The extended postprandial phase in diabetes.
Atherosclerosis is a major complication of diabetes, yet the reason for this remains obscure. Mechanisms of plaque formation are discussed and, in particular, metabolic alterations in the postprandial phase in diabetes are examined. A major metabolic effect of insulin deficiency is a failure to suppress non-esterified fatty acids. The importance of non-esterified fatty acids in the formation of the lipoproteins is discussed, as well as the effects of non-esterified fatty acids on insulin secretion and glucose transport, since the hallmark of Type II diabetes is insulin resistance. The genesis of large triacylglycerol-rich lipoproteins is examined and, in particular, the formation of the intestinally derived chylomicron particle is discussed in some depth with reference to microsomal triacylglycerol transfer protein and apolipoprotein B48, the structural protein for the intestinally derived lipoproteins. The role of microsomal triacylglycerol transfer protein polymorphisms is mentioned. The final section of this review examines alterations to the low-density lipoprotein particle that are found in patients with diabetes and the mechanisms that create an atherogenic low-density lipoprotein particle in diabetes. In conclusion, the lipoprotein cascade is severely disrupted in diabetes, with a major abnormality being found in the metabolism of non-esterified fatty acids. It appears that, at each level of disruption of the normal pathway, the alterations that have been described have the potential to accelerate cholesterol deposition in the plaque and to cause plaque disruption, explaining in part the increased cardiovascular disease found in diabetes.
D000818:Animals; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000494:pharmacology; D001161:Arteriosclerosis; D002318:Cardiovascular Diseases / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism; D002914:Chylomicrons / Q000378:metabolism; D003920:Diabetes Mellitus / Q000473:pathology*; D006801:Humans; D007003:Hypoglycemia / Q000473:pathology; D008074:Lipoproteins / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D019518:Postprandial Period; D014280:Triglycerides / Q000737:chemistry
D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D002352:Carrier Proteins; D002914:Chylomicrons; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein