Plasma Concentration of Interleukin-6 and C-reactive Protein and the Risk of Developing Type 2 Diabetes Mellitus Among Healthy Middle-Aged Women
Background Inflammation may play an important role in the development of type 2 diabetes mellitus. We studied whether plasma concentrations of the inflammatory markers, interleukin-6 (IL-6) and C-reactive protein (CRP), are related to the development of type 2 diabetes in women. Methods We conducted a prospective, nested case-control study among a cohort of middle-aged female health professionals free of diagnosed diabetes mellitus, cardiovascular disease, and cancer to assess the risk of incident type 2 diabetes over a four-year period associated with baseline levels of IL-6 and high-sensitivity CRP (hs-CRP). A diagnostic threshold of 6.5% for hemoglobin A1c (HbA1c) was used to exclude prevalent undiagnosed diabetes. Results Baseline levels of IL-6 (P<0.001) and hs-CRP (P<0.001) were significantly higher among women who subsequently developed diabetes mellitus compared to those who did not. The relative risks of future diabetes for women in the highest as compared to the lowest quartile of these inflammatory markers were 7.5 for IL-6 (95% CI, 3.7 to 15.4) and 15.7 for hs-CRP (95% CI, 6.5 to 37.9). These effects persisted after adjustment for body-mass index, family history of diabetes, smoking, exercise, use of alcohol and hormone replacement therapy; adjusted relative risks for the highest versus lowest quartile were 2.3 for IL-6 (95% CI, 0.9 to 5.6; P-trend = 0.066) and 4.2 for hs-CRP (95% CI, 1.5 to 12.0; P-trend = 0.001). Similar results were seen in analyses limited to individuals with HbA1c ≤ 6.0% and after adjustment for fasting insulin levels. Conclusions Plasma concentrations of interleukin-6 and C-reactive protein are associated with an increased risk of developing type 2 diabetes mellitus in middle-aged women. These data support the inflammatory hypothesis of diabetogenesis.