Insulin resistance is characterized by an abnormally low response of target cells to insulin and is associated with a clustering of risk factors for cardiovascular disease . Obesity is a rapidly increasing health problem in modern society and is also the strongest determinant of the degree of insulin sensitivity . However, conclusive evidence that insulin resistance is associated with atherosclerotic disease is still lacking.
The association between the degree of insulin resistance and atherosclerotic disease has so far been examined in a number of cross-sectional studies in different populations, using varying techniques. A few small studies have used the euglycaemic hyperinsulinaemic clamp technique. Laakso et al. found that insulin resistance was more common amongst subjects with ultrasound-assessed plaques in the carotid or femoral arteries. We performed a pilot study in hypertensive and normal men and were the first to report that insulin-mediated glucose uptake was inversely related to intima–media thickness (IMT) in the common carotid artery . Bressler et al. found that subjects with angiographically documented coronary artery disease were more insulin-resistant than a disease-free control group. The IRAS study, a large, tri-ethnic multicentre study in the USA, used the minimal model technique to assess insulin sensitivity and measured the intima–media thickness in the carotid artery with ultrasound in a mixed population of healthy subjects and patients treated for hypertension or diabetes . The results showed that insulin resistance was associated with atherosclerosis amongst Hispanics and non-Hispanic whites, but not blacks. Three other smaller studies have used the minimal model or other methods to measure insulin sensitivity and ultrasound techniques to assess vascular morphology in normal subjects, diabetics or hypertensives [7–9]. The results were inconsistent, as there was either a varying degree of association between insulin resistance and carotid artery IMT [7,8], or no association at all with plaques in the femoral artery . Most of these studies have also included subjects taking different types of medicine, including antihypertensive agents which are known to affect insulin sensitivity, thereby confounding the relationship to atherosclerosis .
So far, no study has examined the relationship between insulin sensitivity measured using the gold standard technique, i.e. the euglycaemic hyperinsulinaemic clamp method, and assessed IMT in both the carotid and femoral arteries in a population-representative sample. Accordingly, the present study was initiated with the objective of testing the hypothesis that insulin resistance is associated with subclinical atherosclerosis amongst clinically healthy 58-year-old men in the general population with varying degrees of obesity.