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-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.


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.
Herder
Christian
C
Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Institute for Diabetes Research, Düsseldorf, Germany. christian.herder@ddz.uni-duesseldorf.de
Brunner
Eric J
EJ
Rathmann
Wolfgang
W
Strassburger
Klaus
K
Tabák
Adam G
AG
Schloot
Nanette C
NC
Witte
Daniel R
DR
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
D053590:Interleukin 1 Receptor Antagonist Protein