Review Article
Sex differences, endogenous sex-hormone hormones, sex-hormone binding globulin, and exogenous disruptors in diabetes and related metabolic outcomes
性别差异、内源性性激素、性激素结合球蛋白以及外源性干扰因子对糖尿病及其相关代谢结果的影响
Simin Liu,
Qi Sun,
Corresponding Author
Simin Liu
Department of Endocrinology, Guangdong General Hospital/Guangdong Academy of Medical Sciences, Guangzhou, China
Departments of Epidemiology, Brown University, Providence, Rhode Island, USA
Departments of Medicine, Brown University, Providence, Rhode Island, USA
Center for Global Cardiometabolic Health, Brown University, Providence, Rhode Island, USA
Departments of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
CorrespondenceSimin Liu, Center for Global Cardiometabolic Health (CGCH) and Department of Epidemiology, Brown University, 121 South Main St, Providence, RI 20906, USA. Tel: +1 401 863 5247 Fax: +1 401 863 3713 Email: [email protected]Search for more papers by this authorQi Sun
Departments of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
Search for more papers by this authorSimin Liu,
Qi Sun,
Corresponding Author
Simin Liu
Department of Endocrinology, Guangdong General Hospital/Guangdong Academy of Medical Sciences, Guangzhou, China
Departments of Epidemiology, Brown University, Providence, Rhode Island, USA
Departments of Medicine, Brown University, Providence, Rhode Island, USA
Center for Global Cardiometabolic Health, Brown University, Providence, Rhode Island, USA
Departments of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
CorrespondenceSimin Liu, Center for Global Cardiometabolic Health (CGCH) and Department of Epidemiology, Brown University, 121 South Main St, Providence, RI 20906, USA. Tel: +1 401 863 5247 Fax: +1 401 863 3713 Email: [email protected]Search for more papers by this authorQi Sun
Departments of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
Search for more papers by this authorAbstract
enIn 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.
摘要
zh目前在评估2型糖尿病的临床以及病理生理发展过程时, 有关性类固醇轴的关键作用往往被低估了, 特别是许多与心脏代谢结果相关的性别特异性的关系。在本期Journal of Diabetes杂志中, 我们全面概述了许多已经在临床上以及在高质量的大规模、前瞻性、跨种族人群的男性及女性队列研究中观察到的结果, 涉及到了调节性类固醇激素通路基因的种系变异、血浆类固醇激素以及性激素结合球蛋白(sex hormone-binding globulin, SHBG)水平与2型糖尿病风险之间的显著相关性。这些证据表明应该常规将性类固醇激素以及SHBG纳入到2型糖尿病患者的临床特征中, 特别是在筛查糖尿病前期患者时, 例如可以用血浆SHBG水平来筛查合并代谢综合征的患者。鉴于SHBG基因中的一些种系突变也与血浆SHBG浓度以及2型糖尿病的临床表现直接相关, 因此瞄准性类固醇轴信号, 尤其是SHBG, 对于2型糖尿病的预测以及治疗可能具有重要作用。此外, 许多环境内分泌干扰性化学物质经由雌激素或雄激素信号通路可能会对心脏代谢结果产生潜在的不利影响, 这突显了在临床以及人群研究中, 研究2型糖尿病及其并发症的性别特异性发病机制时, 将性类固醇与SHBG作为重要生化标志物的重要性, 以及在男性与女性研究中公平分配资源的必要性。
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