Urine transferrin as an early endothelial dysfunction marker in type 2 diabetic patients without nephropathy: a case control study.
Abstract Background Albumin, along with other proteins, is abnormally eliminated via the urine during early stages of diabetic nephropathy. Moreover, endothelial dysfunction (ED) accompanying early diabetic nephropathy may develop even before microalbuminuria is detectable. Transferrin has a molecular weight comparable to albumin, and transferrinuria and microalbuminuria in a 24-hour urine sample may comparably reflect early diabetic nephropathy. However, transferrin physiochemical properties may be related with ED, but these have not been elucidated yet. This case-control study was aimed to evaluate relation between ED and urinary transferrin concentration before early diabetic nephropathy is present. Methods Patients were enrolled from two study sites in Mexico City: Ticoman General Hospital to evaluate control patients; and Dr. Manuel Gonzalez Rivera Specialized Clinic for the Management of the Diabetic Patient for case patients. All patients provided written informed consent. The primary endpoint was the correlation between urinary transferrin concentration and endothelial dysfunction measured in type 2 diabetic patients without albuminuria. ED was evaluated by ultrasonographic validated measurements, which included carotid intima-media thickness (CIMT) and flow mediated dilation (FMD). A power calculation, to detect a statistical difference, with a p value of 0.05, mandated a sample of 60 patients. The patients were tested for serum biomarkers such as glycated hemoglobin, creatinine, cholesterol, triglycerides, and urinary dipstick for albuminuria and urinary tract infection; using inclusion, exclusion and elimination criteria as described. Results The group with type 2 diabetes was older and showed higher serum transferrin and lower urinary transferrin values. Likewise, the group with type 2 diabetes showed subclinical atherogenic risk characterized by lower FMD and higher CIMT and ABI values. Risk factors associated to endothelial dysfunction measured by CIMT were time from diagnosis of diabetes, insulin resistance, dyslipidemia, and male sex. Hba1c and time since diabetes diagnosis correlated both for risk associated to FMD and CIMT. CIMT was the only factor correlated with urinary transferrin values. Conclusion Urinary transferrin correlated to subclinical endothelial dysfunction measured by CIMT in type 2 diabetic patients without nephropathy and can be used to test for early nephropathy in patients without albuminuria.
