Insulin and Risk of Cardiovascular Disease

Abstract

Background-Our purposes were to estimate the strength of the longitudinal relationship between hyperinsulinemia and cardiovascular diseases (CVD) from the available literature and to identify study characteristics that modify this relationship. Methods and Results-Articles were identified by means of a MEDLINE and Embase search and citation tracking. Eligible studies were prospective population-based cohort studies and nested case-control studies on the relationship between, on the one hand, fasting or nonfasting insulin levels and, on the other hand, myocardial infarction, death from coronary heart disease, and/or ECG abnormalities. Data were extracted pertaining to insulin measurements, type of outcome studied, adjustment for confounding, sex, mean age of the study population, follow-up period, insulin assay, and ethnic background (white or nonwhite). Associations of insulin and CVD were reexpressed in a uniform manner, an estimate of relative risk (RR) and 95% CI, to be used in meta-regression analyses. Twelve of 17 potentially eligible articles provided sufficient information. Overall, a weak positive association was found. The meta-analysis resulted in an estimated summary RR (95% CI) of 1.18 (1.08 to 1.29) for differences in insulin level, equivalent to the difference between the 75th and the 25th percentiles of the general population in the Netherlands. Ethnic background and type of insulin assay modified the relationship between insulin and CVD with borderline significance. Conclusions-Hyperinsulinemia is a weak risk indicator for the occurrence of CVD. The relationship between hyperinsulinemia and CVD was modified by ethnic background and by the type of insulin assay involved. (Circulation. 1998;97:996-1001.)

Glycemic index in chronic disease: a review

“…Although the mechanisms need to be elucidated some evidence suggests that hyperglycemia and hyperinsulinemia may lead to impaired fibrinolysis and thrombosis as shown by clinical (Calles-Escandon et al, 1998) and correlational studies (Juhan-Vague et al, 1989;Meigs et al, 2000), thereby increasing the risk of CHD (Gerstein & Yusuf, 1996;Ruige et al, 1998).…”

Increased expression of CCAAT/enhancer binding protein-β and -δ and monocyte chemoattractant protein-1 genes in aortas from hyperinsulinaemic rats

“…In the atherosclerotic lesion, vascular cells release a number of inflammatory cytokines, such as IL-6, IL-1, TNF-α and chemokine (C-C motif) ligand 2 (CCL2, also known as monocyte chemoattractant protein-1) [2]. The role of insulin in atherogenesis has long been a matter of debate, with many epidemiological studies [3] suggesting that hyperinsulinaemia is a strong independent risk factor for a cardiovascular event [4,5]. Several clinical studies, including the UKPDS [6], have shown that insulin treatment does not increase the risk of cardiovascular disease, therefore, it may be that a decrease in insulin action in the vascular tissue is responsible for increased cardiovascular risk in the hyperinsulinaemic state.…”

High cumulative insulin exposure: a risk factor of atherosclerosis in type 1 diabetes?

“…The benefits of aggressively glucose lowering by means of insulin therapy in type 2 diabetes remains, however, subject to debate. On the negative side, results from observational studies have indicated that high levels of endogenous insulin may increase CVD risk [4]. In addition, experimental studies in animals have shown that high exogenous insulin leads to increased atherosclerosis [5].…”