Retinol-binding protein 4 as a plasma biomarker of renal dysfunction and cardiovascular disease in type 2 diabetes

Objective. The retinol-binding protein 4 (RBP4) has been linked to the insulin resistance state in obesity and type 2 diabetes in animal studies. Data in humans are controversial and their relationship with organ damage in diabetic patients is lacking. We studied the association of plasma RBP4 with organ complications in type 2 diabetic patients. Setting. Sant Joan University Hospital, Reus, Spain. Subjects. 165 nonsmoker type 2 diabetic subjects according to American Diabetes Association criteria, aged 36-79 years, without proteinuria or severely decreased glomerular filtration rates (MDRD-GFR < 30 mL min(-1) 1.73 m(-2)), were included in the study. Main outcome measure. Plasma RBP4 concentrations were the primary outcome variable. Statistics were performed in relation to clinical and subclinical arteriosclerosis, renal function parameters and biochemical data. Results. Plasma RBP4 concentrations were positively correlated with serum creatinine levels (r = 0.322, P < 0.001) and inversely correlated with MDRD-GFR (r = -0.468, P = 0.009). Patients with moderately renal dysfunction (MDRD-GFR < 60 mL min(-1) 1.73 m(-2)) had higher plasma RBP4 concentrations than those with normal to mildly decreased GFR (55.3 +/- 24.6 vs. 40.8 +/- 15.4, P < 0.001). Patients in the top quartile of RBP4 concentrations had an increased adjusted odds ratio for moderately renal dysfunction compared with lower quartiles (4.68; 95% CI: 1.52-14.36, P = 0.007). The presence of microalbuminuria was not associated with RBP4. Plasma RBP4 concentrations were higher in those subjects with previous clinical arteriosclerosis than in event-free subjects (48.8 +/- 24.2 vs. 40.6 +/- 13.9, P = 0.045). The presence of retinopathy or polyneuropathy did not differ across RBP4 quartiles. Conclusions. Plasma RBP4 concentration might be a biomarker of nephropathy and cardiovascular disease in type 2 diabetic subjects.