Retinol-binding protein 4 is associated with components of the metabolic syndrome, but not with insulin resistance, in men with type 2 diabetes or coronary artery disease

Abstract

Aims/hypothesis Retinol-binding protein 4 (RBP4) has recently been reported to be associated with insulin resistance and the metabolic syndrome. This study tested the hypothesis that RBP4 is a marker of insulin resistance and the metabolic syndrome in patients with type 2 diabetes or coronary artery disease (CAD) or in non-diabetic control subjects without CAD. Methods Serum RBP4 was measured in 365 men (126 with type 2 diabetes, 143 with CAD and 96 control subjects) and correlated with the homeostasis model assessment of insulin resistance index (HOMA-IR), components of the metabolic syndrome and lipoprotein metabolism. RBP4 was detected by ELISA and validated by quantitative Western blotting. Results RBP4 concentrations detected by ELISA were shown to be strongly associated with the results gained in quantitative Western blots. There were no associations of RBP4 with HOMA-IR or HbA 1c in any of the groups studied. In patients with type 2 diabetes there were significant positive correlations of RBP4 with total cholesterol, LDL-cholesterol, VLDL-cholesterol, plasma triacylglycerol and hepatic lipase activity. In patients with CAD, there were significant associations of RBP4 with VLDLcholesterol, plasma triacylglycerol and hepatic lipase activity, while non-diabetic control subjects without CAD showed positive correlations of RBP4 with VLDLcholesterol and plasma triacylglycerol. Conclusions/interpretation RBP4 does not seem to be a valuable marker for identification of the metabolic syndrome or insulin resistance in male patients with type 2 diabetes or CAD. Independent associations of RBP4 with pro-atherogenic lipoproteins and enzymes of lipoprotein metabolism indicate a possible role of RBP4 in lipid metabolism.

Role of Retinol-Binding Protein 4 in Obese Asian Indians with Metabolic Syndrome

“…However, the role of RBP4 in IR seems controversial. Earlier studies (12,13) have not found any correlation between RBP4 levels and IR, which is in contrast to other reports (31,32) wherein an association of RBP4 levels and IR has been in dicated. In this study also there was no correlation between RBP4 levels and IR in any of the groups.…”

“…The circulatory RBP4 levels are probably linked to the proatherogenic lipids (5). Serum RBP4 levels have been significantly and independently associated with hepatic lipase activity in patients with type 2 diabetes mellitus and coronary artery disease but not with controls (12). Hepatic lipase hydrolyses VLDL TG lea ding to the accumulation of proathe rogenic small, dense LDL particles, which are accom panied by the presence of increased TG and decreased HDL in MS (36).…”

“…However, the role of RBP4 in humans is controversial. While some reports have associated elevated RBP4 with IR (11), other studies have not demonstrated any role for RBP4 in IR (12,13); on the other hand, RBP4 levels have been implicated with markers of inflam mation and lipid profile (12).…”

RBP4: a controversial adipokine

“…In several studies, circulating RBP4 levels also did not correlate with insulin resistance, impaired glucose tolerance, T2D, or altered insulin secretion (10,72,(74)(75)(76)(77). In adipose tissue and muscle, insulin-sensitizing agent pioglitazone unexpectedly increased RBP4 gene expression (10).…”

Metabolic Aspects of Hepatitis C Virus Infection

“…Lowering RBP4 could be a new strategy for treating T2DM was also deduced then. However, inconsistent observations have been postulated simultaneously and continuously since the discovery of its role in IR (Erikstrup et al, 2006;Janke et al, 2006;Takashima et al, 2006;von Eynatten et al, 2007). Although there was an association between RBP4 and steatosis in G-1 CHC patients, Petta et al suggested RBP4 might be the expression of a virus-linked pathway to steatosis unrelated to IR (Petta et al, 2008).…”