Lower serum testosterone is independently associated with insulin resistance in non-diabetic older men: the Health In Men Study

Abstract

Insulin resistance is associated with metabolic syndrome and type 2 diabetes, representing a risk factor for cardiovascular disease. This relationship may be modulated to some extent by age-related changes in sex hormone status. We examined whether lower testosterone or sex hormone-binding globulin (SHBG) levels in older men are associated with insulin resistance independently of measures of central obesity. Cross-sectional analysis of 2470 community-dwelling non-diabetic men aged > or = 70 years. Age, body mass index (BMI) and waist circumference were measured. Early morning sera were assayed for total testosterone, SHBG, LH and insulin levels. Free testosterone was calculated using mass action equations, and insulin resistance was assessed using a homeostatic model (HOMA2-IR). Total testosterone, free testosterone and SHBG declined progressively across increasing quintiles of HOMA2-IR (all P<0.001) and correlated inversely with log HOMA2-IR (r=-0.27, -0.14 and -0.24 respectively, all P<0.001). After adjusting for age, BMI, waist circumference, high-density lipoprotein and triglyceride levels, total testosterone was independently associated with log HOMA2-IR (beta=0.05, P<0.001), while SHBG was not. Serum total testosterone <8 nmol/l was associated with HOMA2-IR in the highest quintile (odds ratio (OR) 1.67, 95% confidence interval (CI) 1.02-2.73) as was total testosterone > or = 8 and <15 nmol/l (OR 1.29, 95% CI 1.03-1.63). In older men, lower total testosterone is associated with insulin resistance independently of measures of central obesity. This association is seen with testosterone levels in the low to normal range. Further studies are needed to evaluate interventions that raise testosterone levels in men with reduced insulin sensitivity.