The metabolic syndrome (insulin resistance syndrome or syndrome X)

INTRODUCTION

Obesity, particularly abdominal obesity, is associated with resistance to the effects of insulin on peripheral glucose and fatty acid utilization, often leading to type 2 diabetes mellitus. Insulin resistance, the associated hyperinsulinemia and hyperglycemia, and adipocyte cytokines (adipokines) may also lead to vascular endothelial dysfunction, an abnormal lipid profile, hypertension, and vascular inflammation, all of which promote the development of atherosclerotic cardiovascular disease (CVD) [1-4]. A similar profile can be seen in individuals with abdominal obesity who do not have an excess of total body weight [5-8].

The co-occurrence of metabolic risk factors for both type 2 diabetes and CVD (abdominal obesity, hyperglycemia, dyslipidemia, and hypertension) suggested the existence of a "metabolic syndrome" [1,9-11]. Other names applied to this constellation of findings have included syndrome X, the insulin resistance syndrome, the deadly quartet, or the obesity dyslipidemia syndrome [12]. Genetic predisposition, lack of exercise, and body fat distribution all affect the likelihood that a given obese subject will become overtly diabetic or develop CVD.

It should be noted that questions have been raised as to whether the metabolic syndrome, as currently defined, captures any unique pathophysiology implied by calling it a "syndrome," and whether metabolic syndrome confers risk beyond its individual components. These questions raise uncertainty about the value of diagnosing metabolic syndrome in individual patients [13,14]. These arguments will be reviewed at the end of this discussion (see 'A critical look at the metabolic syndrome' below. Regardless of whether the metabolic syndrome is considered a unique entity, the need is unquestioned to identify and manage its individual components to decrease morbidity and mortality associated with diabetes and cardiovascular disease [15,16].

The definition, prevalence, clinical implications, and therapy of the metabolic syndrome will be reviewed here, including the limited data in children and adolescents. The pathogenesis of the relationship between obesity and type 2 diabetes and other causes of insulin resistance are discussed separately. (See "Pathogenesis of type 2 diabetes mellitus", section on 'Role of diet, obesity, and inflammation' and "Insulin resistance: Definition and clinical spectrum".)

The metabolic syndrome should not be confused with another disorder called syndrome X in which angina pectoris occurs in patients with normal coronary arteries. (See "Cardiac syndrome X: Angina pectoris with normal coronary arteries".)