Evidence that kidney function but not type 2 diabetes determines retinol-binding protein 4 serum levels

OBJECTIVE--It has been suggested that retinol-binding protein 4 (RBP4) links adiposity, insulin resistance, and type 2 diabetes. However, circulating RBP4 levels are also affected by kidney function. Therefore, the aim of this study was to test whether RBP4 serum levels are primarily associated with kidney function or type 2 diabetes. RESEARCH DESIGN AND METHODS--RBP4 serum concentration was determined by enzyme-linked immunosorbent assay in 126 nondiabetic and 104 type 2 diabetic subjects. The study population was divided according to estimated glomerular filtration rate (eGFR) into the following groups: eGFR >90 ml/min per 1.73 [m.sup.2] (n = 53), 60-90 ml/min per 1.73 [m.sup.2] (n = 90), 30-60 ml/min per 1.73 [m.sup.2] (n = 38), and RESULTS--RBP4 serum concentration was elevated (2.65 vs. 2.01 µmol/l; P < 0.001) and eGFR was reduced (56 vs. 74 ml/min per 1.73 [m.sup.2]; P < 0.001) in type 2 diabetic vs. nondiabetic subjects, respectively. By stratifying for eGFR, no more differences in RBP4 serum concentration were detectable between type 2 diabetic and nondiabetic subjects. A linear regression analysis revealed an influence of eGFR (r = -0.477; P < 0.001) but not A1C (r = 0.093; P = 0.185) on RBP4 serum concentration. CONCLUSIONS--Existing human data showing elevated RBP4 levels in type 2 diabetic patients may be the result of moderate renal insufficiency rather than support for the suggestion that RBP4 links obesity to type 2 diabetes.
Retinol-binding protein 4 (RBP4) is a small visceral protein (~21 kDa), mainly synthesized in the liver and catabolized in the kidneys after glomerular filtration (1). To prevent the renal loss [...]