Endothelial dysfunction in type-2 diabetics with early diabetic nephropathy is associated with low circulating adiponectin.
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.
Yilmaz
Mahmut Ilker
MI
Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, K56 Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden. mahmutiyilmaz@yahoo.com
Saglam
Mutlu
M
Qureshi
Abdul Rashid
AR
Carrero
Juan Jesus
JJ
Caglar
Kayser
K
Eyileten
Tayfun
T
Sonmez
Alper
A
Cakir
Erdinc
E
Oguz
Yusuf
Y
Vural
Abdulgaffar
A
Yenicesu
Mujdat
M
Stenvinkel
Peter
P
Lindholm
Bengt
B
Axelsson
Jonas
J
D052242:Adiponectin / Q000097:blood; D000328:Adult; D001794:Blood Pressure; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000503:physiopathology; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood* / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D036361:Peptide Hormones / Q000097:blood; D011507:Proteinuria / Q000097:blood / Q000503:physiopathology; D014463:Ultrasonography
C499918:ADIPOQ protein, human; D052242:Adiponectin; D036361:Peptide Hormones