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Department of Physiology Tirunelveli Medical College Tirunelveli – 627 011

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Department of Physiology Tirunelveli Medical College Tirunelveli – 627 011 A CROSS SECTIONAL STUDY TO CORRELATE THE DURATION OF DIABETES, GLYCEMIC CONTROL, AUTONOMIC NEUROPATHY AND DERMATOLOGICAL MANIFESTATIONS IN TYPE 2 DIABETES MELLITUS Dissertation submitted to THE TAMILNADU DR. M.G.R. MEDICAL UNIVERSITY, CHENNAI – 600 032 In partial fulfillment of the requirement for the degree of Doctor of Medicine in Physiology (Branch V) M.D. (PHYSIOLOGY) APRIL – 2017 DEPARTMENT OF PHYSIOLOGY TIRUNELVELI MEDICAL COLLEGE TIRUNELVELI – 627 011. CERTIFICATE This is to certify that the dissertation entitled, “A CROSS SECTIONAL STUDY TO CORRELATE THE DURATION OF DIABETES, GLYCEMIC CONTROL, AUTONOMIC NEUROPATHY AND DERMATOLOGICAL MANIFESTATIONS IN TYPE 2 DIABETES MELLITUS” by Dr. SUJATHA ANDREW, postgraduate in PHYSIOLOGY (2014-2017), is a bonafide research work carried out under our direct supervision and guidance and is submitted to The Tamilnadu Dr.M.G.R. Medical University, Chennai, for M.D., Degree Examination in Physiology (Branch V), to be held in April 2017. Dr. Ratna Manjushree Jayaraman M.D.,D.C.H., Dr.K. Sithy Athiya Munavarah, M.D., Associate Professor and Head , Dean, Department of Physiology, Tirunelveli Medical College, Tirunelveli Medical College, Tirunelveli – 11. Tirunelveli - 11. ENDORSEMENT BY THE GUIDE This is to certify that the dissertation entitled, “A CROSS SECTIONAL STUDY TO CORRELATE THE DURATION OF DIABETES, GLYCEMIC CONTROL, AUTONOMIC NEUROPATHY AND DERMATOLOGICAL MANIFESTATIONS IN TYPE 2 DIABETES MELLITUS’’ is a bonafide research work carried out by Dr. SUJATHA ANDREW in the Department of Physiology, Tirunelveli Medical College & Hospital, Tirunelveli – 11 under my direct guidance and supervision in partial fulfillment of the requirement for the award of the degree of M.D., in PHYSIOLOGY (Branch – V) in April 2017. GUIDE: Dr. R.THENMOZHI M.D., D.C.P., Associate Professor, Department of Physiology, Tirunelveli Medical College, Tirunelveli – 11. DECLARATION I solemnly declare that the dissertation entitled, “A CROSS SECTIONAL STUDY TO CORRELATE THE DURATION OF DIABETES, GLYCEMIC CONTROL, AUTONOMIC NEUROPATHY AND DERMATOLOGICAL MANIFESTATIONS IN TYPE 2 DIABETES MELLITUS’’ is done by myself at Tirunelveli Medical College Hospital, Tirunelveli. The dissertation is submitted to The Tamilnadu Dr. M.G.R. Medical University towards the partial fulfillment of the requirement for the award of M.D., Degree (Branch V) in Physiology. Place :Tirunelveli-11 Dr. SUJATHA ANDREW, Date : Postgraduate Student, M.D. (Physiology), Department of Physiology, Tirunelveli Medical College, Tirunelveli. TIRUNELVELI MEDICALCDLLEGE INSTITUTIONAL RESEARCIIETHICSCOMNI1TTF:F: CERYIFICATE OF REGISTRATION &APPROVAL OFTHETIREC REF NO‹ 750/PHY/ 20 \5 Principallnx•estigator ACKNOWLEDGEMENT I primarily would like to thank the Lord Almighty for enabling me to complete this thesis. I am grateful to Prof. Dr. K. Sithy Athiya Munavarah, M.D., Dean, Tirunelveli Medical College, Tirunelveli for permitting me to carry out this study and for the constant encouragement towards the completion of this thesis. I am immensely thankful to Dr. S. M. Kannan, M.S., Mch., Vice Principal, Tirunelveli Medical College, Tirunelveli, for the support and encouragement. I profoundly thank Dr. Ratna Manjushree Jayaraman, M.D., D.C.H., Associate Professor and Head, Department of Physiology, Tirunelveli Medical College for the indispensible advice, expert guidance, information and support on different aspects of this work. I take this opportunity to thank Dr. R. Thenmozhi, M.D., D.C.P., Associate Professor in Physiology, Tirunelveli Medical College to whom I owe a debt of gratitude for being my guide, who motivated, encouraged, helped and guided me through the completion of this study, which could not have been possible without her expertise. I would like to thank Dr.B.Sujatha M.D., D.A., Associate Professor in Physiology for her constructive guidance and help in every aspect of my research and was imperative for the completion of this degree. I thank Dr. P. Nirmala Devi, M.D., (Derm) Professor and Head, Department of Dermatology, Assistant Professors and Postgraduates of Department of Dermatology, Tirunelveli Medical College Hospital for sparing their valuable time, to help with suggestions for the study. I thank Dr.S.Saravanan ,M.D, D.M., (Neurology) Professor and Head, Department of Neurology, Tirunelveli Medical College Hospital for his support and guidance. I wish to thank the Heads of Department of Medicine and Department of Biochemistry for their help and encouragement. I express my sincere thanks to Assistant professor Dr. S. Sudha, M.D., D.D.V.L., other Assistant professors and Tutors of Department of Physiology for their moral support, advice and help to this study. I thank my Post Graduate colleagues as their assistance, cooperation and experience were essential for the completion of this work. My special thanks to the statistician Mr.R.Jeromia Muthuraj, M.Phil., PhD for his untiring work to accomplish the study in the best way. I certainly thank the Librarian and staff of library, technical and non- technical staff of Central Laboratory, Department of Neurology, Department of Dermatology and Department of Physiology, Tirunelveli Medical College for their kind cooperation and assistance. I thank the participants of this study without them this study would not have been possible. Finally, I thank my family members for their help and support during the entire course of this study. CONTENTS Sl. No. TITLE PAGE No. 1 INTRODUCTION 1 2 AIM AND OBJECTIVES 5 3 REVIEW OF LITERATURE 6 4 MATERIALS AND METHODS 38 5 RESULT ANALYSIS 43 6 DISCUSSION 70 7 SUMMARY AND CONCLUSION 81 8 LIMITATIONS 84 9 FUTURE SCOPE OF STUDY 10 BIBLIOGRAPHY 11 ANNEXURES LIST OF ABBREVIATIONS ANS Autonomic Nervous System ADA American Diabetes Association DM Diabetes Mellitus DPP-4 Di Peptidyl Peptidase 4 FBS Fasting Blood Sugar FDA Food and Drug Administration FFA Free Fatty Acid GLP Glucagon Like Polypeptide GLUT Glucose Transporters HbA1c Glycosylated Hemoglobin HDL High Density Lipoprotein IAPP Islet Amyloid Polypeptide IDF International Diabetic Federation IGT Impaired Glucose Tolerance IGF Impaired Fasting Glucose IGF - I Insulin like Growth Factor I IGF - II Insulin like Growth Factor II IRS Insulin Receptor Substrates LDL Low Density Lipoprotein NCD Non-Communicable Disease PBS Post prandial Blood Sugar PNS Parasympathetic Nervous System SEA South East Asia SGLT Sodium Dependent Glucose Transporters SSR Sympathetic Skin Response TGL Triglycerides WHO World Health Organization A CROSS SECTIONAL STUDY TO CORRELATE THE DURATION OF DIABETES, GLYCEMIC CONTROL, AUTONOMIC NEUROPATHY AND DERMATOLOGICAL MANIFESTATIONS IN TYPE 2 DIABETES MELLITUS INTRODUCTION INTRODUCTION Diabetes mellitus is a non-communicable disease (NCD). NCD contribute to a huge burden on the healthcare system in India as compared to past when it was due to infectious diseases1,2. More than a half of the deaths in India are attributed to NCD of which diabetes mellitus (DM) is on the forefront and has emerged as an epidemic3. The severity of the present situation in the Indian context can be judged from the alarming figures that during 2004, diabetes has been directly responsible for 109,000 deaths, 1157 years of life lost and 2263 disability adjusted life years4. According to Global Report on Diabetes 2016 by World Health Organization5DM mortality rate in South East Asia region is 115.3 per 100,000 in both sexes. Diabetes mellitus is defined by WHO as, ―A metabolic disorder of multiple etiology characterized by chronic hyperglycemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both6. It can lead to long- term complications involving the nervous, cardiovascular, renal, and sensory organ systems. In the sensory organ systems, skin and eyes are affected mainly7.The major cause of morbidity and mortality in DM is mainly because of vascular complications and DM can be considered as a serious disease because of its complications8. 1 Type 2 diabetes mellitus is the commonest form of diabetes worldwide, attributing 90% of cases globally9, 10.Type 2 DM has now become a major public health problem in our country. Our country has the largest number of diabetics in the world second to China11.Though the fact that large numbers of individuals are at risk, 30-80% of the individuals in India are undiagnosed and are left untreated. This is to a large extent due to limited opportunities for diagnosis and lack of public awareness7. From epidemiological studies it is evident that without effective prevention and control programmes, the burden of diabetes is probable to increase worldwide. Because diabetes is affecting workforce people, it has a deleterious impact on both individual and national productivity both in developed and undeveloped countries. The World Health Organization predicts the economic losses in national income for India for about 237 billion7US Dollars.(www.cadiresearch.org).To stress the importance of this global epidemic, on 20th December 2006, the UN General Assembly declared diabetes an international public health issue and declared World Diabetes Day as United Nations Day. To reduce the economic burden of this disease, it is necessary to diagnose early and to manage the observed risks. Skin is affected by both acute metabolic default and the chronic degenerative complication of diabetes12. It is observed from studies that more than 33% of diabetic patients have some dermatologic 2 manifestations on a chronic run13. Atherosclerosis,
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