ABSTRACT
Obesity is strongly associated with multiple metabolic factors that aggregate in families. Some persons may carry genes that initially cause obesity and subsequently lead to metabolic abnormalities secondary to the long-term effects of obesity. Lipid abnormalities, insulin resistance or hyperinsulinemia, hyperglycemia, hyperuricemia, and frank disorders such as gout, diabetes, and hypertension are all strongly associated with obesity and often with each other. Insulin resistance is defined as decreased insulin-mediated rates of whole-body glucose uptake. The most common and convenient method to roughly estimate insulin sensitivity is to determine plasma insulin levels in a fasting blood sample or after a standard glucose challenge. Insulin clamp studies show that tissue sensitivity to insulin is reduced about 40% in individuals who are 40% over ideal body weight. Several investigators have proposed a hypothesis that hyperinsulinemia and/or insulin resistance promote sodium retention, which in turn fosters hypertension. More often obesity is likely attributable to multiple discrete genes or blended polygenes.
