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Relationship between sensitivity to insulin and the risk of atherosclerotic vascular disease: the European RISC Project

14th national competition for scientific and technical research

Cellular and molecular mechanisms of atherosclerosis

Senior Researcher : Rafael Gabriel Sánchez

Research Centre or Institution : Fundación para la Investigación Biomédica. Hospital Universitario La Paz. Madrid.


The RISC II project is a European collaborative study in which our group at La Paz University Hospital in Madrid, the only Spanish centre participating, is taking part. The main aims of the project are:

To calculate the rate of progression of atherosclerotic damage, determined by changes in the intima-media thickness (IMT), degree of stenosis and affected area of the carotid arteries, depending on the degree of sensitivity to insulin. Furthermore,  to estimate the capacity that the presence of insulin resistance (IR) has to predict the development of diabetes, high blood pressure, lipid derangement and vascular atherosclerosis.3) Finally, this project also endeavours to evaluate the role that the interaction between environmental factors (obesity and cardiovascular risk factors) and genetic factors (IR polymorphisms) plays in the appearance of  type-2 diabetes mellitus and other hydrocarbonated metabolism disorders.

To do this, a multi-centre, European prospective (follow-up) study has been designed with a sample group of 1,500 healthy individuals, free from high blood pressure, dyslipemia or diabetes at the start of the study (75 have been provided by  our centre in Madrid), who undergo a further medical examination 4 years after the initial examination. An insulin test (insulinemic-euglycemic clamp) was carried out on each individual taking part at the start of the study (2002) and again after two years, to establish the degree of sensitivity to insulin, as well as an oral glucose tolerance test with excessive oral intake of 75 g. of glucose, in order to discover the presence of glucose intolerance and response to insulin. Furthermore, an exhaustive medical examination is carried out, with multiple anthropometric measurements, bioimpedance analysis of body fat distribution, ambulatory blood pressure monitoring (ABPM), haemodynamic monitoring, physical activity monitoring using an objective measuring system, the Actigraph, and a carotid Doppler scan to determine the intima-media thickness (IMT) of the carotid artery. In the 4th year of monitoring, a further medical examination is carried out, similar to those carried out at the start and after 2 years, adding special biochemical tests for: proinsulin, leptin, adiponectin (RIA), C-reactive protein (immunonephelometry), fibrinogen, PAI-1 and t-PA (ELISA). Genetic markers: TNFalpha, PAI-1, PPARgamma, IL-6, adiponectin, PC-1, IRS-1, calpain-10, lipoprotein lipase, hepatic lipase. The end goal is to find out if there is any link between the different genetic polymorphisms and molecular markers mentioned and the morphological changes (size and number of atherosclerotic plaques), quantitative changes (IMT) and degree of arterial stenosis.

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