Key result
LDL suppression of cholesterol synthesis was reduced in diabetic and hypercholesterolaemic patients compared to controls (e.g., 35.2% vs 59.5%, p<0.01), but unaffected by hypertriglyceridaemia.
Observational
p-value: p=<0.01
Hypertriglyceridemia alters LDL composition but does not impair its ability to regulate cellular cholesterol synthesis, unlike diabetes and hypercholesterolemia.
Reduced LDL suppression in diabetes and hypercholesterolemia may reflect dysregulated cholesterol homeostasis; cross-sectional data leave causal and therapeutic implications open.
The present investigation was undertaken to examine the relationship between serum triglyceride and composition of lipoprotein. Six groups of patients were examined, three with Type 2 (non-insulin-dependent) diabetes and three without diabetes. The groups were further categorized on the basis of their serum cholesterol and triglyceride levels into normocholesterolaemic (serum cholesterol less than 6.5 mmol l-1) and hypercholesterolaemic (serum cholesterol greater than 6.5 mmol l-1) with and without hypertriglyceridaemia (serum triglyceride greater than or less than 3.5 mmol l-1). Low density lipoprotein (LDL) composition was determined and regulation of cholesterol synthesis by LDL was assessed by measuring its effect on [14C]-acetate incorporation into mononuclear leucocyte cholesterol. LDL from the hypercholesterolaemic diabetic patients had a significantly higher esterified cholesterol content when the patients were normotriglyceridaemic (1.14 +/- 0.04 vs 0.76 +/- 0.04 g g-1; p less than 0.01). The ability of LDL to suppress cholesterol synthesis (percent inhibition) was significantly less using LDL from the normocholesterolaemic diabetic patients or hypercholesterolaemic non-diabetic or diabetic patients compared with LDL from the normocholesterolaemic non-diabetic control subjects (47.4 +/- 3.9%, 39.1 +/- 5.1% and 35.2 +/- 4.1% vs 59.5 +/- 1.2%, p less than 0.01). However, hypertriglyceridaemia had no effect on LDL suppression of cholesterol synthesis. We conclude that hypertriglyceridaemia alters LDL composition but the alteration is not associated with the ability of LDL to regulate cholesterol synthesis.
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Owens et al. (1991) conducted an observational in Type 2 diabetes and hyperlipidaemia. Hypertriglyceridaemia, hypercholesterolaemia, and Type 2 diabetes vs. Normocholesterolaemic non-diabetic controls was evaluated on LDL suppression of cholesterol synthesis (percent inhibition) (p=<0.01). LDL suppression of cholesterol synthesis was reduced in diabetic and hypercholesterolaemic patients compared to controls (e.g., 35.2% vs 59.5%, p<0.01), but unaffected by hypertriglyceridaemia.
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