EGIR-RISC European Project: Relationship between Insulin Sensitivity and Cardiovascular Disease

Background and rationale for carrying out the study

Insulin resistance is generally regarded as a characteristic feature of type 2 diabetes mellitus and an important aspect in its pathogenesis [1]. Insulin resistance has also been associated with obesity, essential hypertension, dyslipidaemia, and poorly controlled type 1 diabetes mellitus [2]. Each of these insulin-resistant states carries an increased risk for atherosclerotic cardiovascular disease (CVD). Even in healthy people, the presence of hyperinsulinaemia (which provides a substitute way to measure insulin resistance), tends to cluster with lower glucose tolerance, higher arterial blood pressure, and mild dyslipidaemia [3,4]. In the Pima Indians (in North America) insulin resistance has been shown to predict development of type 2 diabetes [5], whereas in the San Antonio Heart Study hyperinsulinaemia was a predictor of diabetes, hypertension and dyslipidaemia [6].

Insulin resistance may itself be a risk factor for atherosclerotic cardiovascular disease. This important new disease mechanism constitutes an unresolved issue [7]. The evidence for it is largely based on studies in which the possibility of insulin resistance being the consequence rather than the cause of underlying subclinical cardiovascular disease could not be ruled out. All available studies are based on using hyperinsulinaemia as a surrogate (indirect) measure of insulin resistance [8-11]. Plasma insulin levels, it has become clear, are only an approximate estimate of in vivo insulin sensitivity. Furthermore, it is not known whether hyperinsulinaemia, insulin resistance or both contribute to the observed association with cardiovascular disease.

The primary objective of the EGIR-RISC project is to make use of the the expertise available in European to answer the question of whether insulin resistance is a risk factor for progression of carotid artery intima-media thickness (IMT, an index of CVD) independently of other risk factors such as lipids, body weight, haemostatic and inflammatory factors. Secondary aims are to study insulin resistance in relation to: 1) CVD progression measured by other indices such as ECG changes, ankle/arm pressure ratio, clinical symptoms and clinical events; 2) development of diabetes, dyslipidaemia and hypertension.

References

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