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Sex-Specific Association of Circulating Ferritin Level and Risk of Type 2 Diabetes: A Dose-Response Meta-Analysis of Prospective Studies.
J Clin Endocrinol Metab 2019; 104(10):4539-4551JC

Abstract

CONTEXT

Although the role of iron in the development of type 2 diabetes (T2D) has long been a concern, prospective studies directly linking body iron stores to T2D risk in a sex-dependent context have been inconsistent.

OBJECTIVE

A systematic meta-analysis was conducted to explore the sex-specific association of circulating ferritin with T2D risk.

DATA SOURCES

We searched PubMed, Web of Science, and EMBASE databases to identify available prospective studies through 1 August 2018.

RESULTS

Fifteen prospective studies comprising 77,352 participants and 18,404 patients with T2D, aged 20 to 80 years, and with ∼3 to 17 years of follow-up were identified. For each 100-μg/L increment in ferritin levels of overall participants, T2D risk increased by 22% (RR, 1.22; 95% CI, 1.14 to 1.31). Of note, major heterogeneities by sex were identified, with increased ferritin level having an apparently greater effect on T2D risk in women (RR, 1.53; 95% CI, 1.29 to 1.82) than in men (RR, 1.21; 95% CI, 1.15 to 1.27) after exclusion of a study with high heterogeneity (41,512 men and 6974 women for sex-specific analyses; P = 0.020 for sex difference). Further nonlinear analysis between circulating ferritin and T2D risk also showed sex-dimorphic association in that the T2D risk of women was twice as strong in magnitude as that of men at the same ferritin level.

CONCLUSIONS

Greater circulating ferritin levels were independently associated with increased T2D risk, which appeared stronger among women than men. Our findings provide prospective evidence for further testing of the utility of ferritin levels in predicting T2D risk in a sex-specific manner.

Authors+Show Affiliations

The First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China. Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China. The First Affiliated Hospital, School of Public Health, Zhengzhou University, Zhengzhou, China.The First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.Departments of Cardiology and Endocrinology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. Centre for Global Cardiometabolic Health, Department of Epidemiology, Brown University, Providence, Rhode Island.The First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Kong Kong SAR, China.The First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.The First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.The First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.The First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China.Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.The First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.The First Affiliated Hospital, School of Public Health, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China. Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China. The First Affiliated Hospital, School of Public Health, Zhengzhou University, Zhengzhou, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31074789

Citation

Jiang, Li, et al. "Sex-Specific Association of Circulating Ferritin Level and Risk of Type 2 Diabetes: a Dose-Response Meta-Analysis of Prospective Studies." The Journal of Clinical Endocrinology and Metabolism, vol. 104, no. 10, 2019, pp. 4539-4551.
Jiang L, Wang K, Lo K, et al. Sex-Specific Association of Circulating Ferritin Level and Risk of Type 2 Diabetes: A Dose-Response Meta-Analysis of Prospective Studies. J Clin Endocrinol Metab. 2019;104(10):4539-4551.
Jiang, L., Wang, K., Lo, K., Zhong, Y., Yang, A., Fang, X., ... Wang, F. (2019). Sex-Specific Association of Circulating Ferritin Level and Risk of Type 2 Diabetes: A Dose-Response Meta-Analysis of Prospective Studies. The Journal of Clinical Endocrinology and Metabolism, 104(10), pp. 4539-4551. doi:10.1210/jc.2019-00495.
Jiang L, et al. Sex-Specific Association of Circulating Ferritin Level and Risk of Type 2 Diabetes: a Dose-Response Meta-Analysis of Prospective Studies. J Clin Endocrinol Metab. 2019 Oct 1;104(10):4539-4551. PubMed PMID: 31074789.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sex-Specific Association of Circulating Ferritin Level and Risk of Type 2 Diabetes: A Dose-Response Meta-Analysis of Prospective Studies. AU - Jiang,Li, AU - Wang,Kai, AU - Lo,Kenneth, AU - Zhong,Yueyang, AU - Yang,Aimin, AU - Fang,Xuexian, AU - Akezhuoli,Hailati, AU - Song,Zijun, AU - Chen,Liyun, AU - An,Peng, AU - Xu,Mingqing, AU - Min,Junxia, AU - Wang,Fudi, PY - 2019/03/01/received PY - 2019/05/06/accepted PY - 2019/5/11/pubmed PY - 2019/5/11/medline PY - 2019/5/11/entrez SP - 4539 EP - 4551 JF - The Journal of clinical endocrinology and metabolism JO - J. Clin. Endocrinol. Metab. VL - 104 IS - 10 N2 - CONTEXT: Although the role of iron in the development of type 2 diabetes (T2D) has long been a concern, prospective studies directly linking body iron stores to T2D risk in a sex-dependent context have been inconsistent. OBJECTIVE: A systematic meta-analysis was conducted to explore the sex-specific association of circulating ferritin with T2D risk. DATA SOURCES: We searched PubMed, Web of Science, and EMBASE databases to identify available prospective studies through 1 August 2018. RESULTS: Fifteen prospective studies comprising 77,352 participants and 18,404 patients with T2D, aged 20 to 80 years, and with ∼3 to 17 years of follow-up were identified. For each 100-μg/L increment in ferritin levels of overall participants, T2D risk increased by 22% (RR, 1.22; 95% CI, 1.14 to 1.31). Of note, major heterogeneities by sex were identified, with increased ferritin level having an apparently greater effect on T2D risk in women (RR, 1.53; 95% CI, 1.29 to 1.82) than in men (RR, 1.21; 95% CI, 1.15 to 1.27) after exclusion of a study with high heterogeneity (41,512 men and 6974 women for sex-specific analyses; P = 0.020 for sex difference). Further nonlinear analysis between circulating ferritin and T2D risk also showed sex-dimorphic association in that the T2D risk of women was twice as strong in magnitude as that of men at the same ferritin level. CONCLUSIONS: Greater circulating ferritin levels were independently associated with increased T2D risk, which appeared stronger among women than men. Our findings provide prospective evidence for further testing of the utility of ferritin levels in predicting T2D risk in a sex-specific manner. SN - 1945-7197 UR - https://www.unboundmedicine.com/medline/citation/31074789/Sex_specific_Association_of_Circulating_Ferritin_Levels_and_Risk_of_Type_2_Diabetes:_A_Dose_response_Meta_analysis_of_Prospective_Studies_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2019-00495 DB - PRIME DP - Unbound Medicine ER -