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Sex differences, endogenous sex-hormone hormones, sex-hormone binding globulin, and exogenous disruptors in diabetes and related metabolic outcomes.
Liu, S, Sun, Q
Journal of diabetes. 2018;(6):428-441
Abstract
In assessing clinical and pathophysiological development of type 2 diabetes (T2D), the critical role of the sex steroids axis is underappreciated, particularly concerning the sex-specific relationships with many relevant cardiometabolic outcomes. In this issue of the Journal of Diabetes, we provide a comprehensive overview of these significant associations of germline variants in the genes governing the sex steroid pathways, plasma levels of steroid hormones, and sex hormone-binding globulin (SHBG) with T2D risk that have been observed in many clinical and high-quality large prospective cohorts of men and women across ethnic populations. Together, this body of evidence indicates that sex steroids and SHBG should be routinely incorporated into clinical characterization of T2D patients, particularly in screening prediabetic patients, such as those with metabolic syndrome, using plasma levels of SHBG. Given that several germline mutations in the SHBG gene have also been directly related to both plasma concentrations of SHBG and clinical manifestation of T2D, targeting signals in the sex steroid axis, particularly SHBG, may have significant utility in the prediction and treatment of T2D. Further, many of the environmental endocrine disrupting chemicals may exert their potential adverse effects on cardiometabolic outcomes via either estrogenic or androgenic signaling pathways, highlighting the importance of using the sex steroids and SHBG as important biochemical markers in both clinical and population studies in studying sex-specific mechanisms in the pathogenesis of T2D and its complications, as well as the need to equitably allocate resources in studying both men and women.
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Relationship between dietary carbohydrates intake and circulating sex hormone-binding globulin levels in postmenopausal women.
Huang, M, Liu, J, Lin, X, Goto, A, Song, Y, Tinker, LF, Chan, KK, Liu, S
Journal of diabetes. 2018;(6):467-477
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Abstract
BACKGROUND Low circulating levels of sex hormone-binding globulin (SHBG) have been shown to be a direct and strong risk factor for type 2 diabetes, cardiovascular diseases, and hormone-dependent cancers, although the relationship between various aspects of dietary carbohydrates and SHBG levels remains unexplored in population studies. METHODS Among postmenopausal women with available SHBG measurements at baseline (n = 11 159) in the Women's Health Initiative, a comprehensive assessment was conducted of total dietary carbohydrates, glycemic load (GL), glycemic index (GI), fiber, sugar, and various carbohydrate-abundant foods in relation to circulating SHBG levels using multiple linear regressions adjusting for potential covariates. Linear trend was tested across quartiles of dietary variables. Benjamini and Hochberg's procedure was used to calculate the false discovery rate for multiple comparisons. RESULTS Higher dietary GL and GI (both based on total and available carbohydrates) and a higher intake of sugar and sugar-sweetened beverages were associated with lower circulating SHBG concentrations (all P trend < 0.05; Q -values = 0.04,0.01, 0.07, 0.10, 0.01, and <0.0001, respectively). In contrast, women with a greater intake of dietary fiber tended to have elevated SHBG levels (P trend = 0.01, Q -value = 0.04). There was no significant association between total carbohydrates or other carbohydrate-abundant foods and SHBG concentrations. CONCLUSIONS The findings suggest that low GL or GI diets with low sugar and high fiber content may be associated with higher serum SHBG concentrations among postmenopausal women. Future studies investigating whether lower GL or GI diets increase SHBG concentrations are warranted.