Abstract

Objective: Contrasting findings exist regarding the associations between circulating sex hormone-binding globulin (SHBG) and total testosterone (TT) with type 2 diabetes (T2D) and cardiovascular diseases (CVD) in men. We examined prospective associations of SHBG and TT with incident T2D and CVD, in a cohort of community-dwelling men. Methods: Participants were aged 35 years and over at enrolment (n=2563) and followed for an average of 4.95 years. This analysis included men without T2D (1597) or CVD (1492) at baseline, and with fasted morning serum SHBG (chemiluminescent immunoassay) and TT (LCMSMS) at both time points, and without meds affecting TT or SHBG. T2D was identified by either self-report, fasting glucose (≥7.0 mmol/L), HbA1c (≥ 6.5%) and/or prescriptions for diabetes medications. CVD was ascertained by self-report and/or hospital data linkage. Logistic binomial regressions were used to assess associations between SHBG and incident T2D & CVD, adjusting for self-reported psycho-social, demographic and health status and related behavioural factors; measured waist circumference, HBA1c and plasma glucose, triglycerides, high-sensitivity C-reactive protein. Sensitivity analyses assessed mediation effects of anxiety, sleep duration, shift work ≥3years, and obstructive sleep apnoea (OSA). Results: During an average follow-up of 4.95 years, 14.5% (n=232) and 6.7% (n=101) of men developed T2D and CVD, respectively. Baseline TT was independently associated with incident T2D (odds ratio (OR) =0.72, 95%CI= [0.57, 0.92], P=0.01). An inverse association of baseline SHBG levels with incident T2D (OR=0.77 [0.62, 0.95], P=0.02), was insignificant after adjustment for TT (OR=0.91 [0.71, 1.17], P=0.48 for SHBG. Baseline TT (OR=0.71 [0.52, 0.98], P=0.04) and SHBG (OR=1.54 [1.15, 2.06], P=0.003) were independently associated with incident CVD. A decrease in TT between time points was associated with incident T2D (OR=0.81 [0.68, 0.97], P=0.02) and CVD (OR=0.72 [0.56,0.92], P=0.01). There was no association between ΔSHBG and incident T2D and CVD. In the sensitivity analyses there was evidence for mediation effects of shift-work on the association of TT, but not SHBG with CVD (both baseline &change models), and of longer sleep duration, OSA and shift work on the association of TT with T2D (change TT model only). Conclusions Shift-work mediates associations of TT with CVD. All sleep parameters had mediation effects on the association of decreasing TT with T2D. Funding: NH&MRC Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

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