Relationships of serum soluble E-selectin concentration with insulin sensitivity and metabolic flexibility in lean...

The markers of endothelial dysfunction, including soluble E-selectin (sE-selectin), are related to insulin resistance, which is associated with metabolic inflexibility, i.e., impaired stimulation of carbohydrate oxidation and impaired inhibition of lipid oxidation by insulin. Endothelial dysfunction may also be important in the metabolic syndrome. The aim of our study was to analyze the association of sE-selectin with insulin sensitivity and metabolic flexibility in lean and obese women. We examined 22 lean women (BMI < 25 kg m(-2)) and 26 overweight or obese women (BMI > 25 kg m(-2)) with normal glucose tolerance. A hyperinsulinemic euglycemic clamp and indirect calorimetry were performed. An increase in the respiratory exchange ratio in response to insulin was used as a measure of metabolic flexibility. Obese women had lower insulin sensitivity (P < 0.01), higher plasma sE-selectin (P = 0.007), and higher the metabolic syndrome total Z-score (MS Z-score) (P < 0.0001). Insulin sensitivity was negatively correlated with sE-selectin level (r = -0.24, P = 0.04). sE-selectin was associated with the rate of carbohydrate oxidation at the baseline state (r = 0.31, P = 0.007) and was negatively correlated with metabolic flexibility (r = -0.34, P = 0.003). MS Z-score correlated positively with sE-selectin level and negatively with metabolic flexibility and insulin sensitivity (r = 0.49, P < 0.0001, r = -0.29, P = 0.04, r = -0.51, P < 0.0001, respectively). In multiple regression analysis we observed that the relationship between metabolic flexibility and sE-selectin (β = -0.36; P = 0.004) was independent of the other evaluated factors. Our data suggest that endothelial dysfunction as assessed by plasma sE-selectin is associated with metabolic flexibility, inversely and independently of the other estimated factors.