Insulin and Atheroma: 20-Yr Perspective

Abstract

Many clinical studies have shown an increased insulin response to oral glucose in patients with ischemia of the heart, lower limbs, or brain. Hyperinsulinemia also occurs in patients with angiographically proved atherosclerosis without ischemia and thus appears to be related to arterial disease and not to be a nonspecific response to tissue injury. Fasting insulin levels and insulin responses to intravenous stimuli, including glucose, tolbutamide, and arginine, are normal, suggesting a gastrointestinal factor may be involved in the increased insulin response to oral glucose. In patients with atherosclerosis, insulin sensitivity appears to be normal or enhanced with respect to both glucose and lipid metabolism. Five population studies have shown that insulin responses to glucose are higher in populations at greater risk of cardiovascular disease. Many of the hyperinsulinemic populations also had upper-body obesity, hypertriglyceridemia, lower high-density lipoprotein (HDL) levels, and hypertension. These prospective studies support an independent association between hyperinsulinemia and ischemic heart disease, although their results differ in detail. Hyperinsulinemia is associated with raised triglyceride and decreased HDL cholesterol levels. Total and low-density lipoprotein (LDL) cholesterol is less closely related to hyperinsulinemia. Upper-body adiposity is associated (in separate studies) with coronary heart disease, diabetes, hyperinsulinemia, and hypertriglyceridemia. Insulin and blood pressure are closely related in both normotensive and hypertensive people. Although obesity and diabetes are often found in hypertensive people, hyperinsulinemia also occurs in nonobese nondiabetic hypertensive people. Thus, hyperinsulinemia is closely associated with a cluster of cardiovascular risk factors, i.e., hypertriglyceridemia, low HDL levels, hypertension, hyperglycemia, and upper-body obesity. There is a possibility that insulin has a role in the sex differences in ischemic heart disease incidence and their absence in diabetes, but additional work is required for its clarification. Long-term treatment with insulin results in lipid-containing lesions and thickening of the arterial wall in experimental animals. Insulin also inhibits regression of diet-induced experimental atherosclerosis, and insulin deficiency inhibits the development of arterial lesions. Insulin stimulates lipid synthesis in arterial tissue; the effect of insulin is influenced by hemodynamic factors and may be localized to certain parts of the artery. In physiological concentrations, insulin stimulates proliferation and migration of cultured arterial smooth muscle cells but has no effort on endothelial cells cultured from large vessels. Insulin also stimulates cholesterol synthesis and LDL binding in both arterial smooth muscle cells and monocyte macrophages.(ABSTRACT TRUNCATED AT 400 WORDS)

High cumulative insulin exposure: a risk factor of atherosclerosis in type 1 diabetes?

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Effect of the Angiotensin II Receptor Antagonist Telmisartan on Lipoprotein Lipase Mass in Preheparin Serum

“…Insulin resistance is known to affect the physiology of various organs, including skeletal muscles, adipose tissue and liver. Furthermore, recent basic and clinical studies have described the direct effects of insulin resistance at the level of the vessel wall [37][38][39][40] . LpL is known to exist in endothelial cells, showing activity, and LpL was also reported to exist on the coronary lumen surface 41) .…”

Role of plasma insulin concentration in regulating glucose and lipid metabolism in lean and obese Zucker rats

“…3 Insulin resistance is often accompanied by elevated concentrations of plasma insulin and abnormalities in lipid and lipoprotein metabolism, such as hypertriglyceridemia and low concentrations of high-density lipoprotein (HDL) cholesterol. 4,5 These metabolic abnormalities may be risk factors for non-insulindependent diabetes mellitus (NIDDM) and coronary heart disease. 6,7 Although there have been many reports showing a linkage between insulin resistance and glucose intolerance in diabetic animals, 8 Kodama et al clearly demonstrated that the linkage between them was not always observed because insulin resistance occurred before the manifestation of hyperglycemia in young db/db mice.…”