INSULIN-RESISTANCE, HYPERINSULINEMIA, AND HYPERTENSION - CAUSES, CONSEQUENCES, OR MERELY CORRELATIONS

Resistance to the metabolic effects of insulin and compensatory hyperi nsulinemia have been postulated to mediate human essential hypertensio n, especially when associated with obesity. Evidence supporting this h ypothesis has come mainly from epidemiological studies showing correla tions between insulin resistance, hyperinsulinemia, and blood pressure , and from short-term studies suggesting that insulin has renal and sy mpathetic effects that could raise blood pressure if the effects were sustained. However, there have been no studies demonstrating a direct causal relationship between chronic hypertension and insulin resistanc e or hyperinsulinemia in humans. The few long-term studies that have b een conducted in dogs and humans do not support the hypothesis that hy perinsulinemia causes hypertension or potentiates the hypertensive eff ects of other presser agents such as angiotensin II or increased adren ergic tone. To the contrary, multiple studies in dogs and in humans su ggest that the vasodilator action of insulin tends to reduce blood pre ssure. Although resistance to insulin's metabolic effects has been sug gested to be essential for hyperinsulinemia to cause hypertension, chr onic increases in plasma insulin concentrations do not cause hypertens ion in dogs or humans even in the presence of insulin resistance. Also , recent studies have also shown that the blood pressure-lowering effe cts of antihyperglycemic agents, initially believed to lower blood pre ssure by decreasing insulin resistance, may be unrelated to their effe cts on insulin sensitivity. Obesity appears to be a key factor in acco unting for correlations between insulin resistance, hyperinsulinemia, and hypertension, but increased blood pressure in obesity does not app ear to be mediated by insulin resistance and hyperinsulinemia. Althoug h insulin resistance and hyperinsulinemia may not be directly linked t o hypertension, there is increasing evidence that metabolic abnormalit ies associated with insulin resistance may increase the risk of cardio vascular disease (e.g., coronary artery disease) associated with hyper tension and Type II diabetes. For this reason, further studies of the long-term effects of insulin resistance on cardiovascular, renal, and metabolic functions are needed.