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Member Research & Reports

Member Research & Reports

Brown Researchers Review Sex Differences in Diabetes and Metabolic Outcomes

Obesity has long been known to be associated with higher androgen levels and higher testosterone-to-estradiol ratios in women. Increasing evidence now indicates that there are sex-differences in how obesity links to the development of cardiometabolic outcomes such as type 2 diabetes, and the pathways may involve sex-steroid hormones and adipocyte-derived hormones and cytokines. Until recently, much of the evidence supporting the roles of sex-steroid hormones in type 2 diabetes development comes from animal experiments and clinical observations. Nevertheless, recent large and high quality prospective cohorts have directly associated endogenous sex-steroid hormones and sex-steroids binding protein (SHBG) with type 2 diabetes incidence in both women and men across multiple ethnic populations.

[Photo: Dr. Simin Liu]

The purpose of this paper, led by Dr. Simin Liu, professor of epidemiology and director of the Center for Global Cardiometabolic Health, was to review the current evidence regarding these biomarkers and their utility in clinical and public health management of type 2 diabetes. Taken as a whole, this body of evidence indicates that sex-steroids and SHBG should be routinely incorporated into clinical characterization of type 2 diabetes patients particularly in screening pre-diabetic patients using plasma levels of SHBG. Given that several germline mutations in the SHBG gene have also been directly related to both plasma levels of SHBG and clinical manifestation of type 2 diabetes, targeting signals in the sex-steroids axis such as SHBG may have significant utility in the prediction and treatment of type 2 diabetes.

The authors conclude that, collectively, these finding may help us to better characterize the complex pathogenesis of type 2 diabetes that pertains to the environmental exposure-sex hormone-insulin sensitivity axis. It also may have immediate and important implications for the potential utility of plasma sex hormone biomarkers in identifying populations with high diabetes risk. The significant gender dimorphisms highlight the need to focus on studying gender-specific mechanisms in the etiology of chronic diseases related to type 2 diabetes, and to equitably allocate resources in studying diseases in both men and women.

This study was published in Journal of Diabetes (ahead of print).

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