SCIENCE UP THE WORLD
15TH INTERNATIONAL STUDENT CONGRESS OF MEDICAL SCIENCES
JUNE 3RD - 6TH 2008
Abstract Gowsini Joseph
Plasma α-defensin is associated with diabetic nephropathy and mortality in type 1 diabetic patients1Gowsini Joseph, 2Lise Tarnow, 1Troels Krarup Hansen, 2Hans-Henrik Parving, 1Allan Flyvbjerg, 1Jan Frystyk
1Medical Research Laboratories and Medical Department M (Endocrinology & Metabolism), Aarhus University Hospital, Denmark, 2Steno Diabetes Center, Gentofte Hospital, Copenhagen, Denmark
Introduction
α-defensins are antimicrobial peptides of the innate immune system. They are secreted by neutrophils during phagocytosis. In addition, α-defensins are suggested to be involved in atherosclerosis by stimulating binding of lipoproteins and LDL cholesterol to endothelial cells in the blood vessels. By binding to tissue-plasminogen activator, α-defensins inhibit fibrinolysis, causing thrombotic occlusions. Finally, α-defensins may participate in angiogenesis through binding to integrin molecules. To elucidate a potential role of α-defensin in micro- and macrovascular complications, we investigated the association between plasma levels of α-defensin and the presence of diabetic nephropathy as well as cardiovascular disease (CVD) in type 1 diabetic patients.
Material and methods
A total of 391 patients with long lasting type 1 diabetes were recruited through the outpatient clinic at Steno Diabetes Center, Gentofte. Approximately half of the study population (n= 199) had diabetic nephropathy, the rest (n= 192) had normoalbuminuria. After an overnight fast, venous blood was drawn from an antecubital vein and plasma stored at -80°C. Occurrence of CVD and ischemic heart failure were evaluated. Blood pressure, se-creatinine, BMI, HbA1C, cholesterol levels and other clinical parameters were measured. To study the association between plasma α-defensin, the development of vascular complications and mortality, we prospectively followed the study cohort for more than 10 years. Plasma α-defensin was measured using a validated in-house radioimmunoassay (RIA).
Results
The median plasma α-defensin concentration at baseline was 258 μg/L (IQR 205-321 μg/L). Patients with nephropathy had significantly higher levels of plasma α-defensin compared to those with normoalbuminuria: 305 μg/L (IQR 182-263) vs. 223 μg/L (IQR 205-321), P<0.0001. This difference remained significant after adjustment for diabetes duration, HbA1c, BMI, blood pressure, UAE and GFR; nephropathy vs. normoalbuminuria: 302 μg/L (95% CI 287-317) vs. 250 μg/L (95% CI 235- 266), P< 0.0001. During follow-up 76 patients died, hereof 32 from CVD. Patients who died had significantly higher levels of α-defensin than survivors: 335 μg/L (IQR 269-394) vs. 245 μg/L (IQR 200-301), P<0.0001. From ROC curve analysis, an α-defensin level of 310 μg/L was found to be the best predictive cut-off level (sensitivity 0.61, specificity 0.81, area under the ROC curve 0.74, P<0.0001). All-cause mortality in patients with plasma α-defensin levels >310 μg/L was 43% (46 deaths among 107 patients) vs. 11% (30/282) among patients with α-defensin <310 μg/L, hazard ratio 4.9 (95% CI 3.1-7.7), P<0.0001. Of note, a plasma α-defensin level >310 μg/L remained an independent predictor of mortality, even after adjustment for nephropathy status at baseline and for the possible confounding effects of age, sex, HgbA1c, plasma creatinine, BMI, total cholesterol and systolic blood pressure (hazard ratio 2.0, 95% CI 1.1-3.6, P<0.05).
Conclusion
Our data indicate that plasma α-defensin may be related to the development of diabetic nephropathy. Further, our findings suggest that measurements of plasma levels of α-defensin may be used as a prognostic factor for nephropathy and mortality in type 1 diabetic patients.
Keyword(s): α-defensin, diabetes mellitus, diabetic nephropathy, mortality
