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The purpose of the study was to determine the effect of diabetes on the regulation of postprandial cholesterol metabolism. Four groups of patients (n = 8 for each group) were examined: Type 2 diabetic patients with and without hypercholesterolemia and nondiabetic subjects with and without hypercholesterolaemia. Serum lipoproteins, lipoprotein composition, cellular cholesterol, and cellular cholesterol synthesis were measured before and 4 h after a high calorie meal. The BMI for the hypercholesterolaemic diabetic patients of 31.5 ± 0.95 (SEM) was significantly higher than that for the control group of 26.2 ± 1.0 (p < 0.01). Fasting triglyceride levels were significantly higher in the normocholesterolaemic 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 normocholesterolaemic non-diabetic subjects (0.75 ± 0.12 mmol l−1: p < 0.01). The normocholesterolaemic and hypercholesterolaemic diabetic subjects had significantly lower fasting serum high density lipoprotein (HDL) (1.06 ± 0.08 and 1.04 ± 0.06 mmol l−1) compared to the corresponding 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 in all groups with an overall decrease of 1.33 to 0.83 (p < 0.01). Fasting cellular cholesterol in mononuclear leucocytes from normocholesterolaemic diabetic patients was similar to that for hypercholesterolaemic diabetic (36.8 ± 1.2 vs 40.6 ± 5.5 mg g−1 protein) and non-diabetic subjects (36.7 ± 6.8 mg g−1 protein) and significantly greater than cholesterol in cells from control subjects (29.7 ± 1.5 mg g−1 protein, p < 0.05). In cells from control subjects only, there was a significant postprandial increase in cholesterol to 39.4 ± 5.2 mg g−1 protein (p < 0.05) and a corresponding postprandial reduction in cholesterol synthesis from 149 ± 34 to 102 ± 33 nmol g−1 cell protein (p < 0.05). These results demonstrate a lack of correlation between serum and cellular cholesterol in diabetic patients and an inability to suppress cellular cholesterol synthesis postprandially in these patients. The differences may, in part, explain the increased deposition of cholesterol in atheromatous plaques in normocholesterolaemic diabetic patients.

This study investigates compositional differences in low density lipoprotein (LDL) subfractions and their relationship to cellular cholesterol synthesis. We examined ten normocholesterolaemic (serum cholesterol6.5 mM) non-diabetic subjects (group 1) and compared them with ten normocholesterolaemic (group 2) and ten hypercholesterolaemic (group 3) (serum cholesterol6.5 mM) type 2 (non-insulin-dependent) diabetic patients. Serum cholesterol levels for groups 1, 2 and 3 were 5.19 +/- 0.27, 5.20 +/- 0.27 and 7.51 +/- 0.31 mM. LDL (density 1.006-1.028 g/l) and LDL2 (1.028-1.063 g/l) were isolated by density gradient ultracentrifugation. A significantly greater proportion of cholesterol was carried in LDL2 than LDL1 in all groups. There was a significantly lower cholesterol/protein ratio in LDL1 from the hypercholesterolaemic diabetic patients compared with controls. The LDL esterified/free cholesterol ratio was significantly greater in both LDL1 and LDL2 in the hypercholesterolaemic diabetic patients compared with the other two groups. There was a negative correlation between inhibition of cholesterol synthesis and the esterified/free cholesterol ratio of both LDL1 (r = 0.56, P0.002) and LDL2 (r = 0.63, P0.001). Cellular cholesterol of 41.0 +/- 0.3 microgram/mg cell protein in the hypercholesterolaemic diabetic patients was also significantly higher compared with values of 30.32 +/- 2.0 and 34.1 +/- 4.2 micrograms/mg cell protein for the normocholesterolaemic non-diabetic and diabetic groups. In vitro LDL esterification led to a decrease in LDL receptor-mediated binding and resulted in a 40% reduction in the ability of the LDL to suppress cholesterol synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)