Chapter 16

Over the last 60 years, there has been an impressive change in the human environment, behaviors, and lifestyle. These changes have resulted in an increase in both type 2 diabetes and macrovascular disease (myocardial infarction and cerebral ischemic disease). These rises must be attributed to the greater prevalence of obesity and consequent pathophysiologic condition, the so-called metabolic syndrome.1 It has been estimated that 190 million people worldwide have diabetes and it is likely that this will increase to 324 million by 2025.2 This epidemic is taking place both in developed and developing countries and the combination of obesity, diabetes, and metabolic syndrome is now recognized as one of the major threats to human health in the twenty-first century.

Considering the obesity epidemic as the major cause of increasing prevalence of metabolic syndrome, we assumed that obesity-related insulin resistance is the major cause of the metabolic derangement in this population. Insulin resistance is defined clinically as a state in which a given increase in plasma insulin in an individual causes less of an effect in lowering the plasma glucose than it does in a normal population.

The first description corresponding to the metabolic syndrome comes from a paper of Kylin, a Swedish physician who, in 1923, pointed out a clustering of hypertension, hyperglycemia, and gout.3 In 1947, Vague reported that obesity phenotype, android or male-type obesity, was associated with the metabolic abnormalities often seen with diabetes and with cardiovascular disease.4 The clinical importance of the syndrome was highlighted some years later by Reaven, who described the existence of a cluster of metabolic abnormalities, with insulin resistance as a central pathophysiological feature, and named it “Syndrome X.”5 The metabolic syndrome has several synonymous syndromes including the deadly quartet,6 insulin resistance syndrome,7 and dysmetabolic syndrome.8 More important than giving a name is providing a definition for the syndrome.

The first attempt at a global definition of the metabolic syndrome was in 1999 by the World Health Organization (WHO) Consultative Group9 (Table 16–1). Critics of the WHO definition identified several limitations, of which the most important related to the use of the euglycemic clamp to measure insulin sensitivity, making the definition virtually impossible to use either in clinical practice or epidemiological studies. Later, a new version of WHO definition had considered the fasting levels of insulin instead of the euglycemic clamp to measure insulin resistance.10 This definition also introduced waist circumference (94 cm for men and 80 cm for women) as the measure of centripetal adiposity and included modified cut points for other components.

Table 16–1. Current Definitions of the Metabolic Syndrome

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