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Raeisi-Dehkordi, H.* ; Amiri, M.* ; Rathmann, W.* ; Zeller, T.* ; Adamski, J. ; Bano, A.* ; van der Schouw, Y.T.* ; Thorand, B. ; Muka, T.* ; Nano, J.

Sex hormone-binding globulin may explain sex differences for glucose homeostasis and incidence of type 2 diabetes: The KORA study.

Eur. J. Epidemiol., DOI: 10.1007/s10654-024-01136-2 (2024)
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Research has indicated that sex hormone-binding globulin (SHBG) is associated with glucose homeostasis and may play a role in the etiology of type 2 diabetes (T2D). While it is unclear whether SHBG may mediate sex differences in glucose control and subsequently, incidence of T2D. We used observational data from the German population-based KORA F4 study (n = 1937, mean age: 54 years, 41% women) and its follow-up examination KORA FF4 (median follow-up 6.5 years, n = 1387). T2D was initially assessed by self-report and validated by contacting the physicians and/ or reviewing the medical charts. Mediation analyses were performed to assess the role of SHBG in mediating the association between sex (women vs. men) and glucose- and insulin-related traits (cross-sectional analysis) and incidence of T2D (longitudinal analysis). After adjustment for confounders, (model 1: adjusted for age; model 2: model 1 + smoking + alcohol consumption + physical activity), women had lower fasting glucose levels compared to men (β = -4.94 (mg/dl), 95% CI: -5.77, -4.11). SHBG levels were significantly higher in women than in men (β = 0.47 (nmol/l), 95% CI:0.42, 0.51). Serum SHBG may mediate the association between sex and fasting glucose levels with a proportion mediated (PM) of 30% (CI: 22-41%). Also, a potential mediatory role of SHBG was observed for sex differences in incidence of T2D (PM = 95% and 63% in models 1 and 2, respectively). Our novel findings suggest that SHBG may partially explain sex-differences in glucose control and T2D incidence.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Glycemic Control ; Mediation Analysis ; Sex Differences ; Sex Hormone-binding Globulin ; Type 2 Diabetes; Gender-differences; Mediation Analysis; Shbg Levels; Women; Risk; Associations; Obesity; Mellitus; Insulin; Impact
ISSN (print) / ISBN 0393-2990
e-ISSN 1573-7284
Journal European Journal of Epidemiology
Publisher Springer
Publishing Place Van Godewijckstraat 30, 3311 Gz Dordrecht, Netherlands
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Institute of Experimental Genetics (IEG)
Grants Swiss National Science Foundation under the "Spirit grant" (SNSF)
State of Bavaria
Helm-holtz Zentrum Munchen - German Research Center for Environmental Health - German Federal Ministry of Education and Research (BMBF)