Abstract

Objective: Markers reliably identifying vascular damage and risk in diabetes patients are rare and reports on associations of serum adiponectin with macrovascular disease have been inconsistent. In contrast to existing data on serum adiponectin, this study assesses whether urinary adiponectin excretion might represent a more consistent vascular damage marker in type 2 diabetes mellitus (T2DM).

Research Design and Methods: Adiponectin distribution in human kidney biopsies was assessed by immunohistochemistry, and urinary adiponectin isoforms were characterized by western blot analysis. Total urinary adiponectin excretion rate was measured in 156 T2DM patients with a history of diabetic nephropathy and 40 healthy controls by ELISA. Atherosclerotic burden was assessed by common carotid artery intima-media-thickness (IMT).

Results: A homogenous staining of adiponectin was found on the endothelial surface of glomerular capillaries and intrarenal arterioles in non-diabetic kidneys whereas staining was decreased in diabetic nephropathy. Low-molecular adiponectin isoforms (∼30-70kDA) were detected in urine by western blot analysis. Urinary adiponectin was significantly increased in T2DM (7.68±14.26 vs. controls: 2.91±3.85μg/g creatinine, p=0.008). Among T2DM patients, adiponectinuria was associated with IMT (r=0.479, p<0.001) and proved to be a powerful independent predictor of IMT (ß=0.360, p<0.001) in multivariable regression analyses. In a risk prediction model including variables of the ‘UKPDS CHD risk engine’ urinary adiponectin, but not the albumin excretion rate, added significant value for the prediction of increased IMT (p=0.007).

Conclusions: Quantification of urinary adiponectin excretion appears to be an independent indicator of vascular damage potentially identifying an increased risk for vascular events.