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- Title
Association of sex hormone-binding globulin and free testosterone with mortality in men with type 2 diabetes mellitus.
- Authors
Tint, Aye N.; Hoermann, Rudolf; Henry Wong; Ekinci, Elif I.; MacIsaac, Richard J.; Jerums, George; Zajac, Jeffrey D.; Grossmann, Mathis
- Abstract
Objective: Low circulating testosterone levels have been associated with increased mortality in men. We hypothesized that the prognostic role of testosterone in men with type 2 diabetes mellitus (T2DM) is influenced by its carrier protein sex hormone-binding globulin (SHBG). Design: We conducted a prospective cohort study at a tertiary referral centre. Methods: In total, 531 men with T2DM presenting to a diabetes clinic in 2004-2005 were followed prospectively until death, or July 31, 2014, and a survival analysis was performed. The main outcome measure was all cause mortality. Results: Over a mean (S.D.) follow up of 7.6 years (2.6) 175 men (33%) died. In Cox proportional hazard models both higher SHBG (Hazard Ratio (HR) 1.012 (95% CI 1.002-1.022), P=0.02) and lower calculated free testosterone (cFT) (HR 0.995 (95% CI 0.993-0.998), P=0.001) were risk factors for all cause mortality independently of age, BMI, presence of macro-and microvascular disease, duration of T2DM, hemoglobin, renal function, insulin use, C-reactive protein and homeostatic model of insulin resistance. By contrast, the inverse association of total testosterone (TT) with mortality weakened after these adjustments (P=0.11). SHBG remained associated with mortality (P<0.001) both if substituted for or added to TT in the multivariable model. In the fully adjusted model, an increase of SHBG by 17.3 nmol/l (1 S.D.) increased mortality by 22% and a decrease in cFT by 81 pmol/l (1 S.D.) increased mortality by 45%. Conclusions: The association of SHBG with mortality in men with T2DM is novel. Whether SHBG acts via regulation of testosterone, has intrinsic biological roles, or is a marker of poor health requires further study.
- Subjects
PEOPLE with diabetes; PHYSIOLOGICAL effects of testosterone; PHYSIOLOGICAL effects of sex hormones; MORTALITY of men; GLOBULINS; MEDICAL referrals
- Publication
European Journal of Endocrinology, 2016, Vol 174, Issue 1, p59
- ISSN
0804-4643
- Publication type
Article
- DOI
10.1530/EJE-15-0672