RESUMO
BACKGROUND: The association between low testosterone concentration and increased risk of hyperglycemia in men has been demonstrated in observational and interventional studies. However, considering a variety of confounding factors, limited population-based studies have so far been conducted. Also, no information is available regarding the effect of testosterone on progressive development of dysglycemia. OBJECTIVE: To examine the effect of total testosterone on development of pre-diabetes/diabetes in normoglycemic middle-aged and older men. MATERIALS AND METHODS: Data were obtained from the Tehran Lipid and Glucose Study, a community-based prospective cohort of an Iranian population. Analyses were conducted on 903 normoglycemic eligible men aged 30-70 years. An illness-death model was applied to estimate the probabilities of three transitional phases of normoglycemiaâdiabetes, normoglycemiaâpre-diabetes, and pre-diabetesâdiabetes. RESULTS: Over a median follow-up of 12 years, 0.9% individuals developed diabetes. Per unit increase (ng/mL) in testosterone concentration, the transition rate from normoglycemia to pre-diabetes decreased by 6% [hazard ratios (HRs): 0.94 (95% confidence interval (CI): 0.90, 0.99)]. However, no effect for testosterone on the progression of diabetes from normoglycemia or pre-diabetes was observed [HRs: 0.79 (95% CI: 0.44, 1.41) and 0.98 (95% CI: 0.84, 1.16), respectively]. High body mass index was a strong predictor of hyperglycemia within all transitions. DISCUSSION: Independent of major confounding factors, low testosterone was associated with normoglycemia progression to pre-diabetes, but not with pre-diabetes to diabetes, which might indirectly highlight the stronger impact of other risk factors after occurrence of pre-diabetes. CONCLUSION: Low testosterone concentrations in men are associated with progression from normoglycemia to pre-diabetes, but not from pre-diabetes to diabetes.