Sex hormone-binding globulin as an independent predictor of incident type 2 diabetes mellitus in men

J Gerontol A Biol Sci Med Sci. 2010 May;65(5):503-9. doi: 10.1093/gerona/glq002. Epub 2010 Jan 27.


Background: Low levels of sex hormone-binding globulin (SHBG) and total testosterone (T) in men have been associated with increased risk of type 2 diabetes mellitus (T2DM). As total T and SHBG levels are highly correlated, we determined whether SHBG influences the risk of T2DM through T or whether SHBG is an independent predictor of T2DM.

Methods: Longitudinal analyses were conducted on men participating in the Massachusetts Male Aging Study, a population-based study of men aged 40-70 years. Of 1,709 men enrolled in 1987-1989, 1,156 were evaluated 7-10 years later and 853 after 15-17 years. Analyses were restricted to 1,128 men without T2DM at baseline.

Results: Ninety new cases of T2DM were identified. After adjustment for age, body mass index, hypertension, smoking, alcohol intake, and physical activity, the hazard ratio (HR) for incident T2DM was 2.0 for each 1 SD decrease in SHBG (95% confidence interval [CI], 1.42-2.82, p < .001) and 1.29 for each 1 SD decrease in total T (95% CI, 1.01-1.66, p = .04). Free T was not associated with T2DM (HR = 1.03, 95% CI, 0.81-1.31, p = .79). The strong association of T2DM risk with SHBG persisted even after additional adjustment for free T (HR = 2.04, 95% CI, 1.44-2.87, p < .0001) or total T (HR = 1.95, 95% CI, 1.34-2.82, p = .0004).

Conclusions: SHBG is an independent predictor of incident T2DM even after adjusting for free T or total T. Free T is not significantly associated with T2DM. SHBG may contribute to the risk of T2DM through nonandrogenic mechanisms, which should be investigated as they may provide novel targets for diabetes prevention.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aging / blood
  • Aging / physiology
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Regression Analysis
  • Risk Factors
  • Sex Hormone-Binding Globulin / analysis*
  • Testosterone / blood


  • Sex Hormone-Binding Globulin
  • Testosterone