Hyperinsulinemia, Insulin Resistance, and Hypertension

Obesity is the most common reason for insulin resistance with consequent hyperinsulinemia. Other reasons for hyperinsulinemia are type II diabetes mellitus and a genetic predisposition with a family history of hypertension. Hyperinsulinemia is considered to cause blood pressure elevation and is generally accepted as an independent risk factor for atherosclerosis. However, insulin per se does not elevate blood pressure, but rather reduces total peripheral vascular resistance in experimental studies. Blood pressure might be elevated by other mechanisms secondary to hyperinsulinemia, however, such as enhanced renal sodium retention, elevated intracellular free calcium, and increased activity of the sympathetic nervous system. Indeed, subjects whose blood pressure is salt-sensitive exhibit hyperinsulinemia after glucose loading, and normotensive subjects with glucose-induced hyperinsulinemia will develop hypertension within 5 years more often than normoinsulinemic subjects. In primary hypertension, the incidence of insulin resistance and hyperinsulinemia is much higher than in normotensive controls. However, not all reported studies show a relationship between hyperinsulinemia and blood pressure elevation, and in some experimental studies no blood pressure elevation could be induced by prolonged hyperinsulinemia. Therefore, it is still unclear whether hyperinsulinemia induces hypertension or is only casually associated with it. Nevertheless, treatment of hyperinsulinemia is recommended to avoid secondary complications. Treatment should begin with weight reduction and physical exercise, which will improve insulin resistance. Hypertension benefits more from weight reduction than from exercise. If drug therapy of hypertension is required, angiotensin-converting enzyme (ACE) inhibitors and calcium-channel blockers are the drugs of first choice. In addition, beta-blockers and centrally acting drugs appear to be of certain benefit. However, diuretics must be used carefully, because they ameliorate insulin resistance, induce dyslipoproteinemia, and stimulate the sympathetic nervous system.