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Abstract
Inflammation is hypothesized to play a role in development of type 2 diabetes mellitus
(DM); however, clinical data addressing this issue are limited.
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.
Prospective, nested case-control study.
The Women's Health Study, an ongoing US primary prevention, randomized clinical trial
initiated in 1992.
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.
Incidence of confirmed clinically diagnosed type 2 DM by baseline levels of IL-6 and
CRP.
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.
Elevated levels of CRP and IL-6 predict the development of type 2 DM. These data support
a possible role for inflammation in diabetogenesis.