PREVALENCE OF THYROID DYSFUNCTION IN AMBULANT PATIENTS WITH TYPE 2 DIABETES ATTENDING DIABETES CLINICS AT KENYATTA NATIONAL HOSPITAL DISSERTATION SUBMITTED IN PART FULFILLMENT OF THE REQUIREMENTS FOR THE AWARD OF THE DEGREE OF MASTER OF MEDICINE IN INTERNAL MEDICINE OF THE UNIVERSITY OF NAIROBI DR. ROSSLYN NGUGI (SHO INTERNAL MEDICINE) - H58 /63770/2010 MBChB (UoN) DECLARATION This Research proposal is my original work and has not been presented for a degree at any other university. Signed…………………………………………….DATE………………………….. PRINCIPAL INVESTIGATOR, DR ROSSLYN NGUGI, RESIDENT, DEPARTMENT OF CLINICAL MEDICINE AND THERAPEUTICS. ii SUPERVISORS’ APPROVAL This research proposal has been submitted with the approval of my supervisors, namely: PROF. C.F. OTIENO Associate professor Department of Clinical Medicine and Therapeutics, University of Nairobi. SIGNED………………………………………………………DATE………………………… DR. RITESH PAMNANI MBBS, Dip Clinical Pathology, M.D (path) Lecturer, Department of Human Pathology. University of Nairobi. SIGNED………………………………………………………DATE………………………… PROF. C. KIGONDU Thematic Head unit of Clinical Chemistry Department of Human Pathology SIGNED………………………………………………………DATE………………………… ii i ACKNOWLEDGMENT I give thanks to God for having brought me this far in good health and all that I am. I appreciate my supervisors Prof C.F Otieno, Prof C. Kigondu, Dr .R. Pamnani for their unrelenting support, critical review and commitment throughout every stage of my study. I thank all my research assistants who worked tirelessly and assisted me in data collection. I would like to thank Kenyatta National Hospital staff at theDiabetes clinic for their assistance and to the clients who graciously accepted to participate in my study. I would like to thank staff of Immunology laboratory in their assistance in conducting biochemistry investigations. Finally, I am grateful to my family, friends and colleagues for their constant encouragement and motivation. iv TABLE OF CONTENTS DECLARATION........................................................................................................................... ii SUPERVISORS’ APPROVAL ................................................................................................... iii ACKNOWLEDGMENT ............................................................................................................. iv LIST OF TABLES ...................................................................................................................... vii LIST OF FIGURES ................................................................................................................... viii LIST OF ABBREVIATIONS ..................................................................................................... ix ABSTRACT ................................................................................................................................... x 1.0 INTRODUCTION................................................................................................................... 1 1.1 LITERATURE REVIEW ................................................................................................... 2 1.2EPIDEMIOLOGY ............................................................................................................... 2 1.2.1 BURDEN OF DIABETES MELLITUS......................................................................... 2 1.2.2 PREVALENCE OF THYROID DYSFUNCTION ........................................................ 2 1.2.3 PREVALENCE OF THYROID DYSFUNCTION IN TYPE 2 DIABETICS ............... 3 1.3 EFFECT OF DIABETES ON THYROID FUNCTION .................................................. 4 1.4 EFFECT OF HYPERTHYROIDISM ON GLYCEMIC STATUS ................................ 4 1.5 EFFECT OF HYPOTHYROIDISM ON GLYCEMIC STATUS .................................. 5 1.6 EFFECT OF THYROID DYSFUNCTION ON OTHER ORGAN SYSTEMS ............ 7 1.6.1 EFFECT OF HYPOTHYROIDISM ............................................................................. 8 1.6.2 EFFECT OF HYPERTHYROIDISM ............................................................................ 9 1.7 EFFECT OF DRUGS ON THYROID FUNCTION ........................................................ 9 1.8 OUTCOME OF TREATMENT OF THYROID DYSFUNCTION ........................... 10 2.0 STUDY JUSTIFICATION ................................................................................................... 11 3.0 RESEARCH QUESTION .................................................................................................... 11 4.0 OBJECTIVES ....................................................................................................................... 12 4.1 BROAD OBJECTIVE .................................................................................................. 12 5.0 METHODOLOGY ............................................................................................................. 12 5.1 STUDY SITE .................................................................................................................. 12 5.2 STUDY POPULATION ................................................................................................. 12 5.3 STUDY DESIGN ............................................................................................................ 12 5.4 SAMPLE SIZE ............................................................................................................... 12 v 5.5 SAMPLING METHOD .................................................................................................. 13 5.6 CASE DEFINITION ......................................................................................................... 13 5.6.1 TYPE 2 DIABETES – .................................................................................................... 13 5.6.2 THYROID HORMONE REFERENCE RANGES ..................................................... 13 5.7 INCLUSION AND EXCLUSION CRITERIA ............................................................... 14 5.7.1 INCLUSION CRITERIA ............................................................................................. 14 5.7.2 EXCLUSION CRITERIA ............................................................................................ 14 5.8 SCREENING AND RECRUITMENT AND CONSENTING ...................................... 15 5.9 PROCEDURES ................................................................................................................. 15 5.9.1 CLINICAL EXAMINATION ...................................................................................... 15 5.9.2 LABORATORY METHODS ....................................................................................... 15 5.10 QUALITY ASSURANCE ............................................................................................... 16 5.11 STUDY VARIABLES AND DEFINITIONS ................................................................ 17 5.11.1 INDEPENDENT VARIABLES ................................................................................. 17 5.11.2 DEPENDENT VARIABLES ..................................................................................... 17 5.12 DATA MANAGEMENT AND ANALYSIS ................................................................. 17 5.13 STUDY ADMINISTRATION ........................................................................................ 18 5.14 ETHICAL CONSIDERATIONS ................................................................................... 18 6.0 RESULTS .............................................................................................................................. 19 7.0 DISCUSSION .................................................................................................................... 28 8.0 CONCLUSION .................................................................................................................. 32 9.0 LIMITATIONS ................................................................................................................. 32 10.0 RECOMMENDATIONS ................................................................................................ 32 11.0 REFERENCES .................................................................................................................... 33 12.0 APPENDICES ..................................................................................................................... 39 APPENDIX 1: DATA ABSTRACTION TOOL ................................................................... 39 APPENDIX 2: BUDGET ........................................................................................................ 41 v i LIST OF TABLES Table 1: Studies of prevalence of Thyroid dysfunction in patients with type 2 diabetes 3 Table 2: Interaction between thyroid disease and Diabetes Mellitus. 7 Table 3: Assay of thyroid hormones. 13 Table 4: Analysis and Interpretation of thyroid hormones. 14 Table 5: Sociodemographic characteristics of patients with type 2 Diabetes 20 Table 6: Clinical parameters of patients with type 2 Diabetes 21 Table 7: Medication used by study patients with type 2 Diabetes 24 Table 8: History of thyroid disease & management of thyroid disease in patients with type diabetes 24 Table 9: Clinical evaluation for thyroid dysfunction in study participants 26 Table 10: Thyroid function tests results in patients with type 2 Diabetes. 26 vi i LIST OF FIGURES Figure 1: Thyrotoxicosis effect on glucose homeostasis 5 Figure 2: Hypothyroidism effect on glucose homeostasis 6 Figure 3: Relationship between serum TSH and cholesterol 6 Figure 4: Results of study participants 19 Figure 5: Age distribution of patients with type 2 Diabetes 22 Figure 6: Duration of Diabetes Mellitus in study participants 23 Figure 7: Assessment of BMI of patients with type 2 Diabetes 25 Figure 8: Prevalence of thyroid dysfunction of patients with type 2 Diabetes 27 vi ii LIST OF ABBREVIATIONS BMI Body Mass Index. CVD Cardiovascular disease. ELISA Enzyme Linked Immunosorbent Assay. FFA Free Fatty acids. FT3 Free Triiodothyronine. FT4 Free Thyroxine. GAD Glutamic Acid Decarboxylase. GLUT-2 Glucose Transporter type 2. GLUT-4 Glucose Transporter type 4. HTN Hypertension. IR Insulin Resistance. KNH Kenyatta National Hospital. NHANES National Health and Nutritional Examination Survey. PI Principal Investigator. rT3 Reverse Triiodothyronine. TSH Thyroid Stimulating Hormone. TRH Thyroid Releasing Hormone. T2DM Type 2 Diabetes Mellitus UON University of Nairobi US United States. WHO World Health Organisation. ix ABSTRACT Background Thyroid disease and Diabetes are two common endocrinopathies found in the general population. Thyroid disease is a pathological state which can adversely affect Diabetes control and contribute to negative patient outcomes. Hyperthyroidism contributes to hyperglycemia while hypothyroidism contributes to episodes of hypoglycemia. This not only impedes management of Type 2 Diabetes but also worsens metabolic control. However, uncontrolled diabetes on the other hand has been shown to impair TSH response to TRH which normalizes with improvement in glycemic control Objectives To determine the prevalence and patterns of thyroid dysfunction in patients with Type 2 Diabetes Mellitus. Methodology This was a cross-sectional descriptive survey of participants who were over the age of 30 years selected from patients with type 2 Diabetes attending outpatient diabetes clinics. Systematic random sampling was done on patients meeting the inclusion criteria.A sample size of 180 was obtained. Consenting participants’ had their demographic data and medical history collected by use of structured pre-tested questionnaires and a physical examination was done thereafter. This was followed by drawing of venous blood samples for assessment of, i.e. TSH & fT4. Assays for thyroid hormones were done using specific antibodies and enzyme markers for specific thyroid hormones using Enzyme Linked Immuno Sorbent Assay technology. (ELISA) Results In this study, majority of the patients were female (62.4%), with a mean age of 59 years and had a mean duration of 9.5 years with diabetes mellitus. Those with a previous diagnosis of thyroid dysfunction were about 10.6% and 22.7% had a positive family history of thyroid dysfunction. The prevalence of thyroid dysfunction in patients with type 2 Diabetes was found to be 61%, of which subclinical hypothyroidism was the most predominant type at 58%. No patient was found to have evidence of overt hyperthyroidism. x
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