Serum Insulin and Incident Coronary Heart Disease in Middle-aged British Men

Abstract

Earlier studies have not resolved the question of whether elevated circulating insulin levels are independently related to the development of coronary heart disease. Previous studies have not used a specific insulin assay and in all but a minority of studies that have addressed this issue it has not been possible to adjust for possible confounding due to high density lipoprotein (HDL) cholesterol. The authors examined the relation between serum insulin concentration and major coronary disease events (fatal and non-fatal myocardial infarction) in the British Regional Heart Study. The data are based on 5,550 men (aged 40-59 years) in 18 towns whose baseline, non-fasting serum samples were analyzed for insulin using a specific enzyme-linked immunoadsorbent assay (ELISA) method. Known diabetics were excluded. At 11.5 years of follow-up, 521 major coronary disease events had occurred, 261 fatal and 260 non-fatal. A nonlinear relation between serum insulin and coronary disease events was observed with an almost twofold increased relative risk in the 10th decile of the serum insulin distribution (> or = 33.8 mU/liter) relative to the 1st to the 9th deciles combined (age-adjusted relative risk (RR) = 1.9, 95% confidence interval (CI) 1.6-2.4). There was some attenuation of this association on cumulative adjustment for a wide range of biologic and life-style coronary disease risk factors, including HDL cholesterol, though it remained significant in the fully adjusted proportional hazards model (RR = 1.6, 95% CI 1.1-2.3). Similar associations between insulin and coronary disease events were seen in men with and without evidence of coronary disease at screening and in men with baseline serum glucose below the 80th percentile. These data are consistent with the hypothesis that a high level of serum insulin (hyperinsulinemia) is atherogenic, with a threshold effect. However, the markedly nonlinear form of the association and the attenuation in multivariate analysis strongly suggest that elevated insulin levels may only be a marker for common etiologic factors in the development of both coronary disease and non-insulin-dependent diabetes mellitus.

Proinsulin:insulin and insulin:glucose ratios as predictors of carotid plaque growth: a population-based 7 year follow-up of the Tromsø Study

“…Since our surrogate parameter of insulin sensitivity, IGR, was not related to the development of carotid plaques, our results lend support to earlier findings that proinsulin is an independent pro-atherosclerotic factor [2,8,17]. A tentative mechanism explaining this could be altered haemostasis through the association of proinsulin and increased plasminogen activator inhibitor-1 activity and increased fibrinogen levels [4,[18][19][20][21].…”

“…Both the so-called metabolic syndrome (high BP, obesity, dyslipidaemia, insulin resistance with hyperinsulinaemia) and increased proinsulin have been reported to predict atherosclerosis and CVD [1,2]. Whether increased proinsulin is simply an indicator of insulin resistance [3], or if it has other proatherogenic actions has been debated [4]. The relationship between proinsulin and CVD has not been fully clarified, and the results of earlier studies are inconsistent [1,5,6].…”

Tissue Plasminogen Activator, von Willebrand Factor, and Risk of Type 2 Diabetes in Older Men

“…Evidence regarding diabetes was obtained by reports from general practitioners with biennial reviews of the patients' notes (including hospital and clinic correspondence) through to the end of the study period. Cases of diabetes are based on selfreported diagnoses confirmed by primary care records, an approach that has been validated in the present study (25).…”

Hypertension, serum insulin, obesity and the metabolic syndrome

“…19 Serum insulin: Serum insulin concentration was determined by a two-site enzyme-linked immunoadsorbant assay (ELISA) using commercially available monoclonal antibodies raised against human insulin (Novo Nordisk A/S: Denmark), which do not cross-react with proinsulin. 20 Analyses were performed in the Department of Medicine, University of Newcastle upon Tyne, UK, on non-fasting samples, which had been stored at −20°C for between 13 to 15 years. In this laboratory no change in insulin levels was detected in repeat assays of 34 samples, stored at −20°C over an 8-year period (mean difference 0.19 mU/L, P = 0.5).…”