Low total testosterone is associated with increased risk of incident type 2 Diabetes mellitus in men: Results from the Study of Health in Pomerania (SHIP)

Objective: There is increasing evidence suggesting that low total testosterone is associated with incident type 2 diabetes mellitus (T2DM) in men. However, the data so far are inconsistent regarding the direction of association. The aim of our study was to investigate the longitudinal association between low total testosterone and the risk of incident T2DM in men covering a wide age range with data from SHIP. Methods: Of 2,117 men aged 20–79at baseline, 1,589 were followed up 5 years later. Low total testosterone at baseline determined by <10th percentile (10-year age-strata) were used as a risk factor for incident T2DM at follow up. The theory of directed acyclic graphs was applied to select confounders for adjustment. According to our graph, age, waist circumference, and smoking belonged to the minimally sufficient adjustment set. For additional analyses, established clinically thresholds for low total testosterone (<8 nmol/l, <10 nmol/l, <12 nmol/l) were used. To evaluate for potential nonresponse-bias, drop out weights were used in sensitivity analysis. Results: From 1,339 eligible men, 68 (5.1%) developed T2DM. Men with low total testosterone had an increased risk of developing T2DM (odds ratio [OR] 3.4, 95% CI 1.9–6.1), even after adjustment OR 3.0; (95% CI 1.6–5.7). Low baseline total testosterone, regardless of the definition used, was associated with a considerably increased odds of incident T2DM. Recalculated weighted models revealed almost identical estimates indicating no relevant non-response bias. The comparison of crude and adjusted incidence odds ratios revealed that the confounders produced some overestimation of the strength of association. Discussion: Our prospective findings suggest that low total testosterone is associated with incident T2DM in men and might represent a biomarker that might causally be involved in the risk of T2DM. This underlines the importance of measuring total testosterone as the predominant male sex hormone.