Key result
Higher proteinuria is linked to worse endothelial dysfunction in type-2 diabetes.
Why the study?
Type-2 diabetes and diabetic kidney disease increase cardiovascular risk, and proteinuria is an independent predictor of mortality, but the link between early diabetic nephropathy and endothelial dysfunction is unclear.
Cross-Sectional (n=123)
Effect estimate: r2 = -0.32
p-value: p=0.04
Proteinuria in early diabetic nephropathy is an important predictor of endothelial dysfunction and is associated with altered circulating levels of NAMPT/visfatin and adiponectin.
Proteinuria links to endothelial dysfunction in T2D; leaves open causality and therapeutic implications.
BACKGROUND: Type-2 diabetes and diabetic kidney disease have additive effects on cardiovascular risk. Furthermore, the degree of proteinuria is an independent predictor of mortality in this patient group. We hypothesized that altered kidney clearance and/or metabolism of vasoactive peptides occurring during proteinuria could link early diabetic nephropathy to cardio vascular disease (CVD). METHODS: We performed a cross-sectional study of 85 incident patients (51 +/- 5 years, 49 males) with type-2 diabetes and 38 age- and sex-matched controls. We further divided patients by the presence of minor (<500 mg/day; n = 40) or severe (>/=500 mg/day; n = 45) proteinuria. Clinical and anthropometric data, along with ultrasonographic flow-mediated dilatation (FMD) of the brachial artery and carotid intima-media thicknesses (CIMT), were recorded in each group. Circulating NAMPT/visfatin, adiponectin (normalized to BMI), AHSG/fetuin-A and hsCRP levels were also measured using commercial ELISA. RESULTS: Plasma NAMPT/visfatin, CIMT, HOMA index and hsCRP levels were all significantly higher in diabetics than in control subjects, and all but CIMT correlated with proteinuria (rho = 0.46; P < 0.001, rho = 0.54; P > 0.05, rho = 0.32; P = 0.003, rho = 0.76; P < 0.001, respectively). FMD, adiponectin and AHSG/fetuin-A levels were significantly lower, and negatively correlated with proteinuria (rho = -0.54; P < 0.001, rho = -0.56; P < 0.001, rho = -0.48; P < 0.001, respectively). In a multivariate regression analysis, the degrees of proteinuria (r(2) = -0.32, P = 0.04) and plasma levels of NAMPT/visfatin (r(2) = -0.33, P = 0.006) were independently related to FMD. CONCLUSIONS: The present study suggests that the presence of proteinuria, regardless of the degree of renal function impairment, is an important predictor of endothelial dysfunction in early diabetic nephropathy and that it is associated with altered circulating levels of NAMPT/visfatin and adiponectin.
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Yılmaz et al. (2008) conducted a cross-sectional in Type-2 diabetes with early diabetic nephropathy (n=123). Proteinuria vs. Controls without diabetes was evaluated on Flow-mediated dilatation (FMD) (r2 = -0.32, p=0.04). In patients with type-2 diabetes, the degree of proteinuria was independently related to endothelial dysfunction as measured by flow-mediated dilatation (r2 = -0.32, P=0.04).