DOCSLIB.ORG

Integrated Physiology/Obesity

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Integrated Physiology/Obesity INTEGRATED PHYSIOLOGY—INSULIN SECRETION INTEGRATED PHYSIOLOGY—LIVER IN VIVO CATEGORY Figure 1. 2473-PUB Application of Translational Pharmacokinetic and Pharmacody- namic Modeling in the Development of GPR40 Partial Agonists DANIEL A. TATOSIAN, OSKAR ALSKAER, MARIA E. TRUJILLO, GEORGE EIER- MANN, LENA E. FRIBERG, MARIA KJELLSON, KUMAR K. MURALIDHARAN, HUBERT JOSIEN, ADAM WEINGLASS, JERRY DI SALVO, XIAOYAN N. LI, MICHAEL MILLER, PAVAN VADDADY, PRAJAKTI KOTHARE, Kenilworth, NJ, Upp- sala, Sweden, Rahway, NJ, Boston, MA Partial GPR40 agonists have been clinically validated as a mechanism for glucose lowering in patients with type 2 diabetes. A prior GPR40 partial agonist TAK-875 by Takeda was discontinued in Phase 3 due to liver toxic- ity with unknown mechanism. Discovery efforts for identifying novel GPR40 partial agonists have since focused on compounds with low anticipated clinical dose as a mitigation strategy. Given the critical nature of human dose projection for this target, a translational pharmacokinetic and phar- macodynamic model was developed to enhance predictions of clinical dose- response for novel chemical matter. A semi-physiologic glucose and insulin model was developed based on a human model published by Jauslin et al. [J Clin Pharmacol 2007;47:1244– 55]. This compartmental model was allometrically scaled and applied to glu- cose and insulin data observed in man and in Goto-Kakizaki rats. Published and internal data from human trials and rodent experiments under fasted or Supported By: National Natural Science Foundation of China (81200630); Natu- oral glucose tolerance test conditions in single dose and chronic administra- ral Science Fund Committee of Zhejiang Province (LQ12H07001); Wenzhou Science tion were included in the analysis. A model-based in vitro-in vivo correla- and Technology Bureau (H20150001) tion relating potency from a cell-based inositol phosphatase 1 accumulation assay to in vivo response was established to enable predictions. The translational model adequately described data for 5 compounds eval- INTEGRATED PHYSIOLOGY—INSULIN SECRETION uated in preclinical experiments and was predictive of the published human IN VIVO dose-response relationship of TAK875. Simulations from the quantitative model were shown to be consistent with the observed dose-response glu- 2471-PUB cose data both in the fasted state and following meals in the completed GPR40 Knockout Rats Have Diminished Lipid-mediated Potentiation MK-8666 proof of concept study. This model was further used in making of Insulin Secretion quantitative predictions of the dose-response relationship for novel GPR40 TONYA L. MARTIN, JIANYING LIU, MATTHEW M. RANKIN, MEGHAN TOWERS, agonists in discovery phase, and has been used by the development team JENSON QI, LISA D. NORQUAY, ALESSANDRO POCAI, Spring House, PA as a basis for prioritization and decision making around proposed clinical Chronic activation of GPR40, a fatty acid sensing G-protein-coupled recep- development programs. tor, improves glycemic control in type 2 diabetic humans. We used zinc fi nger nuclease technology to generate GPR40 null rats in the 2474-PUB Sprague-Dawley genetic background with a 2 bp deletion resulting in a trun- WITHDRAWN cated GPR40 protein. GPR40 Knockout (GPR40 KO) rats and their wild type (WT) littermates were fed either high fat (HFD, Research Diets 12492, 60% kcals fat) or regular chow (LabDiets 5001, 13% kcals fat) for ten weeks. On regular chow, GPR40 KO rats showed fasting hyperglycemia when compared to WT rats (118 ± 4.5 vs. 94 ± 3.0 mg/dl, p < 0.05); there were no INTEGRATED PHYSIOLOGY—LIVER other differences observed between GPR40 KO and WT rats. HFD-GPR40 KO rats showed fasting hyperglycemia (121 ± 5.1 vs. 93 ± 2.5 2475-PUB mg/dl, p < 0.05) with decreased fasting insulin (471 ± 124.3 vs. 994 ± 105.2 Triple Therapy Utilizing Vitamin E, Milk Thistle, and Carnitine pg/ml, p < 0.05). HFD-WT rats were hyperinsulinemic compared to WT rats Improves ALT and the Metabolic Abnormalities Associated with on regular chow (1201 ± 166 pg/ml vs. 517 ± 80.4 pg/ml, p < 0.05). Insulin NAFLD levels in HF-GPR40 KO rats were similar to GPR40 KO rats on regular chow. JOHN POULOS, VALENTIN MILANOV, Fayetteville, NC After a glucose challenge, the glucose area under the curve (AUC) of HFD- Evidence of scientifi c data in peer reviewed journals indicates that anti- GPR40 KO rats was higher than, but not statistically different from, HFD-WT oxidant supplementation may improve abnormal liver chemistries, glucose rats (24411 ± 660 vs. 22224 ± 1237 mg/dl/120 min). However, the insulin AUC control, and hyperlipidemia, in patients with NAFLD. The primary objective was markedly decreased in the HFD-GPR40 KO rats (264,737 ± 25,702 vs. was to determine the effects of Vitamin E 200IU, Silymarin 750mg, L carni- 479,989 ± 40,157 pg/ml/120 min, p < 0.05). tine 1gm (VSC) on normalization of abnormalities in liver function testing in We examined pancreatic islets from the WT and KO rats. WT and KO islets patients with NAFLD and to determine possible improvements in blood glu- responded similarly to increased concentrations of glucose; however, con- cose, hemoglobin A1c, cholesterol, LDL, triglycerides and CRP. Patients with sistent with the in vivo data, when the islets were challenged with glucose NAFLD were treated with either VSC (n=15) or placebo (n=17) for a period and palmitate, the islets from the KO rats showed a diminished insulin secre- of 24 weeks. The following laboratory values were assessed AST, ALT, trig- tory response. lycerides, HDL, LDL, insulin levels, glucose and CRP. Eleven out of 15 (70%) Taken together, these data demonstrate that GPR40 is required for the patients in the VSC group had normalization of ALT whereas 9 of 17 patients Integrated maintenance of fasting glycemia and the compensatory response of the (54%) had normalization of ALT in the placebo group (p=0.1). Patients treated β-cell to lipid-induced hyperinsulinemia. with VSC had a 3% reduction in serum glucose levels after 24 weeks of Physiology/Obesity treatment, whereas patients on placebo had a 6% increase in serum glu- PUBLISHED ONLY 2472-PUB cose levels. A 17% increase in serum insulin levels was noted in the placebo WITHDRAWN group, while a 18% reduction in insulin was seen in the VSC group. Serum triglycerides were reduced by 12% at week 24 in the VSC treated subjects whereas a 18% increase in serum triglycerides were seen in the placebo group. A trend in the reduction of serum cholesterol, HDL, LDL and CRP was seen in the VSC treated patients in comparison to the placebo treated group. In this 24 week study patients treated with VSC had normalization of ALT and signifi cant reductions in serum glucose, insulin and triglycerides in com- parison to the placebo group. Also noted in this study were reductions in AST, cholesterol, HDL and LDL and CRP levels. The ability of this compound ADA-Supported Research For author disclosure information, see page A696. A617 INTEGRATEDCATEGORY PHYSIOLOGY—LIVER in reducing markers of liver infl ammation, glucose, insulin, and triglycerides 2480-PUB indicates that VSC could play an important role in the treatment of nonalco- Dietary Iron Restriction Prevents the Transition of Fatty Liver to Ste- holic fatty liver disease, diabetes and cardiovascular disease. atohepatitis in Mice Fed a High Fat/High Carbohydrate Diet LIPIKA SALAYE, IELIZAVETA BYCHKOVA, DONALD A. MCCLAIN, Winston-Salem, 2476-PUB NC, Cleveland, OH Pathogenesis of Prediabetes in Asian Indians High iron is associated with increased risk for nonalcoholic steatohepati- SONA VEETTIL, ANANDA BASU, JOHN PORT, RITA BASU, Rochester, MN tis (NASH), although iron has not been implicated causally in its pathogen- The pathophysiology of prediabetes (PD) has not been well explored in esis. We examined progression of NASH in mice fed a model “fast food” Asian Indians (AI) residing in the U.S. The study was conducted to evaluate diet supplemented with different levels of iron (4, 35, 500, or 2000 ppm). glucose metabolism and its association with hepatic fat in AI. 10 controls Mice on the 4 ppm iron diet did not become anemic, and the fold-increase with normal fasting glucose/normal glucose tolerance (NFG/NGT) (7M, age in hepatic iron seen at the highest iron was within the normal human range. 35 ± 13 yr, FPG 5.1 ± 0.2 mM, 2-hr glucose 5.7 ± 0.4 mM, BMI 24.0 ± 3.4 kg/m2, All mice developed similar steatosis. Mice on the 500 and 2000 ppm iron diets developed elevations in serum alanine transaminase (ALT) 3 and 6 mos LBM 43.4 ± 9.2 kg, HbA1c 34.6 ± 2.5 mmol/mol) and 10 subjects with PD (per current ADA guidelines) (4M, 43.4 ± 12.3 yr, FPG 6.3 ± 1.0 mM, 2-hr glucose after initiation of the diet (380±32 IU/L at 6 mo) compared to mice on normal 2 chow (121±40 IU/L, p<0.01). Mice on the 4 ppm diet did not exhibit elevations 9.3 ± 2.1 mM, BMI 25.2 ± 3.2 kg/m , LBM 40.5 ± 6.8 kg, HbA1c 40.0 ± 3.5 2 of ALT (70±15 IU/L at 6 mos). Mice on the 35 pp diet had a delay in the time mmol/mol) were studied using a [6, 6- H2 glucose] labeled 75g oral glucose tolerance test (OGTT). The percentage liver fat fraction (% LFF), and total course of elevation, with elevations of ALT at 6 mos (318±19 IU/L), but not fatty acid (total FA) were measured using magnetic resonance spectros- 3 mos (102±22 IU/L). Only mice on the higher iron diets showed up regula- copy (MRS) with an LC model. Plasma iAUC 0-240 min glucose was signifi - tion of collagen type 2, a marker of liver injury in NASH.
Load more

Recommended publications
  • An Interesting Case Report of Diabetic Myonecrosis Manjula Nagaraja, MD Thomas Jefferson University Hospitals, [email protected]
    The Medicine Forum Volume 14 Article 6 2013 An Interesting Case Report of Diabetic Myonecrosis Manjula Nagaraja, MD Thomas Jefferson University Hospitals, [email protected] Jim Zhang, MD Thomas Jefferson University Hospitals, [email protected] Follow this and additional works at: https://jdc.jefferson.edu/tmf Part of the Medicine and Health Sciences Commons Let us know how access to this document benefits ouy Recommended Citation Nagaraja, MD, Manjula and Zhang, MD, Jim (2013) "An Interesting Case Report of Diabetic Myonecrosis," The Medicine Forum: Vol. 14 , Article 6. DOI: https://doi.org/10.29046/TMF.014.1.007 Available at: https://jdc.jefferson.edu/tmf/vol14/iss1/6 This Article is brought to you for free and open access by the Jefferson Digital Commons. The effeJ rson Digital Commons is a service of Thomas Jefferson University's Center for Teaching and Learning (CTL). The ommonC s is a showcase for Jefferson books and journals, peer-reviewed scholarly publications, unique historical collections from the University archives, and teaching tools. The effeJ rson Digital Commons allows researchers and interested readers anywhere in the world to learn about and keep up to date with Jefferson scholarship. This article has been accepted for inclusion in The eM dicine Forum by an authorized administrator of the Jefferson Digital Commons. For more information, please contact: [email protected]. Nagaraja, MD and Zhang, MD: An Interesting Case Report of Diabetic Myonecrosis An Interesting Case Report of Diabetic Myonecrosis Manjula Nagaraja, MD and Jim Zhang, MD Case Presentation A 49-year-old male with a history of ischemic cardiomyopathy, New York Heart Association class II heart failure with an ejection fraction of 35% status post biventricular implantable cardiac defibrillator (ICD), end stage renal disease on dialysis, diabetes mellitus II, and pancreatitis complicated by pseudocyst presented with a sudden onset of left thigh pain with a palpable mass.
    [Show full text]
  • Diabetes and Depression
    A Thesis Submitted in Partial Fulfilment of the Regulations for the Degree of Doctor of Clinical Psychology (Clin.Psy.D.) in the University of Birmingham Volume I Diabetes and Depression Isabela O. Caramlau School of Psychology University of Birmingham June 2012 University of Birmingham Research Archive e-theses repository This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. THESIS OVERVIEW This thesis is submitted in partial fulfilment of the requirement for the Degree of Doctor of Clinical Psychology at the School of Psychology, University of Birmingham. It comprises two research papers, a public dissemination document, and five clinical practice reports. Volume 1 of the thesis contains the research component. Paper one is a systematic review of longitudinal studies looking at the association between depression and diabetes complications. Paper two describes a prospective longitudinal study, examining risk factors for postnatal depression in women with gestational diabetes. Paper three is a public dissemination document, providing a lay summary of the study described in detail in paper two. Volume 2 of the thesis contains clinical practice reports (CPRs). The reports reflect work conducted during clinical placements, as follows: 1) psychological models CPR (A cognitive-behavioural and psychodynamic formulation of Samuel, a 28-year old man with phobia of falling following an acquired brain injury); 2) service-related CPR (Adherence to initial goal planning meeting clinical standard in an outpatient brain injury rehabilitation service.
    [Show full text]
  • Diabetic Myonecrosis: Uncommon Complications in Common Diseases
    Hindawi Publishing Corporation Case Reports in Endocrinology Volume 2014, Article ID 175029, 3 pages http://dx.doi.org/10.1155/2014/175029 Case Report Diabetic Myonecrosis: Uncommon Complications in Common Diseases Sisira Sran,1 Manpreet Sran,1 Nicole Ferguson,2,3 and Prachi Anand4 1 Department of Medicine, Nassau University Medical Center, 2201 Hempstead Turnpike, East Meadow, NY 11554, USA 2 New York Institute of Technology, College of Osteopathic Medicine, Northern Boulevard, P.O. Box 8000, Old Westbury, NY 11568-8000, USA 3 New York Institute of Technology, College of Osteopathic Medicine, Nassau University Medical Center, East Meadow, NY 11554, USA 4 Department of Rheumatology, Nassau University Medical Center, 2201 Hempstead Turnpike, East Meadow, NY 11554, USA Correspondence should be addressed to Sisira Sran; [email protected] Received 30 December 2013; Accepted 2 February 2014; Published 10 March 2014 Academic Editors: J. P. Frindik, L. Mastrandrea, and X. Zhang Copyright © 2014 Sisira Sran et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. We report a case of sudden thigh pain from spontaneous quadriceps necrosis, also known as diabetic myonecrosis, in a 28- year-old patient with poorly controlled diabetes mellitus. Diabetic muscle infarction is a rare end-organ complication seen in patients with poor glycemic control and advanced chronic microvascular complications. Proposed mechanisms involve atherosclerotic microvascular occlusion, ischemia-reperfusion related injury, vasculitis with microthrombi formation, and an acquired antiphospholipid syndrome. Diabetic myonecrosis most commonly presents as sudden thigh pain with swelling and should be considered in any patient who has poorly controlled diabetes mellitus.
    [Show full text]
  • An Atypical Presentation of Diabetic Myonecrosis
    An atypical presentation of diabetic myonecrosis. Francisco Galeano-Valle, Complutense University of Madrid Estela Benito-Martinez, Ramón y Cajal Hospital Luis Álvarez-Sala-Walther, Complutense University of Madrid Gabriela Oprea, Emory University Guillermo Umpierrez, Emory University Francisco Javier Pasquel, Emory University Journal Title: AACE Clinical Case Reports Volume: Volume 5, Number 1 Publisher: American Association of Clinical Endocrinologists | 2019-01, Pages e77-e81 Type of Work: Article | Post-print: After Peer Review Publisher DOI: 10.4158/ACCR-2018-0228 Permanent URL: https://pid.emory.edu/ark:/25593/trgdf Final published version: http://dx.doi.org/10.4158/ACCR-2018-0228 Copyright information: © 2019 AACE Accessed September 24, 2021 3:27 AM EDT HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author AACE Clin Manuscript Author Case Rep. Author Manuscript Author manuscript; available in PMC 2019 June 14. Published in final edited form as: AACE Clin Case Rep. 2019 ; 5(1): e77–e81. doi:10.4158/ACCR-2018-0228. An atypical presentation of diabetic myonecrosis Francisco Galeano-Valle, MD1, Estela Benito-Martinez, MD2, Luis Álvarez-Sala-Walther, MD1, Gabriela Oprea-Ilies, MD3, Guillermo E. Umpierrez, MD3, and Francisco J. Pasquel, MD,MPH4 1Department of Medicine, School of Medicine, Universidad Complutense Madrid, Spain; Department of Internal Medicine, Hospital General Universitario Gregorio Marañón, Madrid, Spain. Instituto de investigaciones Sanitarias Gregorio Marañón 2Department of Endocrinology. Hospital Universitario Ramón y Cajal, Madrid, Spain. 3Department of Pathology, Emory University School of Medicine, Atlanta, US 4Division of Endocrinology, Emory University School of Medicine, Atlanta, US Abstract Objective: Diabetes myonecrosis, also called diabetic muscle infarction (DMI), is a rare complication of diabetes.
    [Show full text]
  • Case Report Diabetic Myonecrosis: an Atypical Presentation
    Hindawi Publishing Corporation Case Reports in Endocrinology Volume 2013, Article ID 190962, 4 pages http://dx.doi.org/10.1155/2013/190962 Case Report Diabetic Myonecrosis: An Atypical Presentation José Hernán Martínez,1 Oberto Torres,1 Michelle M. Mangual García,1,2 Coromoto Palermo,1 María de Lourdes Miranda,1 Eva González,1 Ignacio Chinea Espinoza,2 Ivan Laboy,2 Mirelis Miranda,2 Kyrmarie Dávila,2 Rafael Tirado,2 and Mildred Padilla2 1 DepartmentofEndocrinology,4thFloor,SanJuanCityHospital,CMMSNo.79,P.O.Box70344,SanJuan,PR00936-8344,USA 2 Internal Medicine Department, San Juan City Hospital, CMMS No. 79, P.O. Box 70344, San Juan, PR 00936-8344, USA Correspondence should be addressed to Michelle M. Mangual Garc´ıa; [email protected] Received 27 March 2013; Accepted 22 May 2013 Academic Editors: J. P. Frindik and W. V. Moore Copyright © 2013 JoseHern´ an´ Mart´ınez et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Diabetic myonecrosis is a frequently unrecognized complication of longstanding and poorly controlled diabetes mellitus. The clinical presentation is swelling, pain, and tenderness of the involved muscle, most commonly the thigh muscles. Management consists of conservative measures including analgesia and rest. Short-term prognosis is good, but long-term prognosis is poor with most patients dying within 5 years. Failure to properly identify this condition will expose the patient to aggressive measures that could result in increased morbidity. To our knowledge this is the first case reported in which there was involvement of multiple muscle groups including upper and lower limbs.
    [Show full text]
  • Diabetic Myonecrosis of Bilateral Thighs in Newly Diagnosed Type 2 Diabetes Mellitus 1 Muhammad Imran, M.D
    Kansas Journal of Medicine 2015 Diabetic Myonecrosis in Type 2 Diabetes Mellitus Diabetic Myonecrosis of Bilateral Thighs in Newly Diagnosed Type 2 Diabetes Mellitus 1 Muhammad Imran, M.D. , Zalina 2 3 Ardasenov, M.D. , Kevin Brown, M.D. , 1 Mehrdad Maz, M.D. , Julian Magadan III, 1 M.D. University of Kansas Medical Center, Kansas City, KS Department of Internal Medicine, 1 Division of Allergy, Clinical Immunology and Rheumatology 2Division of General and Geriatric Medicine 3Department of Diagnostic Radiology Introduction Case Report Diabetes mellitus (DM) and its Our first case was a thirty-six-year old complications remain a global challenge to male with history of type 2 diabetes mellitus health care systems. Diabetic myonecrosis is who had been diagnosed within the past six a rare and under-diagnosed complication of months and treated with oral hypoglycemic DM that was first reported in 1965.1 agents. He presented with bilateral thigh Diabetic myonecrosis affects patients with pain of two-month duration. The pain had poorly controlled and longstanding type 1 worsened with progressive swelling of both diabetes mellitus (DM) and associated thighs. The swelling was acute in onset and microvascular complications.2 Recently, located diffusely over the thighs which diabetic myonecrosis also has been reported severely impaired him from performing in type 2 diabetes mellitus patients.3 activities of daily living. The patient denied Elevation of muscle enzymes such as any history of trauma, intramuscular creatine phosphokinase (CPK) is present in injections, infections, or drug abuse. He had half of all cases of diabetic myonecrosis. It similar history of pain and swelling in the can be misdiagnosed as cellulitis, right thigh five months prior, which resolved inflammatory myopathy, deep vein spontaneously.
    [Show full text]
  • IJBCP International Journal of Basic & Clinical Pharmacology Knowledge, Attitude and Practice of Insulin Use and Its Adve
    Print ISSN: 2319-2003 | Online ISSN: 2279-0780 IJBCP International Journal of Basic & Clinical Pharmacology DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20174783 Original Research Article Knowledge, attitude and practice of insulin use and its adverse effects in adult diabetic population Nivethitha T.1*, Manickavasagam S.1, Paramasivam M.2, Sai Thaejasvi G.3 1Department of Pharmacology, ABSTRACT 2Department of Medicine, Chennai Medical College Background: Diabetes is a disease when left untreated, leads to many Hospital and Research Centre complications. India is emerging as a diabetic capital of the world. Insulin is (SRM Group), Irungalur, widely used as a therapeutic option, and hence this study was conducted to assess the awareness of Insulin use and its adverse effects in diabetic population. Trichy, Tamilnadu, India 3Student, Tamilnadu Dr. M. G. Methods: The study was a questionnaire survey conducted in adult patients with R Medical University, Guindy, diabetes who are on Insulin therapy. The participants’ knowledge, attitude and Chennai- 600032, Tamil Nadu, practice were assessed by using a questionnaire consisting of 32 questions. Scores India were allotted to each question, and evaluated after applying appropriate statistical tests. Received: 01 September 2017 Results: The mean age of the participants was 57.26±11.24 years. About 54% Accepted: 25 September 2017 were males. 46% belonged to rural areas. The mean knowledge score was 17.53±4.40, mean attitude score 7.42±4.85 and the mean practice score was *Correspondence to: 6.56±1.91. 40% responded that they will return the expired insulin vials to the Dr. Nivethitha T., pharmacy.
    [Show full text]
  • Complications of Diabetes Mellitus: a Review R
    Review Article Complications of diabetes mellitus: A review R. Balaji1, Revathi Duraisamy1, M. P. Santhosh Kumar2* ABSTRACT Diabetes mellitus (DM) is a chronic disease characterized by hyperglycemia and complications that include microvascular disease of the eye and kidney and a variety of clinical neuropathies. DM, also known as simply diabetes, is a group of metabolic diseases in which there are high blood sugar levels over a prolonged period. These high blood sugar levels produce the symptoms of repeated urination, increased hunger, and increased thirst. Untreated diabetes can cause many complications. Acute complications include diabetic ketoacidosis (DKA) and non-ketotic hyperosmolar coma. Serious long- term complications include heart disease, stroke, kidney failure, foot ulcers, and damage to the eyes. Metabolic abnormalities in carbohydrates, lipids, and proteins result from the important role of insulin as an anabolic hormone. Low levels of insulin to achieve adequate response and/or insulin resistance of target tissues, mainly skeletal muscles, adipose tissue, and to a lesser extent, liver, at the level of insulin receptors, signal transduction system, and/or effector enzymes or genes are responsible for these metabolic abnormalities. The severity of symptoms is due to the type and duration of diabetes. Some of the diabetes patients are asymptomatic, especially those with type 2 diabetes during the early years of the disease. Others with marked hyperglycemia, especially in children with absolute insulin deficiency, may suffer from polyuria, polydipsia, polyphagia, weight loss, and blurred vision. Uncontrolled diabetes may lead to stupor, coma, and if not treated death, due to ketoacidosis or rarely from non-ketotic hyperosmolar syndrome.
    [Show full text]
  • DIABETES (4 Hours) Diabetes Mellitus, Often Referred to Simply As Diabetes (Ancient Greek “To Pass Through"), Is a Syndro
    DIABETES (4 Hours) Diabetes mellitus, often referred to simply as diabetes (Ancient Greek “to pass through"), is a syndrome of disordered metabolism, usually due to a combination of hereditary and environmental causes, resulting in abnormally high blood sugar levels (hyperglycemia). Blood glucose levels are controlled by a complex interaction of multiple chemicals and hormones in the body, including the hormone insulin made in the beta cells of the pancreas. Diabetes mellitus refers to the group of diseases that lead to high blood glucose levels due to defects in either insulin secretion or insulin action in the body. Diabetes develops due to a diminished production of insulin (in type 1) or resistance to its effects (in type 2 and gestational). Both lead to hyperglycemia which largely causes the acute signs of diabetes: excessive urine production resulting in compensatory thirst and increased fluid intake, blurred vision, unexplained weight loss, lethargy, and changes in energy metabolism. All forms of diabetes have been treatable since insulin became medically available in 1921, but there is no cure. The injections by a syringe, insulin pump, or insulin pen deliver insulin, which is a basic treatment of type 1 diabetes. Type 2 is managed with a combination of dietary treatment, exercise, medications and insulin supplementation. Diabetes and its treatments can cause many complications. Acute complications (hypoglycemia, ketoacidosis, or nonketotic hyperosmolar coma) may occur if the disease is not adequately controlled. Serious long-term complications include cardiovascular disease (doubled risk), chronic renal failure, retinal damage (which can lead to blindness), nerve damage (of several kinds), and microvascular damage, which may cause dysfunction and poor wound healing.
    [Show full text]
  • Nonhealing Cellulitis in a 54-Year-Old Man with Diabetes Mellitus
    IM BOARD REVIEW DAVID L. LONGWORTH, MD, JAMES K. STOLLER, MD, EDITORS STEVEN D. MAWHORTER, MD Department of Infectious Disease, Cleveland Clinic; CREDI! research interests in clinical infectious disease, travel medicine, and the immunology of infections Nonhealing cellulitis in a 54'yeai>old man with diabetes mellitus 54-YEAR'OLD MAN with type 1 (insulin- WHAT IS THE DIAGNOSIS? dependent) diabetes mellitus presents to the emergency department with a 1-week What is the most likely diagnosis in this history of fever with temperatures as high as 1 case? 103°F (39.4°C) and progressive erythema, warmth, swelling, and tenderness of his left • Improper antibiotic therapy of cellulitis medial thigh. He says he has not had any trau- • Diabetic myonecrosis ma to this area. He is admitted to the hospital • Pyomyositis and receives clindamycin 900 mg intra- • Traumatic hematoma venously every 8 hours. Though his white blood cell count declines from 22.0 to 12.0 x Improper antibiotic therapy of cellulitis 109/L, he continues to have significant pain needs to be considered but is unlikely in this and cutaneous signs consistent with cellulitis. patient. The specific bacterial etiology of cel- lulitis is often not known. A leading edge cul- Initial evaluation ture (not done in this case) is instructive only Blood cultures are negative. A duplex ultra- 30% of the time at best. (A leading edge cul- If cellulitis does sound scan is negative for deep vein thrombo- ture is performed by inserting a needle in the not respond sis. Plain radiographs of the left thigh show no subcutaneous tissue and aspirating the gas, foreign body, or evidence of osteomyelitis.
    [Show full text]
  • Impact of Health Counselling on Self Efficacy and Glycemic Level Among Diabetic Adolescent Patients
    International Journal of Advancements in Research & Technology, Volume 4, Issue 8, August -2015 92 ISSN 2278-7763 IMPACT OF HEALTH COUNSELLING ON SELF EFFICACY AND GLYCEMIC LEVEL AMONG DIABETIC ADOLESCENT PATIENTS M.V.Sudhakaran, Associate Professor, TNOU S.Gangadharan, Research Scholar, TNOU Abstract Children and adolescents with diabetes have significant risks for psychological problems, including depression, anxiety, eating disorders and externalizing disorders. These risks increase exponentially during adolescence. Studies have shown that psychological disorders predict poor diabetes management and control as well as consequently, the negative medical outcomes. The presence of psychological symptoms and diabetes problems in children and adolescents are often strongly affected by caregiver/family distress. Research has demonstrated that while parental psychological issues may distort perceptions of the ward's diabetes control, often, they are related to poor psychological adjustment and diabetes control. Maternal anxiety and depression are associated with poor diabetes control in younger adolescents and with reduced positive effect and motivation in older teen. The results of the study indicate that parental anxiety related to the diabetes control among the subjects and health counselling has significantly develops the diabetic control. The study concludes that to avoid both health and Psychological/psychiatric risks the (adolescent) patients should be referred for diabetes education, ongoing care and psychosocial support to a diabetes team with psychopharmacologicalIJOART expertise. Key Words: Health Counselling, Self efficacy, Anxiety, Adolescents Introduction Diabetes is fast gaining the status of a potential epidemic in India with more than 62 million diabetic individuals currently diagnosed with the disease. In 2000, India (31.7 million) topped the world with the highest number of people with diabetes mellitus followed by China (20.8 million) with the United States (17.7 million) in second and third place respectively.
    [Show full text]
  • Diabetic Muscle Infarction: a Rare End-Organ Vascular Complication of Diabetes
    Diabetic muscle infarction: a rare end-organ vascular complication of diabetes Abstract Diabetic muscle infarction (DMI) is a rare microvascular complication of spontaneous ischemic necrosis of skeletal muscle in patients with poorly controlled diabetes. We herein describe the case of a 26-year-old woman with a history of type I diabetes and accompanying diabetic microvascular complications of neuropathy, nephropathy and retinopathy, who presented with sudden onset of swelling and sharp pain in her bilateral thighs. T2-weighted MRI imaging revealed subcutaneous edema and sub-fascial, hyper-intense enhancement of proximal thigh musculature. DMI has a relatively non-specific clinical presentation; therefore, physician awareness is key for early diagnosis, as aggressive management has been associated with poor patient outcomes. With poor long-term prognosis and high reoccurrence, DMI acts as an indicator of vascular end-organ damage. Keywords Diabetic Muscle Infarction, Diabetic Myonecrosis Introduction Diabetic muscle infarction (DMI) is a rare microvascular complication consisting of spontaneous ischemic necrosis of skeletal muscle in patients with poorly controlled diabetes. Though its characteristics have been defined, fewer than 200 cases1,2 have been reported since it was first described in 1965 by Angervall and Stener.3 Originally, it was termed “tumoriform focal muscular degeneration,” owing to the initial cases’ resemblance to tumors, which in that case were completely excised.1,3-7 The condition has also known as diabetic, aseptic,
    [Show full text]