Emergence of the metabolic syndrome in childhood: an epidemiological overview and mechanistic link to dyslipidemia

Abstract

Insulin resistance and type 2 diabetes are rapidly emerging as major disorders of childhood and adolescence. This appears to be closely linked to a rapid rise in the prevalence of obesity in the pediatric population. The development of insulin resistance appears to lead to a "metabolic syndrome" which includes a number of major complications such as dyslipidemia and hypertension. Childhood metabolic syndrome promotes the development of premature atherosclerosis and significantly increases cardiovascular disease risk early in life. The mechanisms linking obesity, insulin resistance, and metabolic dyslipidemia are not fully understood. This review will attempt to discuss some of the key mechanistic issues surrounding insulin resistance and its association with metabolic dyslipidemia. Most of the recent progress in this field has come from the use of genetic and diet-induced animal models of insulin resistance. New data from these animal studies particularly the fructose-fed hamster, a model of metabolic syndrome and dyslipidemia, will be reviewed. Evidence from both animal and human studies suggest a key role for insulin sensitive tissues such as adipose tissue, liver, and intestine in the development of an insulin resistant state and its associated lipid and lipoprotein disorders. The critical interaction of metabolic signals among these tissues appears to govern the transition from an insulin sensitive to an insulin resistant state that underlies dyslipidemic conditions.