Acta Diabetologica (2018) 55:861–872
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
· Sean A. Martin
· Leonie K. Heilbronn
· Andrew D. Vincent
· Anne W. Taylor
Robert J. T. Adams
· Peter D. O’Loughlin
· Gary A. Wittert
Received: 22 March 2018 / Accepted: 18 May 2018 / Published online: 29 May 2018
© Springer-Verlag Italia S.r.l., part of Springer Nature 2018
Aims 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.
Methods 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 cur-
rent 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.
Results 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.
Conclusions In men, low TT, but not SHBG and other sex steroids, best predicts the development of T2D after adjustment
Keywords Sex hormone-binding globulin · Testosterone · Men’s health · Type 2 diabetes
Managed by Massimo Porta.
Electronic supplementary material The online version of this
article (https ://doi.org/10.1007/s0059 2-018-1163-6) contains
supplementary material, which is available to authorized users.
* Gary A. Wittert
Adelaide Medical School, University of Adelaide, Adelaide,
Freemasons Foundation Centre for Men’s Health, Discipline
of Medicine, University of Adelaide, Adelaide, SA 5000,
South Australian Health and Medical Research Institute
(SAHMRI), Adelaide, SA, Australia
Population Research and Outcomes Studies, University
of Adelaide, Adelaide, SA, Australia
The Health Observatory, University of Adelaide, Queen
Elizabeth Hospital, Woodville, SA, Australia
Chemical Pathology, SA Pathology, Adelaide, SA, Australia