Microalbuminuria is a major determinant of elevated plasma retinol-binding protein 4 in type 2 diabetic patients

Abstract

Plasma retinol-binding protein 4 (RBP4) may be a new adipokine linked to obesity-induced insulin resistance and type 2 diabetes. The impact of diabetic nephropathy on plasma RBP4 levels, however, is not known. We tested the hypothesis that microalbuminuria is associated with elevated plasma concentrations of RBP4 in type 2 diabetic subjects. Retinol, its binding protein and transthyretin (TTR) were measured in the plasma and urine of 62 type 2 diabetic subjects, 26 of whom had microalbuminuria. The results were compared to 35 healthy control subjects. Despite no differences in plasma retinol, concentrations of the RBP4 were significantly elevated in plasma of diabetic patients and significantly higher in those with microalbuminuria. The higher plasma levels of the binding protein in subjects with microalbuminuria were accompanied by both significantly elevated plasma TTR and increased urinary levels of RBP4. There were no correlations of plasma-binding protein levels and parameters of insulin resistance. Our study suggests that plasma RBP4 levels in type 2 diabetic patients are affected by incipient nephropathy. Therefore, further studies evaluating RBP4 as a regulator of systemic insulin resistance and type 2 diabetes will need to take renal function into consideration.

Retinol-binding protein 4 is associated with insulin resistance, but appears unsuited for metabolic screening in women with polycystic ovary syndrome.

“…A recent paper by Yao-Borengasser et al (34), in which RBP4 was measured in plasma and serum by the method used here, and by Western blotting, reported the same findings irrespective of the method of RBP4 measurement used. Furthermore, microalbuminuria has been described as a confounding factor that appears to increase RBP4-levels in diabetic patients (36). Since our analyses were restricted to non-diabetic patients significant distortion of the results by undiagnosed diabetic nephropathy appears unlikely.…”

Associations of metabolic factors, especially serum retinol-binding protein 4 (RBP4), with blood pressure in Japanese -the Tanno and Sobetsu study-

“…There was a significant positive correlation be- nificantly increased in end-stage renal disease and that renal excretion is a primary pathway for RBP4 clearance [25]. Previous studies with positive results for a relationship between RBP4 and insulin resistance were conducted for human subjects with impaired kidney function and/or type 2 diabetes mellitus [3,24]. On the other hand, studies conducted for human subjects with normal kidney function did not have positive results for a relationship between RBP4 and insulin resistance [5].…”

Serum Retinol-binding Protein 4 is Elevated and Positively Associated with Insulin Resistance in Postmenopausal Women

“…Second, it may be related to the population of the studies, which was a special postmenopausal group in our study, previous studies reported elevated RbP4 levels were correlated with T2dm were not in such a population. Third, it has been described that RbP4 is elevated in renal disease [36,37] and type 2 diabetic patients with microalbuminuria [38]. The duration of diabetes mellitus is likely to exert an impact on the progression of the renal complication.…”