Jean Davignon

Effects of glucagon on plasma lipids in different types of primary hyperlipoproteinemia

In order to further assess lipid-carbohydrate interactions in familial hyperlipoproteinemia, the acute and chronic effects of glucagon (3 mg i.m.) on plasma total cholesterol, triglycerides, nonesterified fatty acids, and glucose were studied in 24 hospitalized patients with primary hyperlipoproteinemia. A single dose of glucagon significantly lowered plasma triglycerides over a period of 4 hr in types IIa, IIb, and V, but did not produce any significant change in plasma cholesterol in all types of hyperlipoproteinemia. As compared with a control period (5 days), glucagon fiven daily over 10 days lowered plasma total cholesterol significantly in types III, V, IIa, and IIb, but did not either in II homozygous or in IV. Glucagon lowered plasma triglycerides significantly in types III and V but produced only a transient fall followed by a progressive rise in type IIa, IIb, and IV. In all subjects studied, a positive correlation was found between the increase in plasma glucose at 120 min after a single dose of glucagon and the decrease of plasma triglycerides during chronic administration of glucagon (r = 0.451, p < 0.05). The effect of glucagon on plasma lipids was discussed.

Pharmacokinetics of clofibrate in familial hypercholesterolemia.

Some patients with familial hypercholesterolemia (FHC, type II) are highly responsive to the cholesterol-lowering effect of clofibrate, while others are not only resistant to this effect but may even show an increase in plasma beta-lipoproteins. In an attempt to find an explanation for these striking differences, we have studied the pharmacokinetics of clofibrate in FHC patients at both extremes of responsiveness. The results disclosed several major differences between the two groups. Plasma clofibric acid (CPIB) measured during the chronic administration of the drug was significantly higher in the responders than in the non-responders, whether all patients in each group or only those with tendon xanthomas were considered. Plasma CPIB concentrations were negatively correlated with body weight in the responders but not in CPIB-resistant patients. They were also inversely proportional to decreases in plasma beta-lipoprotein cholesterol after chronic clofibrate administration in the responsive group, but directly proportional to increases in the non-responders. Increasing the dose of clofibrate from 2 to 3 g/day in CPIB-resistant patients always resulted in an increase in plasma CPIB levels, but this was followed in some patients by a decrease and in others by an increase in plasma beta-lipoprotein cholesterol concentrations, so that the overall effect was not statistically significant. The half-life of plasma CPIB was measured over 48 h after a single 1-g dose of clofibrate in patients who had not received this drug for at least 3 weeks. Half-life was significantly longer in the responsive patients. In addition, the bioavailability and the rate of absorption of clofibrate tended to be higher in this group than in the resistant patients. We suspect that both groups differ not only in the metabolic handling of clofibrate but also in some aspect of their beta-lipoprotein cholesterol metabolism.

Net esterification in vitro of plasma cholesterol in human primary hyperlipidemia

Net esterification of cholesterol was studied in vitro in the plasma of normal subjects and of patients with different types of hyperlipidemia. Net esterification of cholesterol was found to be significantly enhanced in types IIa, IV and V of human primary hyperlipidemia. In the plasma of all normal and hyperlipidemic subjects taken as a group, net esterification of cholesterol is significantly correlated with free cholesterol (p<0.001) and with phosphatidyl choline (p<0.001).