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Plasma ferritin, C-reactive protein, and risk of incident type 2 diabetes in Singapore Chinese men and women

  • Ye-Li Wang
    Affiliations
    Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, 117549, Singapore
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  • Woon-Puay Koh
    Correspondence
    Corresponding authors at: Huazhong University of Science and Technology, Wuhan 430030, China (A. Pan); Duke-NUS Medical School, Singapore 169857, Singapore (W.-P. Koh).
    Affiliations
    Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, 117549, Singapore

    Duke-NUS Medical School, Singapore 169857, Singapore
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  • Jian-Min Yuan
    Affiliations
    Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA

    Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA
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  • An Pan
    Correspondence
    Corresponding authors at: Huazhong University of Science and Technology, Wuhan 430030, China (A. Pan); Duke-NUS Medical School, Singapore 169857, Singapore (W.-P. Koh).
    Affiliations
    Department of Epidemiology and Statistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province 430030, China
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      Highlights

      • Elevated ferritin was associated with increased type 2 diabetes risk in Chinese.
      • Adjustment for ALT had the strongest impact on the ferritin-diabetes association.
      • There is a significant interaction between hs-CRP and ferritin on diabetes risk.
      • The ferritin-diabetes association was significant among those with HbA1c ≥ 6.5%.
      • The ferritin-diabetes association was not significant in those with HbA1c < 6.5%.

      Abstract

      Aims

      Ferritin is postulated to be involved in diabetogenesis as a marker of iron stores. We prospectively examined the association between ferritin levels and type 2 diabetes (T2D) risk in a Chinese population.

      Methods

      Plasma ferritin concentrations were assayed among 485 diabetes cases and 485 controls nested within the Singapore Chinese Health Study. Cases and controls were matched on age, gender, date of blood collection, and dialect group. Participants were free of diagnosed diabetes, cardiovascular disease, and cancer at blood collection (1999–2004). Incident self-reported T2D cases were identified at follow-up II interview (2006–2010). Multivariable conditional logistic regression models were used to compute the odds ratio (OR) and the corresponding 95% confidence intervals (CIs).

      Results

      After adjusting for T2D risk factors, including high-sensitivity C-reactive protein (hs-CRP), adiponectin, triglycerides, HDL cholesterol and alanine aminotransferase, the OR comparing the highest versus lowest quartile of ferritin levels was 1.87 (95% CI 1.10–3.19) (P-trend = 0.004). When the analysis was limited to participants with hs-CRP < 1.5 mg/L (below median; n = 482), the OR comparing extreme quartiles of ferritin levels was 1.16 (95% CI 0.62–2.16; P-trend = 0.63); while the corresponding OR was 2.51 (95% CI 1.31–4.79; P-trend < 0.001) when confined to those with hs-CRP ≥ 1.5 mg/L (n = 488; P-interaction = 0.022). Compared to participants with both ferritin and hs-CRP levels below median, those with both levels above median had markedly increased T2D risk (P-interaction for multiplicative scale = 0.037).

      Conclusions

      The elevation of blood ferritin levels, in the presence of raised hs-CRP, was significantly associated with increased risk of T2D.

      Keywords

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