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- Title
Accelerated Increase in Serum Interleukin-1 Receptor Antagonist Starts 6 Years Before Diagnosis of Type 2 Diabetes.
- Authors
Carstensen, Maren; Herder, Christian; Kivimäki, Mika; Jokela, Markus; Roden, Michael; Shipley, Martin J.; Witte, Daniel R.; Brunner, Eric J.; Tabák, Adam G.
- Abstract
OBJECTIVE--Although interleukin-1 receptor antagonist (IL-1Ra) treatment is associated with improved β-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. RESEARCH DESIGN AND METHODS--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. RESULTS--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. CONCLUSIONS--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. Diabetes 59:1222-1227, 2010
- Subjects
INTERLEUKIN-1; TYPE 2 diabetes; DIABETIC acidosis; ACUTE phase proteins; DIAGNOSIS of diabetes; CARBOHYDRATE intolerance
- Publication
Diabetes, 2010, Vol 59, Issue 5, p1222
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db09-1199