Poster Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Testosterone therapy reduces glycaemia in males at high risk of type 2 diabetes without altering in vivo or in vitro measures of beta cell function or GLP-1 action (#568)

Mahesh M Umapathysivam 1 2 , Sameena Nawaz 3 , Kristy Robledo 4 , Carolyn Allan 5 , Karen Bracken 4 , Mathis Grossmann 6 , David Handelsman 4 , Warrick Inder 7 , David Jesudason 8 , Bronwyn Stuckey 9 , Bu Yeap 10 , Andrzej Januszewski 4 , Alicia Jenkins 11 , Ann Conway 12 , Benoit Hastoy 3 , Gary Wittert 2
  1. Southern Adelaide Diabetes and Endocrine Service, Flinders Medical Centre, Bedford PArk, SA, Australia
  2. Freemason centre for Men's Health, University of Adelaide, Adelaide, SA, Australia
  3. Radcliffe Department of Medicine, University of Oxford, Headington, Oxfordshire, United Kingdom
  4. University of Sydney, Sydney, New South Wales, Australia
  5. Hudson Institute of Medical Research, Clayton, Victoria, Australia
  6. University of Melbourne, Parkville, Victoria, Australia
  7. Princess Alexandra Hospital, Woolloongabba , Queensland, Australia
  8. University of Adelaide, Adelaide, SA, Australia
  9. Keogh Institute for Medical Research, Nedlands, Western Australia, Australia
  10. University of Western Australia, Crawley, Western Australia, Australia
  11. Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
  12. Concord Hospital, Sydney, New South Wales, Australia

In the ‘Testosterone for the prevention of type 2 diabetes’ (T4DM) Study, treatment with testosterone vs. placebo reduced the OGTT diagnosis of T2D by 40% after 2 years. The mechanism(s) by which testosterone prevents glycaemia and T2D diagnosis remains unclear. Direct effects on beta-cell function, augmentation of the glucagon-like peptide-1 (GLP-1) action and reduction in insulin resistance have all been proposed as mechanisms.


We aimed to assess the mechanism of testosterone protection against T2D by measuring glycaemic traits in a randomised control trial and determining in vitro effects of testosterone on glucose stimulated insulin secretion (GSIS) and GLP-1 action in a human beta-cell line (EndoC-βH1).


Men from T4DM were included if they had fasting bloods at baseline, 18, 66, and 102 weeks (N=743). We compared the change in glycaemia (GA-glycated albumin), insulin secretion (HOMA2-B) and resistance (HOMA-IR) with testosterone or placebo. The effect of acute (20 min) and chronic (2-day) testosterone exposure on GSIS and GLP-1 action was assessed in EndoC-βH1 at 3 testosterone concentrations (5, 10, 15nM).


GA decreased in both groups (p<0.001) and was lower in the testosterone compared with placebo (-3.4 umol/L; 95%CI:1.4-5.4, p<0.001). C-peptide, HOMA-IR and HOMA-B initially decreased (time effect, all P<0.001) but no difference due to testosterone treatment was detected. Exploratory analysis at maximal glycaemic difference between testosterone and placebo (week 66) demonstrated a non-significant reduction of C-peptide (-0.10, p=0.2), HOMA-B (-6.1, p=0.2) and HOMA-IR (-0.20, p=0.3). Acute exposure of EndoC-βH1 to 5nM, 10nM and 15nM testosterone did not increase GSIS compared with control. Testosterone, at 15nM for 2 days did not alter GSIS or GLP-1 mediated insulin secretion.


In men with pre-diabetes or early T2D, testosterone treatment reduces glycaemia in vivo without in vitro evidence of increased insulin secretion or augmentation of GLP-1 action.