Abstract

Context: α-Defensins are antimicrobial peptides of the innate immune system. In addition, experimental evidence suggests that α-defensins are proatherogenic.

Objective: The objective of the study was to examine the predictive value of plasma α-defensin as a clinical marker of cardiovascular disease (CVD) in patients with type 1 diabetes.

Methods: In an observational, prospective design, 389 patients with long-lasting type 1 diabetes were examined for CVD at study start (1993; baseline) and followed up through the Danish National Register for a median of 10.1 yr (range 0.2–10.4 yr). Plasma was collected in 1993 and stored at −80 C until analysis of plasma α-defensin using an in-house RIA.

Results: At baseline, plasma α-defensin was significantly higher in patients with than without nephropathy [median and interquartile ranges: 305 (205–321) vs. 223 (182–263) μg/liter; P < 0.0001]. During follow-up, 98 patients reached the primary end point (fatal and nonfatal events of CVD). Prospectively a baseline α-defensin within the upper vs. the lower tertile significantly increased the covariate-adjusted risk for CVD-related morbidity and mortality to a hazard ratio of 2.8 (1.3–5.9) (median and 95% confidence intervals, P = 0.006).

Conclusion: This study suggests that plasma α-defensin may serve as a clinical risk marker for CVD-related morbidity and mortality in type 1 diabetes. However, future studies are needed to clarify whether plasma α-defensin is causally linked to the development of CVD or an innocent bystander.

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