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

OBJECTIVE Interleukin-1 receptor antagonist (IL-1Ra), a natural inhibitor of interleukin-1 beta, has been shown to improve 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 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.