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Potential Mediating Role of Iron Biomarkers in the Association of Sex With Glucose, Insulin, and Type 2 Diabetes Publisher



Khatami F1, 2, 3 ; Lange T4 ; Groothof D5 ; Ahanchi NS1, 2, 6 ; Quezadapinedo HG7 ; Raeisidehkordi H1, 8 ; De Borst MH5 ; Vidal PM6 ; Sailesh M9, 10 ; Prabhakaran D9, 10 ; Bano A1, 11 ; Bakker SJL5 ; Muka T12 ; Eisenga MF5
Authors
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Authors Affiliations
  1. 1. Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, 3012, Switzerland
  2. 2. Graduate School for Health Sciences, University of Bern, Bern, 3012, Switzerland
  3. 3. Community Medicine Department, Tehran University of Medical Sciences, Tehran, 1417613151, Iran
  4. 4. Department of Public Health, Section of Biostatistics, University of Copenhagen, Copenhagen, DK-1353, Denmark
  5. 5. Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, 9713 GZ, Netherlands
  6. 6. Department of Medicine, Internal Medicine, Lausanne University Hospital, University of Lausanne, Lausanne, 1011, Switzerland
  7. 7. The Generation R Study Group, University Medical Center Rotterdam, Rotterdam, 3000 CA, Netherlands
  8. 8. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, 3584 CX, Netherlands
  9. 9. Centre for Chronic Conditions and Injuries (CCCI), Public Health Foundation of India, Delhi, 110070, India
  10. 10. Centre for Chronic Disease Control (CCDC), Delhi, 110016, India
  11. 11. Department of Cardiology, Bern University Hospital, University of Bern, Bern, 3010, Switzerland
  12. 12. Epistudia, Bern, 3008, Switzerland

Source: Journal of the Endocrine Society Published:2024


Abstract

Context: Sex-specific prevalence and incidence of type 2 diabetes (T2D) have been reported, but the underlying mechanisms are uncertain. Objective: In this study, we aimed to investigate whether iron biomarkers mediate the association between biological sex and glucose metabolism and the incidence of T2D. Methods: We used data from the general population enrolled in the prospective Prevention of REnal and Vascular ENd-stage Disease study in Groningen, The Netherlands. We measured ferritin, transferrin saturation (TSAT), hepcidin, soluble transferrin receptor (sTfR), fasting plasma glucose (FPG), fasting plasma insulin (FPI) levels, and incidence of T2D. We used multivariable regression and mediation analyses to investigate our hypothesis. All iron biomarkers, FPG, and FPI were log-transformed. Results: The mean (SD) age of the 5312 (51.3% female) individuals was 52.2 (11.6) years. Compared with males, females had lower FPG (β = -.01; 95% CI -0.02, -0.01) and FPI (β = -.03; 95% CI -0.05, -0.02) levels. Ferritin, hepcidin, and sTfR showed potential mediating effects on the association between sex and FPG, 21%, 5%, and 7.1%, respectively. Furthermore, these variables mediated 48.6%, 5.7%, and 3.1% of the association between sex and FPI, respectively. Alternatively, TSAT had a suppressive mediating role in the association of sex with FPG and FPI. The incidence of T2D was lower in females than in males (hazard ratio 0.58; 95% CI 0.44, 0.77), with 19.2% of this difference being mediated by ferritin. Conclusion: Iron biomarkers may partially mediate the association between sex and glucose homeostasis. Future studies addressing the causality of our findings are needed. © 2024 The Author(s). Published by Oxford University Press on behalf of the Endocrine Society.
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