Elevated levels of the anti-inflammatory interleukin-1 receptor antagonist (IL-1Ra) precede the onset of type 2 diabetes (Whitehall II Study)

  1. Christian Herder, PHD (christian.herder{at}ddz.uni-duesseldorf.de)1,
  2. Eric J. Brunner, PHD2,
  3. Wolfgang Rathmann, MD MSPH3,
  4. Klaus Strassburger, PHD3,
  5. Adam G. Tabák, MD2,4,
  6. Nanette C. Schloot, MD1,5 and
  7. Daniel R. Witte, PHD2,6
  1. 1Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Institute for Diabetes Research, Düsseldorf, Germany
  2. 2Department of Epidemiology and Public Health, University College London, London, UK
  3. 3Institute of Biometrics and Epidemiology, German Diabetes Center at Heinrich Heine University, Leibniz Institute for Diabetes Research, Düsseldorf, Germany
  4. 4Semmelweis University, Budapest, Hungary
  5. 5Center for Internal Medicine, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
  6. 6Steno Diabetes Center, Gentofte, Denmark

    Abstract

    Objective Interleukin-1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1β, improved beta-cell function and glycemic control in patients with type 2 diabetes. The aim of this study was to investigate whether baseline systemic levels of IL-1Ra are associated with incident type 2 diabetes during more than 10 years of follow-up.

    Research design and methods We measured serum IL-1Ra concentrations in a nested case-control study (181 cases; 376 age-, sex- and BMI-matched normoglycemic controls) within the Whitehall II cohort (UK).

    Results IL-1Ra concentrations were higher in cases (P=0.0006) and associated with incident type 2 diabetes (OR[95%CI] for 1-SD increase of IL-1Ra: 1.48 [1.21-1.80]). This association remained significant after adjustment for multiple potential confounders, but was attenuated by adjusting for 2-hr glucose.

    Conclusions Our findings indicate that individuals who will develop type 2 diabetes are characterized by a complex immune activation that also includes upregulation of the anti-inflammatory cytokine L-1Ra.

    Footnotes

      • Received June 26, 2008.
      • Accepted November 24, 2008.

    This Article

    1. Published online before print December 10, 2008, doi: 10.2337/dc08-1161
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