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Comparison of Efficacy and Safety of Epalrestat with Methylcobalamin in Patients with Diabetic Neuropathy”

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Comparison of Efficacy and Safety of Epalrestat with Methylcobalamin in Patients with Diabetic Neuropathy” DISSERTATION ON “COMPARISON OF EFFICACY AND SAFETY OF EPALRESTAT WITH METHYLCOBALAMIN IN PATIENTS WITH DIABETIC NEUROPATHY” Dissertation submitted to THE TAMILNADU Dr. M.G.R. MEDICAL UNIVERSITY In partial fulfillment of the requirement For the award of the degree of M.D. BRANCH-VI IN PHARMACOLOGY Submitted By Registration Number: 201516452 KARPAGA VINAYAGA INSTITUTE OF MEDICAL SCIENCES AND RESEARCH CENTRE, MADURANTHAGAM THE TAMILNADU Dr. M.G.R. MEDICAL UNIVERSITY, CHENNAI TAMILNADU MAY-2018 CERTIFICATE This is to certify that Dr. C. Preeth, a Post Graduate student in the Department of Pharmacology has carried out the work titled “Comparison of efficacy and safety of Epalrestat with Methylcobalamin in patients with Diabetic neuropathy” under the guidance of Dr.P.JACOB VERGHESE, M.D., PROFESSOR, Department of Pharmacology, towards the partial fulfillment of regulations laid down by The Tamilnadu Dr. M.G.R Medical University, Guindy, Chennai, Tamilnadu, India for the award of Doctor of Medicine (M.D.,) in Pharmacology. Dr.P. JACOB VERGHESE, M.D., DR. R. KAVITHA, M.D., PROFESSOR, PROFESSOR & HOD, Karpaga Vinayaga Institute of Medical Karpaga Vinayaga Institute of Medical Sciences & Research Centre, Sciences & Research Centre, Chinnakolambakkam, Chinnakolambakkam, MaduranthagamTk, MaduranthagamTk, Kancheepuram District– 603 308, Kancheepuram District– 603 308, Tamilnadu, India. Tamilnadu, India. DR. SUFALA SUNIL VISHWASRAO, PRINCIPAL, Karpaga Vinayaga Institute of Medical Sciences & Research Centre, Chinnakolambakkam, Maduranthagam Tk, Kancheepuram District– 603 308, Tamilnadu, India. DECLARATION I declare that dissertation entitled “Comparison of efficacy and safety of Epalrestat with Methylcobalamin in patients with Diabetic neuropathy” submitted by me for the degree of M.D., is the record work carried out by me under the guidance of Dr.P. JACOB VERGHESE, Professor Of Pharmacology, Karpaga Vinayaga Institute of Medical Sciences and Research Centre and has not formed the basis of any Degree, Diploma, Fellowship, titles in this or any other University or other similar Institution of Higher learning. Place: Chinnakolambakkam Signature of the Candidate Date: DR. C. PREETH Signature of the Guide Signature of HOD Dr.P. JACOB VERGHESE, M.D., DR. R. KAVITHA, M.D., PROFESSOR, PROFESSOR & HOD, KarpagaVinayaga Institute of Medical Karpaga Vinayaga Institute of Medical Sciences & Research Centre, Sciences & Research Centre, Chinnakolambakkam, Chinnakolambakkam, MaduranthagamTk, MaduranthagamTk, Kancheepuram District– 603 308, Kancheepuram District– 603 308, Tamilnadu, India. Tamilnadu, India. ACKNOWLEDGEMENTS At the outset I express my sincere thanks to my esteemed guide Dr.P.JACOB VERGHESE M.D., Professor in the Department of Pharmacology, Karpaga Vinayaga Institute of Medical Sciences and Research Centre for his encouragement and valuable guidance in the topic given from time to time for the successful completion of study. I am extremely thankful to the Managing Director, Dr.R. ANNAMALAI, M.S., M.Ch., Principal Dr. SUFALA SUNIL VISHWASRAO, M.D., Medical Director Dr. SATHIYANARAYANAN, Karpaga Vinayaga Institute of Medical Sciences and Research Centre for providing me all the facilities to conduct this study. I express my deep and sincere gratitude to Dr. R. KAVITHA, M.D., Professor and Head, Department of Pharmacology, Karpaga Vinayaga Institute of Medical Sciences and Research Centre for being my mentor and support at all levels. I profusely thank my Co-guide Dr. V. GOPAL DASS, M.D., Professor and Head, Department of General Medicine, Karpaga Vinayaga Institute of Medical Sciences and Research Centre for having permitted to conduct this study and the constant support he extended throughout the study. I thank Dr. D. SRINIVASAN, Ph.D., Professor in the Department of Pharmacology, KarpagaVinayaga Institute of Medical Sciences and Research Centre for his kind guidance and encouragement during the course of this study. I express my deep and sincere gratitude to Dr. B. PRATHAP, M.D., Associate Professor, Department of Pharmacology, Karpaga Vinayaga Institute of Medical Sciences and Research Centre for his guidance and support at all levels. My heartfelt thanks to my Assistant Professors, Dr. E. SESHATHRI, M.D., and Dr. SUNIL M VISHWASRAO, M.D., in guiding me through the course of the study. I owe my sincere thanks to Dr. N. CHANDRAN, B.V.Sc., and AH for encouraging me towards this research. I thank my Senior and Junior Post Graduate colleagues for their greatest help and support through the course. I sincerely thank our bio-statistician GLADIUS JENIFER for her guidance during my dissertation. I am immensely grateful to the staffs at the Department of Pharmacology and Department of General Medicine, Karpaga Vinayaga Institute of Medical Sciences and Research Centre for having provided me technical support throughout the study. Last but no means the least, I am greatly indebted to all the patients who had taken part in this study without whom the study could not have been completed. Finally my dissertation would have not been accomplished without the support of my parents Mr. Chandrasekaran& Mrs. Thiripurasundari, my husband Dr. Chakravarthi, my sons Sibi Aathyandha& Rishi Aathreya and my other family members. Above all I thank my Almighty for his blessings. PLAGIARISM CERTIFICATE PLAGIARISM CERTIFICATE CONTENTS CHAPTER PARTICULARS PAGE NO. 1 INTRODUCTION 1 2 AIMS AND OBJECTIVES 4 3 REVIEW OF LITERATURE 5 4 DRUG PROFILE 33 5 PLAN OF WORK 40 6 MATERIALS AND METHODS 41 7 OBSERVATION AND RESULTS 46 8 DISCUSSION 82 9 SUMMARY 86 10 CONCLUSION 88 11 BIBLIOGRAPHY 89 12 ANNEXURES 99 LIST OF TABLES SL. TITLE PAGE NO NO. Explains blood test levels for diagnosis of diabetes and 1 20 prediabetes. 2 Explains the study groups. 42 Explains the number of males and females among the study 3 49 groups A, B and C. Shows the mean age (in years) of the patients belonging to 4 51 groups A, B and C. Shows the mean BMI of all three groups at baseline and at 5 53 the end of 4th, 8th and 12th weeks. Shows the mean fasting blood glucose level of all three 6 55 groups at baseline and at the end of 4th, 8th and 12th weeks. Shows the mean post prandial blood glucose level of all 7 57 three groups at baseline and end of study. Shows the mean glycosylated haemoglobin level of all three 8 59 groups at baseline and end of study. 9 Shows the mean AST concentration of groups A, B & C. 61 10 Shows the mean ALT concentration of groups A, B & C. 63 11 Shows the mean serum albumin level of groups A, B & C. 65 Explains the mean serum total bilirubin level of groups A, B 12 67 & C. Explains the serum creatinine concentration of groups A, B 13 69 & C. 14 Shows the serum urea concentration of groups A, B & C. 71 15 Shows the urine albumin levels of groups A, B & C. 73 16 Explains the urine sugar levels of groups A, B & C. 74 Shows the frequency of various adverse drug reactions 17 75 between the study groups. 18 Shows the pain intensity scores (VAS Method). 76 Shows the MichiganNeuropathy Screening Instrument 19 78 (MNSI) score- Completed by the person with diabetes. Shows the MichiganNeuropathy Screening Instrument 20 80 (MNSI) score - Completed by health professionals. LIST OF FIGURES SL. TITLE PAGE NO NO. 1 Explains the synthesis, release and actions of insulin 17 2 Explains the pathogenesis of type 1 diabetes mellitus 18 3 Explains the pathogenesis of type 2 diabetes mellitus 19 4 Polyol (Sorbitol) Pathway 24 5 Polyol (Sorbitol) Pathway with accumulation of sorbitol 25 and fructose 6 Shows the percentage of males and females among the 50 study group A. 7 Shows the percentage of males and females among the 50 study group B. 8 Shows the percentage of males and females among the 50 study group C. 9 Illustration of the graphical representation of the mean age 52 of the study groups. 10 Shows the graphical representation of change in mean BMI 54 of all three groups during the visits. 11 Illustration of graphical representation of table 6. 56 12 Shows the graphical representation of table 7. 58 13 Illustration of graphical representation of table 8. 60 14 Illustration of graphical representation of table 9. 62 15 Shows the graphical representation of table 10. 64 16 Illustration of graphical representation of table 11. 66 17 Illustration of graphical representation of table 12. 68 18 Illustration of graphical representation of table 13. 70 19 Shows the graphical representation of table 14. 72 20 Shows the graphical representation of table 18. 77 21 Shows the graphical representation of table 19. 79 22 Illustration of graphical representation of table 20. 81 LIST OF ABBREVIATIONS ACE Angiotensin-converting enzyme ACR Albumin:Creatinine Ratio ALA Alpha Lipoic Acid ALT Alanine Amino Transferase-SGPT ARBs Angiotensin Receptor Blockers AST Aspartate Transaminase – SGOT ATP Adenosine Triphosphate BMI Body Mass Index CBC Complete Blood Count CDC Center for Disease Control CHD Coronary heart disease CNS Central Nervous System DKA Diabetic Ketoacidosis DM Diabetes Mellitus FBS Fasting Blood Glucose FPG Fasting Plasma Glucose GAD Glutamic acid Decarboxylase GFR Glomerular Filtration Rate GIP Gastric Inhibitory Polypeptide GLP Glucagon Like Peptide GLUT2 Glucose Transporter 2 HbA1C Glycosylated Hemoglobin HDL High Density Lipoprotein Hyperosmolar hyperglycaemicnonketotic HHS coma Human Leukocyte Antigen – antigen D HLA-DR Related HNF Hepatocyte nuclear transcription factor IDDM Insulin-Dependent Diabetes Mellitus IDF International Diabetes Federation IEC Institutional Ethical Committee IM Intra
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