Diabetes atherosclerosis link

Recently, the sphingolipid ceramide, which is a product of fatty acyl CoA, has been identified as the link between excess nutrients (i.e., saturated fatty acids) and inflammatory cytokines (i.e., TNFa), to the induction of insulin resistance. Moreover, ceramide has been shown to be toxic to pancreatic P-cells, cardiomyocytes, and endothelial cells, which contributes to diabetes, hypertension, cardiac failure, and atherosclerosis (41). However, the role of ceramide in mediating insulin-resistance humans is still unclear (42). 

Even though the mortality from coronary heart disease has declined recently, atherosclerosis and related vascular disorders still are the leading cause of death in the Western world. The etiology of this disease is multifactorial, with hyperlipidemia, smoking, diabetes mellitus, hypertension, and obesity being well-established risk factors for the development of atherosclerosis. Dietary fat affects plasma lipids, lipoproteins, and vascular inflammation and, thus, is linked to atherosclerosis. 

Cardiovascular disease is a major cause of mortality and morbidity in industrialized countries. Several risk factors have been linked to incidence of cardiovascular disease and include hypertension, lipid abnormahties (high plasma cholesterol and triacylglycerol levels), atherosclerosis, obesity, diabetes, smoking, stress, heredity, and diet. Dietary GLA affects many of these parameters and is discussed below. 

Lipoprotein and hepatic lipases are important enzymes involved in the metabolism of chylomicrons and various fractions of lipoproteins. Both have been the subject of attention, as evidenced by numerous reviews (e.g., Garfinkel and Schotz, 1987 Wang eta/., 1992). This interest stems from the fact that abnormal lipoprotein metabolism has been linked to various disorders, including hyperchylomicronemia, hypercholesterolemia, hypertriglyceridemia, obesity, diabetes, and premature atherosclerosis. Genetic defects in both HL and LPL are now known to be the cause of at least some familial disorders of lipoprotein metabolism. 

DeFronzo, R.A. (2010) Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis the missing links. The Claude Bernard Lecture 2009. Diabetologia 53,1270-1287. 

Diet probably plays a secondary role to the primary metabolic aberration, insulin production. Impairment within the monkey to secrete adequate, functional quantities of insulin undoubtedly lies at the root of most of its inability to adequately control glucose and to maintain normal concentrations of lipids in the blood. Metabolic abnormalities arise because of decreasing reservoirs of insulin secretory capacity in the beta cells. Thus, in the Macaca nigra, there is a direct link between their inability to handle the carbohydrate in their diet, which stems from insulin insufficiency, and the manifestations of the diabetic syndrome which create enough metabolic abberrations to cause increased aortic atherosclerosis. 

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