Evidence that kidney function but not type 2 diabetes mellitus determines retinol-binding protein 4 (RBP4) serum levels

Abstract

Objective: Retinol-binding protein 4 (RBP4) has been suggested to link 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 with type 2 diabetes mellitus.

Research Design and Methods: RBP4 serum concentration was determined by ELISA in 126 non-diabetic and 104 type 2 diabetic subjects. The study population was divided according their estimated glomerular filtration rate (eGFR, in mL/min/1.73 m²) in the groups eGFR > 90 (n = 53), eGFR 60 – 90 (n = 90), eGFR 30 – 60 (n = 38) and eGFR < 30 (n = 49). Each group was subdivided in non-diabetic and type 2 diabetic subjects.

Results: RBP4 serum concentration was elevated (2.65 μmol/L vs. 2.01 μmol/L, p < 0.001) and eGFR was reduced (56 mL/min vs. 74 mL/min, p < 0.001) in type 2 diabetic in comparison to non-diabetic subjects. By stratifying for eGFR, no more differences in RBP4 serum concentration were detectable between type 2 diabetic and non-diabetic subjects. A linear regression analysis revealed an influence of eGFR (r = −0.477, p < 0.001) but not HbA1c (r = 0.093, p = 0.185) on RBP4 serum concentration.

Conclusion: Existing human data showing elevated RBP4 levels in type 2 diabetic patients may be the result of moderate renal insufficiency rather than supporting the suggestion that RBP4 links obesity to type 2 diabetes.