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Context: Previous studies have demonstrated associations of endogenous thyroid hormones with diabetes; less is known about stages of diabetes development at which they are operative, mechanisms of associations, and the role of the hypothalamic-pituitary-thyroid axis. Objective: This study examined associations of thyroid hormones with incident prediabetes and diabetes and with changes in glycemic traits in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), the largest cohort of Hispanic/Latino adults with diverse backgrounds in the United States. Methods: The study includes 592 postmenopausal euthyroid women and 868 euthyroid men aged 45 to 74 years without diabetes at baseline participating in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Baseline hormones included thyrotropin (TSH), free thyroxine (FT4), total triiodothyronine (T3), and indices calculated from thyroid hormones evaluating pituitary sensitivity to thyroid hormone. Transitions to diabetes and prediabetes, and changes in glycemic traits determined at the 6-year follow-up visit, were examined using multivariable Poisson and linear regressions. Results: Among women, T3 (incident rate ratio [IRR] = 1.65; 95% CI, 1.22-2.24; P = .001) and TSH (IRR = 2.09; 95% CI, 1.01-4.33; P = .047) were positively, while FT4 (IRR = 0.59; 95% CI, 0.39-0.88; P = .011) was inversely, associated with transition from prediabetes to diabetes. Among men, the T3/FT4 ratio was positively associated with transition from normoglycemia to prediabetes but not from prediabetes to diabetes. Indices measuring sensitivity of the pituitary to thyroid hormone suggested increased sensitivity in men who transitioned from prediabetes to diabetes. Conclusion: Positive associations in women of T3 and TSH and inverse associations of FT4, as well as inverse associations of thyroid indices in men with transition from prediabetes to diabetes, but not from normoglycemia to diabetes, suggest decreased pituitary sensitivity to thyroid hormones in women and increased sensitivity in men later in the development of diabetes.
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BACKGROUND: Hormones are linked to cardiometabolic diseases and may be impacted by acculturation though multiple mechanisms. We evaluated associations of Hispanic/Latino background and acculturation with levels of sex- and thyroid-related hormones and the potential mediating effect of adiposity, lifestyle factors, and sleep apnea syndrome on these associations. METHODS: We studied 1789 adults, aged 45-74, from a sub-cohort of the Hispanic Community Health Survey/Study of Latinos. Peri/pre-menopausal women and individuals on medications related to hormones were excluded. Our study assessed eleven sex- and thyroid-related hormones, Hispanic/Latino background, and five acculturation measures. Associations were assessed using multivariable linear and logistic regression adjusted for survey design and confounding variables. We explored potential mediation using a path analysis. RESULTS: In postmenopausal women, acculturation score-MESA was associated with decreased thyroid-stimulating hormone (ß = - 0.13;95%CI = - 0.22, - 0.03) while age at immigration greater than the median (vs US-born) was associated with decreased (ß = - 14.6; 95%CI = - 28.2, - 0.99) triiodothyronine (T3). In men, language acculturation and acculturation score-MESA were associated with increased estradiol and sex hormone-binding globulin (SHBG) while age at immigration greater and lesser than the median (vs US-born) was associated with decreased SHBG. Hispanic/Latino background (Mexicans as reference) were selectively associated with sex- and thyroid-related hormone levels in both sexes. Current smoking and sleep apnea syndrome partially mediated the association of Cuban and Puerto Rican heritage (vs Mexican) with T3 levels in men and postmenopausal women, respectively. CONCLUSION: Selected acculturation measures were associated with thyroid-related hormones in postmenopausal women and sex-related hormones in men. Understanding the mechanisms involved in the relationship of acculturation and Hispanic/Latino background with hormones warrants additional investigation.
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Previous studies demonstrated associations of endogenous sex hormones with diabetes. Less is known about their dynamic relationship with diabetes progression through different stages of the disease, independence of associations, and role of the hypothalamic-pituitary gonadal axis. The purpose of this analysis was to examine relationships of endogenous sex hormones with incident diabetes, prediabetes, and diabetes traits in 693 postmenopausal women and 1015 men aged 45 to 74 years without diabetes at baseline participating in the Hispanic Community Health Study/Study of Latinos and followed for 6 years. Baseline hormones included estradiol, luteinizing hormone (LH), follicle stimulating hormone (FSH), sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), and, in men, testosterone and bioavailable testosterone. Associations were analyzed using multivariable Poisson and linear regressions. In men, testosterone was inversely associated with conversion from prediabetes to diabetes (incidence rate ratio [IRR] for 1 SD increase in testosterone: 0.821; 95% CI, 0.676, 0.997; P = 0.046), but not conversion from normoglycemia to prediabetes. Estradiol was positively associated with increase in fasting insulin and homeostatic model assessment of insulin resistance. In women, SHBG was inversely associated with change in glycosylated hemoglobin, postload glucose, and conversion from prediabetes to diabetes (IRR = 0.62; 95% CI, 0.44, 0.86, P = 0.005) but not from normoglycemia to prediabetes. Relationships with other hormones varied across glycemic measures. Stronger associations of testosterone and SHBG with transition from prediabetes to diabetes than from normoglycemic to prediabetes suggest they are operative at later stages of diabetes development. Biologic pathways by which sex hormones affect glucose homeostasis await future studies.
