Hyperinsulinaemia as long‐term predictor of death and ischaemic heart disease in nondiabetic men: The Malmö Preventive Project

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Abstract
Nilsson P, Nilsson J‐Å, Hedblad B, Eriksson K‐F, Berglund G. (University Hospital, Malmö, Sweden) Hyperinsulinaemia as long‐term predictor of death and ischaemic heart disease in nondiabetic men: The Malmö Preventive Project. J Intern Med 2003; 253: 136–145. Objectives. Prospective studies have indicated that hyperinsulinaemia/insulin resistance is a risk factor for ischaemic heart disease (IHD), the risk decreasing with time of follow‐up. Few studies have so far investigated the role of hyperinsulinaemia in the prediction of long‐term total mortality. Setting. Section of Preventive Medicine, Department of Medicine, University Hospital, Malmö, Sweden. Subjects. A total of 6074 nondiabetic, middle‐aged, healthy Swedish males. Screening examination. We determined IHD risk factors including blood glucose and plasma insulin before and 2 h after an oral glucose tolerance test (OGTT). Total follow‐up time was 19 years. Hyperinsulinaemia was defined as values above the 10th decentile of fasting or 2 h insulin concentration. Main outcome measures. Total mortality and cardiac event (CE) rate for IHD. Results. Unadjusted relative risks (RRs) for both death and CE were J‐shaped with the highest relative risk (RR: 1.4–1.6) in the hyperinsulinaemic group compared with all other men. The RRs for death and CE were significant for fasting insulin but became nonsignificant after adjustment for other risk factors and also with a longer follow‐up. The risk of death in hyperinsulinaemic men, defined on the basis of 2‐h insulin level, increased with time of follow‐up and was still significantly increased after 19 years [RR: 1.32 (95% CI: 1.05–1.65], even after adjustment for other risk factors. Conclusions. Fasting hyperinsulinaemia was a predictor of total mortality and IHD in nondiabetic men, although not more significantly after adjustment for other risk factors and with lengthening of follow‐up time. The 2‐h postglucose hyperinsulinaemia appeared to be a stronger and independent predictor of mortality over long‐term follow‐up. These findings support the view that insulin resistance with associated cluster of risk factors predicts increased long‐term risk of mortality and IHD.