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Type IV hyperlipoproteinemia: effects of a caloric restricted type IV diet versus physical training plus isocaloric type IV diet.

Serum lipids, plasma insulin and glucagon, aerobic capacity, and body composition were examined in middle-aged men (X age = 44.2 years) with type IV hyperlipoproteinemia to determine the relative effectiveness of a caloric restricted type IV hyperlipoproteinemia diet (group A) versus physical training plus an isocaloric type IV diet (group B). After 9 weeks of the above interventions, reductions (P less than 0.01) in mean cholesterol levels from 213 to 186 (12% change) and from 205 to 185 mg/dl (9% change), and in triglyceride levels from 332 to 211 (29% change) and from 263 to 138 mg/dl (42% change) were found for groups A and B, respectively. A small reduction in mean fasting insulin level was found only in group B; this reduction appeared inversely associated with increases in aerobic capacity in group B (r = -0.66). Both interventions were without effect on fasting glucagon levels. The physical training program prescribed resulted in a 12% increase in aerobic capacity (group B). Significant mean body weight reductions of 7.7 lb (P less than 0.01) and 2.9 lb (P less than 0.01) were seen for groups A and B, respectively; these absolute body weight reductions differed significantly (P less than 0.05) between groups. Both groups significantly lost body fatness (P less than 0.01). These reductions in body weight and body fatness appeared independent of changes in lipid levels. These results demonstrate that both interventions reduce serum lipids in men with type IV hyperlipoproteinemia but that physical training plus an isocaloric type IV diet may be the more advantageous of the two regimens, since a greater percentage decrease and a more sustained reduction in serum triglyceride levels, and a greater reduction of fasting hyperinsulinemia were observed in group B.

Adult↗

[Treatment of primary hyperlipoproteinemias type IV with different biguanides (author's transl)].

In 12 patients with primary type IV hyperlipoproteinemia the lipid lowering effect of constant doses of the biguanides metformin, phenformin and buformin was compared. After a 2 months dietary period bodyweight and initial triglyceride and cholesterol plasma concentrations were stabilized. The three biguanides were given for two months each, and this 6 months drug period was followed by another dietary period. While, 0.15 g phenformin and 2.55 g metformin reduced triglycerides by about 50% the reduction by 0.30 g buformin was only half. This was due to 4 nonresponders with initial triglycerides of more than 700 mg/100 ml. In contrast the triglyceride lowering effect of the other two biguanides was positively correlated to the pretreatment triglycerides. The cholesterol lowering effect of biguanide treatment was far less pronounced. There were no significant alterations of body weight and no influence on basal insulin and glucose concentrations. In conclusion, all three biguanides tested in a dosis of 3 tablets each are effective in lowering triglycerides although differing in efficiency and depending from the degree of typ IV hyperlipoproteinemia.

Biguanides↗

[Study of lipid metabolic coefficient K2 in patients with hyperlipoproteinemia type IV before and after reduction of triglyceride level by adapted diet therapy].

An intravenous fat tolerance test (IV FTT) was performed in a group of patients with type IV hyperlipoproteinemia before and after reduction of triglyceride level, the latter is obtained through a diet adapted to the nutritional sensitivity, body weight remaining constant. Before the diet the increase in cholesterol (CT) and triglycerides (TG) was related in both obese and non-obese patients to an increase in very-low-density lipoproteins (VLDL), while other lipoprotein fractions were not affected. In these patients, K2 is significantly lower than in controls whatever the nutritional sensitivity. However, K2 is lower in obese patients than in patients with normal weight, VLDL-CT and VLDL-TG are tremendously reduced by the relevant diet and K2 is constantly and significantly increased, although it does not reach a normal value in obese subjects. There is a highly significant correlation between VLDL-TG levels and K2 in obese and non-obese subjects. Several physiopathological explanations are discussed to account for the variation of K2 according to TG levels. The results obtained support the view that the K2 defect is secondary to the hyperlipoproteinemia.

Adult↗

A comparative study of the effects of acipimox and clofibrate in type III and type IV hyperlipoproteinemia.

Acipimox, an analogue of nicotinic acid, is a hypolipidemic drug with antilipolytic activity. Ten patients with type III and 10 with type IV hyperlipoproteinemia participated in a comparative open cross-over study of the effect of acipimox (750 mg/day) and clofibrate (2 g/day) on lipoproteins, apoliproproteins and postheparin lipase activities during 6 weeks. During acipimox treatment 2 type III patients complained of flushing, resulting in one drop-out. In the type III patients serum cholesterol decreased 30% (P less than 0.01) during treatment with acipimox and 24% (P less than 0.01) with clofibrate, and serum triglycerides 48% (P less than 0.01) and 34% (P less than 0.01), respectively. In the type IV patients serum cholesterol remained unchanged and serum triglycerides decreased 34% (P less than 0.05) and 35% (P less than 0.01), respectively. HDL cholesterol increased during treatment with both drugs in both groups between 6 and 15% (P less than 0.05) mainly due to a rise in HDL3 cholesterol (d greater than 1.100 g/ml). LDL cholesterol increased significantly during treatment with clofibrate, but not with acipimox. There were no or slight changes in the apoproteins A and B. Postheparin lipoprotein lipase increased during clofibrate treatment and hepatic lipase decreased during acipimox treatment. We concluded that acipimox in a dose of 750 mg/day has a similar hypolipidemic effect as 2 g clofibrate daily in type III and IV hyperlipoproteinemia.

Adult↗

The effect of weight reduction on biliary lipid metabolism in patients with hyperlipoproteinemia type IV.

Nine slightly obese patients with hyperlipoproteinemia type IV were studied, before and after a mean weight reduction of about 15 kg, with respect to bile acid kinetics, cholesterol balance and biliary lipid composition. The bile acid pool size was not consistently changed. The synthesis of cholic acid and chenodeoxycholic acid was decreased by about 65% and 50%, respectively. The net steroid balance, calculated as bile acid synthesis plus fecal excretion of neutral steroids minus dietary cholesterol intake, was reduced by about 50%. In all but one of the patients bile was supersaturated with cholesterol but weight reduction was not associated with any change in cholesterol saturation. The results indicate that hyperlipoproteinemia type IV may be associated with some metabolic defects which are not corrected for by weight reduction.

Adult↗

Studies of triacyglycerol structure of very low density lipoproteins of normolipemic subjects and patients with type III and type IV hyperlipoproteinemia.

The triacylglycerols of very low density lipoproteins (VLDL-TG) were analyzed in samples from normal subjects and patients with Frederickson's Type III and Type IV hyperlipoproteinemia. VLDL were obtained by conventional ultracentrifugation, and the triacylglycerols were isolated by thin-layer chromatography (TLC). Representative sn-1,2(2,3)- and sn-1,3-diacylglycerols were generated by Grignard degradation of the triacylglycerols, and were resolved by TLC on borate-treated silica gel. The molecular association of the fatty acids in the diacylglycerol moieties was determined by gas-liquid chromatography with mass spectrometry (GC/MS) of the tertiary-butyldimethylsilyl ethers. The positional distribution of the fatty acids was established by the Brockerhoff stereospecific analysis. The results showed a marked asymmetry in the distribution of the fatty acids in all samples, with the saturated acids predominantly in the sn-1-position and the unsaturated fatty acids distributed about equally between the sn-2- and sn-3-positions. In all instances, the molecular species composition of the sn-1,2-, sn-2,3- and sn-1,3-diacylglycerols was found to be similar to that calculated for 1-random 2-random 3-random distribution of triacylglycerols. There were marked differences in the quantitative composition of the molecular species of the VLDL-TG between normal subjects and patients, but these discrepancies were attributed to differences in the fatty acid composition of the samples.

Diglycerides↗

Polyarthritis associated with type IV hyperlipoproteinemia.

Twelve patients had undiagnosed articular disease associated with type IV hyperlipoproteinemia. Objective joint findings involved both large and small joints. Disease was bilateral but asymmetrical and oligoarticular. Synovitis was midly inflammatory and persistent rather than episodic in natrue, and disability was minimal. Serial slinical, laboratory, and radiographic assessment excluded other currently recognized forms of rheumatic disease. Joint radiographs demonstrated large metaphyseal and epiphyseal cysts in five patients. Synovioanalysis and synovial biopsy results are reported in two patients. These cases appear to constitute a clinically homogeneous group. The concurrence of a distinctive articular syndrome and type IV hyperlipoproteinemia suggests a possible causal relationship.

Adult↗

A newly identified heterozygous lipoprotein lipase gene mutation (Cys239-->stop/TGC972-->TGA; LPLobama) in a patient with primary type IV hyperlipoproteinemia.

We investigated measures for identification of heterozygous lipoprotein lipase (LPL) deficiency in unrelated subjects with primary type IV hyperlipoproteinemia in order to acquire a helpful clue for understanding the correlation between hypertriglyceridemia and the status of being a heterozygous carrier of an LPL gene variant. Identification of heterozygous LPL deficiency was performed by monitoring the immunoreactive LPL mass in postheparin plasma (PHP) using our developed sandwich-enzyme immunoassay technique for first screening. Then, in subjects found to have half or less than half of the control LPL mass value in PHP, the polymerase chain reaction-single strand conformation polymorphism method was used to detect LPL gene aberrations as a second screening. This approach was evaluated as being useful as it succeeded in identifying a subject (proband KD) with heterozygous LPL deficiency. The mutation in the LPL gene of proband KD was newly characterized as a nucleotide C972 to A transversion in exon 6, resulting in substitution of a premature termination codon (TGA) for Cys239 (TGC). This nonsense mutation, designated as LPLobama, creates an MboI restriction site and eliminates an HgiAI restriction site, and this allows rapid screening of subjects with type IV as well as type I hyperlipoproteinemia for the mutation. The homozygous state for the LPLobama allele resulted in neither detectable LPL activity nor immunoreactive LPL mass in PHP, and this was seen in two of proband KD's siblings.

Adult↗

Generalized tuberous xanthoma with type IV hyperlipoproteinemia.

We report a case of generalized tuberous xanthoma with type IV hyperlipoproteinemia in a 42-year-old woman who had multiple, grouped, yellowish brown nodules bilaterally on the trunk, knees, elbows, palms, soles, and dorsal sides of multiple interphalangeal joints. On laboratory examination, serum triglyceride levels were elevated, and the pre-beta-lipoprotein band was increased on lipoprotein electrophoresis. Histopathologic findings showed many Touton giant cells and numerous foam cells in the dermis.

Adult↗

Altered platelet deformability in patients with type IIa and type IV hyperlipoproteinemia.

Platelets from subjects with hyperlipoproteinemia (HLP) differ from normal platelets in lipid composition and function depending upon the phenotypic classification of the HLP. The present study has evaluated the deformability of platelets from human subjects with type IIa and type IV HLP. Platelets suspended in autologous plasma diluted 30-fold with buffer were aspirated into micropipettes 0.7-0.8 microns in diameter by step-wise increment in tension, and the resulting extension lengths were recorded. Platelets from type IIa subjects could not be aspirated as far into the micropipettes as normal platelets. However, less tension was required to reach maximum cell extension than with normal platelets, and the initial extension lengths and slopes of the stress responses were the same as the control. In contrast, platelets from subjects with type IV HLP showed a generalized increase in deformability. The initial cell extensions aspirated from type IV platelets were longer than normal, and larger maximum cell extensions were achieved at lower tensions than control platelets. The type IV platelets were also mechanically fragile and fragmented at lower tensions than control or type IIa platelets. The variance in platelet deformability between subjects of the same phenotype was not directly correlated to plasma lipid or lipoprotein concentrations. This study confirms alterations in the structural organization of platelets from subjects with type IIa and type IV HLP.

Blood Platelets↗

Comparative effects of physical training and diet in normalizing serum lipids in men with Type IV hyperlipoproteinemia.

The effect of milk physical training (PT) (group A), Type IV hyperlipoproteinemia (HLP) diet (group B), and PT plus Type IV HLP diet on serum lipids (group C) in 46 men with Type IV HLP was studied. Significant reductions in mean triglyceride (TG) levels from 163, 229, 196, to 136, 145, 116 mg/100 ml serum were found for groups A, B, and C, respectively. Following six weeks of intervention, cholesterol levels also dropped for all groups with the greatest reductions occurring in groups B and C. Minimal weight losses were found for all groups while groups A and C displayed significant reductions in body fatness, but both of these changes appeared independent of lipid reductions. It was concluded that either mild PT or HLP diet or both are effective means of lowering TG levels in Type IV HLP individuals. Furthermore, it appears that patients need to participate regularly in formal programs in order to maintain adherence to these interventions.

Adult↗

Palmar spiny keratoderma associated with type IV hyperlipoproteinemia.

We report the case of a 35-year-old man with acquired palmar spiny keratoderma (SK) in association with type IV hyperlipoproteinemia. Cutaneous lesions appeared 11 years before with no history of any previous skin conditions, topical medication or systemic treatment with Vitamin A-derived drugs, x-irradiation, arsenic poisoning or prolonged sun exposure. Family aggregation for SK or other disorders of keratinization was ruled out. Blood chemistries demonstrated hypertriglyceridemia (422 mg/dl) and elevation in plasma concentration of the pre-beta fraction (VLDL) of lipoproteins pattern compatible with a type IV hyperlipoproteinemia. Family aggregation for this metabolic defect was then confirmed. The histologic hallmark of the 'spine' lesion was a compact column of hyperparakeratotic cells (columnar hyperparakeratosis) continuous with a hypogranular layer, without further evidence of dyskeratotic or vacuolated keratinocytes and inflammatory cells in the corresponding dermis. SK represents a well-definite entity which fulfills precise clinico-histologic criteria. However, three main questions are related to SK: differential diagnosis with porokeratosis on histologic examination (columnar hyperparakeratosis or hyperorthokeratosis alone in SK vs. cornoid lamella accompanied by remarkable dermoepidermal changes in porokeratosis); classificative scheme (proper nomenclature to avoid misleading and confounding names); and nosological arrangement (probably two subsets exist: hereditary or benign; and acquired, or idiopathic, which may be paraneoplastic in about 50% of the patients). To the best of our knowledge this is the first case reporting the association between SK and a metabolic impairment although the real connections linking these conditions are still unclear.

Adult↗