C-Reactive Protein, Interleukin 6, and Risk of Developing Type 2 Diabetes Mellitus

ContextInflammation is hypothesized to play a role in development of type 2 diabetes mellitus (DM); however, clinical data addressing this issue are limited.ObjectiveTo determine whether elevated levels of the inflammatory markers interleukin 6 (IL-6) and C-reactive protein (CRP) are associated with development of type 2 DM in healthy middle-aged women.DesignProspective, nested case-control study.SettingThe Women's Health Study, an ongoing US primary prevention, randomized clinical trial initiated in 1992.ParticipantsFrom a nationwide cohort of 27 628 women free of diagnosed DM, cardiovascular disease, and cancer at baseline, 188 women who developed diagnosed DM over a 4-year follow-up period were defined as cases and matched by age and fasting status with 362 disease-free controls.Main Outcome MeasuresIncidence of confirmed clinically diagnosed type 2 DM by baseline levels of IL-6 and CRP.ResultsBaseline levels of IL-6 (P<.001) and CRP (P<.001) were significantly higher among cases than among controls. The relative risks of future DM for women in the highest vs lowest quartile of these inflammatory markers were 7.5 for IL-6 (95% confidence interval [CI], 3.7-15.4) and 15.7 for CRP (95% CI, 6.5-37.9). Positive associations persisted after adjustment for body mass index, family history of diabetes, smoking, exercise, use of alcohol, and hormone replacement therapy; multivariate relative risks for the highest vs lowest quartiles were 2.3 for IL-6 (95% CI, 0.9-5.6; P for trend = .07) and 4.2 for CRP (95% CI, 1.5-12.0; P for trend = .001). Similar results were observed in analyses limited to women with a baseline hemoglobin A1c of 6.0% or less and after adjustment for fasting insulin level.ConclusionsElevated levels of CRP and IL-6 predict the development of type 2 DM. These data support a possible role for inflammation in diabetogenesis.