The role of sex hormone-binding globulin (SHBG), testosterone, and other sex steroids, on the development of type 2 diabetes in a cohort of community-dwelling middle-aged to elderly men
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Contrasting findings exist regarding the association between circulating sex hormone-binding globulin (SHBG) and testosterone levels and type 2 diabetes (T2D) in men. We examined prospective associations of SHBG and sex steroids with incident T2D in a cohort of community-dwelling men.
Participants were from a cohort study of community-dwelling (n = 2563), middle-aged to elderly men (35–80 years) from Adelaide, Australia (the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study). The current study included men who were followed for 5 years and with complete SHBG and sex steroid levels (total testosterone (TT), dihydrotestosterone (DHT) and oestradiol (E2)), but without T2D at baseline (n = 1597). T2D was identified by either self-report, fasting glucose (≥ 7.0 mmol/L), HbA1c (≥ 6.5%/48.0 mmol/mol), and/or prescriptions for diabetes medications. Logistic binomial regression was used to assess associations between SHBG, sex steroids and incident T2D, adjusting for confounders including age, smoking status, physical activity, adiposity, glucose, triglycerides, symptomatic depression, SHBG and sex steroid levels.
During an average follow-up of 4.95 years, 14.5% (n = 232) of men developed new T2D. Multi-adjusted models revealed an inverse association between baseline SHBG, TT, and DHT levels, and incident T2D (odds ratio (OR) = 0.77, 95% CI [0.62, 0.95], p = 0.02; OR 0.70 [0.57, 0.85], p < 0.001 and OR 0.78 [0.63, 0.96], p = 0.02), respectively. However, SHBG was no longer associated with incident T2D after additional adjustment for TT (OR 0.92 [0.71, 1.17], p = 0.48; TT in incident T2D: OR 0.73 [0.57, 0.92], p = 0.01) and after separate adjustment for DHT (OR 0.83 [0.64, 1.08], p = 0.16; DHT in incident T2D: OR 0.83 [0.65, 1.05], p = 0.13). There was no observed effect of E2 in all models of incident T2D.
In men, low TT, but not SHBG and other sex steroids, best predicts the development of T2D after adjustment for confounders.
KeywordsSex hormone-binding globulin Testosterone Men’s health Type 2 diabetes
Authors thank the MAILES investigators for their contributions to the study. Particular thanks are extended to Professor Alicia J. Jenkins and Dr. Andrzej S. Januszewski for all their support. The authors also acknowledge Siemens Healthcare for providing the immunoassay kits for all Immulite assays. Finally, thanks are extended to our participants and their families for their invaluable contributions.
Study concept and design: GW, RA, AT; Acquisition of funding: GW, RA, AT; Acquisition of data: PG, SM; Statistical analysis: PG, SA, AV; Interpretation of data: All authors. Drafting of the manuscript: PG, SA, GW; Critical revision of the manuscript for important intellectual content: All authors. All authors have approved the final article.
This work was supported by the National Health and Medical Research Council of Australia (NHMRC Project Grant #627227, 2010–2012).
Compliance with ethical standards
Conflict of interest
LH, AV, AT, and PO have nothing to declare. PG was supported by an Australian Government Research Training Program Scholarship and Freemasons Foundation Centre for Men’s Health HDR supplementary scholarship. SM was supported by a NHMRC Early Career Fellowship. RA has received funding from the ResMed Foundation, and nonfinancial support from Embla Systems, Broomfield, Colorado. GW has received research support for investigator initiated projects from Bayer Schering, Eli Lilly, ResMed Foundation, Itamar, Siemens, Weight watchers, Meat and Livestock Australia; Clinical trials for Roche, Pfizer, Astra Zeneca, Takeda, Boehringer, BMS, Amgen, Johnson & Johnson, MSD, GSK, Lawley; Lecture fees from Roche, AbbVie, Amgen, Novo Nordisk, Merck, and Besins; Paid consultant to Elsevier and Lawley Pharmaceuticals.
This study complies with the ethical standards outlined in the Australian Code for the Responsible Conduct of Research from the National Health and Medical Research Council. Ethics approval was obtained through the Royal Adelaide Hospital and The Queen Elizabeth Hospital Research Ethics Committees.
Written informed consent was provided by each of the eligible participants, who signed in-clinic
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