Insulin Resistance and Hyperinsulinemia

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'Insulin resistance' refers to the phenomenon of insensitivity of the cells of the body to insulin's actions. Different tissues may have different insulin sensitivities. For example, adipose tissue may be more sensitive to insulin than muscle tissue, thus favoring the deposition of fatty acids in adipose tissue and diminished fatty acid oxidation in muscle. Insulin resistance is usually associated with hyper-insulinemia. Hyperinsulinemia is an independent marker that predicts the development of atherosclerosis. A causal relationship between hypertension and hyperinsulinemia has not been well established. Hypertension associated with hyperinsulinemia could be due to increased renal sodium retention, increased intracellular free calcium, increased sympathetic nervous system activity, or increased intraabdominal pressure due to increased visceral fat deposition.

The mechanisms of insulin resistance with increasing obesity are not clear, but increased production of cytokines such as tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) is thought to play a role. Basal insulin levels increase with the degree of overweight, perhaps due to increased insulin secretion and/or reduced clearance by the liver. A reduced receptor number and/or post-insulin receptor defects may play a role in insulin resistance. Both basal hyperinsulinemia and insulin resistance decrease with weight reduction.

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