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Low SHBG strongly predicts risk for Type 2 diabetes

From Endocrinology Update:

Low levels of the sex hormone-binding globulin are strongly related to an increased risk of type 2 diabetes, researchers report.

Published online in the New England Journal of Medicine, the study found that women with the lowest levels of SHBG were up to 91% more likely to develop diabetes than those with the highest levels. Similarly, in men with the lowest levels the risk was increased by 90% (p < 0.001 for both).

The case controlled study analysed data from 718 postmenopausal women participating in the Women’s Health study who were not using hormone therapy.

Half of the women had newly diagnosed type 2 diabetes and half were matched controls. The researchers then performed a replication study involving 170 diabetic men and 170 control men who were enrolled in the Physicians' Health Study II.

The researchers measured plasma levels of sex hormone–binding globulin and two polymorphisms of the SHBG gene.

With each standard-deviation decrease in SHBG levels, the risk of diabetes increased by 72% in women and by 71% in men, which the authors said suggested that SHBG "may have a causal role in the risk of type 2 diabetes."

Carriers of a variant allele of the SHBG single-nucleotide polymorphism rs6259 had 10% higher sex hormone–binding globulin levels (P=0.005), and carriers of an rs6257 variant had 10% lower plasma levels (P=0.004), the researchers reported.

"These strong and consistent findings…support the notion that SHBG may play an important role in the development of type 2 diabetes at both the genomic and the phenotypic levels and that SHBG could be an important target in stratification for the risk of type 2 diabetes and early intervention," the authors concluded.

Posted: 8/10/2009 2:34:00 PM

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