THE REGULATION OF POSTPRANDIAL CELLULAR CHOLESTEROL-METABOLISM IN TYPE-2 DIABETIC AND NONDIABETIC SUBJECTS

The purpose of the study was to determine the effect of diabetes on th e regulation of postprandial cholesterol metabolism. Four groups of pa tients (n = 8 for each group) were examined: Type 2 diabetic patients with and without hypercholesterolaemia and non-diabetic subjects with and without hypercholesterolaemia. Serum lipoproteins, lipoprotein com position, cellular cholesterol, and cellular cholesterol synthesis wer e measured before and 4 h after a high calorie meal. The BMI for the h ypercholesterolaemic diabetic patients of 31.5 +/- 0.95 (SEM) was sign ificantly higher than that for the control group of 26.2 +/- 1.0 (p < 0.01). Fasting triglyceride levels were significantly higher in the no rmocholesterolaemic and hypercholesterolaemic diabetic patients and in the hypercholesterolaemic non-diabetic subjects (1.45 +/- 0.22, 2.27 +/- 0.34, and 1.58 +/- 0.18 mmol l-1, respectively) compared with norm ocholesterolaemic non-diabetic subjects (0.75 +/- 0.12 mmol l-1: p < 0 .01). The normocholesterolaemic and hypercholesterolaemic diabetic sub jects had significantly lower fasting serum high density lipoprotein ( HDL) (1.06 +/- 0.08 and 1.04 +/- 0.06 mmol l-1) compared to the corres ponding non-diabetic groups (1.29 +/- 0.11 and 1.45 +/- 0.17 mmol l-1, p < 0.05). The esterified/free cholesterol ratio of very low density lipoprotein (including chylomicrons VLDL-C) decreased postprandially i n all groups with an overall decrease of 1.33 to 0.83 (p < 0.01). Fast ing cellular cholesterol in mononuclear leucocytes from normocholester olaemic diabetic patients was similar to that for hypercholesterolaemi c diabetic (36.8 +/- 1.2 vs 40.6 +/- 5.5 mg g-1 protein) and non-diabe tic subjects (36.7 +/- 6.8 mg g-1 protein) and significantly greater t han cholesterol in cells from control subjects (29.7 +/- 1.5 mg g-1 pr otein, p < 0.05). In cells from control subjects only, there was a sig nificant postprandial increase in cholesterol to 39.4 +/- 5.2 mg g-1 p rotein (p < 0.05) and a corresponding postprandial reduction in choles terol synthesis from 149 +/- 34 to 102 +/- 33 nmol g-1 cell protein (p < 0.05). These results demonstrate a lack of correlation between seru m and cellular cholesterol in diabetic patients and an inability to su ppress cellular cholesterol synthesis postprandially in these patients . The differences may, in part, explain the increased deposition of ch olesterol in atheromatous plaques in normocholesterolaemic diabetic pa tients.