title: Epidemiologic and clinical aspects of insulin resistance and hyperinsulinemia.
abstract: Epidemiologic studies have shown that insulin is a risk factor for coronary heart disease (CHD). Clinical studies have also demonstrated positive correlations between insulin and blood pressure, triglycerides, total cholesterol, fibrinogen, and plasminogen activator inhibitor. Moreover, there is an inverse correlation between insulin and high-density lipoprotein (HDL). These studies have provided evidence in support of the biologic plausibility of epidemiologic observations, but they have not clearly established insulin's role in the pathogenesis of human cardiovascular diseases (CVD) such as hypertension. In fact, there is considerable evidence that insulin resistance (abnormal nonoxidative glucose disposal), not hyperinsulinemia, is the primary insulin-related abnormality in human hypertension, and that hyperinsulinemia occurs as a response to insulin resistance. Skeletal muscle appears to be the primary site of insulin resistance in essential hypertension, although other organs, such as the kidneys and liver--key sites for cell and water homeostasis and lipoprotein regulation, respectively--may respond normally to insulin. Adipocytes also appear to be a site of insulin resistance. Thus, the putative interrelationship between hyperinsulinemia and insulin resistance, on the one hand, and with blood pressure and lipoproteins, on the other, is a complex one and may involve organ-specific insulin resistance. Altered cation transport is one of several mechanisms by which insulin resistance might raise blood pressure. The Na+, K(+)-ATPase and Ca(2+)-ATPase pumps are insulin sensitive. Thus, when insulin resistance is present, the activity of these pumps in the smooth muscle of the arterial wall might be reduced. This would lead to an intracellular accumulation of sodium and calcium, thereby sensitizing the vascular wall to pressor substances. Moreover, secondary hyperinsulinemia will occur, and insulin has been shown to stimulate sympathetic nervous system activity and to increase renal tubular absorption of sodium. Insulin is also a growth factor and therefore might have a trophic effect on the vessel wall, one that could initiate and/or sustain hypertension as well as atherosclerosis. Abnormal lipoprotein metabolism is yet another possible explanation for the accelerated atherosclerosis that has been observed in persons with abnormal carbohydrate tolerance and insulin resistance. Hyperinsulinemia and insulin resistance both play a role in the expression of elevated very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels as well as in the depression of HDL levels. Coronary risk reduction has been disappointing when blood pressure has been lowered with treatment regimens based on thiazide diuretics and/or beta blockers. Thiazides and some beta blockers may further impair tissue insulin sensitivity and often cause blood lipoprotein abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: School of Public Health, Division of Epidemiology, University of Minnesota, Minneapolis.
authors.forename: J M
authors.initials: JM
authors.lastname: Flack
authors.forename: J R
authors.initials: JR
authors.lastname: Sowers
mesh_terms: D000328:Adult; D000368:Aged; D001693:Biological Transport, Active; D001794:Blood Pressure / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D050260:Carbohydrate Metabolism; D002241:Carbohydrates / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D006946:Hyperinsulinism / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism; D006973:Hypertension / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D007333:Insulin Resistance / Q000502:physiology*; D008019:Life Style; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D009132:Muscles / Q000503:physiopathology; D009765:Obesity / Q000150:complications; D012307:Risk Factors
chemical_list: D002241:Carbohydrates; D008055:Lipids; D002118:Calcium