Insulin resistance and coronary artery disease

The purpose of the present study was to quantitate insulin-mediated glucose disposal in normal glucose tolerant patients with angiographically documented coronary artery disease (CAD) and to define the pathways responsible for the insulin resistance. We studied 13 healthy, normal weight, normotensive subjects with angiographically documented CAD and 10 age-, weight-matched control subjects with an oral glucose tolerance test and a 2-h euglycaemic insulin (40 mU . m(-2). min(-1)) clamp with tritiated glucose and indirect calorimetry. Lean body mass was measured with tritiated water. All CAD and control subjects had a normal oral glucose tolerance test. Fasting plasma insulin concentration (66 +/- 6 vs 42 +/- 6 pmol/l, p < 0.05) and area under the plasma insulin curve following glucose ingestion (498 +/- 54 vs 348 +/- 42 pmol . l(-1). min(-1), p < 0.001) were increased in CAD vs control subjects. Insulin-mediated whole body glucose disposal (27.8 +/- 3.9 vs 38.3 +/- 4.4 mu mol . kg fat free mass (FFM)(-1). min(-1),p < 0.01) was significantly decreased in CAD subjects and this was entirely due to diminished non-oxidative glucose disposal (8.9 +/- 2.8 vs 20.0 +/- 3.3 mu mol . kg FFM(-1). min(-1), p < 0.001). The magnitude of insulin resistance was positively correlated with the severity of CAD (r = 0.480, p < 0.05). In the CAD subjects basal and insulin-mediated rates of glucose and lipid oxidation were normal and insulin caused a normal suppression of hepatic glucose production. In conclusion, subjects with angiographically documented CAD are characterized by moderate-severe insulin resistance and hyperinsulinaemia and should be included in the metabolic and cardiovascular cluster of disorders that comprise the insulin resistance syndrome or 'syndrome X'.