Abdominal Obesity, Impaired Nonesterified Fatty Acid Suppression, and Insulin-Mediated Glucose Disposal Are Early Metabolic Abnormalities in Families With Premature Myocardial Infarction

From the Departments of Medicine (J.S.K., R.R.B., J.W., T.J.A., J.S.) and Radiology (L.M.B.), Royal Postgraduate Medical School, Hammersmith Hospital, London; the Institute of Biochemistry (C.J.P.), Royal Infirmary, Glasgow; the Wynn Institute for Metabolic Research (D.C.), London; and the Department of Medicine (S.P.), St Mary's Hospital Medical School, London, UK.

Correspondence to J.S. Kooner, MD, FRCP, Consultant Cardiologist/Senior Lecturer, National Heart and Lung Institute, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Rd, London W12 0NN, UK.

Abstract—British Indian Asian men aged <40 years have a twofold to threefold increased 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 myocardial infarction (MI) by using the hyperinsulinemic-euglycemic clamp in 17 MI patients: 8 Punjabi Sikhs (PSMIs), 9 British whites (BWMIs), and 17 control subjects (9 PSCs and 8 BWCs). Metabolic factors associated with insulin resistance were investigated in 51 MI patients (24 PSMIs and 27 BWMIs) and 53 control subjects (28 PSCs and 25 BWCs). Familial aggregation of defective insulin action was examined by studying five pedigrees of Sikh survivors of MI. Sikh survivors of premature MI demonstrated impaired insulin-mediated glucose uptake (P<.001) by use of 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 impaired insulin-mediated glucose uptake but normal NEFA suppression. Metabolic factors usually associated with insulin resistance, including increased 2-hour post–oral glucose tolerance test triglycerides, smaller low density lipoprotein particle size, and increased plasminogen activator inhibitor-1, were present in white (all P<.05) but surprisingly absent in Sikh (all P>.05) MI patients compared with respective ethnic control subjects. Fasting glucose and total cholesterol levels did not differ between patients and control subjects. Abdominal obesity, impaired NEFA suppression after oral glucose, and fasting hyperinsulinemia were present in Sikh MI patients and their nondiabetic first-degree relatives compared with Sikh control subjects. PS survivors of premature MI demonstrated impaired insulin-mediated glucose disposal and NEFA suppression compared with ethnic control subjects. BWMI patients showed abnormalities of carbohydrate, but not of NEFA, metabolism compared with white control subjects. Defects of insulin action manifested as abdominal obesity, impaired NEFA suppression, and fasting hyperinsulinemia are present in Sikh MI patients and their asymptomatic, nondiabetic, first-degree relatives. We suggest that these defects may be early metabolic markers that predict risk of premature MI among PSs.

Key Words: myocardial infarction • abdominal obesity • nonesterified fatty acids • insulin resistance

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