Diabetes Metab J.  2022 Mar;46(2):307-318. 10.4093/dmj.2020.0287.

Iron Overload and the Risk of Diabetes in the General Population: Results of the Chinese Health and Nutrition Survey Cohort Study

• Gao H
• Yang J
• Pan W
• Yang M

• KMID: 2527723
• DOI: http://doi.org/10.4093/dmj.2020.0287

Abstract

Background
Recent studies have found that there are significant associations between body iron status and the development of diabetes. In the present study, we aimed to analyze the association among iron overload (IO), insulin resistance (IR), and diabetes in Chinese adults, and to explore the sex difference.
Methods
Men and women (age >19 years) who participated in the Chinese Health and Nutrition Survey and did not have diabetes at baseline were followed between 2009 and 2015 (n=5,779). Over a mean of 6 years, 75 participants were diagnosed with incident diabetes. Logistic regression was used to assess the risk factors associated with IO. Cox proportional hazard regression was used to estimate the risk of incident diabetes and to determine whether the risk differed among subgroups. Causal mediation analysis (CMA) was used to explore the mechanism linking IO and diabetes.
Results
According to sex-stratified multivariable-adjusted Cox proportional hazards regression, IO increased the risk of incident diabetes. Women with IO had a higher risk of diabetes than men. Subgroup analysis with respect to age showed that the association between IO and diabetes was stronger in older women and younger men (P<0.001). CMA showed that liver injury (alanine transaminase) and lipid metabolism abnormalities (triglyceride, apolipoprotein B) contributed to the association between IO and diabetes.
Conclusion
IO is associated with diabetes and this association is sex-specific. IO may indirectly induce IR via liver injury and lipid metabolism abnormalities, resulting in diabetes.

Keyword

Diabetes mellitus; Hepatic insufficiency; Insulin resistance; Iron overload; Lipid metabolism disorders; Sex characteristics

Figure

• 

  Fig. 1. Causal mediation analysis (CMA) models for the association of insulin resistance (IR) and triglyceride (TG) metabolism with iron overload (IO). Adjusted for age and high-sensitivity C-reactive protein. (A, B) The circles and solid lines show the point estimates and 95% confidence intervals for the effects of IO on IR and (C, D) TG metabolism. (A, B) The average causal mediation effects (ACMEs) reflect the indirect effects of IO on IR and (C, D) TG metabolism, mediated by alanine aminotransferase. (A, B) The average direct effects (ADEs) reflect the direct effects of IO on IR and (C, D) TG metabolism. The total effects are equal to ACME plus ADE. P indirect represents the P value for ACME.

• 

  Fig. 2. Causal mediation analysis (CMA) models for the association of apolipoprotein B (Apo-B) metabolism and insulin resistance (IR) with iron overload (IO). Adjusted for age and high-sensitivity C-reactive protein. (A, B) The circle and solid line represent the point estimates and 95% confidence intervals for the effects of IO on IR and (C, D) Apo-B metabolism. (A, B) The average causal mediation effects (ACMEs) reflect the indirect effects of IO on IR, mediated by Apo-B; and (C, D) Apo-B metabolism, mediated by triglyceride (TG). (A, B) The average direct effects (ADEs) reflect the direct effects of IO on IR and (C, D) Apo-B metabolism. The total effects are equal to ACME plus ADE. P indirect represents the P value for ACME.

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