Atherosclerosis and Insulin Resistance AIR A cross-sectional study of 58-year old men

Abstract: The main aim of the study was to test the hypothesis that insulin resistance is associated with atherosclerotic disease in the carotid and femoral arteries as measured using the ultrasound technique in clinically healthy 58-year old men with varying degrees of obesity and insulin resistance. The subjects were recruited from the general population and were free from clinical cardiovascular disease, diabetes mellitus and treatment with antihypertensive, lipid-lowering and anti-diabetic drugs (n=818). The study group (n=391) was based on a stratified sampling of all subjects in the lowest and highest quintiles of an estimate of insulin sensitivity and a random selection (1/5) of those in quintiles 2-4 (n=391). Insulin sensitivity was measured in a randomly selected subgroup (n=104) by the euglycemic hyperinsulinemic clamp technique which is considered to be the "gold standard" method. A reproducibility study which was performed in 32 men showed that glucose infusion rate (GIR) for the final 60 minutes adjusted for fat free mass (DEXA) was the most accurate way to measure insulin sensitivity. There was a negative univariate correlation between insulin sensitivity (GIR) and common carotid IMT, but no association with the carotid bulb or common femoral artery IMT. Plasma concentrations of C-peptide, proinsulin, split proinsulin and insulin measured with cross-reacting RIA, but not intact insulin, were univariately associated with common carotid IMT. Intact insulin and C-peptide were associated with common femoral artery IMT. None of the insulin peptides were associated to carotid bulb IMT. There were numerically similar univariate correlations between risk factors which constitute the metabolic syndrome (waist-hip-ratio, triglycerides, HDL cholesterol), and other risk factors such as serum cholesterol, apoB and smoking with common carotid artery, carotid bulb and femoral artery IMT. Plasma insulin measured with cross-reacting RIA and proinsulin were independently related to insulin sensitivity (GIR). There were also an independent association between plasma insulin (RIA) and common carotid IMT. No independent association between common carotid artery IMT and insulin sensitivity or proinsulin was found in this study. In the studied population, the clustering of risk factors which constitute the metabolic syndrome showed a relation to small LDL particles, common carotid, carotid bulb and common femoral IMT. Small LDL particles were also related to common carotid, carotid bulb and common femoral IMT and plaques in the carotid and femoral artery. The conclusion is that in contrast to well-established cardiovascular risk factors such as blood pressure or smoking, insulin sensitivity and hyperinsulinemia were only weakly and inconsistently associated with IMT in the examined arterial beds. The study did not show any independent relationship between proinsulin and IMT. However, there was a consistent association between the metabolic syndrome and common carotid, carotid bulb and femoral artery IMT. Further, small LDL particles were related to the factors in the metabolic syndrome and IMT and plaque in the carotid and femoral arteries.