Plasma alpha-defensin is associated with cardiovascular morbidity and mortality in type 1 diabetic patients.
BACKGROUND
alpha-Defensins are antimicrobial peptides of the innate immune system. In addition, experimental evidence suggests that alpha-defensins are proatherogenic.


OBJECTIVE
The objective of the study was to examine the predictive value of plasma alpha-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 alpha-defensin using an in-house RIA.


RESULTS
At baseline, plasma alpha-defensin was significantly higher in patients with than without nephropathy [median and interquartile ranges: 305 (205-321) vs. 223 (182-263) mug/liter; P < 0.0001]. During follow-up, 98 patients reached the primary end point (fatal and nonfatal events of CVD). Prospectively a baseline alpha-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).


CONCLUSIONS
This study suggests that plasma alpha-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 alpha-defensin is causally linked to the development of CVD or an innocent bystander.
Joseph
Gowsini
G
Medical Research Laboratories, Clinical Institute and Medical Department M (Diabetes and Endocrinology), Aarhus University Hospital, Aarhus University, DK-8000 Aarhus, Denmark.
Tarnow
Lise
L
Astrup
Anne Sofie
AS
Hansen
Troels Krarup
TK
Parving
Hans-Henrik
HH
Flyvbjerg
Allan
A
Frystyk
Jan
J
D000328:Adult; D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000401:mortality; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications*; D003928:Diabetic Nephropathies / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D016016:Proportional Hazards Models; D011446:Prospective Studies; D023084:alpha-Defensins / Q000097:blood*
D015415:Biomarkers; D006442:Glycated Hemoglobin; D023084:alpha-Defensins; C517652:hemoglobin A1c protein, human