Abnormal metabolism of low density lipoprotein in diabetes mellitus

The association of atherosclerosis with lipoprotein disorders is well recognized. Since lipoprotein abnormalities are present in diabetes mellitus, it has been postulated that these abnormalities may constitute a link between diabetes and the accelerated atherogenesis that usually accompanies this disease. The quantitative alterations in lipoproteins are, however, relatively small to be solely responsible for the accelerated atherosclerosis present in diabetes. Other possible explanations have been thought. One of the most attractive hypotheses postulates that the biochemical abnormalities existent in diabetes could lead to the formation of lipoproteins with an abnormal composition and that lipoproteins so formed could interact abnormally with cells and be more atherogenic. We present data showing that the internalization and degradation by cultured fibroblasts of LDL isolated from diabetic patients in poor metabolic control is significantly decreased and that this decrease is further enhanced when the cells are incubated with lipoprotein depleted serum isolated from diabetic patients in poor metabolic control. We discussed several alterations in LDL composition and diabetic serum that may be responsible for the abnormal interaction between cultured cells and LDL isolated from diabetic patients. The relevance of these abnormal cell-LDL interactions in the development of atherosclerosis in diabetes mellitus is also discussed.