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)

We previously reported a compound heterozygote [T(-39)C/T(-93)G] in the human lipoprotein lipase (LPL) gene promoter in one out of 19 patients with familial combined hyperlipidemia (FCHL) and reduced post-heparin plasma LPL levels. The T(-39)C substitution resulted in 85% decrease in LPL promoter activity. Further screening of Caucasian patients with FCHL, coronary artery disease (CAD), and of unselected Caucasian subjects revealed four additional LPL promoter variants. Among the same 19 FCHL patients with reduced LPL levels, we found one heterozygote for a G(-53)C substitution. Among 115 CAD patients, we found five heterozygotes and one homozygote for the T(-93)G substitution and one heterozygote for a CC insertion between +13 and +19 of the 5' untranslated region. In a group of 183 unselected subjects, three heterozygotes with the T(-93)G substitution were found. The G(-53)C substitution led to approximately 70-75% decrease in promoter activity as assayed by transient transfections of THP-1 (macrophage-like) and C2C12 (myotube-like) cells. The T(-93)G substitution resulted in reduction of promoter activity by approximately 40-50%. The CC insertion between +13 and +19 caused a decrease in promoter activity by 20% in THP-1 and 50% in C2C12. Substitutions at -79 and -95, which had no effect on promoter function, were also discovered in the population samples studied. The finding of two promoter mutations (-39 and -53) among 19 FCHL patients with diminished LPL, but not among the other groups of subjects, suggests a potential role of regulatory mutations of the LPL gene in the development of dyslipidemia in FCHL.
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PMID:Regulatory mutations in the human lipoprotein lipase gene in patients with familial combined hyperlipidemia and coronary artery disease. 901 14

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

Hyperlipidemia, hypertriglyceridemia in particular, is a common feature in patients with noninsulin dependent diabetes mellitus (NIDDM) and may associate with insulin insensitivity. Acipimox, being widely prescribed for treating hypertriglyceridemia, is also used in NIDDM patients for their dyslipidemia. In the present study, we evaluated the effect of acipimox in Chinese NIDDM patients with hypertriglyceridemia. A total of 16 patients enrolled in a double-blind, randomized, placebo-controlled and two-period crossover study. After an 8 week run-in period, patients were randomly assigned into two groups receiving either acipimox (250 mg, twice daily) or placebo treatment. A total of 12 weeks later, these two groups switched their treatment for an additional 12 weeks. Blood samples were collected at the end of the run-in period and then at 4-week intervals in the whole study for lipid profile. A modified insulin suppression test was performed at the ends of the run-in period, 12-week and 24-week treatment to assess changes in insulin sensitivity. Our results showed that acipimox significantly lowered serum total triglyceride while compared to those by placebo. However, no difference was observed in serum non-esterified fatty acid, low-density lipoprotein cholesterol, total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C) and HDL-C/ TC ratio between the two groups. Furthermore, glycemic indices and insulin sensitivity were similar during the base-line, placebo or acipimox periods. Taken together, our data suggest that acipimox significantly lowered TG without perturbation of insulin sensitivity in hypertriglyceridemic NIDDM patients.
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PMID:Acipimox attenuates hypertriglyceridemia in dyslipidemic noninsulin dependent diabetes mellitus patients without perturbation of insulin sensitivity and glycemic control. 922 95

Hyperlipidemia is a common clinical finding in postrenal transplant patients. Increasing clinical data suggest that the dyslipidemia seen in these patients is associated with the development of atherosclerotic cardiovascular disease. In addition, recent data suggest that disordered lipid metabolism may be a risk factor for chronic allograft loss. The precise mechanisms whereby dyslipidemia contributes to vascular injury are unknown. No long-term interventional studies of lipid-lowering therapies have been conducted in this patient population. However, a number of short-term studies have shown that the newer antilipemic agents can be safely used in renal transplant patients. Thus, it appears that antilipemic therapy is warranted in renal transplant patients with an atherogenic lipid profile and multiple risk factors.
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PMID:Derangement of lipid metabolism and its management in renal transplant patients. 938 9

Plasma lipoproteins (LP) may be identified on the basis of density properties or apolipoprotein (apo) composition. ApoB-containing LP occur in VLDL, IDL and LDL. There are several types of apoB-containing LP characterized by specific composition of minor apolipoproteins (apoC, apoE etc.) and lipid constituents (triglycerides and cholesterol), metabolic properties and relative atherogenicity. The alterations of lipoprotein metabolism in renal disease resulting in elevated levels of apoB-containing LP may be reflected in hyperlipidemia. Whereas nephrotic syndrome and heavy proteinuria are associated with increased formation of cholesterol-rich apoB-containing LP in LDL and VLDL, the characteristic feature in renal failure is the accumulation of intact or partially metabolised triglyceride-rich LP in IDL and VLDL. The potentially atherogenic apoB-containing LP have been linked to the pathogenic processes that result in progressive glomerular and interstitial lesions and ultimate loss of renal function. The mechanisms of injury are not fully understood. Receptor- and non-receptor mediated uptake of LP by mesangial cells may induce or accelerate proliferative and sclerotic processes in the glomerular mesangium that are analogous to atherosclerosis in the arterial wall. Changes in glomerular permeability can result in increased filtration of LP that may be internalized by tubular cells and elicit corresponding lesions in the interstitial tissues. The negative impact of proteinuria on the prognosis of renal disease could be mediated in part through an increased filtration of lipoproteins. Induction of hyperlipidemia accelerates glomerular and interstitial damage in experimental renal failure. This can be attenuated by treatment with hypolipemic agents. In patients, increased concentrations of apoB-containing LP are associated with more rapid progression of renal insufficiency in both primary renal disease and diabetic nephropathy. It is, however, presently not known to what extent treatment of the renal dyslipidemia can modify the progression of chronic renal failure. Experimental and clinical evidence suggest that apoB-containing LP may play a pathogenetic role in the progression of renal disease.
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PMID:Progression of renal failure: role of apolipoprotein B-containing lipoproteins. 940 33

People with type II diabetes have a twofold to fourfold increased risk of dying from the complications of cardiovascular disease. Atherosclerosis and vascular thrombosis are major contributors. The increased risk is present before fasting hyperglycemia is seen. These individuals often have a sedentary life-style, poor physical conditioning, insulin resistance, centripetal obesity, hypertension, dyslipidemia, and a prothrombotic state. Chronic hyperglycemia is then added to these risk markers. Microalbuminuria may precede hyperglycemia in type II diabetes, occurs in 30% to 40% of these individuals after diabetes is established, and is a predictor of cardiovascular events. Early intervention in high-risk individuals may delay or prevent fasting hyperglycemia. An all-inclusive approach that focuses on early risk factor (or marker) identification and management to prevent or delay accelerated atherosclerosis and thrombosis in type II diabetes is an attractive strategy. However, the database to support this strategy is limited. In particular, large-scale prospective trial data are not available to support the concept of intensive glycemic regulation to prevent progression of macrovascular disease in type II diabetes. This is in contrast to the situation regarding microvascular disease of the eyes and kidneys. Recently, indirect data of a correlative nature have emerged, and short- and long-term prospective trials at early and late stages of type II diabetes are now being reported. These studies are analyzed and interpreted in this report. In contrast, the database to support an intensive antiplatelet regimen to prevent vascular thrombotic events in people with type II diabetes is large, and these studies are reviewed. They are of a type and magnitude to allow definite recommendations for aspirin therapy in type II diabetes. Aggressive therapy directed at hypertension, hyperlipidemia, and elevated urinary albumin in people with type II diabetes appears to be indicated. Increased attention to the multifactorial aspects of treatment of the type II diabetic patient is needed. Our present challenge is to translate these findings for patients and primary health care providers so that effective actions may be implemented.
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PMID:Multifactorial aspects of the treatment of the type II diabetic patient. 943 50

Five thousand five hundred seventy-two newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) patients (3,225 men and 2,347 women; mean age, 58.5 years) were recruited through the General Practitioners (GPs) network in France. All had persistent hyperglycemia after a preliminary 3-month period with dietary and life-style modification. Gliclazide (80 to 320 mg/d) was then prescribed as diabetic pharmacotherapy for 2 years. Additional therapy for hypertension and dyslipidemia was started if necessary. The aim of the study was mainly to determine the feasibility of a GP-directed protocol for the monitoring and treatment of newly diagnosed NIDDM patients, and to assess the effectiveness of diabetic therapy in this cohort. Diabetes was diagnosed in 78% of the cohort during routine screening. Among the women, 6.5% had a history of gestational diabetes. Eighteen percent of the patients had a parental history of diabetes, and the dominant maternal role in the genesis of NIDDM was confirmed. High blood pressure (Joint National Committee V criteria) was found at inclusion in 38.8% of the whole cohort. Hyperlipidemia was known in 44.6%. A history of stroke was present in 1.6% of the patients, and coronary heart disease (CHD) in 6.3%. These data support the relationship between the atherogenic state and development of NIDDM. Microalbuminuria defined as urinary albumin excretion (UAE) of at least 20 mg/L was found in 29.6% of the patients, and retinopathy in 9.8%. Among the included patients, 23% did not complete the study and were excluded from the efficacy analysis. Of these, 14% (808 patients) had only baseline evaluation data and 9% (499 patients) withdrew later. Comparison of mean baseline and final results in study completers uncovered a significant improvement in fasting blood glucose ([FBG] 182 +/- 48 v 137 +/- 40 mg/dL), post prandial blood glucose ([PPBG] 209 +/- 68 v 162 +/- 52 mg/dL), and hemoglobin A1c ([HbA1c] 8.7% +/- 2.5% v 7.3% +/- 2.0%). A slight improvement in total cholesterol (228 +/- 44 v 222 +/- 41 mg/dL), body mass index ([BMI] 28.5 +/- 4.7 v 27.9 +/- 4.5 kg/m2), and waist to hip ratio (0.99 +/- 0.1 v 0.98 +/- 0.1) was observed. There was a decrease in the percentage of patients with high blood pressure (38.5% v 30.7%). A mild increase in the prevalence of retinopathy (10.2% v 11.8%) was noted during the study, while the incidence of microalbuminuria remained unchanged (30.2% v 29.5%). In conclusion, the data indicate that the GPs involved in this study were able to successfully monitor and manage NIDDM patients in accordance with a standardized protocol. Gliclazide appeared to be an effective and well-tolerated treatment. The high prevalence of chronic diabetic complications at diagnosis emphasizes the delay encountered in reaching the diagnosis of NIDDM and the problems associated with this delay. In addition to the classic risk factors for NIDDM exhibited in this patient cohort, we have identified CHD and a maternal genetic component as further potential predicting factors.
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PMID:Management of newly diagnosed non-insulin-dependent diabetes mellitus in the primary care setting: effects of 2 years of gliclazide treatment--the Diadem Study. 943 56

Dyslipidemia is a major factor associated with cardiovascular disease, which is the leading cause of death in hemodialysis patients. Low molecular weight heparin (LMWH) is superior to conventional unfractionated heparin in treating hyperlipidemia in nondiabetic long-term hemodialysis patients and has fewer side-effects. Only a few reports have addressed the influence of LMWH on serum lipids in diabetic patients, although dyslipidemia is common among this population. We investigated the effect of LMWH on serum lipids in 12 nondiabetic and eight diabetic hypercholesterolemic patients receiving long-term hemodialysis. Patients had been receiving hemodialysis with unfractionated heparin for a minimum of 6 months before beginning the study. Continuous LMWH infusion during hemodialysis was administered to all patients for 2 months, followed by unfractionated heparin administration for 2 months. During LMWH treatment, plasma anti-factor Xa activity increased from 0.06 +/- 0.04 IU/mL before dialysis to 0.49 +/- 0.25 IU/mL after 3 hours. Serum total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and apolipoprotein B (Apo B) in both nondiabetic and diabetic patient groups and lipoprotein (a) (Lp(a)) in patients with higher initial values (> or = 15 mg/mL) decreased significantly after LMWH treatment (TC from 6.38 +/- 1.14 to 5.07 +/- 1.09 mmol/L, LDL-C from 3.08 +/- 0.93 to 2.15 +/- 0.88 mmol/L, Apo B from 100 +/- 18 to 78 +/- 18 mg/dL, all p < 0.01; Lp(a) from 41.8 +/- 34.5 to 28.5 +/- 22.8, p < 0.05). They rebounded to pre-LMWH levels after the 2 months on unfractionated heparin (TC 5.72 +/- 1.11 mmol/L, LDL-C 2.97 +/- 1.01 mmol/L, Apo B 98 +/- 20 mg/dL, Lp(a) 38.1 +/- 29.0 mg/dL). We conclude that continuous infusion of LMWH during dialysis reduces serum total cholesterol, low-density lipoprotein-cholesterol, and apolipoprotein B concentrations in both diabetic and nondiabetic hypercholesterolemic hemodialysis patients, and does not increase the risk of bleeding compared with unfractionated heparin.
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PMID:Low molecular weight heparin in diabetic and nondiabetic hypercholesterolemic patients receiving long-term hemodialysis. 948 Oct 65

More than half of the patients with angiographically confirmed premature coronary heart disease (CHD) have a familial lipoprotein disorder. Familial combined hyperlipidaemia (FCHL) represents the most common genetic dyslipidemia with a prevalence of 1.0-2.0%. FCHL is estimated to cause 10-20% of premature CHD and is characterized by elevated levels of cholesterol, triglycerides, or both. Attempts to characterize genes predisposing to FCHL have been hampered by its equivocal phenotype definition, unknown mode of inheritance and genetic heterogeneity. In order to minimize genetic heterogeneity, we chose 31 extended FCHL families from the isolated Finnish population that fulfilled strictly defined criteria for the phenotype status. We performed linkage analyses with markers from ten chromosomal regions that contain lipid-metabolism candidate genes. One marker, D1S104, adjacent to the apolipoprotein A-II (APOA2) gene on chromosome 1, revealed a lod score of Z = 3.50 assuming a dominant mode of inheritance. Multipoint analysis combining information from D1S104 and the neighbouring marker D1S1677 resulted in a lod score of 5.93. Physical positioning of known genes in the area (APOA2 and three selectin genes) outside the linked region suggests a novel locus for FCHL on 1q21-q23. A second paper in this issue (Castellani et al.) reports the identification of a mouse combined hyperlipidaemia locus in the syntenic region of the mouse genome, thus further implicating a gene in this region in the aetiology of FCHL.
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PMID:Linkage of familial combined hyperlipidaemia to chromosome 1q21-q23. 953 21

Subjects with diabetes have a greatly increased risk of CHD, which is only partially related to their elevated glucose. Other factors such as insulin resistance and dyslipidemia are likely to be important. The type of dyslipidemia that is most characteristic of type 2 diabetic subjects is elevated triglycerides and decreased HDL cholesterol levels, although all lipoproteins have compositional abnormalities. Surprisingly few good prospective studies of lipoprotein levels in relation to CHD have been done in diabetic subjects. Available studies suggest that low HDL cholesterol may be the most important risk factor for CHD in observational studies. In studies in which total cholesterol and triglyceride were done, cholesterol and triglycerides were risk factors for CHD, although triglycerides were often a stronger predictor. However, the strength of triglyceride as a risk factor for CHD may depend partially on its association with other variables (e.g., hypertension, plasminogen activator inhibitor 1 [PAI-1], etc.). In clinical trials in diabetic subjects, LDL reduction with statins has led to significant reductions in CHD incidence. In addition, overall mortality was reduced with statin therapy, although the results were not statistically significant. Gemfibrozil has led to reductions in CHD incidence in diabetic subjects, although the results were not statistically significant perhaps because of low sample size. Regarding lipoproteins and CHD risk in diabetic patients, the very positive results of statin trials point to LDL cholesterol being more important than previous realized. Apparently, having a borderline high LDL cholesterol (between 130 and 160 mg/dl) in a diabetic patient is equivalent to a much higher LDL cholesterol in terms of CHD risk for a nondiabetic subject. Therefore, the primary target of therapy in diabetic patients is lowering LDL cholesterol (or possibly, non-HDL cholesterol). Statins are the preferred pharmacological agent in this situation. Once LDL cholesterol levels have been lowered, attention can be given to treatment of residual hypertriglyceridemia and low HDL. The goal here is weight reduction and increased exercise. However, for selected patients, combining a fibric acid (or low-dose nicotinic acid) with a statin also can be considered. Reduction of LDL levels should take priority over reduction of triglycerides in combined hyperlipidemia because of the proven safety of the statin class of drugs as well as greater reduction in CHD incidence.
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PMID:Management of dyslipidemia in adults with diabetes. 953 88


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