Hyperinsulinemia During Oral Glucose Tolerance Test is Associated with Increased Neointimal Tissue Proliferation After Coronary Stent Implantation in Nondiabetic Patients: a Serial Intravascular Ultrasound Study

Objectives: The purpose of this study was to determine whether hyperinsulinemia during the oral glucose tolerance test is associated with increased neointimal tissue proliferation after coronary stent implantation in nondiabetic patients.

Background: Although hyperinsulinemia induces increased vascular smooth muscle cell proliferation in experimental models, it has not been determined whether hyperinsulinemia is associated with increased neointimal tissue proliferation after coronary stent implantation.

Methods: Serial (postintervention and six-month follow-up) intravascular ultrasound (IVUS) was used to study 67 lesions treated with Palmaz-Schatz stents in 55 nondiabetic patients. Cross-sectional images within stents were taken at every 1 mm, using an automatic pullback, and a neointimal index was calculated as the ratio between the averaged neointimal area and averaged stent area. All patients underwent a 75-g oral glucose tolerance test. Plasma glucose (PG) and immunoreactive insulin (IRI) levels were measured at baseline and 1 and 2 h after the glucose load. The sum of PGs (sigmaPG) and the sum of IRIs (sigmaIRI) were calculated. Body mass index (BMI), lipid levels, and glycosylated hemoglobin levels were measured.

Results: There were 27 patients with normal glucose tolerance, and 28 patients with impaired glucose tolerance (IGT). The neointimal index in patients with IGT was greater than that in patients with normal glucose tolerance (42.9 +/- 14% vs. 24.9 +/- 8.3%, respectively, p < 0.0001). Linear regression analysis showed that the neointimal index at follow-up correlated well with sigmaPG (p < 0.0001), fasting IRI (p < 0.0001), sigmaIRI (p < 0.0001), triglyceride level (p = 0.018), and BMI (p < 0.0001). Multiple regression analysis revealed that sigmaIRI (p = 0.0002) and sigmaPG (p = 0.0034) were the best predictors of the greater neointimal index at follow-up.

Conclusions: Serial IVUS assessment shows that hyperinsulinemia during an oral glucose tolerance test is associated with increased neointimal tissue proliferation after coronary stent implantation in nondiabetic patients.