A low serum testosterone concentration has been reported to be an independent risk factor for incident type 2 diabetes (T2D).
In this study, we aimed to determine the relationship between testosterone and incident T2D risk across the range of testosterone concentrations and interactions with WC, age, and HbA1c in a longitudinally followed cohort of middle aged and older men.
Men without T2D, cancer, testosterone treatment, and baseline and 5-yr follow-up assessments in the Men Androgen Inflammation, Lifestyle, and Environment Study (MAILES) Cohort were included. The MAILES cohort comprises 2563, community dwelling men in Adelaide, aged 35-85 years at enrolment. Multivariable logistic regression assessed the association between baseline testosterone and incident T2D risk with and without pairwise interactions and non-linear associations, adjusting for baseline age, WC, HbA1c, family history, smoking, alcohol intake, self-reported physical activity and medication affecting T2D risk. Incident diabetes was defined as HbA1c ≥6.5%, medication to lower blood glucose, or self-reported diagnosis of T2D.
The analysis set of 1315 men included 110 cases of incident T2D (8.4%). A testosterone concentration up to 20 nmol/L (577 ng/dL) at baseline was independently inversely associated with 5-year-incident T2D (OR=0.93, 95%CI=[0.89, 0.98], p=0.003). There were no detectable interactions between testosterone and either WC (p = 0.72), or HbA1c (p=0.38). There was a strong interaction between testosterone and age (p = 0.001), with a testosterone effect in men <65 years (OR=0.85, 95%CI=[0.81, 0.92], p<0.001) and not in men >65 years (OR=1.03, 95%CI=[0.95, 1.11], p=0.51). In both the entire cohort and in men <65 years there was no evidence of non-linearity, with higher testosterone concentrations being continuously associated with lower T2D risk. The results were similar after adjustment for SHBG
Higher baseline testosterone was protective against incident T2D independent of other risk factors at all levels of testosterone in men aged ≤65.