Insulin Resistance: A Multifaceted Syndrome Responsible for NIDDM, Obesity, Hypertension, Dyslipidemia, and Atherosclerotic Cardiovascular Disease

Abstract

Diabetes mellitus is commonly associated with systolic/diastolic hypertension, and a wealth of epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. Thus, when hypertensive patients, whether obese or of normal body weight, are compared with age- and weight-matched normotensive control subjects, a heightened plasma insulin response to a glucose challenge is consistently found. A state of cellular resistance to insulin action subtends the observed hyperinsulinism. With the insulin/glucose-clamp technique, in combination with tracer glucose infusion and indirect calorimetry, it has been demonstrated that the insulin resistance of essential hypertension is located in peripheral tissues (muscle), is limited to nonoxidative pathways of glucose disposal (glycogen synthesis), and correlates directly with the severity of hypertension. The reasons for the association of insulin resistance and essential hypertension can be sought in at least four general types of mechanisms: Na+ retention, sympathetic nervous system overactivity, disturbed membrane ion transport, and proliferation of vascular smooth muscle cells. Physiological maneuvers, such as calorie restriction (in the overweight patient) and regular physical exercise, can improve tissue sensitivity to insulin; evidence indicates that these maneuvers can also lower blood pressure in both normotensive and hypertensive individuals. Insulin resistance and hyperinsulinemia are also associated with an atherogenic plasma lipid profile. Elevated plasma insulin concentrations enhance very-low-density lipoprotein (VLDL) synthesis, leading to hypertriglyceridemia. Progressive elimination of lipid and apolipoproteins from the VLDL particle leads to an increased formation of intermediate-density and low-density lipoproteins, both of which are atherogenic. Last, insulin, independent of its effects on blood pressure and plasma lipids, is known to be atherogenic. The hormone enhances cholesterol transport into arteriolar smooth muscle cells and increases endogenous lipid synthesis by these cells. Insulin also stimulates the proliferation of arteriolar smooth muscle cells, augments collagen synthesis in the vascular wall, increases the formation of and decreases the regression of lipid plaques, and stimulates the production of various growth factors. In summary, insulin resistance appears to be a syndrome that is associated with a clustering of metabolic disorders, including non-insulin-dependent diabetes mellitus, obesity, hypertension, lipid abnormalities, and atherosclerotic cardiovascular disease.

Sagittal abdominal diameter is associated with insulin sensitivity in Chinese hypertensive patients and their siblings

“…2 In the Framingham Offspring Study, Meigs et al used factor analysis to analyse the relation among components of the syndrome. They identified that hypertension was linked to hyperinsulinaemia by obesity.…”

“…Insulin resistance has been proposed to be the key metabolic abnormality linked to hypertension. 2 However, not all hypertensive patients have insulin resistance. In a Swedish study using euglycemic hyperinsulinaemic clamps to assess insulin sensitivity, only about 25% hypertensive subjects were found to be insulin resistant.…”

The ‘carnivore connection’—evolutionary aspects of insulin resistance

“…Insulin resistance and=or hyperinsulinaemia leads to an increased secretion by the liver (Reaven & Chen, 1988) and a decreased clearance of VLDL triglycerides resulting from resistance to the action of insulin on lipoprotein lipase (DeFronzo & Ferrannini, 1991). These abnormalities result in high plasma triglyceride levels and various associated abnormalities of plasma lipoprotein metabolism, eg low HDL cholesterol concentrations and the presence of smaller and denser LDL particles.…”

Insulin sensitivity in Chinese ovo-lactovegetarians compared with omnivores

“…Impaired insulin sensitivity plays an important role in conditions such as obesity, hypertension, dyslipidemia, atherosclerosis (Reaven, 1988;DeFronzo & Ferrannini, 1991;Moller & Flier, 1991) and type II diabetes mellitus (DM) (DeFronzo, 1988). Impaired insulin sensitivity is also associated with impaired vascular endothelial function that may help to account for increased cardiovascular risk (Arcaro et al, 2002).…”