C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus.
BACKGROUND
Inflammation is hypothesized to play a role in development of type 2 diabetes mellitus (DM); however, clinical data addressing this issue are limited.


OBJECTIVE
To 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.


METHODS
Prospective, nested case-control study.


METHODS
The Women's Health Study, an ongoing US primary prevention, randomized clinical trial initiated in 1992.


METHODS
From 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.


METHODS
Incidence of confirmed clinically diagnosed type 2 DM by baseline levels of IL-6 and CRP.


RESULTS
Baseline 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 A(1c) of 6.0% or less and after adjustment for fasting insulin level.


CONCLUSIONS
Elevated levels of CRP and IL-6 predict the development of type 2 DM. These data support a possible role for inflammation in diabetogenesis.
Pradhan
A D
AD
Manson
J E
JE
Rifai
N
N
Buring
J E
JE
Ridker
P M
PM
D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D012306:Risk; D018709:Statistics, Nonparametric
D015415:Biomarkers; D015850:Interleukin-6; D002097:C-Reactive Protein