Need for the Study s3

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA BANGALORE.

ANNEXURE - II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. NAME OF THE CANDIDATE DR. SAMSKRUTHI. H. S. SHETTY AND ADDRESS ROOM NO. 7, CHETHANA HOSTEL, KIMS, (in block letters) HUBLI.

2. NAME OF THE INSTITUTION KARNATAKA INSTITUTE OF MEDICAL SCIENCES, HUBLI, KARNATAKA.

3. COURSE OF STUDY AND MEDICAL SUBJECT M.S. IN OBSTETRICS AND GYNAECOLOGY

4. DATE OF ADMISSION TO 27 MAY 2013 COURSE

5. TITLE OF THE TOPIC “THE VALIDITY OF ONE STEP-75GRAMS ORAL GLUCOSE CHALLENGE TEST WHICH SERVES BOTH AS A SCREENING AS WELL AS A DIAGNOSTIC TOOL FOR GESTATIONAL DIABETES MELLITUS-A PROSPECTIVE STUDY.”

6. BRIEF RESUME OF THE INTENDED WORK : 6.1 Need for the study: Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance with recognition or onset during pregnancy, irrespective of the treatment with diet or insulin. The importance of GDM is that two generations are at risk of developing diabetes in the future. Women with a history of GDM are at increased risk of future diabetes, predominately type 2 diabetes, as are their children1. Besides, any abnormal glucose intolerance during pregnancy also has adverse fetal outcome. Increasing maternal carbohydrate intolerance in pregnant women without GDM is associated with a graded increase in adverse maternal and fetal outcomes2 However, for the detection and diagnosis of GDM, controversy concerning optimal strategy still continues. The American Diabetes Association (ADA) recommends two step procedures for screening and diagnosis of diabetes in selective population. Compared with selective screening, universal screening for GDM detects more cases and improves maternal and offspring prognosis3. In the Indian context, screening is essential in all pregnant women as the Indian women have an eleven fold increased risk of developing glucose intolerance during pregnancy compared to Caucasian women4.

Ethnically Indian women have a high prevalence of diabetes and the relative risk of developing GDM in Indian women is 11.3 times compared to White women, necessitating universal screening for glucose intolerance during pregnancy GDM diagnosis is overlooked in about 1/3rd of the women where selective rather than universal screening is performed6 and when this is applied to the 20 million reproductive age women in India, we are missing a lot of women likely to have glucose intolerance.

The two step procedure of screening with 50 g (Glucose Challenge Test) GCT and then diagnosing GDM based on the cut off values with 100 g (Oral Glucose Tolerance Test) OGTT is not practical as the pregnant women have to visit the clinic at least twice and the number of blood samples drawn vary from 3 to 5, which women resent. For universal screening, a single GCT with a 75 g of oral glucose load and diagnosing women with 2 hour Post Prandial Glucose (PPG) > 140 mg/dL as GDM is a preferred method. This method, recommended by WHO serves both as a one step screening and diagnostic procedure and is easy to perform besides being economical10.

For this, we need a simple procedure which is economical and feasible. Hence, this study is undertaken to find out a one step procedure which serves both as a screening and a diagnostic tool at the same time, and which is acceptable, economical and feasible to perform in the Indian context.

6.2 REVIEW OF LITERATURE

1. A study conducted by R. Deveer , M . Deveer , E. Akbaba et al, concluded that among patients with positive 50 g GCT and negative 100 g OGTT. A plasma glucose value of 140 mg/dL was used as the threshold to define an abnormal GCT result. In group 1 50 patients were given a caloric diet and compared with group 2 with 50 patients without a given diet. Patients were followed up until delivery and evaluated for birth weight, number of LGA babies, total maternal weight gain, gestational age and route of delivery. The mean gestational age at delivery was 38.7±1.2 weeks in group 1 and 38.9±1.1 weeks in group 2 (p = 0.615).

The mean birth weight in group 1 was 3328±399 g and 3623±485 g in group 2 (p = 0.007), cesarean rate was 32% in group 1 and 40% in group 2 (p = 0.405).12

2. The study conducted by V Seshiah, V Balaji, Madhuri S Balaji, CB Sanjeevi, A Green et al, concluded that as a pregnant woman in second or third trimester checks into the antenatal clinic, she was given 50 gm oral glucose load and blood sample was collected after one hour.

This test was performed on 1251 pregnant women. They were requested to come after 72 hours for the 75 gm OGTT recommended by WHO. Among the 1251 women, 891 responded.

The blood sample was taken in the fasting stateand at 2 hours after 75 gm of oral glucose.

Diagnosis was based on the WHO criteria for gestational diabetes mellitus (GDM). The mean age of these pregnant women was 23 ± 4 years. There was a significant increase in the prevalence of GDM in relation to gravida. Of the 1251 women who underwent the 50 gm oral glucose challenge test, 670 (53.55%) had one hour plasma glucose ≥ 130 mg/dl. Among the

891 pregnant women who had 75 gms OGTT, 168 (18.9%) were diagnosed as GDM, taking both FPG ≥ 126 mg/dl and/or 2 hr PPG ≥ 140 mg/dl as cut-off values. Taking only 2 hr plasma glucose for analysis, 144 (16.2%) had a value ≥ 140 mg/dl.15

3. Manisha Sahay, Rakesh K Sahay, Girish Narayan, Anuradha concluded in their study 3131 pregnant women who underwent both the screening and the diagnostic tests. We randomly selected data on half the women and used them to derive new screening strategies. We categorized each woman's risk of gestational diabetes mellitus on the basis of her age, body- mass index before pregnancy, and race. We developed strategies that entailed no screening for low-risk women, usual care for intermediate-risk women, and universal screening with lower thresholds — plasma glucose values of 130 mg per deciliter (7.2 mmol per liter) or 128 mg per deciliter (7.1 mmol per liter) — for high-risk women. The strategies were validated with data on the other half of the women. The new strategies allowed a 34.6 percent reduction in the number of screening tests performed (95 percent confidence interval, 32.3 to 37.0 percent) and detected 81.2 to 82.6 percent of the women with gestational diabetes as compared with the 78.3 percent detected through usual care. The percentage of false positive screening tests was significantly reduced, from 17.9 percent with usual care to 16.0 percent (P = 0.02) or 15.4 percent (P<0.001) with the new strategies, depending on the threshold values for high-risk women.16

4.Mohammad Iqbal Sheikh, Mir Iftikhar Bashir, Shariq Rashid Masoodi, Bashir Ahmad

Laway, Arshad Iqbal Wani, Mohammad Hayat Bhat et al, concluded in their study Two thousand pregnant women (divided into groups A and B, being the first and last 1000 consecutive women) attending various antenatal clinics in six districts of Kashmir valley were screened for GDM by 1h 50g oral glucose challenge test. Four hundred and fourteen (20.8%) women (216 from group A and 198 from group B) had an abnormal screening test and proceeded to oral glucose tolerance testing. Women from group A had a 3h 100gram oral glucose tolerance test (OGTT) and GDM was as classified by Carpenter and Coustan. A 2h

75g OGTT was performed on group B subjects and WHO criteria applied for diagnosis of

GDM. The overall prevalence of GDM was 3.8% (3.1% in group A versus 4.4% in group B—

P-value 0.071). GDM prevalence steadily increased with age (from 1.7% in women below 25 years to 18% in women 35 years or older). GDM occurred more frequently in women who were residing in urban areas, had borne three or more children, had history of abortion(s) or

GDM during previous pregnancies, had given birth to a macrosomic baby, or had a family history of diabetes mellitus.17 5. V Seshiah et al, concluded in their study one step procedure recommended by WHO for screening instead of two step procedure using preliminary screening with 50 gm one hr test .

The sensitivity of the 50 gm 1 hr test was 79.8% when compared to the low specificity of

42.7%. Combined with a relatively small number of false negative subjects, this yielded reasonable high values of sensitivity (79.8%, confidence limits: 72.7%-85.4%) and predictive value of a negative 50 gm-1 hr test (90.1%, confidence limits: 86.3%-92.9%). However, there was a substantial number of subjects false positive for the 50 gm-1 hr test, resulting in poor values of specificity (42.7%, confidence limits: 39.1%-46.4%) and predictive value of a positive 50 gm-1 hr test (24.5%, confidence limits: 21.0%- 28.3%). Since the specificity of using 50 gm-1 hr test is low, instead of performing screening test using 50 gm-1 hr test and then 100 gm / 75 gm OGTT4, a one step procedure of performing 75gm OGTT directly is ideal as we need to perform universal screening for glucose intolerance in pregnancy18

6.3 OBJECTIVES OF THE STUDY :

PRIMARY OBJECTIVE

To study the validity of ONE STEP-75GRAMS ORAL GLUCOSE CHALLENGE TEST which serves both as a screening as well as a diagnostic tool for gestational diabetes mellitus.

SECONDARY OBJECTIVE

1. To study the complications in pregnancy and in labour

2. To study the fetal outcome 7. MATERIALS AND METHODS:

7.1 STUDY DESIGN

Type of Study:

This study will be a hospital based prospective analytical study.

Place of study:

The study will be conducted in KARNATAKA INSTITUTE OF MEDICAL SCIENCES, HUBLI (Karnataka).

Sample and Sampling Technique:

This study shall be conducted from dec 2014 to nov 2015 . 200 pregnant women 24 to 28 weeks of gestation will be undergoing newer one step procedure as well as the standard procedure. This study population will be representative of our general population attending the antenatal clinic. Pregnant women satisfying the following inclusion criteria will be included in the study.

SAMPLE SIZE

200 patients undergoing 75gm 2hr OGCT & 3hr OGTT with 100gm

7.2 METHOD OF COLLECTION OF DATA

INCLUSION CRITERIA  Willingness to participate in the study  Women should be planning to follow up regularly at the department of Obstetrics and Gynecology, Karnataka Institute of Medical Sciences, Hubli.  Singleton pregnancy  Age >23 years  Family h/o type 2DM  Obesity (BMI > 27.5 kg/m2)  H/o GDM in previous pregnancy  H/o Macrosomia in previous pregnancy  H/o fetal loss after 20 wks of gestation in previous pregnancy.  H/o prematurity, congenital anomalies or unexplained fetal loss in previous pregnancy.  Women meeting the inclusion criteria will be included after written informed consent is obtained.

EXCLUSION CRITERIA  Multiple pregnancy  Diabetes Mellitus diagnosed before pregnancy  History of intake of drugs that effect glucose metabolism like corticosteroids or progesterones  Patients who refused to undergo screening and diagnostic test for GDM

STATISTICAL ANALYSIS: Percentages, proportions, chi-square ,correlation.

METHODOLOGY

The investigation will be conducted as part of a prospective randomized clinical trial designed to study the merits, demerits and validity of a one step procedure which serves both as a screening as well as a diagnostic tool at Karnataka Institute of Medical Sciences, Hubli.

This hospital was chosen to evaluate the unbiased data of the pregnant women with glucose intolerance as the pregnant women belonging to different socio-economic status attend the hospital for antenatal checkup and confinement in our country. Pregnant women between 24 -28 week of gestation who will be checked into the antenatal clinic will be given 75 g oral glucose challenge test (OGCT) recommended by WHO , and venous blood will be drawn after 2hrs. They will all be requested to come after a week on an empty stomach for 100g oral glucose tolerance test recommended by Carpenter Couston. Venous blood will be drawn in the fasting state, 1hr, 2hr & 3hr. Details of family history of diabetes, history of previous pregnancies, and the socio-economic status will be obtained, and the blood pressure measurement and the body mass index will be recorded.

The results will be analyzed taking into consideration WHO recommendation and comparing it with age old gold standard test of Carpenter Couston criteria.

Table – 1 Diagnosis of GDM.

100g OGTT Fasting 95mg/dl (5.3 mmol/L) 1 hour 180 mg /dl (10mmol/L) 2 hour 155 mg/dl (8.6 mmol/L) 3 hour 140 mg/dl (7.8 mmol)

Two or more of the venous plasma concentrations must exceed the above values for a positive diagnosis of GDM. WHO recommends performing 2 hour 75 g OGCT and diagnosing GDM with a threshold plasma glucose concentration greater than 140 mg/dL (7.8 mmol/L) at 2 hours similar to that of impaired glucose tolerance test (IGT) in the non-pregnant .

Table 2. WHO criteria.

Fasting plasma 2 hours post plasma glucose glucose (mg/dL) (mg/dL) Impaired glucose tolerance < 126 140 – 200 Diabetes > 126 > 200

Pregnant women who meet WHO criteria for impaired glucose tolerance (IGT) or diabetes with 75 g glucose challenge in non pregnant women are classified as having GDM. Hence GDM is diagnosed if the plasma glucose is within the IGT range of non pregnant women which is 2 hour post plasma glucose (PPG) > 140 mg/dL. If the woman has fasting plasma glucose more than 126 mg/dL and / or 2 hour post glucose more than 200 mg/mL probably she has been having undetected diabetes prior to conception (pre-gestational diabetes).

Maternal outcome: 1) PIH 2) IUGR 3) Hydramnios 4) Preterm labour 5) Prolonged labour 6) Ketoacidosis 7) Postpartum hemorrhage 8) Mode of delivery

Fetal outcome: 1) Congenital anomalies 2) Macrosomia 3) Fetal distress and birth asphyxia 4) Brachial plexus injuries 5) Hypoglycemia 6) Polycythemia 7) Still births, sudden IUD 8) Neonatal jaundice 9) Shoulder dystocia 10) Neonatal ICU admission and the outcome 11) Poor APGAR score 7.3 Does the study require any investigation or intervention to be conducted of patients or other human or animal. If so please describe briefly. Yes. It requires investigation to be conducted to the patients 75gm 2hr OGCT & 100gm 3hr OGTT

7.4 Has Ethical clearance been obtained from your institution in case of 7.3? Yes.

8 LIST OF REFERENCES : 1. Dornhorst A, M. Rossi, Risk and prevention of type 2 diabetes in women with gestational diabetes. Diabetes Care. 1998; 21(2): B43-9.

2. Sermer M, Naylor CD, Farine D et al, The Toronto Tri Hospital Gestational Diabetes Project – A preliminary review. Diabetes Care. 1998; 21(2): B33 -42.

3. Cosson E. Screening and insulin sensitivity in gestational diabetes. Abstract volume of the 40th Annual Meeting of the EASD. Sept 2004; A350.

4. Dornhorst A, Paterson CM, Nicholls JS, Wadsworth J, Chiu DC, Elkeles RS et al, High prevalence of GDM in women from ethnic minority groups. Diabet Med. Nov1992; 9 (9): 820-5.

5. Cosson E, Benthimol M, Carbilon L et al, Universal screening for gestational diabetes mellitus improves maternal and fetal outcomes compared with selective screening. In : Mateclinsky FM (ed). Abstract book of the 64th Scientific Sessions of the American Diabetes Association. Florida. American Diabetes Assocaition. 2004; A61.

6. Seshiah V, Balaji V, Madhuri S Balaji, Scope for Prevention of Diabetes –Focus Intrauterine milieu Interieur. J Assoc Physic of India. Feb 2008; 56: 109-113.

7. Griffin ME, Coffey M, Johnson H, Scanlon P, Foley M, Stronge J et al, Universal versus risk factor-based screening for gestational diabetes mellitus: detection rates, gestation at diagnosis and outcome. Diabet Med. Jan 2000; 17(1): 26 – 32.

8. Metzger BE, Coustan DR. Summary and Recommendations of the Fourth International workshop-Conference on Gestational Diabetes Mellitus. Diabetes Care. Aug 1998; 21 (2): B161-167.

9. O’Sullivan JB, Mahan C. Criteria for OGT in pregnancy. Diabet Med. 1964; 13: 278-85.

10. Magee MS, Walden CE, Benedetti TJ, Knopp RH. Influence of diagnostic criteria on the incidence of GDM and perinatal morbidity. JAMA 1993; 269(5): 609-15.

11. De Aguiar LG, de Matos HJ, de Brito Gomes M. Could fasting plasma glucose be used for screening high-risk outpatients for Gestational Diabetes Mellitus? Diabetes Care. 2001; 24(5): 954-5.

12. R. Deveer, M. Deveer, E. Akbaba, Y. Engin-Ustun, P. Aydogan, H. Celikkaya et al, The effect of diet on pregnancy outcomes among pregnants with abnormal glucose challenge test. Eur Rev Med Pharmacol Sci. 2013; 17: 1258-1261.

13. Coustan DR. Making the diagnosis of Gestational Diabetes Mellitus. Clin Obstet Gynecol. 2000; 43 (1):99-105.

14. Anjalakshi C, Balaji V, Balaji MS, Ashalata S, Suganthi S, Seshiah V et al, A single test procedure to diagnose gestational diabetes mellitus. Acta Diabetol. Mar 2009; 46 (1): 51-54.

15. Seshiah V, Balaji V, Madhuri S Balaji, Sanjeevi CB, Green A, Gestational Diabetes Mellitus in India, J Assoc Physic of India. Sept 2004; 52(1): 707 – 711.

16. M. Sahay, R. Sahay, Girish. N, Anuradha, New – onset diabetes after transplantation - Role of Oral Glucose Tolerance Test for diagnosis and study of risk factors. Sau Jr Kid Dis Trans.2013;24(5):897-1078.

17. Zarqar AH, Sheikh MI, Bashir MI, Masoodi SR, Laway BA, Wani AI, et al , Prevelance Of Gestational Diabetes Mellitus in Kashmiri women from the Indian Subcontinent. Diabetes Res Clin Pract. Nov 2004;66(2):139-45.

18. Seshiah V, Balaji V , Madhuri S Balaji , Aruna Sekar , Sanjeevi C B, Anders Green, One step procedure for screening and diagnosis of gestational diabetes mellitus. J Obstet Gynecol India. Nov/Dec 2005; 55(6): 525-529.

9 SIGNATURE OF THE CANDIDATE 10 REMARKS OF THE Efficient selective screening for GDM helps in preventing GUIDE maternal and foetal morbidity. Thereby it improves the pregnancy outcome.

Dr. M.G. HIREMATH. M.D. 11 NAME & DESIGNATION. PROFESSOR AND HEAD, 11.1 GUIDE DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY, KARNATAKA INSTITUTE OF MEDICAL SCIENCES, HUBLI, KARNATAKA.

11.2 SIGNATURE

11.3 HEAD OF THE Dr. M.G. HIREMATH. M.D. DEPARTMENT PROFESSOR AND HEAD, DEPARTMENT OF OBSTETRICS AND GYNAECOLOGY, KARNATAKA INSTITUTE OF MEDICAL SCIENCES, HUBLI, KARNATAKA.

11.4 SIGNATURE

12 REMARKS OF THE CHAIRMAN & PRINCIPAL

12.1 SIGNATURE