Improvement of glycemic control by 1 year of insulin therapy leads to a sustained decrease in sE-selectin concentrations in type 2 diabetes.

OBJECTIVE To examine whether and how improvement of glycemic control by long-term insulin therapy decreases endothelial activation as measured by serum levels of the soluble adhesion molecules sE-selectin and vascular cell adhesion molecule (VCAM-1) and whether the drug used to lower blood glucose in addition to insulin influences such a response. RESEARCH DESIGN AND METHODS Circulating adhesion molecules were measured before and after 3 and 12 months of therapy in 81 patients with type 2 diabetes and 41 subjects without diabetes. The patients were treated with bedtime administration of NPH insulin combined with either glibenclamide (n = 19), metformin (n = 17), glibenclamide and metformin (n = 17), or morning administration of NPH insulin (n = 23). RESULTS Before insulin therapy, serum sE-selectin level was 71% higher in the patients with type 2 diabetes (77 +/- 4 ng/ml) than in the normal subjects (45 +/- 3 ng/ml, P < 0.001), whereas levels of sVCAM-1 were comparable (420 +/- 25 vs. 400 +/- 11 ng/ml, respectively). Glycemic control in all patients improved as judged from a decrease in HbA1c from 9.7 +/- 0.2 to 7.6 +/- 0.1% (P < 0.001). sE-selectin decreased to 67 +/- 4 ng/ml by 3 months (P < 0.001 vs. 0 months) and then remained unchanged until 12 months (70 +/- 4 ng/ml P < 0.001 vs 0 months). sVCnM-1 levels at 12 months was similar to those at 0 months (416 +/- 25 ng/ml). The change in glycemic control, measured by HbA1c, but not in other parameters, was correlated with the change of sE-selectin (r = 0.41, P < 0.001) within the patients with type 2 diabetes. The decreases in sE-selectin were not different between the various treatment groups. CONCLUSIONS We conclude that improvement in glycemic control by administration of insulin alone or insulin combined with either glibenclamide, metformin, or both agents induces a sustained decrease in sE-selectin, the magnitude of which seems to be dependent on the degree of improvement in glycemia. These data suggest that sE-selectin might provide a marker of effects of treatment of chronic hyperglycemia on endothelial activation.