Factoring the metabolic X syndrome
Metabolic X syndrome is a multisystem disease that requires screening, counseling, assessment, and treatment for a wide variety of metabolic problems.
There are a number of risk factors for development of the metabolic syndrome, including family history, ethnicity, physical activity, and tobacco exposure. Children of parents with early heart disease are more likely to be overweight and have glucose impairment, insulin resistance, central obesity, and abnormal lipid levels.6,7 African American and Hispanic children experience higher rates of the components of metabolic syndrome compared with white children.4 Physical inactivity is associated with development of cardiovascular disease and the individual components of the metabolic syndrome, but increasing activity mediates these risk factors.8-11 Tobacco exposure also may predispose adolescents to the development of insulin resistance.12
The pediatrician needs to focus on identifying obese and overweight children and then aggressively manage risk factors. There are no specific guidelines, but it is prudent to look for elevated BP, hepatomegaly, and acanthosis nigricans in addition to assessing smoking status and family history, as all are associated with components of metabolic syndrome.
Abdominal obesity is associated with increased risk of cardiovascular disease. Although body mass index (BMI) is routinely calculated in pediatric practices, increased BMI does not always indicate increased waist circumference and accumulation of visceral fat. Increased waist circumference is associated with insulin resistance, hypertension, and dyslipidemia in pediatric patients.4 Measuring waist circumference will help the pediatrician identify patients that are at risk for pediatric metabolic syndrome. In the National Heart, Lung, and Blood Institute (NHLBI) Growth and Health Study, every 1-cm increase in waist circumference was associated with a 7.4% increase in risk of metabolic syndrome.13-15
Free fatty acid accumulation in the liver leads to insulin resistance and abnormalities in lipid levels. Elevated triglycerides and low HDL)levels are associated with insulin resistance. The American Academy of Pediatrics (AAP) recommends screening all pediatric patients aged between 9 and 11 years and again between 17 and 21 years, with earlier screening for children with risk factors for cardiovascular disease.16 In the NHLBI Growth and Health study, increasing triglycerides also increased risk of development of metabolic syndrome.
There is a strong relationship between elevated BP and insulin resistance. Insulin resistance impacts endothelial function, increases sympathetic tone, and inhibits the vasodilatory function of blood vessels. Elevated levels of free fatty acids also inhibit vasodilation. In fact, it is the cluster of insulin resistance and elevated lipid tests rather than any component alone that is most associated with elevated BP.4
As a result, the pediatrician needs to treat the entire cluster rather than just the individual components.
Whereas nonalcoholic fatty liver disease (NAFLD) is not part of the diagnostic criteria for metabolic syndrome, it commonly coexists and increases risk of significant liver pathology such as fibrosis, cirrhosis, and hepatic cellular carcinoma. In addition to its association with metabolic syndrome, NAFLD increases risk for cardiovascular disease, type 2 diabetes mellitus (T2DM), and chronic kidney disease through the same mechanisms of insulin resistance, inflammation, and dyslipidemia.17
Insulin resistance and T2DM
Insulin resistance leads to impaired fasting glucose and subsequent diagnosis of T2DM. Risk of developing diabetes increases 3- to 5-fold when metabolic syndrome components are present.4,18-20