“A Study on Diastolic Dysfunction in Asymptomatic
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“A STUDY ON DIASTOLIC DYSFUNCTION IN ASYMPTOMATIC TYPE 2 DIABETES MELLITUS WITH NORMAL SYSTOLIC FUNCTION” Dissertation submitted in partial fulfilment of the requirement for the award of the Degree of DOCTOR OF MEDICINE – BRANCH I GENERAL MEDICINE APRIL 2016 TIRUNELVELI MEDICAL COLLEGE HOSPITAL THE TAMIL NADU DR.M.G.R. MEDICAL UNIVERSITY CHENNAI ,TAMIL NADU. 1 CERTIFICATE This is to certify that the Dissertation entitled “A STUDY ON DIASTOLIC DYSFUNCTION IN ASYMPTOMATIC TYPE 2 DIABETES MELLITUS WITH NORMAL SYSTOLIC FUNCTION” submitted by Dr. M.ILAMARAN to The Tamilnadu Dr. M.G.R. Medical University, Chennai, in partial fulfilment for the award of M.D. Degree (GENERAL MEDICINE) is a bonafide work carried out by him under my guidance and supervision during the academic year 2013-2016. This dissertation partially or fully has not been submitted for any other degree or diploma of this university or other. Prof.Dr.RAVICHANDRAN M.D Prof. Dr.VAIRAMUTHURAJU M.D UNIT CHIEF, UNIT III, PROFESSOR AND HOD, DEPARTMENT OF MEDICINE, DEPARTMENT OF MEDICINE, TIRUNELVELI MEDICAL COLLEGE, TIRUNELVELI MEDICAL COLLEGE, TIRUNELVELI – 627011. TIRUNELVELI – 627011. Dr. SITHY ATHIYA MUNAVARAH M.D THE DEAN, TIRUNELVELI MEDICAL COLLEGE TIRUNELVELI -627011 2 DECLARATION I, Dr.M.ILAMARAN, solemnly declare that the Dissertation titled “A STUDY ON DIASTOLIC DYSFUNCTION IN ASYMPTOMATIC TYPE 2 DIABETES MELLITUS WITH NORMAL SYSTOLIC FUNCTION” has been prepared by me. This is submitted to the Tamilnadu Dr.M.G.R. Medical University, Chennai, in partial fulfillment of the regulations for the award of MD Degree Branch I (MEDICINE). It was not submitted to the award of any degree/diploma to any University either in part or in full previously. Place: TIRUNELVELI DR.M.ILAMARAN, Date : POST GRADUATE, M.D.GENERAL MEDICINE, TIRUNELVELI MEDICAL COLLEGE HOSPITAL 3 ACKNOWLEDGEMENT At the outset I wish to thank our retired Dean Dr.THULASIRAM, MS, and the incumbent Dean Dr. SITHY ATHIYA MUNAVARAH M.D for permitting me to carry out this study in our hospital.I express my sincere thanks to my Professor and H.O.D DR.VAIRAMUTHU RAJU M.D for his support and encouragement throughout the study. I am also deeply indebted to my chief Prof DR.RAVICHANDRAN M.D,who was the main motivator behind the study. I also thank Prof DR.THOMAS KINGSLEY M.D for his encouragement and valuable guidance to the study. I am thankful to my assistant Professors DR.SANKARANARAYANAN M.D,D.M DR.RAJESH BABU M.D for their valuable suggestions and support to conduct this study. I am also thankful to Dr. Thrilokchandar M.D who was the brain behind this topic for study. I am thankful to the HOD department of cardiology Dr.RAVICHANDRAN EDIWIN M.D.D.M for helping me conduct this study. I am immensely grateful to the Asst professor of cardiology Dr.BALACHANDAR M.D.D.M who helped me in the evaluation of diastolic dysfunction I also thank the department of Ophthalmology for helping me to confirm the fundus study .I am also thankful to my statistician, DR.DINESH KUMAR for the guidance provided in the analysis and interpretation of the data. I also thank the Department of Biochemistry, for the laboratory support to this study. Last but not the least, I sincerely thank all the patients and their parents who cooperated with me by participating in the study 4 5 6 CONTENTS S.NO. TITLE PAGES 1. INTRODUCTION 8-10 2. AIM 11-12 3. REVIEW OF LITERATURE 13-62 4. MATERIALS AND METHODS 63-76 5. OBSERVATIONS AND RESULTS 77-89 6. DISCUSSION 90-94 7. CONCLUSION 95-96 8. BIBLIOGRAPHY 97-102 9. APPENDIX ANNEXURE 1 103-105 ANNEXURE 2 106-111 ANNEXURE 3 112 ANNEXURE 4 113 7 INTRODUCTION 8 A STUDY ON DIASTOLIC DYSFUNCTION IN ASYMPTOMATIC TYPE 2 DIABETES MELLITUS WITH NORMAL SYSTOLIC FUNCTION INTRODUCTION The incidence of diabetes mellitus (DM) is on the raise across the world and it is turning out to be an epidemic of non communicable disease. Diabetic heart disease and Diabetic Cardiomyopathy as a separate entity has been proposed in the last couple of decades. Diastolic heart failure, otherwise called as heart failure with preserved ejection fraction, is common finding of hypertensive heart disease, but various studies report a high incidence of diastolic heart failure in patients with type 2 diabetes mellitus inspite of the absence of coronary artery heart disease and hypertension. Observations point to a diastolic dysfunction occurring before systolic dysfunction in the setting of myocardial damage due to diabetes. There is also prevalence of a pre-clinical diastolic dysfunction in diabetics. The patho-physiology of an impaired diastolic dysfunction in diabetes is poorly understood. Diabetic cardiomyopathy is proposed to be a disease independent coronary artery disease. Metabolic derangements involving hyperglycemia, hyperlipidemia, hyperinsulinemia, myocyte loss, interstitial fibrosis, autonomic neuropathy, microvascular 9 dysfunction have all been proposed as underlying the development of Diabetic cardiomyopathy. The objective of this study is to find out the association between Type 2 Diabetes Mellitus and Diastolic Dysfunction, even in the asymptomatic diabetic population. To ascertain the prevalence of left ventricular diastolic dysfunction and to determine its correlation with duration of diabetes mellitus, obesity parameters, HbA1c levels, patient’s age and diabetic microvascular complications we conducted this case control study. 10 AIM 11 AIM 1) To determine the prevalence of dysfunction of left ventricle in diastole in type 2 diabetes mellitus patients with duration greater than 5 years 2) To compare the prevalence of left ventricular diastolic dysfunction of non diabetic individuals with that of asymptomatic type II diabetes patients 3) To know the correlation of diastolic dysfunction in diabetes with age of patients, HbA1c levels, duration of diabetes, duration of diabetes, retinopathy, autonomic neuropathy. 12 REVIEW OF LITERATURE 13 Diabetes affects the heart in 3 ways: (1) Coronary Artery Disease (CAD) due to accelerated atherosclerosis (2) Cardiac Autonomic Neuropathy (CAN) and (3) Diabetic Cardiomyopathy (DbCM). Although there is high awareness among clinicians about the first two disease entities, DbCM is poorly recognized by most physicians and diabetologists. Various studies have reported the presence of cardiac abnormality apart from coronary artery disease in asymptomatic diabetes patients. In 1991 Galderisi et al reported the incidence of increased left ventricular mass in diabetes mellitus in women through the Framingham heart study. In 1997 Lee et al reported the presence of increased left ventricular mass in diabetes mellitus in both men and women in the cardiovascular health study. In 2000, Devereux et al in Strong health study showed that there is increased left ventricular mass, decreased endocardial fractional shortening and midwall fractional shortening in diabetes mellitus. In 2001 Ilercil et al showed that there is increased left ventricular thickness and relative wall thickness in impaired glucose tolerance. In 2003Rutter et al used Framingham heart study and reported the presence of progressive increase in left ventricular mass, relative wall thickness in both impaired glucoe tolerance and diabetes mellitus. 14 Poulsen et al in a study of 300 patients in 2010 observed that there is high prevalence of diastolic dysfunction in patients with type 2 diabetes with no previous history of coronary artery disease and abnormal left ventricular filling was associated with impaired myocardial perfusion. Soldatos et al did a case control study with 60 patients and found a significant incidence of diastolic dysfunction in diabetic individuals. Masugata et al conducted a case control study with 78 patients with normal blood pressure. He found the the presence of diastolic dysfunction with normal systolic function was correlating to duration of type 2 diabetes and age of patients. Mishra et al observed, from their case control study of 70 patients, that when compared to normal individuals, patients with diabetes have reduced diastolic and systolic function. He also found that the systolic and diastolic disturbances were correlating with diabetes duration and the microvascular complications. Between 1996-2007 From et al conducted a study with 485 subjects and observed that diastolic dysfunction of left ventricle was associated with diabetes mellitus with duration > 4 years. Sohail et al in a study with 211 patients observed a 30% incidence of diastolic dysfunction in type 2 diabetes. 15 Exiara et al in a study with 115 patients observed that, patients without hypertension and properly controlled diabetes have diastolic dysfunction and it correlates with duration of diabetes. Diamant et al found that the echo findings of E, A, E/A ratio and other diastolic function indices were decreased in uncomplicated diabetes that was diagnosed recently. Bonito et al states that the left ventricular diastolic dysfunction correlates with micro vascular complications. Aaron et al with a study of 1700 patients found a 23 % incidence of diastolic dysfunction in type 2 diabetes. Takeda et al in a study of 500 Japanese diabetes patients observed that there is a major role for diastolic dysfunction in producing heart failure with preserved systolic function. Poanta et al observed, through a study of 50 patients, that left ventricular diastolic dysfunction was associated with cardiac autonomic neuropathy which was asymptomatic. Patil et al in a study with 122 diabetes patients found that the prevalence of left ventricular diastolic