Novel Insights into the Pathogenesis and Management of the Metabolic Syndrome

Abstract

The metabolic syndrome, by definition, is not a disease but is a clustering of individual metabolic risk factors including abdominal obesity, hyperglycemia, hypertriglyceridemia, hypertension, and low high-density lipoprotein cholesterol levels. These risk factors could dramatically increase the prevalence of type 2 diabetes and cardiovascular disease. The reported prevalence of the metabolic syndrome varies, greatly depending on the definition used, gender, age, socioeconomic status, and the ethnic background of study cohorts. Clinical and epidemiological studies have clearly demonstrated that the metabolic syndrome starts with central obesity. Because the prevalence of obesity has doubly increased worldwide over the past 30 years, the prevalence of the metabolic syndrome has markedly boosted in parallel. Therefore, obesity has been recognized as the leading cause for the metabolic syndrome since it is strongly associated with all metabolic risk factors. High prevalence of the metabolic syndrome is not unique to the USA and Europe and it is also increasing in most Asian countries. Insulin resistance has elucidated most, if not all, of the pathophysiology of the metabolic syndrome because it contributes to hyperglycemia. Furthermore, a major contributor to the development of insulin resistance is an overabundance of circulating fatty acids. Plasma fatty acids are derived mainly from the triglycerides stored in adipose tissues, which are released through the action of the cyclic AMP-dependent enzyme, hormone sensitive lipase. This review summarizes the latest concepts in the definition, pathogenesis, pathophysiology, and diagnosis of the metabolic syndrome, as well as its preventive measures and therapeutic strategies in children and adolescents.

Keywords: Diabetes; Dyslipidemia; Hyperglycemia; Insulin resistance; Obesity.

Fig. 1. Criteria for clinical diagnosis of the metabolic syndrome in childhood and adolescence. The definition of the metabolic syndrome in this age group is central obesity plus the presence of two or more than two components.

HDL-C: high-density lipoprotein cholesterol.

Fig. 2

Obesity and insulin resistance play a key role in the pathogenesis of the metabolic syndrome in childhood and adolescence. Ch GS: cholesterol gallstones, NAFLD: nonalcoholic fatty liver disease.

Fig. 3. Because obesity is associated with increased risk of type 2 diabetes and cardiovascular disease, this may continue into childhood and adolescence until adulthood. Therefore, lifestyle modifications, including eating healthy diet and appropriate amounts of total calories, increasing physical activity, and maintaining the right weight, are the main options for the prevention of the metabolic syndrome by halting the development of metabolic abnormalities in childhood and adolescence.