Role of Insulin Resistance Associated With Compensatory Hyperinsulinemia in Ischemic Stroke

Abstract

Background and Purpose Although insulin resistance and hyperinsulinemia play a crucial role in the pathogenesis of atherosclerosis, little is known about their roles in ischemic stroke. The purpose of this study was to clarify whether insulin resistance and hyperinsulinemia are causative factors in the pathogenesis of ischemic stroke. Methods Thirty-four consecutive patients with ischemic stroke, who were normotensive, nondiabetic, and not obese, were classified into three groups—atherothrombotic infarction (n=16), lacunar infarction (n=10), and cardioembolic infarction (n=8)—based on clinical findings, brain imaging, and cerebral angiography. Both oral glucose tolerance tests and lipid analyses were performed. Insulin sensitivity was determined by the steady state plasma glucose method with the use of octreotide acetate. Data were compared with those of healthy control subjects (n=15). Results Steady state plasma glucose levels were significantly higher in the atherothrombotic infarction group compared with control subjects and the other two stroke groups, indicating the presence of insulin resistance in patients with atherothrombotic infarction. In the atherothrombotic infarction group, the 2-hour insulin area (area under the plasma insulin concentration curve) during a 75-g oral glucose tolerance test was significantly increased and dyslipidemic changes (increased triglyceride and apolipoprotein B, decreased high-density lipoprotein) were observed, whereas these changes were not found in the lacunar infarction and cardioembolic stroke groups. Conclusions Insulin resistance in association with compensatory hyperinsulinemia and dyslipidemia may be an important pathogenetic factor underlying the development of atherothrombotic infarction.