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.
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.
Authors: J F Sallis; W L Haskell; P D Wood; S P Fortmann; T Rogers; S N Blair; R S Paffenbarger Journal: Am J Epidemiol Date: 1985-01 Impact factor: 4.897
Authors: Chris J Malkin; Peter J Pugh; Richard D Jones; Dheeraj Kapoor; Kevin S Channer; T Hugh Jones Journal: J Clin Endocrinol Metab Date: 2004-07 Impact factor: 5.958
Authors: David E Laaksonen; Leo Niskanen; Kari Punnonen; Kristiina Nyyssönen; Tomi-Pekka Tuomainen; Veli-Pekka Valkonen; Riitta Salonen; Jukka T Salonen Journal: Diabetes Care Date: 2004-05 Impact factor: 19.112
Authors: J J Corrales; R M Burgo; B Garca-Berrocal; M Almeida; I Alberca; J M González-Buitrago; A Orfao; J M Miralles Journal: Metabolism Date: 2004-05 Impact factor: 8.694
Authors: Manthos G Giannoulis; Finbarr C Martin; K Sreekumaran Nair; A Margot Umpleby; Peter Sonksen Journal: Endocr Rev Date: 2012-03-20 Impact factor: 19.871
Authors: Andre B Araujo; Julia M Dixon; Elizabeth A Suarez; M Hassan Murad; Lin T Guey; Gary A Wittert Journal: J Clin Endocrinol Metab Date: 2011-08-03 Impact factor: 5.958
Authors: Anne K Monroe; Adrian S Dobs; Xiaoqiang Xu; Frank J Palella; Lawrence A Kingsley; Mallory D Witt; Todd T Brown Journal: J Acquir Immune Defic Syndr Date: 2011-10-01 Impact factor: 3.731
Authors: T G Travison; W V Zhuang; K L Lunetta; D Karasik; S Bhasin; D P Kiel; A D Coviello; J M Murabito Journal: Clin Endocrinol (Oxf) Date: 2013-06-27 Impact factor: 3.478
Authors: Grace Huang; Karol M Pencina; Zhuoying Li; Shehzad Basaria; Shalender Bhasin; Thomas G Travison; Thomas W Storer; S Mitchell Harman; Panayiotis Tsitouras Journal: J Clin Endocrinol Metab Date: 2018-04-01 Impact factor: 5.958