Effect of testosterone on insulin sensitivity, oxidative metabolism and body composition in aging men with type 2 diabetes on metformin monotherapy

Diabetes Obes Metab. 2016 Oct;18(10):980-9. doi: 10.1111/dom.12701. Epub 2016 Jul 12.

Abstract

Aims: To evaluate the effect of testosterone replacement therapy (TRT) on body composition, insulin sensitivity, oxidative metabolism and glycaemic control in aging men with lowered bioavailable testosterone (BioT) levels and type 2 diabetes mellitus (T2D) controlled on metformin monotherapy.

Materials and methods: We conducted a randomized, double-blind, placebo-controlled study in 39 men aged 50-70 years with BioT levels <7.3 nmol/L and T2D treated with metformin monotherapy. Patients were randomized to testosterone gel (TRT, n = 20) or placebo (n = 19) for 24 weeks. Lean body mass (LBM), total and regional fat mass were measured using whole-body dual-energy X-ray absorptiometry scans. Whole-body peripheral insulin sensitivity, endogenous glucose production (EGP) and substrate oxidation were assessed by euglycaemic-hyperinsulinaemic clamp with glucose tracer and combined with indirect calorimetry. Coefficients (β) represent the placebo-controlled mean effect of intervention.

Results: LBM (β = 1.9 kg, p = 0.001) increased after TRT, while total fat mass (β = -1.3 kg, p = 0.009), fat mass trunk (β = -0.7 kg, p = 0.043), fat mass legs (β = -0.7 kg, p = 0.025), fat mass arms (β = -0.3 kg, p = 0.001), and HDL cholesterol (β = -0.11 mmol/L, p = 0.009) decreased after TRT compared with placebo. Insulin-stimulated glucose disposal rates did not change in response to TRT compared with placebo (p = 0.18). Moreover, glycated haemoglobin, and basal and insulin-stimulated rates of EGP, lipid- and glucose-oxidation were unaltered after TRT.

Conclusion: TRT in aging men with lowered BioT levels and T2D controlled on metformin monotherapy improved body composition; however, glycaemic control, peripheral insulin sensitivity, EGP and substrate metabolism were unchanged.

Keywords: clinical trial; insulin sensitivity; male hypogonadism; testosterone therapy; type 2 diabetes mellitus.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aging / blood
  • Aging / drug effects
  • Aging / physiology
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Body Composition / drug effects*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Double-Blind Method
  • Eunuchism / complications
  • Eunuchism / drug therapy*
  • Eunuchism / metabolism
  • Hormone Replacement Therapy / adverse effects
  • Humans
  • Insulin / metabolism
  • Insulin Resistance*
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Oxidation-Reduction / drug effects
  • Placebos
  • Testosterone / pharmacology*
  • Testosterone / therapeutic use
  • Young Adult

Substances

  • Blood Glucose
  • Insulin
  • Placebos
  • Testosterone
  • Metformin