Elevated Levels of the Anti-Inflammatory Interleukin-1 Receptor Antagonist Precede the Onset of Type 2 Diabetes: The Whitehall II Study

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.