Genetic Variation, C-Reactive Protein Levels, and Incidence of Diabetes

  1. Abbas Dehghan1,
  2. Isabella Kardys1,
  3. Moniek P.M. de Maat2,
  4. Andre G. Uitterlinden13,
  5. Eric J.G. Sijbrands3,
  6. Aart H. Bootsma3,
  7. Theo Stijnen1,
  8. Albert Hofman1,
  9. Miranda T. Schram14 and
  10. Jacqueline C.M. Witteman1
  1. 1Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, the Netherlands
  2. 2Department of Hematology, Erasmus Medical Center, Rotterdam, the Netherlands
  3. 3Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
  4. 4Department of Gerontology, Leiden University Medical Center, Leiden, the Netherlands
  1. Address correspondence and reprint requests to J.C.M. Witteman, PhD, Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, P.O. Box 2040, 3000 CA Netherlands. E-mail: j.witteman{at}


C-reactive protein (CRP) has been shown to be associated with type 2 diabetes, but whether CRP has a causal role is not yet clear. We examined the association in the Rotterdam Study, a population-based prospective cohort study. The association of baseline serum CRP and incident diabetes during follow-up was investigated, and a meta-analysis was conducted on the BMI-adjusted relation of CRP and diabetes. Furthermore, the association of CRP haplotypes with serum CRP and risk of diabetes was assessed. The age- and sex-adjusted hazard ratio for diabetes was 1.41 (95% CI 1.29–1.54) per 1 SD increase in natural logarithm of CRP, and it was 1.88, 2.16, and 2.83 for the second, third, and fourth quartiles of CRP, respectively, compared with the first quartile. The risk estimates attenuated but remained statistically significant after additional adjustment for obesity indexes, which agreed with the results of the meta-analysis. The most common genetic haplotype was associated with a significantly lower CRP level compared with the three other haplotypes. The risk of diabetes was significantly higher in the haplotype with the highest serum CRP level compared with the most common haplotype (OR 1.45, 95% CI 1.08–1.96). These findings support the hypothesis that serum CRP enhances the development of diabetes.


  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted December 12, 2006.
    • Received July 5, 2006.
| Table of Contents