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)

Glucose-6-phosphatase-alpha (G6PC) is a key enzyme in glucose homeostasis that catalyzes the hydrolysis of glucose-6-phosphate to glucose and phosphate in the terminal step of gluconeogenesis and glycogenolysis. Mutations in the G6PC gene, located on chromosome 17q21, result in glycogen storage disease type Ia (GSD-Ia), an autosomal recessive metabolic disorder. GSD-Ia patients manifest a disturbed glucose homeostasis, characterized by fasting hypoglycemia, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, lactic acidemia, and growth retardation. G6PC is a highly hydrophobic glycoprotein, anchored in the membrane of the endoplasmic reticulum with the active center facing into the lumen. To date, 54 missense, 10 nonsense, 17 insertion/deletion, and three splicing mutations in the G6PC gene have been identified in more than 550 patients. Of these, 50 missense, two nonsense, and two insertion/deletion mutations have been functionally characterized for their effects on enzymatic activity and stability. While GSD-Ia is not more prevalent in any ethnic group, mutations unique to Caucasian, Oriental, and Jewish populations have been described. Despite this, GSD-Ia patients exhibit phenotypic heterogeneity and a stringent genotype-phenotype relationship does not exist.
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PMID:Mutations in the glucose-6-phosphatase-alpha (G6PC) gene that cause type Ia glycogen storage disease. 1844 99

Glycogen storage disease type 1a (GSD-1a) is a metabolic disorder characterized by fasting-induced hypoglycemia, hepatic steatosis, and hyperlipidemia. The mechanisms underlying the lipid abnormalities are largely unknown. To investigate these mechanisms seven GSD-1a patients and four healthy control subjects received an infusion of [1-(13)C]acetate to quantify cholesterogenesis and lipogenesis. In a subset of patients, [1-(13)C]valine was given to assess lipoprotein metabolism and [2-(13)C]glycerol to determine whole body lipolysis. Cholesterogenesis was 274 +/- 112 mg/d in controls and 641 +/- 201 mg/d in GSD-1a patients (p < 0.01). Plasma triglyceride-palmitate derived from de novo lipogenesis was 7.1 +/- 9.4 and 86.3 +/- 42.5 micromol/h in controls and patients, respectively (p < 0.01). Production of VLDL did not show a consistent difference between the groups, but conversion of VLDL into intermediate density lipoproteins was relatively retarded in all patients (0.6 +/- 0.5 pools/d) compared with controls (4.3 +/- 1.8 pools/d). Fractional catabolic rate of intermediate density lipoproteins was lower in patients (0.8 +/- 0.6 pools/d) compared with controls (3.1 +/- 1.5 pools/d). Whole body lipolysis was similar, i.e., 4.5 +/- 1.9 micromol/kg/min in patients and 3.8 +/- 1.9 micromol/kg/min in controls. Hyperlipidemia in GSD-1a is associated with strongly increased lipid production and a slower relative conversion of VLDL to LDL.
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PMID:Increased de novo lipogenesis and delayed conversion of large VLDL into intermediate density lipoprotein particles contribute to hyperlipidemia in glycogen storage disease type 1a. 1852 Mar 34

Glycogen storage disease type III (GSD III) is a very rare disorder caused by a deficiency in the activities of glycogen debranching enzymes (amylo-1-6-glucosidase and 4-alpha-glucanotransferase). GSD III is characterized by the accumulation of abnormal glycogen in the liver and skeletal muscle. The primary clinical manifestations are hepatomegaly, fasting hypoglycemia, and hyperlipidemia in infants. We report a rare case of GSD III in an adult. A 52-year-old woman presented to our clinic due to dyspnea on exertion, severe general weakness, and hepatomegaly. Hypertrophic cardiomyopathy was diagnosed based on echocardiogram findings. The microscopic findings of liver and skeletal muscle biopsies were consistent with the diagnosis of GSD. DNA analysis prompted by clinical and pathologic findings led to a definitive diagnosis of GSD IIIa. Diet therapy with cornstarch was started, and the patient was followed closely. This represents the first reported case of GSD IIIa diagnosed in an adult in Korea.
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PMID:An adult case of glycogen storage disease type IIIa. 1861 70

Glycogen storage diseases are a group of genetic disorders involving pathways for storage of glycogen and its utilization to maintain blood glucose. Clinical manifestations include hypoglycaemia, hepatomegaly, delayed adolescence and hyperlipidaemia. Hyperlipidaemia is frequent and patients surviving long enough are thought to be at increased risk of atherosclerosis. However, no cases have previously been reported. Presented is a 27-year-old male with glycogen storage disease type 1A who sustained a pontine infarction due to basilar artery stenosis. It is believed the cause of this infarction was accelerated atherosclerosis. This is of major significance to those with this disease process who are now surviving into their third and later decades due to improved management of this condition.
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PMID:Cerebrovascular disease in type 1A glycogen storage disease. 1864 98

PRESENT (Physicians' Routine Evaluation of Safety & Efficacy of NovoMix 30 Therapy) is a 6-month observational study of safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) in 31,044 type 2 diabetes patients from 15 countries. The aim of this article is to describe the study protocol and assess baseline characteristics of patients in various countries according to diabetes duration (<5 years, 5 to <or=10 years, 10 to <or=20 years and >or=20 years), to improve treatment decisions in clinical practice. Glycaemic control was similar across all groups: HbA1c 9.3-9.4%; fasting plasma glucose 11.3-11.6 mmol/L; postprandial glucose 15.9-16.3 mmol/L. Major hypoglycaemia was reported by 5% of all patients, minor hypoglycaemia increased with diabetes duration (25.4-30.3%); overall hypoglycaemia rate was 6.7 events/patient/year. Complications increased with diabetes duration; the most reported were hypertension (40.6-71.0%) and hyperlipidaemia (39.4-56.6%). Of patients 38% previously received OADs only, 28% insulin only, 19% insulin with OADs, and 13% received no therapy. Glycaemic control appeared independent of diabetes duration. HbA1c was well above targets and the clinical inertia was quite apparent; even patients with diabetes for <5 years had high HbA1c levels. Patients suffered high rates of complications and hypoglycaemia before starting BIAsp 30 therapy.
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PMID:Study design and baseline characteristics of patients in the PRESENT study. 1867 9

While the presence of hyperlipidaemia in glycogen storage disease (GSD) type Ia and Ib is generally accepted, few investigators have adequately assessed lipid profiles of GSD III in children, in whom the presence of hyperlipidaemia may be most prominent. We analysed the lipid profiles in 44 GSD III patients from 6 months to 30 years of age. Hypertriglyceridaemia and hypercholesterolaemia were common in children younger than 3 years of age. Hypertriglyceridaemia correlated negatively with age, and may reflect increased severity of hypoglycaemia in this younger population. The presence of hyperlipidaemia during childhood in these patients identifies another GSD population that could be at risk for early cardiovascular disease (CVD). Consequently, the outcome of clinical trials investigating the vascular effect of hyperlipidaemia in GSD applies to types other than GSD I.
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PMID:Hyperlipidemia in glycogen storage disease type III: effect of age and metabolic control. 1870 45

Cardiovascular disease is the predominant cause of death in diabetic patients, and reducing the risk of cardiovascular disease in diabetics has recently been the focus of several highly publicized large trials, including ACCORD (Action To Control Cardiovascular Risk in Diabetes), ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation), and VADT (Veterans Affairs Diabetes Trial). These studies randomized high-risk diabetic patients into either intensive treatment or standard treatment. The glycemic control arm of ACCORD was terminated 17 months before the planned end of the study because of a finding of significantly increased all-cause and cardiovascular mortality in the intensive treatment group. These findings were not duplicated in either ADVANCE or VADT. Multiple possible explanations have been brought forward, including a higher incidence of death from unrecognized hypoglycemia, effects due to increased exposure to particular antidiabetic medications, adverse effects of rapid correction of hyperglycemia, weight gain, and differences in baseline characteristics. None of these were validated in post hoc analyses of the trial data, and the cause of the increased mortality remains elusive. Subgroup analyses suggest that those who start off with better control of their diabetes or without preexisting cardiovascular disease may have the most to gain from tight glycemic control. Reducing the risk of macrovascular disease and death in diabetic patients requires not only attention to glucose control but also meticulous attention to control of nonglycemic risk factors, including hypertension, hyperlipidemia, smoking, lack of exercise, and unhealthy diet as well as timely prescription of medications with proven preventative benefits, such as aspirin and statins.
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PMID:Glycemic targets for patients with type 2 diabetes mellitus. 1942 66

In nonalcoholic fatty liver disease, oxidative stress is believed to play a crucial role as a second-hit for the progression of simple steatosis to steatohepatitis. Thioredoxin (TRX) is a potent antioxidant molecule that exerts anti-apoptotic and anti-inflammatory functions. TRX-binding protein-2 (TBP-2) is an endogenous negative regulator of TRX. Deficiency of TBP-2 in mice causes hyperlipidemia, hepatic steatosis, hypoglycemia, and bleeding tendency, resembling Reye syndrome in a fasting/glucose-deficient state. The aim of this study was to investigate the role of TBP-2 in the development of nonalcoholic steatohepatitis (NASH). TBP-2-deficient (TBP-2(-/-)) and wild-type (WT) mice were fed either a normal or methionine-choline-deficient (MCD) diet for up to 10 weeks. Compared with WT mice, TBP-2(-/-) mice showed severe simple steatosis rather than steatohepatitis. However, oxidative stress determined by lipid peroxidation and DNA damage, neutrophil infiltration, and hepatic fibrosis were attenuated in TBP-2(-/-) mice. PCR analysis showed the expressions of fibrosis-inducing and inflammatory cytokine-related genes were less in TBP-2(-/-) mice. Moreover, leptin, SREBP1c, PPARgamma, and adipogenesis-lipogenesis-related genes were upregulated in TBP-2(-/-) mice. These results strongly suggested that TBP-2 might be involved in pathogenesis of NASH in WT mice, and inhibitors of TBP-2 could be useful in the prevention or treatment of NASH.
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PMID:Thioredoxin-binding protein-2 deficiency enhances methionine-choline deficient diet-induced hepatic steatosis but inhibits steatohepatitis in mice. 1976 81

Type 1 diabetes mellitus (T1DM) results from autoimmune destruction of insulin-producing beta cells and is characterised by the presence of insulitis and &and beta-cell autoantibodies. Up to one third of patients develop an autoimmune polyglandular syndrome. Fifteen to 30% of T1DM subjects have autoimmune thyroid disease (Hashimoto's or Graves' disease), 5 to 10% are diagnosed with autoimmune gastritis and/or pernicious anaemia (AIG /PA), 4 to 9% present with coeliac disease (CD), 0.5% have Addison's disease (AD), and 2 to 10% show vitiligo. These diseases are characterised by the presence of autoantibodies against thyroid peroxidase (for Hashimoto's thyroiditis), TSH receptor (for Graves' disease), parietal cell or intrinsic factor (for AIG /PA), tissue transglutaminase (for CD), and 21-hydroxylase (for AD). Early detection of antibodies and latent organ-specific dysfunction is advocated to alert physicians to take appropriate action in order to prevent full-blown disease. Hashimoto's hypothyroidism may cause weight gain, hyperlipidaemia, goitre, and may affect diabetes control, menses, and pregnancy outcome. In contrast, Graves' hyperthyroidism may induce weight loss, atrial fibrillation, heat intolerance, and ophthalmopathy. Autoimmune gastritis may manifest via iron deficiency or vitamin B12 deficiency anaemia with fatigue and painful neuropathy. Clinical features of coeliac disease include abdominal discomfort, growth abnormalities, infertility, low bone mineralisation, and iron deficiency anaemia. Adrenal insufficiency may cause vomiting, anorexia, hypoglycaemia, malaise, fatigue, muscular weakness, hyperkalaemia, hypotension, and generalised hyperpigmentation. Here we will review prevalence, pathogenetic factors, clinical features, and suggestions for screening, follow-up and treatment of patients with T1DM and/or autoimmune polyglandular syndrome.
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PMID:Type 1 diabetes and autoimmune polyglandular syndrome: a clinical review. 2000 14

Glycogen storage disease type I (GSD I) is caused by inherited defects of the glucose 6-phosphatase complex, resulting in fasting hypoglycemia, lactic acidosis, hyperuricemia and hyperlipidemia. Sixteen out of 26 (61.5%) GSD I patients in our study had suboptimal levels (<30 ng/ml) of 25-hydroxyvitamin-D (25(OH)D) despite supplementation of vitamin D and/or vitamin D + calcium based on WHO standards in 24/26 (92.3%) patients. The restrictive nature of the GSD I diet, metabolic derangements and intestinal malabsorption seen in GSD I are possible reasons for the observed hypovitaminosis D. Our results suggest that measurement of 25(OH)D should be considered in the routine evaluation of GSD I patients.
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PMID:Hypovitaminosis D in glycogen storage disease type I. 2006 Mar 50


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