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

Objective: To examine the predictive value of plasma -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 through the Danish National Register for a median of 10.1 years (range 0.2 – 10.4 years). Plasma was collected in 1993 and stored at -80°C till analysis of plasma -defensin using an in-house radioimmunoassay.

Results: At baseline, plasma -defensin was significantly higher in patients with than without nephropathy (median and interquartile ranges: 305 (205–321) vs. 223 (182–263) µg/L; P < 0.0001). During follow-up, 98 patients reached the primary end-point (fatal and non-fatal events of CVD). Prospectively, a baseline -defensin within the upper versus the lower tertile significantly increased the co-variate 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 -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 -defensin is causally linked to the development of CVD or an innocent bystander.