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- Title
Accelerated increase in serum interleukin-1 receptor antagonist starts 6 years before diagnosis of type 2 diabetes: Whitehall II prospective cohort study.
- Authors
Carstensen M; Herder C; Kivimäki M; Jokela M; Roden M; Shipley MJ; Witte DR; Brunner EJ; Tabák AG; Carstensen, Maren; Herder, Christian; Kivimäki, Mika; Jokela, Markus; Roden, Michael; Shipley, Martin J; Witte, Daniel R; Brunner, Eric J; Tabák, Adam G
- Abstract
<bold>Objective: </bold>Although interleukin-1 receptor antagonist (IL-1Ra) treatment is associated with improved beta-cell function and glycemic control in patients with type 2 diabetes, its role in the development of type 2 diabetes remains unclear. We used repeated measurements to characterize IL-1Ra trajectories in individuals who developed type 2 diabetes.<bold>Research Design and Methods: </bold>This case-cohort study, nested within the Whitehall II cohort, was based on 335 incident type 2 diabetes cases and 2,475 noncases. We measured serum IL-1Ra levels at up to three time points per individual and estimated retrospective trajectories of IL-1Ra before diabetes diagnosis (case subjects) or end of follow-up (control subjects) using multilevel analysis. Models were adjusted for age, sex, and ethnicity.<bold>Results: </bold>IL-1Ra levels were already higher in the case than control subjects 13 years before diabetes diagnosis/end of follow-up (mean [95% CI] 302 [290-314] vs. 244 [238-249] pg/ml). In control subjects, IL-1Ra levels showed a modest linear increase throughout the study period. In case subjects, IL-1Ra trajectories were parallel to those in control subjects until 6 years (95% CI 7.5-4.5) before diagnosis and then rose steeply to 399 (379-420) pg/ml at the time of diagnosis (P < 0.0001 for slope difference). Adjustment for BMI and waist circumference as time-varying covariates had little impact on these trajectories.<bold>Conclusions: </bold>We show elevated IL-1Ra levels for 13 years and an accelerated increase during the last 6 years before type 2 diabetes diagnosis, indicating the presence of an anti-inflammatory response that may act to counterbalance the metabolic and immunologic disturbances that precede type 2 diabetes.
- Publication
Diabetes, 2010, Vol 59, Issue 5, p1222
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db09-1199