Insulin resistance: trigger or concomitant factor in the metabolic syndrome.
The metabolic syndrome (MS) is a cluster of metabolic abnormalities with insulin resistance as a major characteristic. The main adverse consequence of the MS is cardiovascular disease (CVD). Complex, mutually reinforcing interactions between obesity and insulin resistance largely account for the pathogenesis of MS. Central pathophysiologic features include: insulin resistance, atherogenic dyslipidemia, chiefly present as low HDL-C together with increases in triglycerides and small dense, low density lipoprotein particles, hypertension, a proinflammatory state, with increases in acute-phase reactants, and a prothrombotic state. Although lifestyle and overeating seem to be the triggering pathogenic factors, genetic elements are also involved in the pathogenesis of MS. When present, insulin resistance results in impaired insulin action in insulin-sensitive tissues such as muscle, fat, and liver. Insulin resistance results in abnormalities of glucose metabolism, with reduced peripheral disposal of glucose in muscle and increased hepatic glucose output in the fasting state. But, most importantly, the progressively increasing concentration in circulating glucose leads to various abnormalities in insulin secretion. Elevated insulin levels themselves are atherogenic by inducing an oxidative stress and by stimulating sympathetic-nerve activity. Ectopic fat deposition, stress, proinflammatory state, and a maladaptive response of innate immunity may together concur to the development of the MS. When this condition is acknowledged, substantial modification of life style and correction of each single risk factor should be pursued without uncertainties and without hierarchical approach; this means that each risk factor should be treated and brought to target.
Avogaro
A
A
Unit of Metabolic Diseases, Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy. angelo.avogaro@unipd.it
D002318:Cardiovascular Diseases / Q000209:etiology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000150:complications; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000473:pathology; D024821:Metabolic Syndrome / Q000150:complications / Q000209:etiology* / Q000503:physiopathology; D012307:Risk Factors; D013312:Stress, Physiological / Q000150:complications
D005230:Fatty Acids, Nonesterified