NDT Advance Access originally published online on January 5, 2008
Nephrology Dialysis Transplantation 2008 23(5):1621-1627; doi:10.1093/ndt/gfm828
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Endothelial dysfunction in type-2 diabetics with early diabetic nephropathy is associated with low circulating adiponectin
1 Nephrology Department of Gülhane School of Medicine, Etlik-Ankara, Turkey 2 Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden 3 Radiology Department of Gülhane School of Medicine, Turkey 4 Internal Medicine Department of Gülhane School of Medicine, Turkey 5 Biochemistry Department of Gülhane School of Medicine, Etlik-Ankara, Turkey
Correspondence and offprint requests to: Mahmut Ilker Yilmaz, Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, K56 Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden. Tel: +46-8-58582532; Fax: +46-8-58582532; E-mail: mahmutiyilmaz{at}yahoo.com
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Abstract |
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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 (
= 0.46; P < 0.001, = 0.54; P > 0.05, = 0.32; P = 0.003, = 0.76; P < 0.001, respectively). FMD, adiponectin and AHSG/fetuin-A levels were significantly lower, and negatively correlated with proteinuria ( = –0.54; P < 0.001, = –0.56; P < 0.001, = –0.48; P < 0.001, respectively). In a multivariate regression analysis, the degrees of proteinuria (r2 = –0.32, P = 0.04) and plasma levels of NAMPT/visfatin (r2 = –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.
Keywords: albuminuria; CVD; fetuin-A; NAMPT/visfatin; PBEF-1
Received for publication: 14. 7.07
Accepted in revised form: 24.10.07
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