Abstract
BackgroundInsulin resistance is accompanied by a cluster of metabolic changes, often referred to as metabolic syndrome. Metabolic syndrome is associated with an increased cardiovascular risk in patients with manifest arterial disease. We investigated whether insulin resistance is associated with an increased risk for cardiovascular events in patients with manifest arterial disease without known diabetes and whether this can be explained by the components of the metabolic syndrome or by inflammation.MethodsProspective cohort study in 2611 patients with manifest arterial disease without known diabetes. Homeostasis model of insulin resistance (HOMA-IR) was used to quantify insulin resistance. The relation of HOMA-IR with cardiovascular events (vascular death, myocardial infarction or stroke) and all cause mortality was assessed with Cox regression analysis. In additional models adjustments were performed for the single components constituting the metabolic syndrome and for inflammation.ResultsHOMA-IR increases with the number of metabolic syndrome components (mean HOMA-IR ± SD in groups with 0, 1, 2, 3, 4 and 5 metabolic syndrome components: 1.4 ± 0.7; 1.8 ± 1.2; 2.4 ± 1.5; 3.1 ± 1.8; 4.0 ± 2.6; and 5.6 ± 3.6 respectively). High HOMA-IR was independently associated with an increased risk of cardiovascular events (tertile 2 vs. 1 HR 1.92; 95%CI 1.20-3.08) (tertile 3 vs.1 HR 1.78; 95%CI 1.10-2.89) and with all cause mortality (tertile 2 vs. 1 HR 1.80; 95%CI 1.04-3.10) (tertile 3 vs.1 HR 1.56; 95%CI 0.88-2.75). These relations were not influenced by the individual components of metabolic syndrome or by inflammation.ConclusionsIn patients with manifest arterial disease without known diabetes, insulin resistance increases with the number of metabolic syndrome components, and elevated insulin resistance increases the risk of new cardiovascular events.
Highlights
Insulin resistance is accompanied by a cluster of metabolic changes, often referred to as metabolic syndrome
Waist circumference, fasting glucose level, triglyceride level and systolic blood pressure were higher in patients within the highest Homeostasis model of insulin resistance (HOMA-IR) tertile, whereas HDL-cholesterol level was lower
It is shown that HOMA-IR increases with an increment in the number of components of metabolic syndrome, adjusted for age and gender (p-value for trend < 0.001)
Summary
Insulin resistance is accompanied by a cluster of metabolic changes, often referred to as metabolic syndrome. We investigated whether insulin resistance is associated with an increased risk for cardiovascular events in patients with manifest arterial disease without known diabetes and whether this can be explained by the components of the metabolic syndrome or by inflammation. Both insulin resistance and metabolic syndrome are recognized as important factors in the development of cardiovascular disease [1,2]. Obesity-induced insulin resistance is considered to be the major driver of the clustering of interrelated metabolic disturbances (e.g. Metabolic syndrome is highly prevalent in patients with manifest arterial disease (46%)[15] and is associated with advanced vascular damage [16], thereby identifying those patients with an even higher cardiovascular risk. It is not known whether insulin resistance per se has an influence on the elevated cardiovascular risk or that it is mediated by the components of metabolic syndrome
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