SAT-051 Effects of Testosterone Replacement on Glycemic Control and Other Cardiovascular Risk Factors in Hypogonadal Men with Uncontrolled Type 2 Diabetes (Stride Study): Design, Implementation and Baseline Data

Abstract

Up to 40% of men with type II diabetes are testosterone deficient. There is growing evidence that testosterone therapy has a beneficial effect on glycemic control, insulin resistance and may have a cardioprotective effect, contrary to the traditional view that testosterone is detrimental to the heart. Our study aims to evaluate the effect of testosterone therapy on glycaemic control other cardiovascular risk factors, symptomatic benefit and quality of life in a randomised double-blind placebo controlled add-on of testosterone therapy to their normal hypoglycemic medication in hypogonadal men with uncontrolled type 2 diabetes. The study population includes 65 eligible men (140 screened) with poorly controlled diabetes (HbA1c between 53 and 80 mmol/mol) and confirmed hypogonadism by early morning [0800−1200h] total testosterone [TT] ≤12 nmol/L or calculated free testosterone ≤255 pmol/L on two occasions ≥1 week apart, with at least two symptoms of hypogonadism. The trial is divided into 2 phases. Phase 1: patients are randomly assigned to either treatment (depot testosterone undecanoate) arm or the placebo arm for 6 months. Phase 2: open label phase for 6 months with subjects on placebo on placebo initiated on to testosterone therapy while subjects in the treatment group continue to receive treatment for the 12 month duration. No change to anti- glycaemic therapy was made during the first phase of the study. The primary endpoint is HbA1c. Secondary endpoints include body composition (bioelectrical impedence DEXA scan), HOMA-IR, lipid profile, blood pressure (24 hr BP monitor), carotid media intima thickness, monocyte mRNA cytokine expression, Questionnaires include AMS (Aging Male Symptom Score), IIEF-5(International Index of Erectile Dysfunction), SF36-Quality of life, Mini mental score, New questionnaire for hypogonadism in diabetes (to be validated), NERI (New England Research Institute) hypogonadal screener. Baseline data indicate the mean age 59 (42-77) years. Mean Duration of diabetes was 8.6(0-21) years. 18 men were on Insulin. The remaining 47 men were either diet controlled or on oral hypoglycaemic medications. 9 men had pre-existing history of MI and 4 had history of angina. Mean HbA1c at baseline was 65(53-80) mmol/mol. Mean total testosterone level was 8.9(2.1-16.9) nmol/l. Mean weight and BMI at baseline were 107(71-187) kg and 34.5(24-52) respectively. Mean waist circumference was 115.7(46-160) cm The primary aim of this is to determine if testosterone therapy improves glycemic control in men with uncontrolled diabetes. Secondly to assess beneficial effects on specific cardiovascular parameters as well as QOL. This could have a major clinical implication on how we treat patients with hypogonadism and type 2 diabetes.