Elevated Levels of the Anti-Inflammatory Interleukin-1 Receptor Antagonist Precede the Onset of Type 2 Diabetes

The Whitehall II Study

  1. Christian Herder, PHD1,
  2. Eric J. Brunner, PHD2,
  3. Wolfgang Rathmann, MD, MSPH3,
  4. Klaus Strassburger, PHD3,
  5. Adam G. Tabák, MD24,
  6. Nanette C. Schloot, MD15 and
  7. Daniel R. Witte, PHD26
  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, U.K.
  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
  1. Corresponding author: Christian Herder, christian.herder{at}ddz.uni-duesseldorf.de


OBJECTIVE—Interleukin-1 receptor antagonist (IL-1Ra), a natural inhibitor of interleukin-1β, has been shown to improve β-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 case and 376 age-, sex-, and BMI-matched normoglycemic control subjects) within the Whitehall II cohort (U.K.).

RESULTS—IL-1Ra concentrations were higher in case subjects (P = 0.0006) and associated with incident type 2 diabetes (odds ratio for a 1-SD increase of IL-1Ra 1.48 [95% CI 1.21–1.80]). This association remained significant after adjustment for multiple potential confounders but was attenuated by adjusting for 2-h 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 IL-1Ra.


  • Published ahead of print at http://care.diabetesjournals.org on 10 December 2008.

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    • Accepted November 24, 2008.
    • Received June 26, 2008.
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  1. Diabetes Care vol. 32 no. 3 421-423
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