Insulin resistance as an independent risk factor for cardiovascular disease : clinical assessment and therapy approaches

Insulin resistance of glucose metabolism is a typical feature of type 2 diabetes mellitus but it can be observed in several other common clinical conditions and also in many apparently healthy subjects. Overall, as many as 30-40% of subjects from the general population are insulin resistant. The euglycemic hyperinsulinemic clamp is the gold standard technique in the assessment of insulin resistance but it cannot be used in epidemiological and clinical settings. In these situations a feasible surrogate approach might be the Homeostasis Model Assessment, based upon the measurement of fasting glucose and insulin concentrations. Insulin possesses a number of biological effects that can be regarded as anti-atherogenic. These effects are blunted in insulin resistant states, predisposing to the development and the progression of atherosclerosis. Yet, insulin resistance is strongly related to several classic cardiovascular risk factors such as hyperglycemia, obesity, high triglycerides, low HDL cholesterol, hypertension and microalbuminuria. Finally, insulin resistance is related to many non-traditional risk factors like PAI-1, fibrinogen, CRP and other markers of inflammation. Therefore, insulin resistance is the common denominator of a constellation of risk factors and in most cases it plays a causal role: it is a pathogenic factor of several risk factors. In a number of cross-sectional and longitudinal studies insulin resistance of glucose metabolism was able Revisión Av Diabetol 2005; 21: 255-261 E. Bonora Insulin resistance as an independent risk factor for cardiovascular disease: clinical assessment and therapy approaches Recibido: 7 de Enero de 2006 / Aceptado: 16 de Enero de 2006 Acrónimos: BMI, body mass index; CRP, C-reactive protein; CVD, cardiovascular disease; ESR, erythrocyte sedimentation rate; FFA, free fatty acid; HOMA, Homeostatic Model Assessment; HOMA-IR, HOMA insulin resistance score; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; IL-6, interleukin6; IST, insulin suppression test; ITT, insulin tolerance test; IVGTT+MinMod, intravenous glucose tolerance test with the minimal model analysis; PAI-1, plasminogen activator inhibitor-1; TNFα, tumor necrosis factor-α; UKPDS, UK Prospective Diabetes Study; VWF, von Willebrand Factor Endocrinology and Metabolic Diseases. University of Verona. Verona (Italy) Correspondencia: Prof. Enzo Bonora. Endocrinologia e Malattie del Metabolismo. Ospedale Maggiore I-37126 Verona, Italy e-mail: enzobonora@virgilio.it to predict prevalent or incident cardiovascular disease also independently of classic and, in some studies, also of non-traditional risk factors. Insulin sensitizing strategies based upon changes in life style (e.g., reducing caloric intake and/or increasing physical activity) in non-diabetic subjects as well as the use of insulin sensitizers like metformin or thiazolidinediones in type 2 diabetic subjects yielded a prevention of cardiovascular disease. These data confirm the major role played by insulin resistance in cardiovascular disease and suggest that this common metabolic disorder should be effectively targeted in order to reduce cardiovascular risk.