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



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.



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.



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.
Department of Endocrinology, Odense University Hospital, Odense, Denmark. line.magnussen@rsyd.dk.
Line V
LV
Magnussen
Department of Endocrinology, Odense University Hospital, Odense, Denmark.
Dorte
D
Glintborg
Department of Endocrinology, Odense University Hospital, Odense, Denmark.
Pernille
P
Hermann
Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
David M
DM
Hougaard
Department of Endocrinology, Odense University Hospital, Odense, Denmark.|Section of Molecular Diabetes and Metabolism, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Kurt
K
Højlund
Department of Endocrinology, Odense University Hospital, Odense, Denmark.
Marianne
M
Andersen
D000328:Adult; D000368:Aged; D000375:Aging / Q000097:blood / Q000187:drug effects / Q000502:physiology; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D005058:Eunuchism / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects; D010919:Placebos; D013739:Testosterone / Q000494:pharmacology* / Q000627:therapeutic use; D055815:Young Adult
D001786:Blood Glucose; D007328:Insulin; D010919:Placebos; D013739:Testosterone; D008687:Metformin
clinical trial; insulin sensitivity; male hypogonadism; testosterone therapy; type 2 diabetes mellitus