Accelerated increase in serum interleukin-1 receptor antagonist starts 6 years before diagnosis of type 2 diabetes: Whitehall II prospective cohort study

Maren Carstensen, Christian Herder, Mika Kivimäki, Markus Jokela, Michael Roden, Martin J. Shipley, Daniel R. Witte, Eric J. Brunner, Adam G. Tabák

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90 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1222-1227
Number of pages6
JournalDiabetes
Volume59
Issue number5
DOIs
Publication statusPublished - May 1 2010

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Carstensen, M., Herder, C., Kivimäki, M., Jokela, M., Roden, M., Shipley, M. J., Witte, D. R., Brunner, E. J., & Tabák, A. G. (2010). Accelerated increase in serum interleukin-1 receptor antagonist starts 6 years before diagnosis of type 2 diabetes: Whitehall II prospective cohort study. Diabetes, 59(5), 1222-1227. https://doi.org/10.2337/db09-1199