Context: Retinol-binding protein (RBP) 4 is secreted by adipose tissue and is postulated to be a determinant of insulin sensitivity. The mechanisms of RBP4 insulin desensitizing action remain unclear.

Objective: The aim of the present study was to estimate the relationships between serum RBP4 concentration with insulin sensitivity and oxidative and non-oxidative glucose metabolism in lean and obese women.

Design and participants: The study group consisted of 67 women with normal glucose tolerance, 27 lean and 40 overweight or obese. Insulin sensitivity was estimated with the euglycemic hyperinsulinemic clamp. Glucose and lipid oxidation was measured with indirect calorimetry in the basal state and during the last 30 minutes of the clamp. Non-oxidative glucose metabolism was calculated in insulin-stimulated conditions by subtracting glucose oxidation from total glucose metabolism.

Results: There was no difference in serum RBP4 concentration between lean and obese women. Serum RBP4 was inversely related to insulin sensitivity and non-oxidative glucose metabolism in the entire group (r=-0.36, p=0.003 in both cases) and within the subgroups of lean (r=-0.41, p=0.034 and r=-0.41, p=0.031) and obese women (r=-0.41, p=0.009 and r=-0.40, p=0.01, respectively). These relationships were independent of potential confounding factors. RBP4 levels were not associated with oxidative metabolism of glucose or lipid.

Conclusions: Our data indicate that serum RBP4 is related to decreased insulin sensitivity mostly through its association with non-oxidative glucose metabolism.