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Plasma -Defensin Is Associated with Cardiovascular Morbidity and Mortality in Type 1 Diabetic Patients

Medical Research Laboratories (G.J., T.K.H., A.F., J.F.), Clinical Institute and Medical Department M (Diabetes and Endocrinology), Aarhus University Hospital, and Faculty of Health Sciences (H.-H.P.), Aarhus University, DK-8000 Aarhus, Denmark; and Steno Diabetes Center (L.T., A.S.A., H.-H.P.), Gentofte Hospital, DK-2820 Copenhagen, Denmark

Address all correspondence and requests for reprints to: Dr. Jan Frystyk, Medical Research Laboratories, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark. E-mail: jan{at}frystyk.dk.

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

Objective: The objective of the study was 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 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 -defensin using an in-house RIA.

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/liter; P < 0.0001]. During follow-up, 98 patients reached the primary end point (fatal and nonfatal events of CVD). Prospectively a baseline -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 -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.