Sex hormone-binding globulin levels predicted type 2 diabetes risk in women, men

Posted on September 23, 2009

Sex hormone-binding globulin levels predicted type 2 diabetes risk in women, men

Low circulating levels of sex hormone-binding globulin are a strong predictor for type 2 diabetes in both women and in men.

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Because it is uncertain whether circulating sex hormone-binding globulin levels — which are associated with insulin resistance — can predict the risk for developing type 2 diabetes, researchers performed a nested case-control study of postmenopausal women included in the Women’s Health Study who were not using hormone therapy. Three hundred fifty-nine of these women had newly diagnosed type 2 diabetes, and 359 served as controls.

Researchers then conducted a replication study that included 340 men from the Physicians’ Health Study II; 170 had newly diagnosed type 2 diabetes.

Higher plasma levels of sex hormone-binding globulin were associated with a lower risk for type 2 diabetes in women. Multivariate ORs in women were 1.00 for the first quartile of plasma levels, 0.16 for the second quartile (95% CI, 0.08-0.33), 0.04 for the third quartile (95% CI, 0.01-0.12) and 0.09 for the fourth quartile (95% CI, 0.03-0.21; P<.001 for trend).

The OR for the highest quartile of plasma levels vs. the lowest quartile in men was 0.10 (95% CI, 0.03-0.36; P<.001 for trend).

Mendelian randomization analyses revealed a predicted OR of 0.28 (95% CI, 0.13 to 0.58) for type 2 diabetes per standard deviation increase in the sex hormone-binding globulin plasma level among women; this OR was 0.29 (95% CI, 0.15-0.58) among men. The researchers wrote that this finding suggests that sex hormone-binding globulin may play a causal role in type 2 diabetes risk.

Ding EL. N Engl J Med. 2009;361:1152-1163.

Low levels of sex hormone-binding globulin are associated with the insulin resistance/metabolic syndrome because high insulin levels supress hepatic production of sex hormone-binding globulin.Therefore, it is less than suprising that higher levels of SHBG are associated with a lower risk of developing type 2 diabetes.

– David S.H. Bell, MB, FACE

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