Elevated serum retinol-binding protein 4 concentrations are associated with renal dysfunction and uric acid in type 2 diabetic patients

Background: While some studies have reported that retinol-binding protein 4 (RBP4) might induce insulin resistance, other studies have demonstrated that the presence of albuminuria in diabetic patients and increased uric acid are related to insulin resistance. Therefore, this study attempted to further investigate the relationship among serum RBP4, serum uric acid, and the severity of albuminuria in diabetic patients.

Methods: A total of 95 type 2 diabetic patients and 16 healthy subjects participated in this study. Diabetic patients were classified into normoalbuminuria, microalbuminuria and macroalbuminuria groups according to their urine albumin-to-creatinine ratio (ACR). Serum RBP4 was measured by an enzyme-linked immunosorbent assay (ELISA).

Results: Serum RBP4 was significantly elevated in type 2 diabetic patients with normoalbuminuria (43.4 +/- 14.9 microg/mL), microalbuminuria (57.3 +/- 24.2 microg/mL) and macroalbuminuria (64.7 +/- 27.6 microg/mL) as compared with control patients (32.6 +/- 10.0 microg/mL). Serum RBP4 was also significantly elevated in type 2 diabetic patients with microalbuminuria or macroalbuminuria as compared with the normoalbuminuric group. Serum RBP4 in diabetic subjects was positively correlated with triglycerides, uric acid and ACR, and negatively correlated with low-density lipoprotein cholesterol and estimated glomerular filtration rate (eGFR; with age and gender adjustment in each parameter). Multiple stepwise linear regression analysis showed that uric acid and eGFR remained significantly associated with serum RBP4.

Conclusions: Both eGFR and uric acid are significant determinants of serum RBP4, suggesting that the impaired renal clearance of early diabetic nephropathy affects RBP4 and indirectly supporting the hypothesized link among metabolic syndrome, uric acid and insulin resistance.