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CLINICAL STUDY

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

^a Division of Cardiology, Kobe General Hospital, Minatojima Nakamachi, Kobe, Japan
^* Division of Cardiology, Department of Internal Medicine, Kawasaki Medical University, Kurashiki, Japan

Manuscript received August 6, 1999; revised manuscript received March 15, 2000, accepted April 26, 2000.

Reprint requests and correspondence: Tsutomu Takagi, Division of Cardiology, Kobe General Hospital, Minatojima Nakamachi 4-6, Chuo-ku, Kobe, Japan
tx-tkg{at}ka2.so-net.ne.jp

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 (PG) and the sum of IRIs (IRI) 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 PG (p < 0.0001), fasting IRI (p < 0.0001), IRI (p < 0.0001), triglyceride level (p = 0.018), and BMI (p < 0.0001). Multiple regression analysis revealed that IRI (p = 0.0002) and PG (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.

Abbreviations and Acronyms   BMI = body mass index   DM = diabetes mellitus   HbA1c = glycosylated hemoglobin level   IGT = impaired glucose tolerance   IRI = immunoreactive insulin level   IVUS = intravascular ultrasound   MLA = minimal lumen area   MLD = minimal lumen diameter   NIDDM = non-insulin-dependent diabetes mellitus   OGTT = oral glucose tolerance test   PG = plasma glucose level   VSMC = vascular smooth muscle cell

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