Potential Mediating Role of Iron Biomarkers in the Association of Sex With Glucose, Insulin, and Type 2 Diabetes
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Potential Mediating Role of Iron Biomarkers in the Association of Sex With Glucose, Insulin, and Type 2 Diabetes. / Khatami, Farnaz; Lange, Theis; Groothof, Dion; Ahanchi, Noushin Sadat; Quezada-Pinedo, Hugo G.; Raeisi-Dehkordi, Hamidreza; De Borst, Martin H.; Vidal, Pedro Marques; Sailesh, Mohan; Prabhakaran, Dorairaj; Bano, Arjola; Bakker, Stephan J.L.; Muka, Taulant; Eisenga, Michele F.
In: Journal of the Endocrine Society, Vol. 8, No. 7, bvae098, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Potential Mediating Role of Iron Biomarkers in the Association of Sex With Glucose, Insulin, and Type 2 Diabetes
AU - Khatami, Farnaz
AU - Lange, Theis
AU - Groothof, Dion
AU - Ahanchi, Noushin Sadat
AU - Quezada-Pinedo, Hugo G.
AU - Raeisi-Dehkordi, Hamidreza
AU - De Borst, Martin H.
AU - Vidal, Pedro Marques
AU - Sailesh, Mohan
AU - Prabhakaran, Dorairaj
AU - Bano, Arjola
AU - Bakker, Stephan J.L.
AU - Muka, Taulant
AU - Eisenga, Michele F.
N1 - Publisher Copyright: © 2024 The Author(s). Published by Oxford University Press on behalf of the Endocrine Society.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - glucose hemostasis
KW - iron biomarkers
KW - sex
KW - type 2 diabetes
U2 - 10.1210/jendso/bvae098
DO - 10.1210/jendso/bvae098
M3 - Journal article
AN - SCOPUS:85195428424
VL - 8
JO - Endocrine Research Communications
JF - Endocrine Research Communications
SN - 0743-5800
IS - 7
M1 - bvae098
ER -
ID: 394973793