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

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