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“ELEVATED LIVER ENZYMES AS A PREDICTOR FOR TYPE 2 DIABETES MELLITUS IN HIGH RISK INDIVIDUALS”

By

Dr.T.D.Varun Kumar Reddy, M.B.B.S
Dissertation Submitted to the NTRUHS, Vijayawada, A.P.

In partial fulfillment Of the requirements for the award of

POSTGRADUATE DEGREE IN GENERAL MEDICINE
Under the Guidance of

Dr. S.NAGARAJ
M.D. (Gen. Med.) PROFESSOR

DEPARTMENT OF GENERAL MEDICINE

SANTHIRAM MEDICAL COLLEGE
NTRUHS, Vijayawada, A.P.

i

DECLARATION BY THE CANDIDATE I hereby declare that this dissertation entitled “ELEVATED LIVER ENZYMES AS A PREDICTOR FOR TYPE 2 DIABETES MELLITUS IN HIGH RISK INDIVIDUALS” is a bonafide and genuine research work carried out by me under the guidance of Dr. Nandyal.D. Santhiram Medical College.NAGARAJ. Date: Place: NANDYAL Dr. S. Professor. T. Department of General Medicine.Varun Kumar Reddy ii .

D..Varun Kumar Reddy. S.Of General Medicine. Professor.D. Dept . Santhiram Medical College. T. iii .CERTIFICATE BY THE GUIDE This is to certify that the dissertation entitled “ELEVATED LIVER ENZYMES AS A PREDICTOR FOR TYPE 2 DIABETES MELLITUS IN HIGH RISK INDIVIDUALS” is a bonafide research work done by Dr. in partial fulfillment of the requirement for award of POSTGRADUATE DEGREE IN GENERAL MEDICINE. M. Date: Place: NANDYAL Dr. Nandyal.NAGARAJ.

R. T. in partial fulfillment of the requirement for award of POSTGRADUATE DEGREE IN GENERAL MEDICINE. Dr. Professor and HOD. PRINCIPAL / HEAD OF THE INSTITUTION This is to certify that the dissertation entitled “ELEVATED LIVER ENZYMES AS A PREDICTOR FOR TYPE 2 DIABETES MELLITUS IN HIGH RISK INDIVIDUALS” is a bonafide research work done by Dr.D.NAGARAJ. Nandyal. Santhiram Medical College.ENDORSEMENT BY THE HOD. of General Medicine. MD. Date: Place: Nandyal Date: Place: Nandyal iv .. Principal.PRABHAKAR RAO . Nandyal.Varun Kumar Reddy. Dr. Dept. Santhiram Medical College. S. M..D.

Institutional Ethical Committee. Santhiram Medical College. Kurnool. M. Nandyal..Varun Kumar Reddy in the Department of General Medicine.M.N. T. This is to confirm that this work has been done within the ambit of ethical norms of research. Kurnool.S. v .. RADHA KRISHNA MURTHY D.D.D.Sc. Santhiram Medical College.. M.A. during the period of 2011-2014 is reviewed and verified. Date : Place : Nandyal Dr.ETHICAL COMMITTEE CERTIFICATE This is to certify that “ELEVATED LIVER ENZYMES AS A PREDICTOR FOR TYPE 2 DIABETES MELLITUS IN HIGH RISK INDIVIDUALS” which is a genuine dissertation work done by Dr.K. The Chairman. Nandyal.

P.D. Date: Place: NANDYAL Dr. A. use and disseminate this dissertation in print or electronic format for academic/ research purpose. Vijayawada. shall have the rights to preserve.COPYRIGHT DECLARATION BY THE CANDIDATE I hereby declare that the NTRUHS.Varun Kumar Reddy vi . T.

.Prabhakar Rao. I encountered a noble soul and untarnished brilliant academician Dr. I will seek from him his advice and wisdom like one follower from his priest.G.S.G.ACKNOWLEDGEMENT This finished task is a compliment in itself to a man who conceived the idea of this work. Dr. I must gratitude and thanks because in one way or the other I have undoubtedly received help and encouragement. To Dr.Emiretus.VijaiBabu. Santhiram Medical College. my chief guide. going in to the deep intricacies of a problem and solving things with endurance and patience which is unknown to an average man.He has given me an absolute. Professor and Head of the Department. In this long walk punctuated by many difficulties.Vijaykumar. I must add my many grateful thanks for such an unstinting help which went a long way in completing this thesis.Harinath reddy. M. MBBS.Dr.Dr..Nagaraj.Saivani.D. Santhiram Medical College.Prash ath. the apparatus involved in it and the various hurdles that came in the way of such an unsurmountable task-Professor Dr. To my teachers. the proper method and the manner of doing a research work.Siva Prasad.G. From this man’s mind flowed constant encouragement and continuous wisdom which lubricated the wheels on which I was working. Dr.Madhukar.Lokendranath.N. The help rendered by him has become a permanent memory cod in my brain and whenever the winds of emotion will sweep my mind.Dr.Venkataswamy.D. Dr. M. I have learned at the feet of such a masterly research worker. Sometime a friend becomes a mentor. Late Dr. I shall remember him..Dr.D. Department of General Medicine. Dr. M. masterly and undivided attention for which I will remember him from his time to time and whenever I will be at cross roads of my life.S.R. General Medicine. an engineer responsible for smooth sailing of a ship faced with a storm and stears it vii .Praveen. Professor. who gave a firm footing to this thesis.

Bala Subramanyam. I owe gratitude and thanks to Dr.Amritha.D r.out faithfully.Dr.Dr. viii .Aditya. Dr.Someswar.Nikil.Y.Aruna and Shankar for extending their support to complete this work.Aparna.Dr. such was the guidance and skillful help I received from revered friend Dr.Sarath. I wish to thank Mrs.Dr.Pavan.Dr.Anirudh and Dr.Vamsi for all their support.

LIST OF ABBREVIATIONS USED ADA ALT AST ALP BP CVD FBS FFA’s GGT GDM HTN HDL IR IFG IGT IGF LDL NAFLD OGTT PPBS ROS PCOD TG’s American Diabetes Association Alanine Amino Transferase Aspartate Amino Transferase Alkaline Phosphatase Blood Pressure Cardiovascular Disease Fasting Blood Sugar Free Fatty Acids Gamma Glutamyl Transferase Gestational Diabetes Hypertension High Density Lipoprotein Insulin Resistance Impaired Fasting Glucose Impaired Glucose Tolerance Insulin-like Growth Factors Low Density Lipoprotein Non-alcoholic Fatty Liver Disease Oral Glucose Tolerance Test Post Prandial Blood Sugar Reactive Oxygen Species Polycystic Ovarian Disease Triglycerides ix .

23 and P < 0.01).20 P < 0. Type2 Diabetes Mellitus.34 and P < 0. At the end of one year 3 subjects who were nondiabetic had raised fasting glucose levels and became glucose intolerant.22 and P < 0. Keywords: Elevated Liver Enzymes.52 and P < 0. AST.001 and ALT: r = 0.05 and ALT: r = -0. The WHO predicts that developing countries will bear the brunt of this epidemic in the 21st century.05 and ALT: r = 0. Methods: About 100 nondiabetic subjects aged between 30-59 years who had risk factors for diabetes defined by the ADA and had elevated liver enzymes were included and followed up for FBS and PPBS at one year.001). These enzymes were also found to have positive correlation with BMI (GGT: r = 0.ABSTRACT Background: The prevalence of diabetes is rapidly rising all over the globe at an alarming rate. GGT and ALP) in prediction of onset of type2 diabetes mellitus. There was a negative correlation with HDL (GGT: r = -0. Results: GGT was found to have positive association with FBS (r = 0.48 and P < 0. Alanine Amino Transferase. Conclusion: Our study findings indicate that elevated levels of liver enzymes mainly GGT and ALT are markers of risk of type2 diabetes in high risk individuals and suggests a potential role of the liver in the pathogenesis of type2 diabetes mellitus.20 and P < 0.001) and PPBS (r = 0.43 and P < 0.32 and P < 0. Objective: To test the hypothesis that elevated liver enzymes conventionally associated with liver dysfunction predict the occurrence of type2 diabetes in high risk individuals.58 and P < 0. Gamma Glutamyl Transferase.001). Aim: The aim of the present study was to evaluate the association of liver enzymes (ALT.001) and PPBS (r = 0.48 and P < 0. This figure is likely to double by 2030.001) and ALT was also found to have positive association with FBS (r = 0. at least 171 million people world wide have diabetes.01 and ALT: r = 0. According to the World Health Organization. Impaired Glucose Tolerance.53 and P < 0.05) Systolic Blood Pressure (GGT: r = 0. x .05) and positive with Triglyceride levels (GGT: r = 0. Aspartate Amino Transferase.

........................................ 6...................................................................................... 3....................... 7.........................................92 Summary ...........................................................................................................04 Methodology ..104 Proforma Consent Key to Master Chart Master Chart xi ..................94 Annexures………………………………………………...LIST OF CONTENTS 1.........................................66 Results .................................................... 8..... 4...................... 5.88 Conclusion ..........................93 Bibliography ..................... 10............................... 2... Introduction ...74 Discussion .....01 Objectives .....................................03 Review of Literature .......................................................................................... 9....

9. 16. 19. 18th & 19th Centuries 20th Century Sex Distribution Age and Sex Distribution in the Study Percentage Risk Factors in Study Group Subjects with More than one Risk Factor Mean Enzyme Levels Age Group Wise Distribution of Mean Enzyme Levels Mean Enzyme Levels in Three Important Risk Group Mean Fasting and Post Prandial Glucose Levels at Baseline Mean Serum Lipid Profiles Age Group and Mean Lipid Profile Mean FBS and PPBS Levels at One Year Percentage Increase in FBS and PPBS at One Year Correlation Coefficient with Different Enzymes in Relation to FBS at One Year Correlation Coefficient with Different Enzymes in Relation to PPBS at One Year Correlation Coefficient of Liver Enzymes to Systolic Blood Pressure Correlation Coefficient of Liver Enzymes to Diastolic Blood Pressure Correlation Coefficient of Liver Enzymes to Body Mass Index Correlation Coefficient of Liver Enzymes to High Density Lipoprotein Correlation Coefficient of Liver Enzymes to Triglycerides Page No. 18. 2. 1. 20. 12. 17. 13. 21. 3. 11. 5. Table Important Landmarks in the History of Diabetes 17th. 14. 8. 15. 10. 7. 4. 04 04 74 75 76 78 79 80 80 81 82 83 84 85 85 86 86 86 87 87 87 xii . No.LIST OF TABLES Sl. 6.

1. Insulin Synthesis Insulin Secretion Insulin Action Figure Page No.LIST OF FIGURES Sl. 2. 5. 12 13 14 15 20 Mechanism of Turning Off Insulin Signal Obesity and Insulin Resistance xiii . No. 4. 3.