Abstract

Alterations in low-density lipoprotein (LDL) composition in diabetes affect its function with respect to control of de novo cholesterol synthesis. We examined the effect of 4 weeks of an oleic-acid-rich diet on LDL composition and function in eight Type 2 diabetic and eight non-diabetic control subjects. LDL (density 1.019-1.063 g/l) was isolated by sequential ultracentrifugation. LDL composition was measured and LDL fatty acids were determined by gas liquid chromatography. Cholesterol synthesis was measured by [14C]-acetate incorporation into the freshly isolated mononuclear leucocytes. Fasting blood glucose fell from 9.3 +/- 2.0 to 8.2 +/- 1.2 mmol/l (p < 0.05) and fasting serum insulin increased from 8.3 +/- 2.8 to 10.4 +/- 5.0 mIU/l (p > 0.05) in the diabetic patients. LDL oleic acid increased in the diabetic patients from 18.8 +/- 1.8% to 22.5 +/- 1.9% (p < 0.01) and in the non-diabetic subjects from 19.9 +/- 1.8% to 23.3 +/- 2.8% (p < 0.01). The LDL-esterified to free cholesterol ratios of 3.0 +/- 0.6 and 2.7 +/- 0.2 for the diabetic and non-diabetic patients were similar, and decreased significantly (p < 0.01) to 2.4 +/- 0.5 and 2.2 +/- 0.4, respectively. Baseline [14C]-acetate incorporation was similar in the two groups, and decreased after diet from 437 +/- 239 to 249 +/- 144 ng/g cell protein (p < 0.05) in the diabetic patients. There was a negative correlation between the LDL-esterified to free cholesterol ratio and the ratio of oleic to linoleic acid in the LDL (r = -0.39, p < 0.05) and a negative correlation between fasting blood glucose and LDL oleic acid in the diabetic patients (r = -0.51, p < 0.05). Enrichment of LDL with oleic acid appears to improve its ability to regulate endogenous cholesterol synthesis in both control and diabetic subjects. In the diabetic population, the diet had a favourable effect on glycaemic control.

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