H.J.J. van Barlingen

Triglyceride-rich lipoproteins in non-insulin-dependent diabetes mellitus: post-prandial metabolism and relation to premature atherosclerosis.

Non‐insulin‐dependent diabetes mellitus is frequently associated with premature atherosclerosis. Abnormalities in lipid and lipoprotein metabolism contribute to the increased risk of coronary heart disease. One of the most common lipid abnormalities in non‐insulin‐dependent diabetes mellitus is hypertriglyceridaemia. In the present paper, the authors review the metabolism of triglyceride‐rich lipoproteins, with special emphasis on the post‐prandial state. Several studies have demonstrated that levels of atherogenic post‐prandial lipoproteins are increased in patients with non‐insulin‐dependent diabetes mellitus. An increased supply of glucose and free fatty acids contributes to overproduction of very low‐density lipoproteins, increasing the burden of triglyceride‐rich lipoproteins on the common lipolytic pathway at the level of lipoprotein lipase. Low lipoprotein lipase activity and increased amounts of lipolysis‐inhibiting free fatty acids further impair lipolysis of post‐prandial lipoproteins. The clearance of atherogenic remnants is also delayed in non‐insulin‐dependent diabetes mellitus. There is evidence that a relative hepatic removal defect exists, secondary to impaired remnant‐receptor interaction and increased competition with very low density lipoprotein remnants. Correction of the increased post‐prandial lipaemia in non‐insulin‐dependent diabetes mellitus is advisable, as it may contribute to attenuation of the risk on premature atherosclerosis. When dietary measures and hypoglycaemic agents have failed to achieve acceptable lipid levels, lipid‐lowering drugs should be advised. Fibric acids and hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors are the drugs of choice.

Lipoprotein lipase gene mutations D9N and N291S in four pedigrees with familial combined hyperlipidaemia

Abstract. The role of the lipoprotein lipase (LPL) gene in familial combined hyperlipidaemia (FCH) is unclear at present. We screened a group of 28 probands with familial combined hyperlipidaemia and a group of 91 population controls for two LPL gene mutations. D9N and N291S. LPL‐D9N was found in two probands and one normolipidaemic population control. LPL‐N291S was found in four probands and four population controls. Subsequently, two pedigrees from probands with the D9N mutation and two pedigrees from probands with the N291S mutation were studied, representing a total of 24 subjects. Both LPL gene mutations were associated with a significant effect on plasma lipids and apolipoproteins. Presence of the D9N mutation (n = 7) was associated with hypertriglyceridaemia [2.69± 1.43 (SD) mmol L‐1] and reduced plasma high‐density lipoprotein cholesterol (HDL‐C) concentrations (0.92± 0.21 mmol L‐1) compared with 11 non‐carriers (triglyceride 1.75± 0.64 mmol L‐1; HDL‐C 1.23± 0.30 mmol L‐1, P= 0.03 and P= 0.025 respectively). LPL‐D9N carriers had higher diastolic blood pressures than non‐carriers. LPL‐N291S carriers (n= 6) showed significantly higher (26%) apo B plasma concentrations (174± 26 mg dL‐1) than non‐carriers (138± 26 mg dL‐1; P= 0.023), with normal post‐heparin plasma LPL activities. Linkage analysis revealed no significant relationship between the D9N or N291S LPL gene mutations and the FCH phenotype (hypertriglyceridaemia, hypercholesterolaemia or increased apo B concentrations). It is concluded that the LPL gene did not represent the major single gene causing familial combined hyperlipidaemia in the four pedigrees studied, but that the LPL‐D9N and LPL‐N291S mutations had significant additional effects on lipid and apolipoprotein phenotype.

Danaparoid: an antithrombotic agent without major impact on triglyceride hydrolysis capacity in humans.

van Barlingen HHJJ, van Beek A, Erkelens DW, de Bruin TWA (Department of Internal Medicine, Laboratory of Lipid Metabolism, University Hospital, Utrecht University, PO Box 85 500, 3508 GA Utrecht, The Netherlands). Danaparoid: an antithrombotic agent without major impact on triglyceride hydrolysis capacity in humans. J Intern Med 1997; 242: 125–29.