Improved plasma lipids and body weight in overweight/obese patients with type III hyperlipoproteinemia after 4 weeks on a low glycemic diet.

BACKGROUND & AIM: The optimal diet for type III hyperlipoproteinemia is unknown. We examined blood lipids and body weight following low or high glycemic index diets in comparison with a lipid-lowering diet. MATERIALS AND METHODS: Sixteen overweight/obese men completed a cross-over study where they followed a standard lipid-lowering diet, a high and a low glycemic index diet, each lasting 4 weeks. Measurements were obtained at the end of each diet intervention. RESULTS: The lipid-lowering diet reduced significantly LDL cholesterol, and apolipoprotein B by 24%, and 17%, whereas high glycemic index increased LDL cholesterol with 21%. The low glycemic index diet reduced (p<0.05) total and LDL cholesterol and apolipoprotein B compared with the lipid-lowering diet. A moderate weight loss (p<0.05) was achieved after the lipid-lowering diet compared with baseline: 1.4 (-3.6-0.2; median, 95% CI) kg and similar to that after high glycemic index diet. A low glycemic index diet resulted in 2.4 (-3.9-1.4) kg weight loss compared with the high glycemic index diet (p<0.05). CONCLUSION: A low glycemic index diet may be superior to that of a standard lipid-lowering diet in type III hyperlipoproteinemia.

Severe xanthomatosis associated with familial apolipoprotein E deficiency.

AIM: To present the clinical, dermatological, and histological features of a patient with generalised xanthomatosis, familial apolipoprotein (apo) E deficiency, and unusual type III hyperlipoproteinaemia (HLP). METHODS: The underlying molecular defect was disclosed using molecular biological techniques. The unusual xanthomas were histologically analysed and the morphology of the abnormal lipoprotein particles examined using electron microscopy. RESULTS: A 10 base pair deletion in exon 4 of the proband's apo epsilon gene (base pairs 4037-4046 coding for amino acids 209-212 of the mature protein) was identified. This is predictive for a reading frameshift encoding a premature stop (TGA) in codon 229. The mutation is responsible for delayed catabolism of atherogenic lipoprotein remnants, lipid storage in monocyte/macrophages, and phenotypic expression of xanthomatosis early in life. CONCLUSIONS: Familial apo E deficiency is a rare genetic disease which offers the unique opportunity to study the impact of apo E on lipoprotein metabolism and development of atherosclerosis in humans.

Influence of probucol on enhanced LDL oxidation after fish oil treatment of hypertriglyceridemic patients.

The susceptibility of low-density lipoprotein (LDL) to oxidation was studied in hypertriglyceridemic men (5 with type III and 5 with type IV) at baseline on a low-saturated-fat, low-cholesterol diet, after 6 weeks of dietary supplementation with fish oil (Promega, 12 g/d), and after 6 weeks of fish oil combined with probucol (500 mg BID). The relative content of n-3 polyunsaturated fatty acids in plasma and LDL was increased during the two treatment periods, and a low alpha-tocopherol to n-3 polyunsaturated fatty acids ratio was observed. Plasma thiobarbituric acid-reactive substances (TBARS) levels were unchanged after 6 weeks of fish oil, but the ratio of lipid peroxides to the reduced triglyceride (TG) levels (MDA:TG) was significantly higher (P < .01). Addition of probucol lowered both absolute levels of TBARS (P < .01) and the MDA to TG ratio (P < .001). The susceptibility of LDL to Cu(2+)-catalyzed oxidation was evaluated over a 5-hour time course by determining TBARS formation, free amino group levels, and changes in LDL electrophoretic mobility. TBARS levels that were higher in native LDL (1.019 < d < 1.050 g/mL) after 6 weeks of fish oil than at baseline (P < .01) were reduced 52.3 +/- 11.3% by the addition of probucol (P < .001). With fish oil alone, TBARS production after exposure of LDL to Cu2+ for 5 hours was increased 17.0 +/- 5.8% compared with corresponding baseline values (P < .001), whereas a 64.1 +/- 14.3% reduction from the previous period was observed with fish oil + probucol (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Response to therapy of a type III hyperlipoproteinemic subject with the rare apolipoprotein E1 (Gly127----Asp, Arg158----Cys) variant.

In a preceding paper, we described the molecular biological defects in a patient with a severe form of the familial lipoprotein disorder type III hyperlipoproteinemia (HLP) and an unusual apolipoprotein (apo) E1 phenotype and epsilon 1/"null" genotype. The index case was a 60-year-old white male of German ancestry who suffered from a myocardial infarction at age 50 years. He had distinctly elevated levels of plasma lipids (triglycerides 551 mg/dl and cholesterol 747 mg/dl, respectively) and typical clinical signs of this inborn error of lipoprotein metabolism. His mutant apo E1 was shown to be identical to a rare (already described) apo E1 (Gly127----Asp, Arg158----Cys) variant. A second independent defect at the molecular level was a nucleotide deletion of a guanosine (G) in the codon for amino acid 31 of the proband's apo epsilon 3 allele. This single base deletion (not described before) changed his apo epsilon 3 allele to a nonfunctional "null" allele devoid of a stable gene product. Here we describe the response to combined dietary and medical treatment of the patient with this unusual form of type III HLP. His response to therapy was excellent, similar to patients with "classical" type III HLP and homozygosity for apo E2. However, the correct diagnosis of this familial lipoprotein disorder seems to be necessary, even in patients without the expected apo E2/2 phenotype, in terms of the prompt and beneficial response to therapeutic interventions.

Treatment of type III hyperlipoproteinemia with gemfibrozil to retard progression of coronary artery disease.

Eight type III hyperlipoproteinemic (type III HLP), homozygous E 2/2 patients were enrolled in two periods of long-term diet-gemfibrozil treatment. The combined therapy resulted in highly significant decreases in their low-density lipoprotein cholesterol, very-low density lipoprotein cholesterol, very-low density lipoprotein triglycerides, and increases in their high-density lipoprotein cholesterol during the first treatment period of 24 to 28 months. Type III HLP reasserted itself following an 8-week interruption of gemfibrozil therapy. Resumption of gemfibrozil therapy again lowered the high lipid-lipoprotein concentrations of these patients toward normal. Tuboeruptive xanthomata, palmar xanthoma, and xanthoma striata palmare subsided with treatment. Follow-up coronary arteriograms performed 2.5 to 3.0 years after initiation of diet-drug treatment showed stabilization of coronary arterial lesions, which was associated with improvement in exercise tolerance.

[Dietetic treatment of hyperlipoproteinemias]. / Traitement diététique des hyperlipoprotéinémies.

The authors mention the previous conditions to the prescription of a diet for primary hyperlipoproteinemia : definition of the metabolic disease and of its nutritional dependence, precise knowledge of earlier nutritional uses, demonstration of vascular risk factor linked to the hyperlipoproteinemia, i.e. obesity which always requires a hypocaloric diet. A low cholesterol and saturated fatty acid diet reduces by 10% the cholesterolemia, and sometimes exempts from use of medical drugs in moderate hypercholesterolemia. The exceptional hyperchylomicronemia are reduced by drastic reduction of the lipid fraction of the diet, which is compensated by use of MCT. The dietetic treatment of endogenous hypertriglyceridemia depends on their nutritional dependence : an alcohol dependence implies a complete suppression of alcoholic drinks. A glucid dependence implies the suppression of simple carbohydrates and a reduction of the glucidic fraction of the diet.

[Diet treatment of hyperliproteinemias]. / Traitement diététique des hyperlipoprotéinémies.

The authors mention the previous conditions to the prescription of a diet for primary hyperlipoproteinemia: definition of the metabolic disease and of its nutritional dependance, precise knowledge of earlier nutritional uses, demonstration of vascular risk factor linked to the hyperlipoproteinemia, i.e. obesity which always requires a hypocaloric diet. A low cholesterol and saturated fatty acid diet reduces by 10% the cholesterolemia, and sometimes exempts from use of medical drugs in moderate hypercholesterolemia. The exceptional hyperchylomicronemia are reduced by drastic reduction of the lipid fraction of the diet, which is compensated by use of MCT. The dietetic treatment of endogenous hypertriglyceridemia depends on their nutritional dependance: an alcohol dependance implies a complete suppression of alcoholic drinks. A glucid dependance implies the suppression of simple carbohydrates and a reduction of the glucidic fraction of the diet.

Reduction of high density lipoprotein cholesterol and apoliproprotein A-I concentrations by a lipid-lowering diet.

Nine hyperlipoproteinaemic patients were treated with a serum lipid-lowering diet during 4 weeks in a metabolic ward. The diet contained 35% energy from fat and the ratio between polyunsaturated and saturated fats (the P/S ratio) was 2.0. This treatment caused a reduction of the serum concentrations of the low density lipoprotein cholesterol (Chol) by 17% (P less than 0.01), of the apolipoprotein (apo) B by 27% (P less than 0.01), of high density lipoprotein (HDL) Chol by 15% (P less than 0.05) and of the apo A-I by 9% (P less than 0.02). The apo B/apo A-I ratio decreased by 19% (P less than 0.01). It is suggested that the reduced HLD Chol and apo A-I concentrations may be due to both the qualitative change to more polyunsaturated fats in the diet and to the reduction of the total dietary fat intake.

Dietary control of hyperlipoproteinemia.

A prospective study of the effect of dietary control of hyperlipoproteinemia (HLP) was carried out in 1,800 adult out-patients. The patients with type II A were treated with a diet low in saturated fat and cholesterol, with substitution of polyunsaturated fat. Additional carbohydrate and alcohol restriction was applied to patients with types II B, III and IV HLP. Caloric restriction was prescribed for overweighted patients. These diets were followed by sequences of stabilizing diets which were modified quarterly. After 7 years the best results were obtained for type IV (50%) followed by II B (22%). The nutritional HLP treatment, in keeping with the metabolic dependence, corrected HLP to one third of the initial sample, without improving the objective cardiovascular disturbances.