Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To establish whether insulin resistance and/or postprandial fatty acid metabolism might contribute to familial combined hyperlipidemia (FCH) we have examined parameters of insulin resistance and lipid metabolism in six FCH kindreds. Probands and relatives (n = 56) were divided into three tertiles on the basis of fasting plasma triglycerides (TG). Individuals in the highest tertile (TG > 2.5 mM; n = 14) were older and had increased body mass index, systolic blood pressure, and fasting plasma insulin concentrations compared with individuals in the lowest tertile (n = 24). The former also presented with decreased HDL cholesterol and increased total plasma cholesterol, HDL-TG, and apoprotein B, E, and CIII concentrations. Insulin concentrations were positively correlated with plasma apo B, apo CIII, apo E, and TG, and inversely with HDL cholesterol. Fasting nonesterified fatty acids (NEFA) were elevated in FCH subjects compared to six unrelated controls and five subjects with familial hypertriglyceridemia. Prolonged and exaggerated postprandial plasma NEFA concentrations were found in five hypertriglyceridemic FCH probands. In FCH the X2 minor allele of the AI-CIII-AIV gene cluster was associated with increased fasting plasma TG, apo CIII, apo AI, and NEFA concentrations and decreased postheparin lipolytic activities. The clustering of risk factors associated with insulin resistance in FCH indicates a common metabolic basis for the FCH phenotype and the syndrome of insulin resistance probably mediated by an impaired fatty acid metabolism.
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PMID:Impaired fatty acid metabolism in familial combined hyperlipidemia. A mechanism associating hepatic apolipoprotein B overproduction and insulin resistance. 810 Aug 34

Hypoalphalipoproteinemia (HA) is a common finding in patients with premature coronary artery disease. To characterize the common familial forms of HA, we studied 102 families of probands with premature coronary artery disease; 40 probands (39.2%) had HA. Of these, 25 had at least one first-degree relative affected with HA; 11 had familial hypertriglyceridemia with HA (FTgHA); 10 had familial combined hyperlipidemia (FCH); and 4 had familial HA (FHA) with no other lipoprotein abnormalities. In the remaining 15 families, no lipoprotein abnormalities were observed in first-degree relatives. We measured apolipoprotein (apo) A-I, B, C-III, and E levels as well as lipoprotein particle (Lp) levels of LpA-I (containing apoA-I only), LpA-I:A-II (containing both apoA-I and A-II), LpB:E, and LpB:C-III. Compared with a reference group of healthy men (n = 103) and women (n = 106), probands with familial forms of HA had lower high-density lipoprotein cholesterol levels by selection criteria. Triglyceride levels were higher in FTgHA and FCH probands than in the reference group or FHA subjects. Despite selection of FTgHA and FCH by low-density lipoprotein (LDL) cholesterol, the latter was not significantly different between the three groups and the reference group. ApoA-I levels were decreased in FCH, FHA, and FTgHA probands, and LpA-I and LpA-I:A-II were lower in FHA and FTgHA probands. ApoB levels were significantly higher in all familial HA groups compared with the reference group, being highest in FCH individuals, but not significantly higher between FCH, FTgHA, or FHA probands. LpB:E levels were higher in the FCH and FTgHA groups than in the reference group. There were no significant differences between groups for apoE, apoC-III, and LpB:C-III. LDL particle size was smaller in all three forms of FHA, which, in combination with higher apoB levels, reflects an increased number of smaller, denser LDL particles. Affected children had, on average, higher apoB and LpB:E levels than nonaffected siblings. Our data suggest that common forms of FHA in subjects with coronary artery disease represent a spectrum of overlapping disorders characterized by an increase in apoB-containing lipoproteins, especially LpB:E particles, and smaller, denser LDL particles. When using appropriate age- and gender-adjusted cutpoints, approximately half the offspring (in young adulthood) appeared to be affected.
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PMID:Familial hypoalphalipoproteinemia in premature coronary artery disease. 824 Oct 92

The intact triacylglycerol profiles for VLDL and LDL of healthy and primary hypertriglyceridemic patients were obtained by high temperature capillary gas chromatography. The data were treated by the methods of computerized analysis. Marked individual heterogeneity was found. This can be explained by either genetic polymorphism or multiple lipoprotein triacylglycerol pools within one density class. Suspecting genetic polymorphism and determination type IV (familial hypertriglyceridemia) seems to be a pure overproduction of endogenous VLDL, while in type II B (familial combined hyperlipidemia) an altered mechanism of triacyglycerol synthesis can be supposed.
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PMID:Triacylglycerol composition of human endogenous lipoproteins. 857 32

Suboptimal lipolysis of very low density lipoproteins (VLDL) due to reduced substrate affinity for lipoprotein lipase (LPL) may contribute to the accumulation of apolipoprotein (apo) B in familial combined hyperlipidemia (FCH) or the characteristic increase in triglyceride-rich lipoproteins in familial hypertriglyceridemia (FHTG). To investigate this hypothesis in detail, the VLDL composition and substrate affinity for lipoprotein lipase was determined in 22 normolipidemic controls, 16 FCH probands, and 12 FHTG subjects. VLDL from FCH subjects were enriched in cholesterol and phospholipid. VLDL from FHTG subjects were enriched in triglycerides, cholesterol and phospholipid. Potential apolipoprotein regulators of LPL activity including apo C-II, apo C-III and apo E were not significantly different between FCH and controls when expressed per VLDL apo B. High apo C-III concentrations were present in FHTG-VLDL, and the apo C-III/E-ratio was significantly higher than in FCH- and control-VLDL. An increase of C-III-0, the desialylated isoform, was observed in FHTG-VLDL. The kinetic indicators for in vitro triglyceride hydrolysis by LPL, KM and VMAX, were not significantly different between the groups. KM values measured in vitro were remarkably and consistently high (1.54 mmol VLDL-TG/I), predicting saturation of LPL when VLDL-TG levels exceed 5.5 mmol/l (2 times KM + 2S.D.). In conclusion, VLDL from individuals with FCH or FHTG are normal substrate for lipoprotein lipase in spite of significant differences in lipid and apolipoprotein composition. The high apo C-III content of FHTG-VLDL supports a role in the expression of hypertriglyceridemia.
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PMID:In vitro lipolysis of human VLDL: effect of different VLDL compositions in normolipidemia, familial combined hyperlipidemia and familial hypertriglyceridemia. 867 26

One hundred forty-seven relatives of 43 patients with "classical" type III hyperlipoproteinemia (HLP) having the apolipoprotein (apo) E2/2 phenotype were studied to determine the occurrence of hyperlipidemia and the presence of further possible genes for lipoprotein disorders in these families. In 12 pedigrees primary dyslipidemia was prevalent among patients and respective blood-relatives. In these kindreds the coexistent presence of genes for familial combined hyperlipidemia (n = 6), familial hypertriglyceridemia (n = 5), and familial hypercholesterolemia (n = 1), respectively, was supposed. Our results, therefore, confirm and extend previous data on the multifactorial genesis of the diseases. Besides homozygosity for a receptor binding-defective isoform of apo E (apo E2), additional genes for familial lipoprotein disorders might operate in the pathogenesis of type III HLP. This is the largest family study performed so far in this primary lipoprotein disorder.
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PMID:Genetics of type III hyperlipoproteinemia. 918 57

Excessive production of cholesterol has been associated with type IV hyperlipidemia, but the influence of the confounding variable of obesity has been difficult to ascertain. Moreover, cholesterol metabolism has not been systematically evaluated in patients with familial hypertriglyceridemia (FHT), one of the two major subsets of type IV patients. We used isotope dilution to measure cholesterol production, pools, and kinetic constants in 8 hypertriglyceridemic subjects, 6 of whom could be confidently classified as FHT. These were compared with measurements in 9 control subjects matched for sex, age, serum cholesterol, and body mass index (BMI). By t test, hypertriglyceridemic subjects did not differ from controls with respect to cholesterol production, size of readily or slowly miscible pools, or kinetic transfer coefficients. Results were the same whether controls were compared with all hypertriglyceridemic patients or only the 6 with definite FHT. By analysis of covariance (ANCOVA), serum triglyceride level was not a significant determinant of any parameter of cholesterol metabolism. However, BMI was a highly significant determinant of cholesterol production (p = 0.0001) and size of both readily and slowly miscible pools (p = 0.001 to 0.008). These data suggest that FHT per se is not associated with abnormalities of cholesterol metabolism but that an apparent association could result from the confounding variable of obesity.
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PMID:Cholesterol metabolism in familial hypertriglyceridemia: effects of obesity versus triglyceride level. 942 37

This review provides an overview of the recent data evaluating triglyceride and low-density lipoprotein (LDL) size, two highly interrelated, genetically influenced, risk factors for cardiovascular disease (CVD). An examination of new epidemiologic studies continues to demonstrate that plasma triglyceride levels predict CVD. The first prospective study of the familial forms of hypertriglyceridemia has shown that relatives in familial-combined hyperlipidemia families are at increased risk for CVD mortality and that triglyceride levels predicted 20-year, CVD mortality among relatives in familial hypertriglyceridemia families. A meta-analysis of three, large-scale, prospective studies in men, and the first study to examine the correlation of LDL particle size distribution and vascular changes measured by B-mode ultrasound, add to growing evidence that small, dense LDL is atherogenic. Quantitative genetic analysis has recently shown substantial pleiotropic (common) genetic effects on triglyceride and LDL size. At least part of this may be explained by variation at the cholesterol ester transfer protein locus on chromosome 16, possibly through its role in reverse cholesterol transport. Taken together, these data provide new insights into the importance of triglyceride and LDL particle size for understanding genetic susceptibility to cardiovascular disease and its prevention.
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PMID:Triglyceride, small, dense low-density lipoprotein, and the atherogenic lipoprotein phenotype. 1112 45

Obesity is frequently associated with high plasma triglyceride and reduced plasma high-density lipoprotein (HDL)-cholesterol (HDL-C) levels, and an increased concentration of apoB-carrying lipoproteins. The effects of obesity on lipid metabolism are mainly mediated by insulin resistance and, as central (visceral) obesity significantly increases insulin resistance, it aggravates these lipid changes. We have reviewed the impact of obesity on lipid metabolism in different types of primary hyperlipidemias. Obesity is not common in primary (familial and polygenic) hypercholesterolemias, and insulin resistance is infrequent; various investigators have found no or only a weak association between plasma cholesterol concentrations and insulin levels. On the other hand, in familial hypertriglyceridemia (type IV) and familial combined hyperlipidemia (FCH), obesity and insulin resistance are common and, when present, contribute to a further deterioration in the lipid profile. Weight loss in most of these patients is accompanied by a significant decrease in plasma triglyceride levels and an increase in HDL-C. Reviewing the data published by our group, we show that insulin resistance is an important component of the metabolic derangement in FCH subjects; high fasting plasma free fatty acids and triglycerides levels correlate to insulin resistance, thus linking this abnormality to lipid metabolism. A high waist/hip ratio (indicating visceral fat deposits) exacerbates insulin resistance, but this is also present in lean FCH subjects. Furthermore, insulin resistance is associated with a higher prevalence of coronary heart disease in this group of subjects.
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PMID:Impact of obesity in primary hyperlipidemias. 1188 32

Lipemia retinalis is a rare ocular manifestation of certain types of hyperlipidemia. A case of a newborn with lipemia retinalis evaluated by laboratory and dinical findings is described. A creamy white appearance of all retinal blood vessels was demonstrated by color fundus photographs. The patient had elevated levels of triglycerides (29,000 mg/dL) and cholesterol (1,470 mg/dL). Lipid electrophoresis indicated hyperprebetalipoproteinemia. Type IV primary hyperlipoproteinemia was diagnosed.
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PMID:A newborn with lipemia rednalis. 1275 99

A 33-year-old secundipara with a history of gestational diabetes and familial hypertriglyceridemia exacerbated during her previous pregnancy was admitted in the 36th week of gestation with diffuse abdominal pain, vomiting, low-grade fever, and general malaise. A blood sample had a lipemic, milky-pink appearance and plasma concentrations were as follows: triglycerides 2173 mg/dL, cholesterol 320 mg/dL, amylase 801 U/L, lactate dehydrogenase 650 U/L, creatinine 1.5 mg/dL, glucose 380 mg/dL, and left-shifted white cells. Acute pancreatitis was diagnosed and owing to signs of fetal distress, a cesarean was performed under light general anesthesia with propofol, succinylcholine, and sevoflurane. After the umbilical cord was cut, rocoronium and fentanyl were administered. The neonate was healthy and the patient's condition evolved favorably with conservative treatment. The incidence of pancreatitis during pregnancy is low but related morbidity and mortality are high. The usual cause is biliary tract disease, although rare metabolic alterations such as hyperlipidemia may occasionally act as the trigger. Early diagnosis and treatment are the keys to successful surgery and postoperative recovery.
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PMID:[Hypertriglyceridemic pancreatitis and pregnancy]. 1475 42


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