. Novel use of glucagon in a closed-loop system 2014;371(4):313-325. for prevention of hypoglycemia in type 1 20. El-Khatib FH, Russell SJ, Magyar KL, et al. diabetes. Diabetes Care. 2010;33(6):1282- Autonomous and continuous adaptation of a 1287. bihormonal bionic pancreas in adults and 11. El-Khatib FH, Russell SJ, Nathan DM, et al. adolescents with type 1 diabetes. The Journal A bihormonal closed-loop artificial pancreas of Clinical Endocrinology & Metabolism. for type 1 diabetes. Science translational 2014;99(5):1701-1711. medicine. 2010;2(27):27ra27-27ra27. 21. Russell SJ. Progress of artificial pancreas 12. Del Favero S, Place J, Kropff J, et al. devices toward clinical use: The first outpatient Multicenter outpatient dinner/overnight studies. Current opinion in endocrinology, reduction of hypoglycemia and increased time diabetes, and obesity. 2015;22(2):106. of glucose in target with a wearable artificial 22. Russell SJ. Automating Glycemic pancreas using modular model predictive Management in Diabetes Mellitus with a Bionic control in adults with type 1 diabetes. Diabetes, Pancreas. Journal of Clinical Research in Obesity and Metabolism. 2015;17(5):468-476. Pediatric Endocrinology. 2016;8(1).

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 52 Management Of Renal Nutcracker Syndrome

Dr Ashok Chandna, Dr Rajiv Aggarwal, Dr Pawan Goel

NCS (Nut Cracker syndrome) is a manifest renal venous hypertension. This is termed as variant of nutcracker phenomenon, renal vein anterior NCS. NCS also occurs in association entrapment syndrome, or mesoaortic with a retro-aortic course of the left renal vein. compression of the left renal vein.It is caused The retro-aortic position of the left renal vein by compression of the left renal vein1 between facilitates compression of the left renal vein the aorta and the superior mesenteric artery between the aorta and the vertebral column where it passes in the fork formed at the leading to left renal venous hypertension. This bifurcation of these arteries and results in left is termed as posterior NCS4. Combined NCS renal venous hypertension. occurs in association with the duplication of the left renal vein where the anterior tributary Prevalence: NCS is relatively more common in of the left renal vein was compressed between women, most cases present in the 3rd or 4th the aorta and the SMA while the posterior decades of their lives although few patients tributary between the aorta and the vertebral have presented in adolescence and others in column. Causative factors Possible factors in later years. Many patients are of above average relation to the SMA include abnormally low or height and tend to have an asthenic built. lateral origin from the aorta, abnormal However, the exact incidence of the configuration of its origin or abnormal symptomatic nutcracker syndrome is not branching. Venous anomalies noted in cases of known2. NCS include the abnormal course of the left Abnormality: The normal angle between the renal vein behind the aorta or bifurcation of the superior mesenteric artery (SMA) and the left renal vein with tributaries coursing in front abdominal aorta is approximately 90°. A and behind the aorta. Secondary stretching of normally positioned left renal vein passes the left renal vein over the aorta and anterior to the aorta through the fork formed abnormally high course of the left renal vein by the abdominal aorta and the SMA3. Under Excessive fibrous tissue at the origin of the normal circumstances, SMA originates from SMA, which can contribute to the compression the aorta in almost a rectangular configuration of the left renal vein. Normal pressure gradient so that SMA has a 4–5 mm course in the ventral between LRV and inferior vena cava is less than direction before beginning a caudal descent 1 mmHg.9 The pressure gradient between the thus resulting in an inverted J configuration. left renal vein and vena cava may rise up to This anatomical arrangement normally 3mmHg due to compression by the SMA prevents compression of the left renal vein by leading to rupture of the thin walled septum the SMA. In contrast, SMA in cases of NCS has between the small veins and the collecting been noted to branch from the aorta at an acute system in the renal fornix leading to angle (less than 90°) with initial steep caudal haematuria5. descent causing compression of the left renal Clinical Manifestations: The syndrome is vein in the narrow slit between the aorta and manifested by left flank and abdominal pain, the superior mesenteric artery resulting in left with or without unilateral macroscopic or

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 53 microscopic haematuria. The other common excellent diagnostic yield although has the mode of presentation is a symptom complex disadvantage of radiation exposure. Magnetic called, ‘pelvic congestion syndrome’ resonance angiography offers the advantage of characterized by symptoms of dysmenorrhea, multi-planer imaging in transverse, coronal dyspareunia, post-coital ache, lower and sagittal planes of the body thus, allowing abdominal pain, dysuria, pelvic, vulvar, gluteal an excellent anatomical definition, the or thigh varices and emotional disturbances. advantage of being radiation free. Retrograde Systemic manifestations have also been phlebography and cine video-angiography reported in adolescents including a headache, w i t h re n o - c ava l p re s s u re g ra d i e n t determination is accepted as the gold standard abdominal pain fainting and tachycardia in establishing the final diagnosis of NCS, it mimicking clinical symptoms of an orthostatic allows visualisation of the point of disturbance6. compression of the left renal vein at the meso- Investigations Sequential diagnostic tests for aortic crossing and demonstrates peri-renal the confirmation of classical cases which and peri-ureteral venous collaterals with reflux includes: phase contrast microscopy, into the adrenal and gonadal veins and abdominal ultrasound and intravenous stagnation of the contrast in the renal vein7. urography, coagulation profiles, tests for Management :The available options can be sub- urinary bilharziasis, cystoscopic localization of classified into five groups. Surveillance Open the haematuria, selective urine cytology, surgical procedures Intra vascular stents: Uses flexible uretero-reno-scopy, renal biopsy, CT expandable metallic stents, is performed under and/or MR angiography, renal vein and IVC digital subtraction angiography (DSA) phlebography and venous pressure guidance under local anaesthesia. Extra manometry. The sequence of diagnostic tests, vascular stents: Uses a ring reinforced PTFE however, should depend on the mode of graft and is performed by open surgery. Intra- presentation Real-time ultrasonic imaging and pelvic chemical cauterization: The patient with Doppler flow scanning (duplex scanning) may intermittent gross haematuria and left loin be employed as the initial diagnostic test in pain is treated with instillations of 0.1% silver patients with suspected nutcracker syndrome. nitrate solution into the renal pelvis through Measurements should be made of the aureteroscope, twice in a week8. anteroposterior diameter and peak velocity at Conclusion From the number of cases reported two points in the transverse plain of the left in the world literature, it is evident that this renal vein; (1) at the level of the renal hilum (2) condition is not very common. Its diagnosis is at the point where left renal vein crosses based on history and physical examination, between the aorta and SMA. Diagnosis of basic lab tests. The sequence of imaging has nutcracker phenomenon should be suspected been rationalized to USS with Doppler studies, when anteroposterior diameter and peak CT or MR angiography and finally velocity at these two points exceeds by a factor phlebography with renal vein and IVC of five. Following an initial Doppler ultrasound, manometry to confirm the diagnosis patients suspected of having NCS should undergo computerized angiographic tomography of the abdomen to delineate the anatomical relation of LRV with aorta and SMA. CT angiography is non-invasive and has

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 54 References: 5. Hilgard P, Oberholzer K, Meyer 1. Kurklinsky A, Rooke T (June 2010). zumBüschenfelde KH, Hohenfellner R, Gerken "Nutcracker Phenomenon and Nutcracker G (July 1998). "[The "nutcracker syndrome" of the renal vein (superior mesenteric artery Syndrome". Mayo Clinic Proceedings. 85 (6): syndrome) as the cause of gastrointestinal 552–559. complaints]".Dtsch. Med. Wochenschr. (in 2. Sugimoto I, Takashi O, Ishibashi H, German). 123 (31–32): 936–40. Takeuchi N, Nagata Y, Honda Y (2001). "Left 6. Little AF, Lavoipierre AM (June 2002). Renal Vein Entrapment Syndrome (Nutcracker "Unusual clinical manifestations of the Syndrome) treated with Left Renal Vein Nutcracker Syndrome".AustralasRadiol. 46 Transposition". Jnp J Vasc Surg. 10: 503–7. (2): 197–200. doi:10.1046/j.1440-1673 3. Oteki T, Nagase S, Hirayama A, et al. (July 7. Mohamadi A, Ghasemi-Rad M, Mladkova 2004). "Nutcracker syndrome associated with N, Masudi S (August 2010). "Varicocele and severeanemia and mild proteinuria". Clinical nutcracker syndrome: sonographic findings". Nephrology. 62 (1): 62–5. Journal of Ultrasound in Medicine. 29 (8): 1153–1160. 4. Barnes RW, Fleisher HL, Redman JF, Smith JW, Harshfield DL, Ferris EJ (October 8. Takebayashi S, Ueki T, Ikeda N, Fujikawa 1988). "Mesoaortic compression of the left A (January 1999). "Diagnosis of the nutcracker syndrome with color Doppler sonography: renal vein (the so-called nutcracker correlation with flow patterns on retrograde syndrome): repair by a new stenting left renal venography". American Journal of procedure". J. Vasc. Surg. 8 (4): 415–21. Roentgenology. 172 (1): 39–43.

Authors Information Dr Ashok Chandna Dr Rajiv Aggarwal Dr Pawan Goel MD (Med) MD (Med) MD (Med) Sr.Consultant-Physician Sr.ConsultantPhysician Sr Consultant-Physician Faridabad Palwal Rewari

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 55 Correlation of Renal Resistivity Index with the Occurrence of Hepatorenal Syndrome (HRS) and Severity of Liver Disease In Patients of Cirrhosis Liver. Dr. Geeta Kampani, Dr. Anjali Chouksey

ABSTRACT: pathophysiology
similar
to
prerenalazotemia.
Background: Hepatorenal syndrome is a The
annual
frequency
of
HRS
in
cirrhotic
common complication in cirrhosis liver which patients
with
ascites
has
been
described
from
is associated with high morbidity and 8%
[1]


to
as
high
as
40%.

It
is
a
one
of
the
mortality. It is also a major determinant of post important
prognostic
factors
when
liver
liver transplant survival. Therefore, it is transplantation
is
being
considered... important to identify renal failure at an early

( )


stage before overt HRS develops by sensitive Hepatorenal syndrome HRS is characterized methods so that appropriate measures can be by
renal
vasoconstriction[2],
which
can
be
taken. Doppler ultrasonography of the renal explained
by
a
physiological
response
to
arteries is a non-invasive tool to assess renal vascular

under
filling

occurring
in
patients
of
resistance index (RRI) as an indicator for cirrhosis
liver
with
ascitis.
vasoconstriction in cirrhotic patients Renal
hemodynamic
changes
with
intense
Aims: The aim of this study is to correlate the intrarenal
vasoconstriction
begin

early
in
the
occurrence of HRS with RRI in patients of course
of
liver
disease
before
changes
in
the
cirrhosis liver. level
of
serum
urea
and
serum
creatinine.
Methods: It was a cross-sectional study Although
the
assessment
of
kidney
function
is
conducted in VMMC & SAFDARJUNG HOSPITAL of
great
clinical
importance
in
patients
with
NEW DELHI during the period of 2014-2017. It liver
cirrhosis
and
ascites,
serum
creatinine
was conducted on 50 patients with liver and
even
creatinine
clearance
are
not
accurate
cirrhosis selected after applying inclusion and indicators
of
renal
impairment
in
patients
exclusion criteria. All routine investigation with
advanced
liver
cirrhosis.
Serum
including kidney function test were done. Each creatinine
has
disadvantages
as
it
depends
on
subject underwent Renal Duplex Doppler muscle

mass

and
physical

activity.
Therefore,
evaluation. KFT were repeated every alternate renal
function
based
on
serum
creatinine
can
day during the hospital stay until patient was be
overestimated
in

patients

with

advanced
discharged or developed HRS. cirrhosis. Results: In our study total 8 patients developed HRS. Out of these 8 patients, 7 (87.5%) patients Renal
vasoconstriction
in
cirrhotic
patients
had RRI ≥0.7 whereas only 1 (12.5%) of them can
be
documented
by
using
Doppler
had RRI < 0.7 (p=0.05). Thus RRI value is ultrasound
(US)
analysis
of
renal
arteries,
significantly higher in patients of cirrhosis showing
increased
resistive
index[3].
In
liver who developed HRS as compared to those patients
with
normal
serum
creatinine,
who do not developed HRS. increased
RRI
seems
to
be
correlated
with
a
Conclusion:
We
conclude
that
renal
duplex
higher
risk
of
subsequent
deterioration
in
Doppler
ultrasound
is
useful
as
a
non-invasive
renal
function[4].
Therefore,
Doppler
method
for
the
evaluation
of
the
renal
ultrasound
may
be
an
early
marker
of
renal
hemodynamic
in
cirrhotic
patients dysfunction.
Thus,
timely
identification,
Key words: Hepatorenal syndrome, Renal prioritisation
for
transplant,
and
early
resistivity index initiation
of
vasoconstrictor
therapy
may
INTRODUCTION:
HRS
is
functional
renal
contribute
to
better
management
plan.

In
failure
in
cirrhotic
patients
with
candidates
for
transplantation,
high
renal
RRI

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 56 is
associated
with
a
greater
risk
of
renal
2.
Serum
creatinine>
133
μmol/L
(1.5
mg/dL) dysfunction
and
dialysis
post-transplantation 3.
No
sustained
improvement
of
serum
[5].
Thus,
RRI
also
has
a
role
in
prediction
of
creatinine
(decrease
to
a
level
of
133
μmol/L
mortality
in
patients
of
liver
cirrhosis
who
or
less)
after
at
least
2
day
of
diuretic
develop
HRS
and
also
in
cases
awaiting
liver
withdrawal
and
volume
expansion
with
transplant albumin;
the
recommended
dose
of
albumin
is








RRI plays an additional role in evaluating the 1
g/kg
of
body
weight
per
day
up
to
a






.
severity and prognosis of the liver disease maximum
of
100
g/d This
may
help
in
identifying
subgroups
of
4.
Absence
of
shock cirrhotic
patients
who
need
more
intense
.






monitoring. 5 No current or recent treatment with
RRI
is
determined
from
the
spectral
nephrotoxic drugs waveforms
and
corresponds
to
the
following
6.
Absence
of
parenchymal
disease
as
formula:
(peak
systolic
frequency
shift
–
indicated
by
proteinuria
> lowest
diastolic
frequency
shift)/peak
systolic
500
mg/d
microhematuria
(>
50
red
blood
frequency
shift. cells
per
high-power
field)
and/or
abnormal
With
this
background
we
sought
to
analyze
renal
ultrasonography RRI
in
liver
cirrhosis
patients
and
compare
it
All
routine
investigation
along
with
Renal
with
healthy
controls
thus
further
establishing
doppler,
Kidney
function
test

was
done
at
the
its
importance
in
predicting
subsequent
time
of
admission.
KFT
was
repeated
every
development
of
HRS.
It
can
be
included
in
the
alternate
day
during
the
hospital
stay
until
battery
of
investigation
routinely
performed
patient
was
discharged
or
developed
HRS.
for
monitoring
in
patients
of
liver
cirrhosis
so








that
appropriate
measures
can
be
taken
timely
Renal Duplex Doppler evaluation of the renal to
prevent
the
occurrence
of
HRS.
arteries
using
PHILIPS
HD
2-5-MHz
convex
METHOD:
The
hospital
based
cross-sectional
transducer
was
performed
by
an
experienced
study
was
conducted
on
50
patients
with
liver
radiologist.
Average
measurement
of
RRI
in
cirrhosis
admitted
in
the
General
Medicine
the
three
regions
of
each
kidney
was
taken
as
wards
VMMC
&
SAFDARJUNG
HOSPITAL
NEW
RRI
of
interlobar
artery.
The
RRI
was
DELHI
during
the
period
of
2014-2017
. calculated
with
the
formula Each
patient
was
subjected
to
detailed
history
RRI

=



(Peak
Systolic
Velocity
–
End
and
examinations
of
past
records,
with
special
Diastolic
Velocity)

emphasis
on
records
of
hypertension,
chronic
Peak
Systolic
Velocity
,

,

kidney disease diabetes mellitus other RRI
of
>0.70
was
considered
as
indicative
of
comorbid
conditions
and
recent
use
of
increased
renal
artery
resistance. nephrotoxic
drugs.
30
healthy
subjects








without
any
liver
or
kidney
disease
were
Severity of liver diseases was assessed by




( )

enrolled
in
study
and
taken
as
control
group.
using Child Turcott Pugh score CTP and





( )
.
The
patients
with
history
of
hypertension,
Model of end stage liver disease MELD score We
aimed
to
study

the
association
of
RRI
with
diabetes
mellitus,
pre-existing
renal
disease,
the
occurrence
of
hepatorenal
syndrome
(HRS)
recent
history
of
nephrotoxic
drug
intake
and




.


decreased
kidney
size
on
USG
were
excluded
in patients of cirrhosis liver We also






from
the
study. correlated the RRI with severity of liver disease
as
assessed
by
Child
TurcottsPughs
Diagnosis
of
Hepatorenal
syndrome
(HRS)
was
score
and
MELD
score
in
cirrhosis
liver
based
on
International
Ascitic
Club[6] patients. 1.
Cirrhosis
with
ascites

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 57 STATISTICAL ANALYSIS:
Data
was
entered
than
or
equal
to
0.7.
While
in
patients
with
into
Microsoft
Excel
work
sheet
for
analysis.
MELD
Score
>20,
RRI
was
more
than
or
equal
Descriptive
Statistics
i.e
mean,
median
and
to
0.7
in
20
(66%)
patients
and
less
than
0.7
in
standard
deviation
(SD)
for
continuous
10
(33%)
patients.
Thus
RRI
is
significantly
variables
and
frequency
distribution
and
their
higher
in
the
patients
with
MELD
score
>
20

percentage
for
categorical
variables
will
be
with
significant
p
value
of
<0.005. .




calculated All continuous variables were Among
the
cases
that
were
included
in
this







analysed using Student t Test for normally study,
total
8
patients
developed
HRS.
Out
of



-



distributed data and Mann Whitney U test for these
8
patients,
7
(87.5%)
patients
had
RRI

.



skewed data Categorical variables were equal
to
or
more
than
0.7
whereas
only
1


-


’
analysed using Chi square Test and Fisher s (12.5%)
of
them
had
RRI
less
than
0.7
(p=0.05).



.


exact test as applicable Correlation and Thus
RRI
value
is
significantly
higher
in





regression analysis were performed to patients
of
cirrhosis
liver
who
developed
HRS




examine relationships between Renal as
compared
to
those
who
do
not
developed


(
)


&
Resistivity Index RRI and clinical HRS
during
their
hospital
stay.(Table
3) biochemical
variables.
DISCUSSION:
Hepatorenal
syndrome
(HRS)
is
2.
Serum
creatinine>
133
μmol/L
(1.5
mg/dL) a
frequent
complication
in

patients
with
OBSERVATION: The study was conducted on cirrhosis
and
ascites,
which
is
due
to
a
80 adults, 50 cases of cirrhosis liver were vasoconstriction
of
the
renal
circulation.
enrolled after fulfilling the inclusion and Though
effective
therapeutic
options
are
exclusion criteria with age and sex matched 30 available
for
management
of
hepatorenal
healthy controls from population. The mean syndrome,
it
is
still
associated
with
significant
age of cases was 50.72 ( ± 10.9 ) yrs, while in morbidity
and
mortality.
Liver
transplantation
control it was 48.5 ( ± 8.75) yrs. Out of the 50 forms
the
cornerstone
for
its
management.
cases of cirrhosis liver , 44 (88%) patients were Thus,
it
is
still
necessary
to

develop

improved
males and 6 (12%) prognostic
markers
that
can
be
utilised

in

patients
were
females. daily
practice.
RRI
was
found
to
be
equal
to
or
more
than
0.7
Duplex
Doppler
ultrasonography
of
the








in
25
(50%)
and
less
than
0.7
in
25
(50%)
kidneys is an useful method to assess blood flow
and
arterial
vascular
resistance
as
a
patients
of
cirrhosis
liver
cases.
In
control
parameter
for
vasoconstriction[7].
In
our
population
RRI
was
equal
to
or
more
than
0.7
study,
we
accessed
the
RRI,
based
on
in
only
9
(30%)

and

less
than
0.7
in
21
(70%).
sonographic
measurements
of
intrarenal
The
mean
RRI
of
cases
is
0.67
±
0.07,
while
resistance,
as
an

effective
,
non
-invasive,

that
of
control
is
0.64
±
0.07.9
economical
functional

test
that

predicts
the
(Table
1) future
development
of
HRS
in
patients
with

. It
was
also
observed

that
RRI
had
a
significant
increased RRI positive
correlation
with
Child
Pugh
class
with
In
our
study,
the
mean
age
of
cases
was
50.72
p
value
of
0.032
as
regards
RRI
showed
a
(±
10.9)
yrs.
The
age
of
the
Ptients
showed
no
significant
difference
with
Child
C
patients
association
with
the
future
development
of
having
highest
mean
RRI
followed
by
Child
B
HRS
in
cases
of
cirrhosis
liver
as
indicated
by
patients
and
lastly
Child
A
patients
(0.64
±
insignificant
p
value
of
0.23
in
logistic
0.06,
0.65
±
0.08and
0.7
±
0.07
respectively).
regression
analysis.
This
is
concordance
with
(Table
2) the
results
in
the
study
done
by
SundeepGoyal
et
al[8]
where
also
age
(p=0.76)
was
not
found

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 58 to
have
independent
association
with
future
s
correlation
factor
r
=
0.6
and
p
value
of
<
0.03
.
HRS
development. Ahmed
Mohamed
Hussein
et
al[10].
also
found
In
our
study,
out
of
the
20
patients
with
MELD
that
there
was
a
significant
positive
score
≤ 20,
15
(75%)
patients
had
RRI
less
correlation
between
RRI
and
MELD
(r=0.859,
than
0.7,
while
5
patients(
25%)
had
RRI
more P<0.001).
Patient
with
high
RRI
(n
=
57)
had
significantly
higher
MELD
score
(21.63±3.15
The
study
indicated
that
RRI
was
higher
vs.
14.56± 3.2,
P<0.001)
than
patients
with
among
cases
as
compared
to
healthy
normal
RRI
(n
=
63). individuals
of
control
group
with
an
increased

frequency
of
25
(50%)
and
9
(30%)
respectively,
We
have
divided
patients
of
liver
cirrhosis
in
which
on
statistical
analysis,

was
found
to
be

two
groups
based
on
their
RRI
values.
Within

highly
significant
with
p
value
of

<
0.005.
the

group

of

25
patients

with
RRI

≥

0.70,
These
results
were
in
concordance
with
the
20
(80%)

developed

MDRD
eDFR
worsening
result
of
the
studies
done
previously.

and

7
(28%)
developed
hepatorenal

Goetzberger
et
al[9]
found
in
his
study
that

syndrome,

whereas

only
8
(32%)

of

the

mean

RRI

level

was

significantly

higher

in

patients

with

normal

RRI

<0.70

developed
cirrhotic

patients
(RRI

=

0.70)

than

in
MDRD
eDFR
worsening
at

the

end

of

3rd
control

subjects

(RRI

=

0.62,

p<0.01). day.
(p=0.001).

Among
8

patients
who
developed
HRS,
7
(
87.5%)
patients
had
RRI
In
the
study
by
SundeepGoyal
et
al[8]

control
equal
to
or
more
than
0.7
whereas
only
1
group
mean
RRI
was
0.52
±
0.02.
In
cirrhosis
(12.5%)
of
them
had
RRI
less
than
0.7
(p=0.05). group
without
ascites,
RRI
analysis
showed
a
mean
value
of
0.62
±0.06.
In
the
second
group,
The
relationship
between
RRI
and
occurrence
patients
with
ascites,
showed
significantly
of
HRS
in
patients
of
liver
cirrhosis
has
been







increased
RRI
with
mean
0.72
±
0.02. evaluated in many of the previous studies conducted
by
Maroto
et
al,
Platt
et
al.
and


,





In our study RRI had a significant positive Alberto
et
al. correlation
with
Child
class
as
regards
RRI


[ ]




showed
a
significant
difference
(P
=0.032)
with
Maroto et al 11 investigated 32 cirrhotic with Child
C
patients
having
highest
mean
RRI
ascites.
The
subgroup
of
17
cirrhotic
patients
followed
by
Child
B
patients
and
lastly
Child
A
with
renal
failure
showed
elevated
RRIs
of
patients
(0.64
±
0.06,
0.65
±
0.08and
0.7
±
0.74
±
0.01.
Follow-up
revealed
the
RRI
as
an
0.07
respectively). indicator
of
impaired
survival
in
the
univariate
analysis.
In
another
study,
Alberto
et
al[12],
Findings
fromour

research
showed

that

RRI

concluded
that
patients
with
HRS
had
significantly

increased

from

Child-Pugh
significantly
higher
values
of
RRI
than
those
stages

A

to

C.

These
results
indicate

that

without
HRS.
The
relative
risk
of
developing
RRI

is

directly

influenced

by

severity
of
HRS
in
patients
with
an
RRI
=
0.70
was
high.
liver

disease
in
patients
with
liver
cirrhosis. Our
findings
are
in
agreement
with
previous
Out
of
the
20
patients
with
MELD
score
≤20,
re-sults
showing
a
mean
RRI
of
0.76
±
0.04
in
15
((75%)
had
RRI
less
than
0.7,
while
5
(25%)
the
8
patients
who
subsequently
developed
had
RRI
more
than
or
equal
to
0.7.
While
in
HRS.
patients
with
MELD
Score
>20,
RRI
was
more

In
an
Indian
study
Sikarwar
et
al,[13]
positive
than
or
equal
to
0.7
in
20
(66%)
patients
and
co-relation
between
blood
urea
&
mean
RRI
less
than
0.7
in
10
(33%)
patients
with

.
significant
p
value
of
<0.005.On
statistical
was seen analysis,
there
is
a
positive
correlation
In
astudy
done
by
Goetzberger
et
al[9],
RRI

between
MELD
Score
and
RRI,
with
Pearson’ was
found
to
be
significantly

higher

in

those

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 59
patients

than

in

cirrhotic

patients

with

of
hepatic
decompensation.
We
recommend
normal

serum

creatinine

(n

=

40,

RRI

=

that
RRI
should
be
determined
initially
for
0.69)

(p<0.05).
every
cirrhotic
patient
and
then
to
be
followed
For
the
prediction
of
renal
outcome,
logistic
on
routine
follow
up
visits
every
6– 12
regression
was
performed
for
the
occurence
of
months
with
patients
with
high
RRI
followed
hepatorenal
syndrome
with
the
individual
up
at
shorter
interval
than
others. parameters
assessed
in
our
study.
Results
References indicated
CTP
score
>9
(p=0.018)
was
1.
Arroyo
V,
Fernandez
J,
Gines
P.
independently
associated
with
future
HRS
Pathogenesis
and
treatment
of
hepatorenal
development.
(Table
4) syndrome.
Semin
Liver
Disease.
2008;28:81– In
the
study
done
by
SundeepGoyal
et
al[8],
RI
95.
>0.70(p=0.006),
and
CTP
score
>9
(p=0.04)
2.
GineÁs P, RodeÂs J: Clinical disorders of renal were
independently
associated
with
future
function in cirrhosis with ascites. In: Ascites HRS
development.
In
addition,there
was
a
and Renal Dysfunction in Liver Disease: tendency
for
HRS
to
be
associated
with
MELD
Pathogenesis, Diagnosis, and Treatment, score
>14.
Although
this
was
non-significant
edited by Arroyo V, GineÁs P, RodeÂs J, Schrier (p=0.06).
The
difference
in
the
results
of
the
RW, Malden, MA, Blackwell Science, 1999,36- logistic
regression
analysis
can
be
attributed
62. to
the
smaller
sample
size
and
shorter
follow
3. Platt JF, RubinJM and Eills JH. Intrarenal up
period
in
our
study
as
compared
to
study
arterial Doppler sonography in patients with done
by
SundeepGoyal
et
al.
They
followed
the
non-obstructive renal disease: correlation of patients
for
6
months
after
the
enrollment
and
resistive index with biopsy findings. Am J found
that
later
renal
outcome
was
Roentgenol. 1990;154:1223–1227. significantly
worse
in
those
with
RRI
elevated
4. J.F. Platt, C.S. Marn, P.K. Baliga, J.H. Ellis, J.M. >0.70. Rubin, R.M. Merion. Renal dysfunction in In
our
study,
number
of
cases
of
cirrhosis
liver
hepatic disease: early identification with renal included
was
small.
Only
50
cases
of
cirrhosis
duplex Doppler US in patients who undergo liver
were
included
whom
we
followed
during
l i v e r t r a n s p l a n t a t i o n . R a d i o l o g y. their
hospital
stay
for
the
development
of
HRS.
1992;183:801–806. Out
of
these
50
cases,
only
8
patients
5. Platt J, Ellis JH, Rubin JM, Merion RM, Lucey MR. Renal duplex Doppler ultrasonography : A developed
HRS
during
their
hospital.
It
is
noninvasive predictor of kidney dysfunction possible
that
if
the
patients
were
followed
for
and hepatorenal failure in liver disease longer
period,
more
patients
who
later
Hepatology. 1994;20:362-369 developed
HRS
could
be
picked.
Thus
a
6. Garcia-Tsao G, Parikh CR, Viola A: Acute longitudinal
study
with
larger
cohorts
and
kidney injury in cirrhosis. Hepatology. 2008; long
term
follow-up
would
further
strengthen
48:2064–2077. our
finding
of
increase
incidence
of
HRS
in
7. Platt JF. Duplex Doppler evaluation of native cirrhosis
liver
patients
with
RRI
>
0.7. kidney dysfunction: obstructive and non Thus,
based
on
the
observation
from
our
study,
obstructive disease. AJR Am J Roentgenol. we
conclude
that
renal
duplex
Doppler
1992;158:1035–1042. ultrasound
is
useful
as
a
non-invasive
method
8. Goyal S, Dixit VK, Jain AK, Shukla RC, Ghosh J, for
the
evaluation
of
the
renal
hemodynamic
Kumar V. Intrarenal resistance index (RI) as a changes
in
cirrhotic
patients
with
good
predictor of early renal impairment in patients correlation
to
the
severity
of
liver
disease.
The
with liver cirrhosis. Tropical Gastroenterology renal
resistive
index
increases
with
the
degree 2013;34(4):235–239.

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 60 9. Gotzberger M, Kaiser C, Landauer N, Dieterle TABLE 2 : COMPARISON OF DIFFERENT C, Heldwein W , Schiemann U. Intrarenal VARIABLES AMONG CASES resistance index for the assessment of early VARIABLES RRI<0.7(n=25) RRI ≥0.7 (n=25) P value renal function impairment in patients with Platelet count 216160 ± 82039.97 175000 ± 81509.71 0.081 liver cirrhosis.Eur J Med Research. Serum bilirubin 4.27 ± 3.54 6.2 ± 6.82 0.214 2008;13:383–387. SGOT 118 ± 36.43 100.88 ± 37.51 0.108 10. Sameh Ahmed Abdel-bary, EslamSafwat, SGPT 65.32 ± 31.08 63.2 ± 46.64 0.851 Hany Ali Hussein, Ahmed Mohamed Hussein, ALP 102.96 ± 30 107.36 ± 43.54 0.679 SamerMalakBotros. Value of renal resistive Serum Albumin 2.46 ± 0.54 2.41 ± 0.71 0.771 index in hepatitis C virus related liver cirrhosis Serum sodium 135.88 ± 5.75 134.08 ± 7.12 0.330 and its response to midodrine. The Egyptian Prothrombin time 23.07 ± 6.07 29.78 ± 8.63 0.003 Journal of Radiology and Nuclear Medicine. INR 1.8 ± 0.4 2.54 ± 0.78 0.0001 2014;45:1079–1087. CTP A 2 2 11. Maroto A, Ginès A, Saló J, Clària J, Ginès P, CTP B 17 8 Anibarro L, et al. Diagnosis of functional renal CTP C 6 15 No of cases developing 1 7 failure of cirrhosis with Doppler sonography: HRS prognostic value of resistive index. Hepatology. Mean MELD Score 23.36 ± 5.71 23 ± 4.12 0.9 1994;20:839–844. TABLE
3:
CORRELATION
BETWEEN 12. Bardi A, Sapunar J, Oksenberg D, Poniachik OCCURRENCE
OF
HRS
AND
RRI J, Fernández M, Paolinelli P, et al. Intrarenal RRI grouping arterial doppler ultrasonography in cirrhotic OCCURRENCE OF HRS 1) <0.7 2) ≥ 0.7 TOTAL patients with ascites, with and without No 24 (96.00%) 18 (72.00%) 42 (84.00%) hepatorenal syndrome. Rev Med Chil. 2002;130:173-180. Yes 1 (4.00%) 7 (28.00%) 8 (16.00%) 13. Sikarwar JS, Muchhoria S, Singh R, TOTAL 25 (100.00%) 50 (100.00%) 50 (100.00%) BhujadeH,AhirwarV.Study of Resistive Index in TABLE
4
:
RELATIONSHIP
BETWEEN various stages of Liver Cirrhosis and its




significance in Calculating the Risk for OCCURRENCE OF HRS AND RRI WITH
HepatorenalSyndrome.Journal of Evolution of OTHER VARIABLES Medical and Dental Sciences 2014;3:1195- P value Odds ratio 95% C.I. for odds ratio 1205. Lower Upper Sodium (<125) 0.230 5.857 0.327 104.903 TABLE 1: COMPARISON OF DIFFERENT VARIABLES IN CASES AND CONTROL RRI (>0.7) 0.113 4.000 0.721 22.183 Day1 SC (>1.2) 0.618 0.680 0.149 3.099

VARIABLES CASES CONTROL P value Age (>35) 0.230 0.171 0.010 3.058 Serum bilirubin 5.24 ± 5.47 1.11 ± 0.34 <0.0005 INR (>1.5) 0.397 3.59 0.186 69.239

SGOT 109.44 ± 37. 6 65.97 ± 12.46 <0.005 CTP Score (>9) 0.018 14.000 1.565 125.257 SGPT 64.26 ± 39.24 51.9 ± 13.12 0.101 MELD Score (>14) 0.793 1.506 0.071 31.950 ALP 105.16 ± 37.07 88 ± 10.43 0.003 Serum albumin (<3) 0.307 3.138 0.349 28.180 Serum Albumin 2.44 ± 0.62 3.7 ± 0.36 <0.005

Prothrombin time 26.42 ± 8.12 13.9 ± 2.94 <0.005 P
value
Odds
ratio
95%
C.I.
for
odds
ratio Haemoglobin 7.64 ± 1.54 10.08 ± 2.33 <0.005

:

Corresponding Author's information Anjali INR 2.17 ± 0.72 1.15 ± 0.21 <0.005 Chouksey Contact
no :
91-8587883897

RRI 0.67 ± 0.07 0.64 ± 0.07 0.0073 Department
of
General
Medicine,
VMMC
and
Safdarjung
Hospital,
New
Delhi. Haryana Medical Journal - March 2017, Vol. 40, Issue 01 61 Research Article :- “ THE CONNOTATION OF CYTOLOGICAL EXAMINATION OF THE PLEURAL FLUID IN THE DIAGNOSIS OF PLEURAL EFFUSION IN CENTRAL INDIA.” AUTHORS: DR. DIVYA TANEJA, DR. K.B. MISHRA, DR. AKSHAT TANEJA 1 P.G. 3rd year, 2 H.O.D. & Professor DEPARTMENT OF PATHOLOGY, L.N. MEDICAL COLLEGE & RESEARCH CENTRE, BHOPAL, MADHYA PRADESH, 3 J.R., TANEJA HOSPITAL & HEART CENTRE, GURGAON, HARYANA. ABSTRACT the tissue. Although cytology does not of In developing countries, where investigations always replace excisional biopsy and and health facilities are scarce and cost of histopathologic examination, however, it’s treatment is inflated, cytological examination considered less invasive, more simple, of body fluids is considered an economical, inexpensive, allows faster diagnosis with low rapid and highly effective tool in pointing incidence of false positive diagnosis, which towards the etiology of effusion with divination may reach less than 1% and it facilitates cancer of the underlying disease process. Cytological screening in some cases.1 Examples of examination can detect malignant cells in common sources of cytologic specimens effusions and sometimes, its superior to biopsy include cutaneous and subcutaneous masses, in detecting serosal malignancy. Good clinical body cavity fluids, lymph nodes, liver, spleen, history, history of any exposure, absence of pancreas, bone marrow, rectal swabs, vaginal malignancy elsewhere in the body and swabs. radiologic findings are very salient aids in The pleural space is a potential space between confirmation of cytological diagnosis of the visceral and parietal layers of the pleurae malignancy. Although, at times, the definite that normally contains 0.1-0.2 mL/ kg body diagnosis is not attained by cytology alone and weight of fluid. 2 Pleural effusion is an the need for tissue biopsy or ancillary methods abnormal accumulation of fluid in the pleural becomes mandatory. The slides of total 108 cavity and remains the most common cases of pleural effusion stained with Giemsa manifestation of pleural pathology. 3 and papanicolau stains were collected from Although, a variety of clinical conditions may archives of the Cytology Unit, Pathology be the cause of pleural effusion, the possibility Department, L.N. Medical College & Research of a malignant involvement of pleural cavity Centre, Bhopal, during the period of January 1, should always be considered in difficult-to- 2016 till November 30, 2016. The slides were diagnose cases. revised and results were stastically analysed.IN Because percutaneous access of the pleural CONCLUSION: Cytology plays a central role in space is relatively simple, techniques such as the etiological clarification of pleural effusion pleural biopsy and thoracoscopy have become specially if good clinical data are available and very popular. However, such facilities are sometimes, it has an instructive significance in available only in advanced pulmonary diagnosis of malignancy even where clinical medicine centers, pleural fluid analysis diagnosis is missed. analysis and cytology remain the mainstay for KEY WORDS: Cytology, Pleural effusion, diagnosing the various pulmonary diseases.4 Transudate, Exudate, Malignant effusions, Anlaysis of pleural fluid can have an important Mesothelioma. contribution for investigation of patients with INTRODUCTION: pleural effusion.5 Cytological examination of CYTOLOGY is the examination of the individual pleural fluids is of great diagnostic significance cells regardless of the architectural structure of in both non-neoplastic and neoplastic Haryana Medical Journal - March 2017, Vol. 40, Issue 01 62 effusions.6 Cytology also plays a central role in of Pathology, L.N. Medical College & Research the etiological clarification of pleural effusion.7 Centre, Bhopal, Madhya Pradesh, during the Pleural effusion can be broadly classified as period January ‘16 till November ‘16. Data transudative & exudative.8 The number & type acquired from the cytopathology sheet of non-neoplastic cells found in pleural included; age, sex, clinical history, clinical effusions depend on a large extent on the diagnosis and the gross appearance of the fluid pathogenic mechanisms of fluid formation, received. which determine whether an effusion is The available archival slides were previously classified as exudate or transudate. 9 stained with hematoxylin and eosin Transudative pleural effusion is caused by fluid Papanicolaou technique (both after fixation leaking into the pleural space. Such leakage with 95% propanol) as well as giemsa stain may be due to a variety of reasons but the most after air drying. All available slides were common one is the failure of the left ventricle. cytomorphologically revised & reported. Patients suffering from complications after Cytomorphological evaluation: cardiac surgery have also often been diagnosed All the available slides were evaluated & with transudative pleural effusion. Pulmonary r e p o r t e d b a s e d o n t h e f o l l o w i n g embolism and cirrhosis are other common cytopathological features: causes for this form of pleural effusion.10 • Cells – as regards to their arrangement Exudative pleural effusion is caused by leaky (clusters, singly, sheets), type, number, size. blood vessels, which in turn, caused mainly due to lung disease. Some of the most common • Presence of rosettes, acini (groups with causes of exudative pleural effusion are an empty center) & papillae (finger like tuberculosis, lung infections, bacterial arrangement). pneumonia, pulmonary embolism, breast or • Amount of cytoplasm & presence of lung cancer. 11 Rare causes being pancreatic, cytoplasmic vacuoles. liver and kidney diseases, viral and fungal • Nuclei- shape, size, nuclear membrane, infections and mesothelioma.10 chromatin pattern & presence of nucleoli. Diagnostic difficulties in effusion cytology • Presence of malignant criteria- marked include distinguishing between reactive and nuclear & cellular pleomorphism, nuclear & malignant effusions with determination of cytoplasmic moulding, large prominent malignancy if present.12 These difficulties may nucleoli, irregular nuclear contours, with be aided by other ancillary methods such as hyperchromasia& abnormal chromatin special stains, IHC, electron microscopy, flow clumping, granularity of chromatin & absence cytometry and PCR.13 of nuclear membrane, high N/C ratio, nuclear The aim of the present study was to revise the haloes, atypical mitosis and multiple levels of available archival slides of pleural effusion cells in sheets or clusters. s a m p l e s a n d to c o r re l a te b e t we e n • Background: either proteineaous or cytomorphological features detected and the dirty background (tumor diathesis) contained clinicopathological data present in the RBC’s, inflammatory cells, debris & others as requisition forms, with special; highlights on psammoma bodies. malignant cases. Statistical analysis : MATERIAL & METHODS Analysis of data was done by SPSS (statistical This is a retrospective study. The material program for social science version 22). Data collected included 101 cases of pleural effusion were expressed as frequency & percentage or smear slides. The slides were obtained from mean & range as appropriate. Chi-square test the archives of the Cytology Unit, Department Haryana Medical Journal - March 2017, Vol. 40, Issue 01 63 was used to examine the relation between Upon cytological examination of the s smears qualitive variables; comparison between two prepared (87/101), 86.13% were exudates & quantitative variables was done using t-test. P- 13.86% were transudates. value <0.05 was considered statistically In the exudative pleural effusions, the benign significant &<0.001 as highly significant. types were the most predominant presenting OBSERVATIONS & RESULTS 89.6%, most of them were reactive In the present study, 101 cases of pleural inflammatory representing 74.1% of benign effusion were examined. The age of patients exudates. Regarding malignant exudates ranged between 2-95 years, with the mean age (10.9%), 5 were non-mesothelioma while 4 of 49 years. The highest percentage of cases i.e. were mesotheliomas. 29% were in 50-60 years’ group. The male Table 2: Types of pleural fluid on bases of predominance wasnoted in 56.5% cases while cytological examination. females were 43.5%. Most cases of pleural effusion were Cytology No. of Percent clinically associated with benign conditions cases presenting 80.2% of cases, among which (N=101) respiratory diseases were found to be the most common cause presenting 92.6% of cases. Exudates 87 86.13% The pleural effusion cases associated with Benign 78 89.6% clinically diagnosed malignant conditions Tuberculosis 31 39.74% presented 19.8% of cases, among which lung & Lymphocytic 31 39.74% pleural tumors whether primary or secondary effusion were the most common presenting malignant Eosinophilic 4 5.12% conditions, followed by GIT tumors. effusion Table 1: Clinical conditions associated with Necrotizing 4 5.12% pleural effusion cases. ( As reported on lesion requisition forms from clinicians). Cardiac 2 2.56% Clinical Number Percent Hepatic 2 2.56% diagnosis N=101 (%) CRF 2 2.56% Benign 81 80.2 Autoimmune 1 1.28% conditions Respiratory 75 92.6 Trauma 1 1.28%

Cardiac 2 2.47 Malignant 9 10.35% Hepatic 1 1.23 CRF 1 1.23 Autoimmune 1 1.23 Non- 6 66.66 % Trauma 1 1.23 mesothelioma Malignant 20 19.8 Conditions Mesothelioma 3 33.33% Lung & 9 45 pleural tumors Transudates 14 13.86% GIT tumors 5 25 Breast 2 10 tumors In cytologically diagnosed malignant exudative Mediastinal 1 5 effusions associated with tumors other than Lymphoma 1 5 mesothelioma, metastatic carcinoma of Ovarian 1 5 tumors unknown primary was the most common cause Bone tumors 1 5 presenting 50% of cases.

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 64 Mesothelioma was diagnosed in 3 samples. As regards to the gross appearance, pleural Mesothelial cells were arranged singly or in fluid was hemorrhagic in 19.8 % of benign three dimensional clusters forming spherical, exudates and 57.9% of malignant cases, the morule-like configuration with knobby correlation between the gross appearance of borders. Single atypical scattered cells were the fluid and cytological diagnosis was also seen. Atypical nuclear features like considered highly significant (p value <0.001). variation in nuclear size, multinucleation, Regarding the clinically diagnosed benign hyperchromasia and enlarged nucleoli were conditions (81/101), 70/ 81 were associated noted with cytologically benign pleural exudates as Table 3: Types of malignant exudative well, while 1/81 was diagnosed cytologically as pleural effusion other than mesothelioma malignant exudate. The remaining (10) cases were diagnosed cytologically as transudates. Tumor type Number Percent The correlation between benign and the (N=6) malignant pleural exudates as regards clinical Unknown 3 50% data and gross features are tabulated in Table 4. primary Table 4: Correlation between benign and the Lung 1 16.66% malignant pleural exudates as regards the Carcinoma clinical data and gross features. Breast 1 16.66% Parameter Cytological P Carcinoma diagnosis value Benign Malignant Lymphoma 1 16.66% exudates exudates N=78 N= 9 Regarding the clinical presentation; in Age/ years mesothelioma, patients presented with pleural Mean 49 years 50 years 0.6 effusion in 1 case, while pleural thickening and Sex nodules in 1 each, while tumors other than Male 57.8% 51.6% 0.4 mesothelioma , patients presented clinically Female 42.2% 48.4% with pleural effusion or the cytological Clinical diagnosis preceded the clinical diagnosis of diagnosis: malignancy in 3 cases, where 1 case each of Benign 87.17% 11.11% 0.001 non-specific respiratory symptoms, liver conditions cirrhosis & another with cardiac condition. Malignant 12.82% 88.88% conditions In this study, the mean age of patients having Gross benign exudate was 49 years while the mean Features age of patients having malignant exudate was Turbid 62.2% 38.6% 51 years. The relationship between type of yellow 0.001 exudate and patients age was statistically Hemorrhagic 19.8% 57.9% insignificant. Clear yellowish 18% 38.6% Malignant exudates were found to be more common in males (51.6%) than females The clinically diagnosed malignant cases (20), (48.4%), while benign exudates were 57.8% in it was found that 10/ 20 were associated with males and 42.2% in females. benign pleural exudative effusion, while 8/20 The correlation between type of exudate and cases were associated with malignant exudates sex of the patient was also statistically mostly due to lung or pleural malignancy and 2 insignificant. cases were transudates. (Table 5)

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 65 Table 5: Cytological diagnosis of the clinically diagnosed malignant conditions associated with pleural effusion.

Clinical Cytological diagnosis diagnosis

Benign Malignan Transudat exudat t exudate e e

Malignant Lung and 4 5 1 Figure 2: shows Giemsa stained slide with pleural reactive mesothelial cells. (Low power view) tumors (9) GIT 3 2 0 tumors (5) Breast (2) 1 1 0 Mediastina 1 0 0 l (1) Lymphom 1 a (1) Ovarian 0 0 1 (1) Bone (1) 0 0 TOTAL 10 8 2 Figure 3: Pap stained smear showing (20) atypical reactive mesothelial cells. The correlation between clinical diagnosis and cytological diagnosis was considered highly significant (p value <0.001).

Figure 4: Pap stained smear showing malignant mesothelial cells with irregularly outlined cluster with window.

Figure 1: shows H & E stained smear of pleural fluid with reactive mesothelial cells with moderately enlarged nuclei with regular smooth nuclear borders & occasional prominent nucleoli against a proteinaceous background. (Low power view)

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 66 Figure 5: showing smear with malignant at selected centers, and furthermore, its cost is cells against hemorrhagic background. very high for an economically average person (High power view) in a developing country such as India.4 A Survey revealed that even in the USA, only 6% of pulmonologists are currently trained in and perform thoracoscopy.17 Hence, thoracentesis still remains a popular diagnostic procedure in cases of pleural effusion. Body cavity effusions are challenging as the static fluids almost always accumulate neutrophils and macrophages. Protein content and cell number give some insight into exudate Figure 6: Giemsa stained smear showing versus transudate.11 The number and type of malignant tumor cells forming clusters and non-neoplastic cells commonly found in serous sheets. effusions is classified as a transudate or an DISCUSSION exudate. 9 Serous body cavities contact virtually all In this retrospective study of 101 cases of internal organs. Therefore, all types of pleural effusion were revised and statistically processes that can affect these tissues (benign analysed. The age range of patients was from 2 or malignant) can manifest changes in the to 95 years (mean age 49 years) with the serous fluid and always the effusion represents highest percentage of cases in the age group an underlying pathology.7 50-60 years. These results were in concordance with what was reported by The relative ease of pleural fluid aspiration, Kushwaha et al., 18 who examined 100 pleural analysis and cytological examination has kept fluid samples and found the maximum cases in alive the search for a test to unequivocally the 6th decade. Also, Dagli and colleagues 19, differentiate the various causes of effusion. The examined 298 cases, where mean age was 58.4 cytological examination of body effusion is a years. complete diagnostic modality which aims at pointing out the etiology of effusions. The Sex distribution among pleural effusion cases diagnostic performance of the cytologic study showed slight male predominance (56.5%), of the fluid may be attributable to the fact that which was again in corcordance with the cell population present is representative of Kushwaha et al.,18 who also noted male a much larger surface area than that obtained predominance with ratio 1.2:1. Dagli et al.19 by needle biopsy.14,15 and Samar et al.20 also showed male predominance. Thoracocentesis has been a very popular diagnostic as well as therapeutic procedure for The clinical diagnosis of pleural effusion cases tapping pleural effusions and with very few showed 80.2 % as benign conditions, while procedural complications.4 It is usually done 19.8 % malignant. These results were in through the 2nd intercostal space below the agreement to what was reported by Hackbarth fluid level.16 Medical thoracoscopy by a et al., 21 that non-malignant conditions were pulmonologist is a safe and effective procedure found in 80% while malignancy-related made for the diagnosis and therapy of various pleural up remaining 20%. diseases, but it is more invasive and expensive Respiratory cause (of which tuberculosis) was procedure, with a risk of complications such as the most common cause of clinically diagnosed pneumothorax. Very few pulmonologists are benign conditions associated with pleural trained in thoracoscopy and it is available only effusion cases. This finding agreed with what

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 67 was noted byAlusi et al.22 , Valdes et al., 23 and CONCLUSION Kushwaha et al.18 Henceforth, the present study concludes that in The present study revealed 86.13% were developing countries like ours, pleural fluid exudates & 13.18% were transudates, where cytology should continue to be a first-line Kushwaha et al.18 reported 82% exudates and investigation to screen out the pleural effusion 18% tranusdates& Samar et al.20 reported cases, being convenient, cost-effective and safe 86.5% exudates. investigation. It is a complete diagnostic Among the pleural exudates examined 89.6% modality, which aims at pointing out the were benign, most of them were reactive etiology even before the clinical diagnosis. The inflammatory smears 74.1%. The most study of cytomorphologic features of various frequent cause of exudativeeffusion was malignant cells may provide definite clues tuberculosis and lymphocytic effusion. towards the primary lesion. Malignant pleural exudates presented 10.4%, Thus, patients with pleural effusion should be of which 33.33% were diagnosed as evaluated in an individualized stepwise mesothelioma, while 66.66% were tumors manner with initial steps being relatively non- other than mesothelioma among which invasive inclusive of clinical evaluation and metastatic carcinoma of unknown primary, cytologic study. lung, metastatic breast carcinoma, lymphoma REFRENCES was detected. In pleura, secondary tumors are more common 1. VARGHESE C., VENKATARAMAN K. and than the primary tumors. Adenocarcinoma is BHAGWAT S: Role of Diagnostic Cytology: In the most common malignancy encountered Manual For Cytology, Manuals for Training in followed by mesothelioma, in concordance Cancer Control. Directorate General of Health with Biswajit et al.,24Mesothelial cells were Services. Ministry of arranged singly or in three dimensional Health and Family Welfare. Government of groups. These cell clusters had spherical India. Page9, 2005. morule like configuration. Grandos et al.25, showed sim ila r fin din g s. However, 2. Rahman NM, Chapman SJ, Davies RJ. K u s h w a h a 1 8 e t a l s h o w e d 2 1 . 4 % Pleural effusion: A structured approach to care. mesothelioma cases and Dagli et al.19, Br Med Bull. 2004;72:31–47. reported 22.6% cases, Samar et al.20, 28% 3. Pandit S, Chaudhuri AD, Datta SB, Dey A, cases. Bhanja P. Role of pleural biotpsy in etiological The difference could be attributed to the diagnosis of pleural effusion. Lung India. different geographic regions and variable 2010;27:202–4. sample size. 4. Gaur DS, Chauhan N, Kusum A, Harsh M, Upon comparing the cytological diagnosis with Talekar M, Kishore S, et al. Pleural fluid analysis clinic-pathological variables, it was found that - Role in diagnosing pleural malignancy. J Cytol. pleural effusions associated with clinically 2007;24:183–8. diagnosed malignant conditions are not always malignant. In addition, in certain instances 5. Soe Z, Shwe WH, Moe S. A study on cytological diagnosis of malignancy may tuberculous pleural effusion. Int J Collab Res precede the clinical diagnosis. Intern Med Public Health. 2010;2:32–48. The correlation between clinical diagnosis & 6. S M I T H N . J . : B o d y f l u i d cytological diagnosis was considered highly cytology.http://pathlabmed.uchc.edu/pdf/uid significant. 404.pdf.

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 68 7. KHALBUSS E.W. and MONACO S.E.:3495 16. Ihsanullah, Khan N, Jadoon H, Zaman M, Fluid Cytology Update: Cytomorphology, Ahmed A. Yield of Abrams needle pleural Pitfalls and Ancillary Studies. Annual Meeting- biopsy in exudative pleural effusion. J Ayub Chicago, IL. American Society for Clinical Med Coll Abbottabad. 2009;21:116–8. Pathology, 2009. 17. Mathur PN, Loddenkemper R. Biopsy 8. AL-EYD G.J.: Laboratory diagnosis of techniques in the diagnosis of pleural diseases. pleural & peritoneal effusions: A multimodal EurRespir J. 2002;7:120–30. a p p r o a c h . We b s i t e : Ava i l a b l e a t : 18. KUSHWAHA R., SHASHIKALA P., http://www.pathuae.org/catalog/060515_19 HIREMATH S. and BASAVARAJ H.G.: Cells in 4722% 5CGaith.pdf. Accessed on 20/3/2011, pleural fluid and their value in differential 2005. diagnosis. Journal of Cytology, 25 (4): 138- 143, 9. NAYLOR B: Pleural, Peritoneal , and 2008. Pericardial Effusions. In Comprehensive 19. DAGLI A.F., KUCUK S., SEZER M. and cytopathology; 3rd Edition, 510-577, Elsevier UCER O.: Cytopathologic Diagnosis in Pleural Inc.,2008. Effusion and Cyto-Histopathologic Correlation. Turkish Journal of Pathology. Jan., 27 (1): 12-6, 10. DIAZ-GUZMAN E. and DWEIK R.A.: 2011. Diagnosis and management of pleural effusions. A practical approach. Compr. Ther. 20. SAMAR A. EL-SHEIKH: The diagnostic Winter, 33 (4): 237-46, 2007 (Medline). value of pleural fluid cytology in Benign and Malignant Pleural Effusions. Med J. Cairo Univ., 11. CIBAS E.S.: Pleural, Pericardial and Vol. 80, No.2, June:95-103,2012. Peritoneal Fluids. In Cytology: Diagnostic Principles and Clinical Correlate; 3rd edition, 21. HACKBARTH J.S., MURATA K., REILLY 132-153, Elsevier Inc., 2009 W.M. and SCHIMNICH A.A.: Performance of CEA and CA 19-9 in identifying pleural effusions 12. MICHAEL C.W.: Cytology of Pleural caused by specific malignancies. Clin. F l u i d . A v a i l a b l e a t : Biochem., 43: 1051-1055, 2010. http://www.pathology.med.umich.edu/NewF 22. Alusi FA. Pleural effusion in Iraq: A r o n t i e r s / prospective study of 100 cases. Thorax 07/Saturday%2029SEP/Case%2017_Michael. 1986;41:492-3. pdf. Access-ed on 15/1/2011, 1999. 23. VALDES L., ALVAREZ D., VALLE J.M., 13. MOHANTY S.K. and DEY P.: Serous POSSE A. and JOSE S.E.: The etiology of pleural effusions: Diagnosis of malignancy beyond effusions in an area with high incidence of cytomorphology. An analytic re-view. Postgrad tuberculosis. Chest., 109: 158- 162, 1996. Med. J., 79: 569-574, 2003. 24. Biswajit Biswas, Sudershan Kumar 14. Frist B, Kahan AV, Koss LG. Comparison Sharma, Narsimhalu Niranjan: Pleural of the diagnostic values of biopsies of the effusion: Role of pleural fluid cytology, Ada and pleura and cytologic evaluation of pleural pleural biopsy in diagnosis; J Cytol.2016 Jul- fluids. Am J ClinPathol 1979;72:48-51. Sep;33(3). 15. Sherwani R, Akhtar K, Naqvi AH, Akhtar 25. Granados R, Libas ES, Fletcher JA. S, Abrari A, Bhargava R. Diagnostic and Cytogenetic analysis of effusions from prognostic significance of cytology in effusions. malignant mesothelioma. Acta Cytol J Cytol 2005;22:73-7. 1994;38:711-7.

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 69 AUTOIMMUNE CONGENITAL HEART BLOCK– A CASE REPORT *DR. AJAY GUPTA, DR. RAJIV TANGRI, DR. JASBIR SINGH, DR.MAMTA KUMARI, DR. SHAKTI AGGARWAL SRL CLINICAL RESEARCH & REFERENCE LAB, GURGAON, HARYANA CASE SUMMARY – pregnancies exposed to anti SSA , SSB We describe a case report of a 3 day old baby Autoantibodies. It has been estimated that only girl presenting with isolated Bradycardia 1 of every 15,000 to 20,000 live births result in sincebirth . However there was no structural babies with isolated Congenital Heart Block. cardiac abnormality. The Echo was normal . CASE PRESENTATION – ECG showed complete AV Block with Heart rate A Three day old baby presented with – = 50 / min. Birth wt was around 2.9 kg & it was a • Bradycardia( Heart Rate = 50/ min. normal vaginal delivery. In lab investigations, • Complete AV block on ECG peripheral smear showed Normocytic • Echo showed no structural abnormality N o r m o c h r o m i c A n e m i a w i t h • Normocytic normochromic anemia with Thrombocytopenia. All the body functions KFT thrombocytopenia. / LFT including USG Abdomen was normal. Normal vaginal delivery, Liver & Kidney No Antenatal records of USG , Double / Tripple functions - normal .USG Abdomen was also markers & other investigations of mother were normal. available but she was asymptomatic Mother- asymptomatic throughout the throughout the pregnancy . The case was pregnancy . No previous records of pregnancy referred to paediatric cardiologist as baby had including the investigations / USG were bradycardia only. The Advised investigations available. ANA, DsDNA , ENA’s (antibodies against extractable nuclear antigens) to exclude INVESTIGATIONS – Autoimmune disorder were sent to SRL,GGN Investigations of baby- Reference lab. These investigations showed a • CBC = Hb- 10.5 gm % , TLC – 7,300 / strongly positive ANA, NegativeDsDNA& a cumm, PLT – 1.40 Lakhs/cumm, MCV – 95 fl strongly positive SSA-Ro, SSB-La antibodies. ,MCH – 32pg , MCHC – 27.7 g/dl Based on the results of baby’s investigations , P e r i p h e r a l s m e a r s / o N o r m o c y t i c mother was also screened for ANA , DsDNA , N o r m o c h ro m i c b l o o d p i c t u re w i t h ENA’s. She was also found to be positive for ANA Thrombocytopenia & SSA-Ro & SSB-La .Based on the results of the • LFT & KFT = WNL ( within normal limits ) investigation , Correlation withclinical findings • USG Abdomen – Normal of mother & baby ,a final diagnosis of • ANA – 1:640 , 4+ , Speckled ( Strong Autoimmune Congenital heart block was made. positive ) BACKGROUND - • DsDNA - Negative Congenital heart block is a immunemediated • ANA Profile ( ENA’s ) – Ro52 3+ , SSA 3+ disease occurring as a result of placental ,SSB 3+ transfer of maternal antibodies specific to Ro & CVS - La autoantigens. Irreversible complete AV • Heart Rate – 50/ min. block may be the only manifestation . Many • Complete AV Block on ECG females are asymptomatic during pregnancy & • Echo was normal are diagnosed to have autoimmune disease Investigations of Mother – after delivery ie- baby presenting with isolated ANA – 1:640 , 4+ , Speckled ( strongly positive ) Heart block & presence of SSA ( Ro )& SSB ( La ) DsDNA - Negative autoantibodies. This can be seen in SLE also. SSA 3+ , SSB 3+ , Ro 52 3+ Congenital Heart block occurs in 1-2% of Haryana Medical Journal - March 2017, Vol. 40, Issue 01 70 ECG:- TAKE HOME MESSAGE – • Autoimmune Congenital Heart block is an immune mediated uncommon condition occurring as a result of passage of maternal autoantibodies via placenta .The most commonly being SSA ( Ro ) & SSB (La )& less frequently with anti RNP . • Mothers may be asymptomatic during pregnancy & diagnosed after delivery. • Isolated , Irreversible Complete Heart block is the most important manifestation which points to the diagnosis of Congenital Autoimmune Disease. POSSIBLE DIFFERENTIAL DIAGNOSIS – • Screening for ANA ( IFA ) in women with • Pediatric Acquired third degree AV Block Bad Obstretic history &pts with family history • Pediatric Viral Myocarditis of Autoimmune disease should be done before • Transposition of Great Vessels / during early pregnancy. • Most cases require an implantation of TREATMENT & OUTCOME – permanent pacemaker as a mode of treatment. The baby was advised & referred tothe higher REFERENCES – centrefor Pacemaker Implantation. • FVV( facts , views , vision ) in ObsGyn ( DISCUSSION - Deyetal ) 2014 Autoimmune Congenital heart block is an • ActaGyn Port 2015 ; 9 ( 4 ) : 318 – 321 uncommon frequently undiagnosed condition , produced by the passage of Maternal • Autoimmune – associated congenital antibodies through the placenta which bind to heart block ( Jill P Buyonetal ) Journal of the the cardiomyocytes , the AV conduction system American College of Cardiology ( JACC ) ,vol 31 , is disrupted by inflammation with subsequent issue 7,1998 fibrosis and calcification leading to a complete • Arthritis &Rheumatology ,vol 44 , issue 8 AV block. Mainly anti Ro/SSA , La/SSB & less .Risk of congenital complete heart block in new frequently anti-RNP are involved in the borns& anti Ro/La detected .A prospective pathogenesis of this disease. Mothers can be study of 100 women. ( Antonio Brucatoetal ) asymptomatic during the time of diagnosis. A similar case report published in 2014 , FVV Obs&Gyn ( Deyetal )saw the presence of AUTHORS- Congenital heart block , Heart rate – 54 /min. , DR.AJAY GUPTA MD ( Chief author ) – Senior Echo – normal , moderately positive ANA with Immunopathologist strongly positive SSA , SSB antibodies. Mother DR. MAMTA KUMARI MD( Co-author ) – Chief was asymptomatic but was also positive for Microbiologist SSA , SSB antibodies. Another case published in ActaGyne Port 2015 DR.RAJIV TANGRI MD( Co-athor )- Lab Director demonstrated the presence of complete heart DR.SHAKTI AGGARWAL MD( Co-author )- block in a new born with positive SSA & SSB Senior Biochemist antibodies however mother was symptomatic DR.JASBIR SINGH DNB( Co-author )- & positive for SSA , SSB . Histopathologist Haryana Medical Journal - March 2017, Vol. 40, Issue 01 71 Case Report :- ACROMEGALY PRESENTING AS REFRACTORY DIABETES Deepak Khandelwal, Sameer Aggarwal

*Department of Endocrinology, Maharaja Agrasen Hospital, Punjabi Bagh, Delhi, India ** Department of Medicine, Pandit Bhagwat Dayal Sharma Post-graduate Institute of Medical Sciences (PGIMS), Rohtak, Haryana, India Corresponding Author: Deepak Khandelwal, Department of Endocrinology, Maharaja Agrasen Hospital, Punjabi Bagh, Delhi-110026, India; Phone-09968878561 Email- [email protected]

Abstract Subsequently patient came to us for evaluation Acromegaly is a disorder resulting from and management. On direct questioning he uncontrolled hypersecretion of growth gives history of acral enlargement in the form hormone (GH) and associated GH-mediated of coarsening of facial features, increase in production of insulin like growth factor-1 (IGF- hand size, tightening of rings, increase in shoe size and prominence of jaw. He also gives 1) from the liver. The prevalence of diabetes history suggestive of obstructive sleep apnea in mellitus in acromegalic patients ranges from the form of excessive snoring and increased 20% to 56%. We herein present a case of day time sleepiness. There was no history of acromegaly that presented as refractory hypertension. He is a married man for last 10 diabetes. year, with no children. Couple was investigated Key words: acromegaly, diabetes, growth for primary infertility 5 years back and he was hormone told to have oligospermia. On examination his Case Report weight was 71 kg, height was 175 cm (Father’s 36 year old male presented to us for evaluation height 163 cm, mother’s height 150 cm, mid of poor glycemic control. His diabetes was parental height 163 cm, younger brother’s diagnosed 4 year back when he had osmotic height 160 cm, elder brother’s height 180 cm, who is apparently healthy and elder sister’s symptoms in the form of polyuria, polydipsia height 150 cm). He had frontal bony and 2- 3 kilograms of weight loss. He was prominence, prognathism, fleshy nose, started on glimepiride and metformin, but his enlarged lips, oily skin, macroglossia, and acral blood sugars were uncontrolled on these oral enlargement. His blood pressure was 116/68 hypoglycemics in maximal doses. For last 1 mmHg in supine position. Clinically, a diagnosis year, before presenting to us he was started on of Acromegaly was considered. Biochemically, insulin in view of poor glycemic control. significantly elevated basal and post glucose Initially he was tried on once daily basal insulin suppressed growth hormone (GH) levels in combination with oral hypoglycemics, confirmed the diagnosis of acromegaly (table subsequently on 2 doses of premix, and finally 1). Other pituitary hormones are also on multiple basal- bolus insulin injections per summarized in table 1. For tumor localization day. However, his blood glucose remained contrast enhanced magnetic resonance uncontrolled on up to 100 units/day insulin. imaging (MRI) sella was done, which showed

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 72 2 х 1.6 х 1.7 cm sellar- suprasellar mass with an expanding tumor, such as visual-field mass effect over optic chiasma and defects and headache, might accompany the involvement of right cavernous sinus with clinical presentation. The diagnosis of tumor. Fundus and visual field examinations acromegaly is frequently delayed due to its were normal. indolent and insidious nature and 6–10 years Subsequently patient was admitted to us. of active disease may precede diagnosis1. He was started on injection octreotide 100 µg However, untreated acromegaly is associated subcutaneously every 8 hourly. For glycemic with a significant morbidity and a reduced life control he was put on insulin infusion and expectancy3. required approximately 150 units/day of Hyperinsulinaemia, mpaired glucose insulin for glycemic control. He underwent tolerance, and overt diabetes mellitus are s u b - l a b i a l t r a n s s p h e n o i d a l t u m o r common features of active acromegaly and it is decompression. Postoperatively there were no likely, that these abnormalities contribute to surgical/ metabolic complications. He felt the observed increase in cardiovascular subjective improvement in soft tissue changes in lips, hands and throat. His insulin morbidity and mortality. The prevalence of requirement decreased significantly to 64 diabetes in acromegalic patients ranges from units’/day in immediate postoperative period 20% to 56% and that of glucose intolerance and later on follow up his glycemic control ranges from 16% to 46%, depending on the maintained just with 8 units’ basal insulin series4. GH excess leads to insulin resistance at given once a day. Histopathology of surgical the level of the liver or in the periphery. specimen showed features of pituitary Successful treatment of acromegaly, with adenoma with diffuse immuno-positivity for normalization of GH and IGF-1, is usually growth hormone. Postoperative MRI after 3 accompanied by striking improvements in months did not show any residual/ recurrent g l u c o s e t o l e ra n c e a n d re ve r s a l o f tumor. For his secondary hypogonadism he hyperinsulinaemia, as well as by normalization was started on injection human chorionic of insulin sensitivity5. g o n a d o t ro p i n ( h C G ) , wh i c h l e d t o Although our patient had overt features improvement in serum testosterone levels of acral enlargement, because of insidious (Table 1), as well as sperm count. progression of same patient didn’t bother and even, these were overlooked by multiple Discussion physicians. The majority of patients in spite of clear signs and symptoms complain of the Acromegaly is a disorder resulting from uncontrolled hypersecretion of GH and delay in diagnosis: this is related to the associated GH-mediated production of insulin ignorance of many physicians about this like growth factor-1 (IGF-1) from the liver. The disease because they never encountered one of elevated GH and IGF-I levels in acromegaly, lead these patients during their training or their to a wide range of cardiovascular, respiratory, practice. So, physician should be very careful to endocrine, and metabolic morbidities1. The suspect and look features of acromegaly. clinical manifestations range from subtle signs Clinical diagnosis is suggested by the typical of acral overgrowth, soft-tissue swelling, disfigurement of the patient related to arthralgias, jaw prognathism, fasting progressive acral enlargement and hyperglycemia, and hyperhidrosis to florid modification of facial appearance, as assessed osteoarthritis, frontal bone bossing, diabetes by serial photographs. Moreover, his refractory mellitus, hypertension, and respiratory and diabetes also warrants investigation for cardiac failure2. Additionally, symptoms from secondary causes.

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 73 References 4. Colao A, Ferone D, Marzullo P et al. 1. Chanson P, Salenave S, Kamenicky P, Systemic complications of acromegaly: Cazabat L, Young J. Pituitary tumours: epidemiology, pathogenesis, and management. acromegaly. Best Pract Res Clin Endocrinol Endocrine Reviews 2004; 25:102–152. Metab. 2009 Oct;23(5):555-74. 5. Ganda OP, Simonson DS. Growth 2. Melmed S. Medical progress: acromegaly. hormone, acromegaly and diabetes. Diabetes N Engl J Med 2006; 355(24):2558–2573. Rev 1993; 1:2886-3000. 3. Wright AD, Hill DM, Lowy C, Fraser TR. Mortality in acromegaly. Q J Med 1970; 39(153):1–16. Table 1. Hormonal analysis before, 3 months and 1 year after pituitary surgery Biochemical test Pre surgery 3 months after surgery 1 year after surgery

Basal GH (≤1 ng/ml ) 88.0 0.03 1.5

Post glucose suppressed GH 29.6 Not done 1.35 (≤1 ng/ml )

Total T4 (5.1-14.1 µg/dl) 6.94 7.70 9.08

TSH (0.27- 4.2 µIU/ml) 1.05 1.17 2.23

8 AM Cortisol (6.2-19.4 µg/dl) 19.89 23.31 18.14

Plasma ACTH (7.2-63.3 pg/ml) 23.36 34.29 20.08

LH (1.7- 8.6 mIU/ml) 1.02 1.77 2.70

FSH (1.5- 12.4 mIU/ml) 3.72 4.59 3.17

S Testosterone(2.4- 8.3 ng/ml) 1.05 3.13 3.36

S Prolactin (4.6- 21.4 ng/ml) 20.6 14.32 18.05

Abbreviations: GH- Growth hormone; TSH- Thyroid stimulating hormone, ACTH- Adrenocorticotropic hormone, LH- Luteinizing hormone, FSH- Follicle-stimulating hormone

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 74 TOPIC : SPECTRUM OF LYMPH NODE LESIONS ENCOUNTERED ON FNAC IN A TERTIARY CARE HOSPITAL IN CENTRAL INDIA : AUTHORS : Dr. Akanksha Mishra, Dr. Ashish Kr Sharma, Dr. Urvashi Bhardwaj, Dr. Manish Kr Sharma, Dr. Mukul Mishra, Dr. Nisha Awasthi L.N. MEDICAL COLLEGE AND RESEARCH CENTRE , BHOPAL ( MADHYA PRADESH )

ABSTRACT : carcinoma is the most common metastatic Lymphadenopathy is one of the most common lesions. clinical presentations of patients , attending AIMS AND OBEJECTIVES : the outdoor clinics in most of the hospitals. The 1.To study the frequency of various lymph node etiology varies from an inflammatory process lesions in all age groups & their cytological to a underlying malignancy .(1) correlation . The use of fine needle aspiration cytology 2. To compare the frequency for involvement of ( F N A C ) i n t h e i n v e s t i g a t i o n o f diffuse lymph node sites. lymphadenopathy has become an acceptable & v METHODOLOGY : widely practiced , safe , simple , rapid , painless with minimally invasive & outpatient • FNAC was done and the standard method technique with high cost effectivity & high for the procedure was adopted. All the slides accuracy. were reviewed and diagnosis was given. The present study was conducted to evalaute Inclusion criteria: the usefullness of FNAC as a diagnostic tool in All superficial lymph node swellings of the the management of patients with superficial body. lymphadenopathy . The study was also carried Exclusion criteria: out to know the distributionof various lesions 1. All non-lymphoid aspirates from the body among the different age groups. The present 2. Inadequate aspirate randomized study was undertaken to study v cytological features of non neoplastic & MATERIAL : neoplastic lesions of enlarged lymph nodes by 1. 5ml/10ml disposable syringe FNAC in 275 patients presenting with 2. 22-26 gauge needle lymphadenopathy in the LN Medical college & 3. Cameco syringe holder research centre ,Bhopal over a period of one 4. Clean non grease glass slide year and 4 months ( September 2014 to December 2015 ).There were 137 males & 138 5. Cotton swab females patients with an age range from 1-70 6. Methylated spirit years .Tuberculous lymphadenitis was most 7. 95% ethyl alcohol in coupling jars common lesion followed by reactive 8. Haematoxylene & Eosin stain Hyperplasia , Metastatic carcinoma , Suppurative lymphadenitis , non Hodgkins 9. Giemsa stain. lymphoma than hodgkins lymphoma. v METHOD: Cervical L.N. was the most commonly involved The material was obtained from 275 outdoor & lymphnode Incidence of metastatic carcinoma indoor patients of age group ( 1 to 70 years) was high during & after 40 years of age& seen attending cytology laboratory of tertiary care more common in males.Squamous cell hospital from september 2014 to December

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 75 2015 . In each instance , a brief history & The aspiration cytology is now considered as a physical examination along with evalaution of valuable daignostic aid & is gaining popularity relevant investigations was carried out as it provide ease in following patients with .Peripheral lymph nodes were aspirated using known malignancy & ready identification of 22G needle attached to 10 – 20 ml disposable metastasis or reoccurence .(4) syringe. The aspirated material was expressed RESULTS : onto the slides & smear prepared , air dried & Tuberculous lymphadenitis & reactive s t a i n e d w i t h M a y G r u n w a l d hyperplasia were the most common lesions Giemsa(MGG)stain. Whereever needed alcohol seen ( 35.6% & 25.8% respectively ) followed fixed smear was prepared & stained by by metastatic carcinoma (19.6%), suppurative papanicolaou (Pap method ) . Also , Ziehl lymphadenitis in ( 14.5%),non hodgkins Nelson staining performed for the lymphoma ( 2.5%)& lastly hodgkins lymphoma demonstration of Acid fast bacilli (AFB) . (1.8%) in the( Table 1). INTRODUCTION : Reactive hyperplasia was seen most often (32.3%) in first two decades of life ( Table 2 ) , Lymphadenopathy is one of the most common tuberculous lymphadenitis in the second and clinical presentation of patients attending the third decades( 61.22%) & incidence of outdoor department (2) . metastatic caracinoma are high during fourth Lymph nodes are an important part of immune decade & after 40 years of age system because lymph nodes become enlarged TABLE 1 : CYTOLOGICAL DAIGNOSIS OF 275 in a wide specturum of diseases including CASES OF LYMPHADENOPATHY infection & malignancy. Management of such cases depends on lymph node pathology , which can be studied by collecting material from lymph node through fine needle cytology(3). The present study is a Double blinded cross section Prospective study with a Randomized study design was undertaken to study non- neoplastic & neoplastic lesions of enlarged lymph nodes by FNAC in patients presenting with lymphadenopathy reffered to cytology section of pathology department from OPD, IPD of teritory care hospital over a period of 1 year & 4 months . The study was carried out to know the It is seen that the Males shows preponderance distribution of various lesions among the of reactive hyperplasia , lymphoma & different age group. metastatic carcinoma , while females shows The present study also tried to evalaute the slight preponderance of tuberculous FNAC as a daignostic tool in our clinical setup lymphadenitis . because of early availabilty of results , TABLE 2 : AGE AND INCIDENCE OF simplicity , minimal trauma & complications. LYMPHADENOPATHY

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 76 TABLE 5 : COMPARISION OF THE INCIDENCE OF LYMPHADENOPATHY DUE TO DIFFERNT AETIOLOGY FACTORS

Cervical lymph node were involved in all types of lymphadenitis (Table 3). Cervical lymph node is the most common site for metastasis of squamous cell carcinoma (Table 3 ) Axillary lymph nodes are common for metastasis from breast malignancy. Squamous cell carcinoma is the most common metastatic lesion of lymphnode & comprise of (68.5%) of the cases (Table 4).Metastatic ADENOCARCINOMANON – HODGKINS lesions of lymph nodes are more common in LYMPHOMA males where as metastatic from carcinoma breast were seen exclusively in females . TABLE 3 : LYMPH NODE INVOLVED IN VARIOUS TYPE OF LYMPHADENOPATHY

Hyperplasi DUCTAL CARCINOMA BREAST UNDIFFERENTIATED CARCINOMA

TABLE 4: INCIDENCE OF DISTRIBUTION OF SQUAMOUS CELL CARCINOMA METASTATIC LESIONS GRANULOMATOUS LYMPHADENITIS

SUPPURATIVE LYMPHADENOPATHY REACTIVE HYPERPLASIA

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 77 DISCUSSION : affected groups of nodes (8). The highest Lymph nodes react to a variety of incidence of tuberculous lymphadenitis was microorganism & nonspecific stimuli by seen in second and third decade with females expansion of the follicles centres or preponderance and decreasing incidence with interfollicular tissue .This results in age . Patra en all had 37.8 % cases of tuberculor enlargement of nodes , which may be lymphadenitis and present study has 35.6 % . considerable.The clinical management of This has shown quite resemblence to our study. patients with enlarged lymph nodes varies A similiar study was done by Khajuria et all with factors such as Age, the presence of known which showed tubercolous lymphadenitis as infection & previous medical history . For eg , 52.3 % & Bhaskara et all found 67.57 % ( Table children can present with massive local 5 ). All the studies including our present study lymphadenopathy even after mild infections. has shown that tuberculous lymphadenitis is Enlarged lymph nodes are accesible for FNAC & the most common cause of lymph node lesions. are of importance specifically to diagnose The highest incidence of reactive hyperplasia primary & secondary malignancies . was seen in first two decades of life ( 32.3%) FNAC was introduced in most of medical centre with male preponderance . These findings are with a view to reduce the number of excisional agreement with experiance of other studies (9 , biopsies of lymphnodes & it is inexpensive , 10). completaly safe & quick method for daignosis Metastaic malignancies are significantly more of lymphadenopathy. common in males . the superficial lymph nodes So here we have presented our experiance with are common sites of metastasis . cervical lymph 275 cases of lymphadenopathy over a period of node is the most common lymphnode invoved 1 year & 4 months in a Tertiary care hospital of in the metastasis & Squamous cell carcinoma is central India . In the present study , daignosis the most common form of metastatic lesion . was baesd on definite cytomorphological Metastatic carcinoma was observed in 14.5 % findings with clinicocytological correlation. of cases bt Patra AK et all , 3.8 % cases by Ruchi Primary aim of this study was to help clinician Khajuria & 5.6 % cases by Bhaskar et all and our in arriving at early daignosis in cases present study showed 19.6 % . presenting with lymphadenopathy . The The slight variation in results of different pattern of lesion consisted of tuberculous studies is due to difference in age groups of lymphadenitis , reactive hyperplasia , patients (Table 4 ) . metastatic carcinoma , suppurative The reason behind for higher metastasis is the lymphadenitis , lymphoma seen in our study , regional variation , as in this area ( central India more or less is samereported in other studies ) beetal & tobacco chewing is most commonly in India & other developing countries (5,6,7). seen irrespective of sex , which is one of the Maximum number of cases seen in our study major predisposing factor for malignancy . were of tuberculous lymphadenitis . In India Benign reactive inguinal lymphadenopathy is tuberculous lymphadenitis continues to be the most common etiologies , and inguinal major health problem . In patients with cervical lymphadenopathy is of low suspicion for lump , tuberculosis remains a common cause . malignancy . In our study we received least Tuberculous lymphadenitis is the most amount cases of inguinal lymphadenopathy . common form of extra pulmonary tuberculosis carcinoma of external genital region , the & cervical lymph nodes are most common lymphomas & melanoma involved this group

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 78 of lymph node. The anatomical siteof involved node along with age & sex may give some 2) Greig EDW , Gray ACH : Note on indication to the location of primary lymphatic glands in sleeping sickness Lancet 1: carcinoma. 1570 , 1904 For eg. Axillary lymph node are most 3) Steel B,Schwartz MR,Ramzy I. Fine commonly involved in the metastatic needle aspiration biopsy in the daignosis of deposition from Breast , lungs & ovaries of l y m p h a d e n o p a t h y i n 1 , 1 0 3 middle aged females . patients.Role,limitation and analysis of The incidence of squamous cell carcinoma is daignostic pitfalls.Acta Cytol.1995;39:76-81 the most common metastaic lesion of lymph 4) K l i n e T S , K h a n a n V , L i n e node , which is comparable to other studies . IK.Lymphadenopathy and aspiration biopsy cytology review of 376 superficial lymphnodes.Cancer 1984;54:1076-81 5) Patra AK, Nanda BK, Mahapatra BVK, Panda AK. Diagnosis of lymphadenopathy by fine needle aspiration cytology. Indian J Pathol Microbiol. 1983;26:272-8. 6) Bhaskaran CS, Kumar GH, Sreenivas M, Kamleshwari R, Rao G, Aruna CA. Fine needle aspiration cytology review of 1731 cases. Indian J Pathol Microbiol. 1990;83:387-97. 7) Khajuria R, Goswami KC, Singh K, Dubey VK. Pattern of lymphadenopathy on fine needle CONCLUSION : aspiration cytology in Jammu. JK Sci. In the evalaution of lymph nodes lesions , FNAC 2006;8(3):157-9. is established as a minimally invasive , cost 8) Hafez NH, Tahoun NS. Reliability of fine effective & rapid daignostic tool . it has very needle aspiration cytology (FNAC) as a high degree of patient acceptance because it diagnostic tool in cases of cervical doesnot cause any scars , inconvinient incision lymphadenopathy. J Egypt Natl Cancer Inst. lines . it is one of the reliable daignostic tool in 2011;23:105-14. evalaution of lymphadenopathy for both 9) Paul PC, Goswami BK, Chakrabarti S, Giri A, screening & follow up and can be performed as Pramnik R. Fine needle aspiration cytology of outpatient procedure. lymphnodes - an institutional study of 1448 REFRENCES: cases over a five year period. J Cytol. 1) Arora B , Beena KR. Utility of FNAC in 2004;21:187-90 lymphadenopathies . J. cytology . 16(2); 1999 : 10) Mohanty R, Wilkinson A. Utility of fine 61-66 needle aspiration of lymph nodes. IOSR J Dent Med Sci. 2013;8(5):13-8.

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 79 Branches Activities IMA - BHADURGARH 1.New team of ofIMA,bahadurgarh took over charge from previous team on 16th march 2016 & was privileged to organize various activities in the year 2016 under able leadership of Dr Prempunani- President, Dr S Bansal –Secy, Dr Jyoti Malik-Secyfinance and admin. 2.Doctors’s day celebration : On the eve of Doctors day, IMA Bahadrurgarh in association with other social organizations conducted a mass tree plantation campaign. 3.CMEs:29th July-CME withwith Apollo spectra hospital organized scientific programme in multiple topics like Advances on Varicose veins,Recent trends in management of Arthritis etc.On 26th August- held at Akashtower,Bahadurgarh under joint chairman ship of Dr Pawan Gupta and Dr Kathuria. Dr Surender kumar,Sr Physician and endocrinologist from Sir Gangaram hospital delivered a lecture on Deficiency of Growth Hormones;on 7th Oct OVULATION:UNDERSTANDING IMPACT OF LIFESTYLE,MONITORING AND DIAGNOSING, was presented By Dr Jyoti Malik; 21-10-206- EARLY DIAGNOSIS AND MANAGEMENT OF STROKE was given by Dr RajuAggarwal(DM-Neuro);07-12-2016- PAEDIATRIC NEPHROLOGY CASE BASED DISCUSSION by Dr Sonia Sharma-Consultant Paediatric nephrology. IMA - FARIDABAD IMA Faridabad organized IMA Carnival 2016 (Annual Family Get Together). On 25th Dec.2016 at “Aravali Golf Club. The attendance in the Carnival was 400 +.There were variety of Games for Children, Tambola for Adults and last but not the least Catwalk by IMA members. Everyoneincluding the Kids enjoyed the evening to the fullest. The members enjoyed great Indian Chat and Sumptuous Dinner.- Lohri celebrations including the Cultural program was organized by the IMA Faridabad at Asian Hospital Faridabad, in association with “Asian Hospital” on 14th January 2017. The program was attended by Approximately 300+ members and their families. It was a night filled with Masti, Music and Dance with scintillating stage performance by IMA members followed by sumptuous dinner. Annual IMA Sports meet was organized by IMA Faridabad on 21st and 22nd January 2017 in association with “Sarvodaya Hospital Faridabad”. In this event we tried to involve each age group. On 21st January Mini Marathon was organized. This was a perfect blend of fun, exercise and love. On 22nd January various sports event including badminton, Table Tennis, Track and field events were organized at “ManavRachna Sports Academy” with facilities of international standards. Large number of IMA members and their wards participated. It was also a stupendous success. IMA - GURGAON CME: 15 CMEs were organized.30/5/16 - Chest Pain: Clinic to Cath by Dr.SanjeevChaudhary; 11/6/16- Rheumatology Dia. & Treatment byVedChaturvedi; Role of Robotic Surg. in urology& Deep Brain Stimulation Surgery& Screening of Cancer by Dr.Rajat Taneja, Dr.SudhirTyagi,Dr. Sapna Nangi;27-06-2016 by TB Care in India by WHO & Min. of health &Family Welfare by Dr. DPS Sudan,Dr. Vijay Kumar;Neurological disorder by Dr. A. N. Jha,Dr.ArunGarg;30-07-2016-Neuroscience: Past, Present, Future by Dr.SumitSingh,Dr. Aditya Gupta, Dr.Vipul Gupta;13-8-2016-Organ Transplantation Present ScenarioDr. A.S. Soin, Dr. A. Taneja;24-09-2016-Diabetic Management DPP4 in era Of SGLT2 inhibitor by Dr.Abhay Ahluwalia;15-10-2016 Strategies to Prevent Heart Attack Dr. S. K. Chugh;14-11-2016- Complex Angioplasty + Vimochan of IMA Telephone Directory by Dr. (Col.) M. S. Sandhu;5-12-2016- Lipid Update Inauguration of Medanta Health Card byDr. R. R. Kasliwal,Dr.Naresh Trehan;10-12-2016- Liver & G I Update Dr.KaushalMadan& Team SOCIAL:1-07-2016- Blood Donation Camp 42 Volunteers donated;8-07-2016-Income Declaration Scheme2016 & Related IssueDr.NehaChaudhary,Asst. Commissioner, I.T.;17-07-2016-Free Health Check-up in Asso. HT 315 Patients were examined;31-07-2016-Free Health Check up CampJustice Gopal Singh Charitable Hospital and Navbharat Times450 Patients were examined; Diabetic Retinopathy Screening Camp 36 Patients were examined;Ante-natalCheck up camps as per PM programme. (27 Drs participating.) EXECUTIVE,GENERALBODy,FAMILY GET-TOGETHERS & SPORTS MEET,Participation at Ambala in Cultural meet. IMA - SONEPAT Under presidentship of Dr DivyaSaxena,IMASonepatconducted a workshop on BASIC LIFE SUPPORT. IMA Sonepatobserved National Solidarity Day on 17th Jan.2017. All doctors wore black ribbons to register their protest against brutal murder of Dr Bawa and Dr Bansal.IMASonepat also gave a press release;expressing its anguish against incidences of violence in the past ; assurance of prompt action by authorities against any atrocity against doctors.Press release were also sent. IMA Sonepat celebrated Republic day with a family get-together & cultural programme. On 5th Feb a general health & cancer check up was organized with free ECG/Bl.Sugar/Hb.370 patients were examined. Delegation from IMA Sonipat went Ro Khanpur Medical College to support medical students against next exam.

Haryana Medical Journal - March 2017, Vol. 40, Issue 01 80

GLIMPSES OF IMA HARYANA

IMA ANNUAL FUNCTION - ROHTAK

IMA - AMBALA

IMA - BAHADURGARH

IMA - BHIWANI

IMA - FARIDABAD BRANCH ACTIVITIES

IMA - GURGAON

IMA - ROHTAK

IMA - SONEPAT

IMA - SHAHBAD

IMA - SIRSA