Serum sex hormone-binding globulin is a mediator of the association between intrahepatic lipid content and type 2 diabetes: the Maastricht Study.

Autor: Simons PIHG; Department of Internal Medicine, Division of Endocrinology and Metabolic Diseases, Maastricht University Medical Centre, Maastricht, the Netherlands.; Laboratory for Metabolism and Vascular Medicine, Maastricht University, Maastricht, the Netherlands.; CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands., Valkenburg O; Department of Reproductive Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands., van de Waarenburg MPH; Laboratory for Metabolism and Vascular Medicine, Maastricht University, Maastricht, the Netherlands.; CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands., van Greevenbroek MMJ; Laboratory for Metabolism and Vascular Medicine, Maastricht University, Maastricht, the Netherlands.; CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands., Kooi ME; CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.; Department of Radiology and Nuclear Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands., Jansen JFA; Department of Radiology and Nuclear Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.; School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.; Department of Electrical Engineering, University of Eindhoven, Eindhoven, the Netherlands., Schalkwijk CG; Laboratory for Metabolism and Vascular Medicine, Maastricht University, Maastricht, the Netherlands.; CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands., Stehouwer CDA; Laboratory for Metabolism and Vascular Medicine, Maastricht University, Maastricht, the Netherlands.; CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.; Department of Internal Medicine, Division of General Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands., Brouwers MCGJ; Department of Internal Medicine, Division of Endocrinology and Metabolic Diseases, Maastricht University Medical Centre, Maastricht, the Netherlands. mcgj.brouwers@mumc.nl.; CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands. mcgj.brouwers@mumc.nl.
Jazyk: angličtina
Zdroj: Diabetologia [Diabetologia] 2023 Jan; Vol. 66 (1), pp. 213-222. Date of Electronic Publication: 2022 Sep 17.
DOI: 10.1007/s00125-022-05790-7
Abstrakt: Aims/hypothesis: Serum sex hormone-binding globulin (SHBG) has been proposed to act as a hepatokine that contributes to the extrahepatic complications observed in non-alcoholic fatty liver disease (NAFLD). However, it remains uncertain whether serum SHBG mediates the association between intrahepatic lipids (IHL) and type 2 diabetes. Therefore, we studied whether, and to what extent, serum SHBG mediates the association between IHL content and type 2 diabetes.
Methods: We used cross-sectional data from the Maastricht Study (n=1554), a population-based cohort study with oversampling of individuals with type 2 diabetes. Type 2 diabetes status was assessed by oral glucose tolerance test, and IHL content was measured using 3T Dixon MRI. Mediation analyses were performed to assess the role of serum SHBG in mediating the association between IHL content and type 2 diabetes.
Results: IHL content was significantly associated with type 2 diabetes in women and men (OR 1.08 [95% CI 1.04, 1.14] and OR 1.12 [95% CI 1.08, 1.17], respectively). Serum SHBG significantly mediated the association between IHL content and type 2 diabetes. The contribution of serum SHBG was higher in women (OR 1.04 [95% CI 1.02, 1.07]; proportion mediated 50.9% [95% CI 26.7, 81.3]) than in men (OR 1.02 [95% CI 1.01, 1.03]; proportion mediated 17.2% [95% CI 9.6, 27.6]). Repeat analyses with proxies of type 2 diabetes and adjustment for covariates did not substantially affect the results.
Conclusions/interpretation: In this large-scale population-based cohort study, serum SHBG was found to be a mediator of the association between IHL content and type 2 diabetes. These findings extend our understanding of the potential mechanisms by which NAFLD is a risk factor for type 2 diabetes, and further elaborate on the role of SHBG as a hepatokine.
(© 2022. The Author(s).)
Databáze: MEDLINE
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