ABDOMINAL OBESITY, IMPAIRED NONESTERIFIED FATTY-ACID SUPPRESSION, ANDINSULIN-MEDIATED GLUCOSE DISPOSAL ARE EARLY METABOLIC ABNORMALITIES IN FAMILIES WITH PREMATURE MYOCARDIAL-INFARCTION

British Indian Asian men aged <40 years have a twofold to threefold in creased risk of death from coronary heart disease (CHD) compared with British whites. Epidemiological studies have suggested an association between glucose intolerance and hyperinsulinemia with premature CHD in Indian Asians. We tested the association of insulin action with myoca rdial infarction (MI) by using the hyperinsulinemic-euglycemic clamp i n 17 MI patients: 8 Punjabi Sikhs (PSMIs), 9 British whites (BWMIs), a nd 17 control subjects (9 PSCs and 8 BWCs), Metabolic factors associat ed with insulin resistance were investigated in 51 MI patients (24 PSM Is and 27 BWMIs) and 53 control subjects (28 PSCs and 25 BWCs). Famili al aggregation of defective insulin action was examined by studying fi ve pedigrees of Sikh survivors of MI. Sikh survivors of premature MI d emonstrated impaired insulin-mediated glucose uptake (P<.001) by use o f the clamp technique and nonesterified fatty acid (NEFA) suppression (P<.05) by using both clamp techniques and the oral glucose tolerance test, as compared with Sikh control subjects. White patients had impai red insulin-mediated glucose uptake but normal NEFA suppression. Metab olic factors usually associated with insulin resistance, including inc reased 2-hour post-oral glucose tolerance test triglycerides, smaller low density lipoprotein particle size, and increased plasminogen activ ator inhibitor-1, were present in white (all P<,05) but surprisingly a bsent in Sikh (all P>.05) MT patients compared with respective ethnic control subjects. Fasting glucose and total cholesterol levels did not differ between patients and control subjects. Abdominal obesity, impa ired NEFA suppression after oral glucose, and fasting hyperinsulinemia were present in Sikh MI patients and their nondiabetic first-degree r elatives compared with Sikh control subjects. PS survivors of prematur e MI demonstrated impaired insulin-mediated glucose disposal and NEFA suppression compared with ethnic control subjects. BWMI patients showe d abnormalities of carbohydrate, but not of NEFA, metabolism compared with white control subjects, Defects of insulin action manifested as a bdominal obesity, impaired NEFA suppression, and fasting hyperinsuline mia are present in Sikh MI patients and their asymptomatic, nondiabeti c, first-degree relatives. We suggest that these defects may be early metabolic markers that predict risk of premature MI among PSs.