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)

This article reviews the literature from 1986 to early 2001 relating to apoB100 and apoB48 kinetics in humans using amino acid precursors labeled with stable isotopes. The following subjects are reviewed: (1) methodology; (2) normal individuals and the effects of aging; (3) diet; (4) hereditary dyslipidemias: familial hypercholesterolemia, familial combined hyperlipidemia, cholesteryl ester storage disease, cholesteryl ester transfer protein deficiency, lipoprotein lipase deficiency, familial hypobetalipoproteinemia, and truncated forms of apoB; (5) hormonal perturbations: estrogen, insulin, diabetes, obesity, and growth hormone; (6) the nephrotic syndrome; and (7) the effects of the statin class of drugs. Because of the advances which have been made in mass spectrometry techniques, the advantages of using non-radioactive tracers in humans have made stable isotope kinetic studies the present day standard in this area of research.
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PMID:Apolipoprotein B metabolism in humans: studies with stable isotope-labeled amino acid precursors. 1199 42

Glucose effectiveness is impaired in type 2 diabetes. We hypothesize that chronic hyperglycemia and hyperlipidemia contribute importantly to this defect. To test this hypothesis, we compared the effect of acute hyperglycemia on glucose turnover in type 2 diabetic subjects in good control (GC) (n = 14, age 51.7 +/- 3.7 years, BMI 28.4 +/- 1.0 kg/ m(2), HbA(1c) 5.9 +/- 0.2%) and poor control (PC) (n = 10, age 50.0 +/- 2.5 years, BMI 27.9 +/- 1.5 kg/m(2), HbA(1c) 9.9 +/- 0.6%) with age- and weight-matched nondiabetic subjects (ND) (n = 11, age 47.0 +/- 4.4 years, BMI 28.5 +/- 1.0 kg/m(2), HbA(1c) 5.1 +/- 0.2%). Fixed hormonal conditions were attained by infusing somatostatin for 6 h with replacement of basal insulin, glucagon, and growth hormone. Glucose fluxes ([3-(3)H]glucose) were compared during euglycemic (5 mmol/l, t = 180-240 min) and hyperglycemic (Hy) (10 mmol/l, t = 300-360 min, variable glucose infusion) clamp intervals. Acute hyperglycemia suppressed hepatic glucose production (GP) by 43% and increased peripheral glucose uptake (GU) by 86% in the ND subjects. Conversely, GP failed to suppress (-7%) and GU was suboptimally increased (+34%) in response to Hy in the PC group. However, optimal glycemic control was associated with normal glucose effectiveness in GC subjects (GP -38%, GU +72%; P > 0.05 for GC vs. ND). To determine whether short-term correction of hyperglycemia and/or hyperlipidemia is sufficient to reverse the impairment in glucose effectiveness, five PC subjects were restudied after 72 h of normoglycemia ( approximately 100 mg/dl; variable insulin infusions). These subjects regained normal effectiveness of glucose to suppress GP and stimulate GU and in response to Hy (GP -47%, GU + 71%; P > 0.05 vs. baseline studies). Thus, chronic hyperglycemia and/or hyperlipidemia contribute to impaired effectiveness of glucose in regulating glucose fluxes in type 2 diabetes and hence to worsening of the overall metabolic condition. Short-term normalization of plasma glucose might break the vicious cycle of impaired glucose effectiveness in type 2 diabetes.
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PMID:Glycemic control determines hepatic and peripheral glucose effectiveness in type 2 diabetic subjects. 1208 48

This review consists of an explanation of the significance and sources of blood lipids and lipoproteins and an evaluation of the effects on triglycerides, cholesterol, and phospholipids of estrogens and progestagens taken combined or separately by normal or hyperlipidemic subjects. Normal blood contains alpha and beta lipoproteins (binding cholesterol and phospholipids) in morning, and chylomicrons (with dietary triglycerides) and prebeta-lipoproteins (with endogenous triglycerides) after a meal. Estrogens or combined pills raise triglycerides to 1.5 gm per 100 ml, the upper range of normal limits, due to an elevation of heavy prebeta-lipoproteins (0-12 SF). Th is elevation may be related to decreased lipoprotein lipase (post-heparin-lipolytic activity) seen in women taking estrogen. Heightened triglycerides have been observed in mixed and endogenous hyperlipidemia and types 1, 4, 5 (Frederickson classification), but not essential or type 2 hyperlipidemia. Progestogens lower triglycerides and raise lipoprotein lipase in normal subjects and in those with endogenous hyperlipidemia type 5. Results of studies of total cholesterol are variable: androgenic progestogens decrease cholesterol, but other progestagens increased it in some studies. A norethisterone and ethinyl estradiol combination has been shown to raise high- and very high-density lipoproteins, cephalin and lecithin, but to depress lyso-le cithin. Besides altered lipoprotein lipase, these lipoprotein changes c ould be due to elevated insulin, cortisol, thyroxin, or growth hormone, or their protein carriers.
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PMID:[Study of metabolism of circulating lipids during oral contraception]. 1230 67

Incidence of CVD in diabetic men was reported to be twice as that of non-diabetics and almost three times greater in diabetic women in the Framingham Study. It is postulated that excessive glycation and oxidation, endothelial dysfunction and increased platelet aggregation may be responsible for endothelial proliferation and thickening of plasmatic membrane in small blood vessels ('lipohyalinosis') leading to lacunar infarction. Prothrombotic state may precipitate a stroke, however, platelet aggregability, elevated fibrinopeptide A (FPA) and D-dimer were not significantly related to stroke in diabetic mellitus (DM), whereas suppressed fibrinolytic activity was a common finding. Of many unknown factors in pathogenesis, the deficient insulin secretion, resistance to action of insulin at level of 'insulin receptors', changes in counter regulatory hormones (e.g. glucagon, pancreatic polypetides, growth hormone, catecholamines, etc.) and decrease in the hepatic sensitivity to insulin action in suppressing glucose output have received more attention. Hyperosmolar state can simulate stroke syndromes. Early recognition and treatment of risk factors such as hypertension or better glycemic control, correction of hyperlipidemia or obesity in diabetic population are important. In diabetic subjects already showing recurrent transient cerebral ischemic attacks (TIAs) or minor strokes, the benefit of antiplatelet agents or antithrombotic therapy in prevention of major strokes is well established. Ramipril has been found to be effective in reducing stroke risk by 33% in diabetic patinets in HOPE study.
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PMID:Cerebrovascular disease in type 2 diabetes mellitus. 1257 84

Recently, adipose triglyceride lipase (ATGL, also called desnutrin and calcium-independent phospholipase A2 [iPLA(2)] zeta) was isolated as a novel adipose-expressed triglyceride lipase which is downregulated in obesity and may contribute to obesity-associated metabolic disorders such as hyperlipidemia and insulin resistance. To clarify expression and regulation of this fat-derived lipase, ATGL mRNA was measured in 3T3-L1 adipocytes by quantitative real-time reverse transcription-polymerase chain reaction after treatment with isoproterenol, tumor necrosis factor (TNF) alpha, insulin, and growth hormone (GH) which have been shown to influence lipolysis and insulin sensitivity profoundly. Interestingly, treatment of adipocytes with 100 nM isoproterenol, 30 ng/ml TNF alpha, and 100 nM insulin for 16 h significantly decreased ATGL mRNA to 74%, 17%, and 49% of control levels, respectively. GH did not influence ATGL synthesis. The effect of isoproterenol, TNFalpha, and insulin on ATGL expression was time- and dose-dependent. Similarly, HSL mRNA was downregulated by the three hormones. Furthermore, signaling studies suggested that activation of Gs-protein-coupled pathways by forskolin and cholera toxin is sufficient to significantly downregulate ATGL mRNA. Moreover, p44/42 mitogen-activated protein kinase appears to partly mediate the negative effect of insulin but not TNFalpha on ATGL. Taken together, downregulation of ATGL by isoproterenol, TNFalpha, and insulin might contribute to dysregulated expression and function of this lipase in obesity, hyperlipidemia, and insulin resistance.
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PMID:Isoproterenol, TNFalpha, and insulin downregulate adipose triglyceride lipase in 3T3-L1 adipocytes. 1600 85

Studies in our laboratory and elsewhere have demonstrated numerous abnormalities of steroid and polypeptide hormone secretion in obesity: hyperestrogenemia and hypogonadotropic hypogonadism in obese men; diminished SHBG levels in both sexes; elevated free testosterone and free estradiol in obese women; PCOS-like gonadotropin and sex-hormone abnormalities in obese women; elevated serum insulin in both sexes; blunted stimulability of prolactin, growth hormone, and vasopressin in both sexes; and elevated basal levels and blunted stimulability and suppressibility of beta-endorphin in both sexes. All of these abnormalities have been clearly shown to be partly or completely reversible with weight loss, with the exception of the endorphin abnormalities. In that area, four out of the five studies reported show no reversibility with weight loss. Reversibility of nearly all the hormonal abnormalities of obesity (i.e., all but the hyperendorphinemia) by weight loss suggests that none of them is causative of obesity. Nevertheless, some of the reversible abnormalities may secondarily amplify the morbidity associated with obesity: the hyperinsulinemia may be related to the increased risk of hypertension, hyperlipidemia, coronary disease, and Type II diabetes; the elevated levels of free estradiol in obese women may be related to their increased risk of breast and endometrial cancer. The role of hyperendorphinemia in obesity clearly requires further investigation, since it is the only observed hormonal abnormality that appears to be non-reversible by weight loss, and also since there seems to be increased sensitivity to beta-endorphin in obesity. The possibility that endorphin abnormalities may be causal in obesity cannot be ruled out.
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PMID:A perspective on the hormonal abnormalities of obesity: are they cause or effect? 1635 9

Lipodystrophy (LD) with varying degrees of lipohypertrophy, lipoatrophy, hyperlipidemia, and insulin resistance is one of the complications of highly active antiretroviral therapy (HAART) and occurs in one to 33 % of HAART-treated, HIV infected children. We summarize the data on the role of leptin, adiponectin, the growth hormone axis, glucocorticoids, sterol response element binding protein 1c (SREBP-1c), the tumor necrosis factor alpha axis (TNF-alpha), interleukin-6 (IL-6), interleukin- 18 (IL-18), interferon-alpha (IFN-alpha), tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI-1) in the pathophysiology of LD. Adiponectin levels are generally decreased in LD, whereas leptin levels are increased. Systemic cortisol levels are not elevated in LD, even though glucocorticoids seem to play an important role in LD and the phenotype can be reminiscent of Cushing syndrome. GH resistance in LD needs to be better characterized. While some cytokines show promise as markers for LD, it is difficult to tell whether their derangement is a cause of or the effect of LD.
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PMID:HIV--associated lipodystrophy in children. 1636 13

Albright hereditary osteodystrophy (AHO) is a genetic disorder caused by heterozygous inactivating mutations in GNAS, the gene that encodes the alpha-chain of Gs (G alpha s). This syndrome is associated with short stature, obesity, brachydactyly, and subcutaneous ossifications. Patients with GNAS mutations on maternally-inherited alleles are resistant to multiple G-protein-coupled hormones, including parathyroid hormone (PTH), thyroid-stimulating hormone (TSH), luteinizing hormone/follicle-stimulating hormone (LH/FSH), and glucagon. This variant of AHO, termed pseudohypoparathyroidism (PHP) type 1a, is due to tissue-specific paternal imprinting of G alpha s. We investigated whether patients with PHP type 1a exhibited evidence of resistance to growth hormone releasing hormone (GHRH) (1), another hormone requiring G alpha s function. In addition, G alpha s transcripts are imprinted in the pituitary somatotrophs responsible for growth hormone (GH) secretion which could thereby influence GHRH-dependent stimulation of somatotrophs. We therefore hypothesized that patients with PHP type 1a may be GH deficient which could contribute to the obesity and short stature in this condition. We found that GH deficiency is common in PHP type 1a (69%) with a prevalence that is much greater than in the general population (0.03%). We propose that GH status be evaluated in all patients with this condition. Treatment with recombinant GH could lead to improvements in height in children, as well as other physical (eg, obesity, hyperlipidemia, osteoporosis, reduced renal function) and psychological (fatigue and diminished sense of well-being) parameters in GH-deficient PHP type 1a patients of all ages.
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PMID:Short stature, obesity, and growth hormone deficiency in pseudohypoparathyroidism type 1a. 1667 31

HIV infection recently has been complicated by the emergence of a rare metabolic dysmorphic disorder characterised by fat atrophy, redistribution and accumulation in the setting of hyperlipidaemia and, on occasion, hyperglycaemia. The disorder, sometimes referred to as HIV-associated Adipose Redistribution Syndrome (HARS), has a prevalence rate of about 50 to 60% and seems temporally related to the advent of highly active antiretroviral therapy, especially the usage of protease inhibitors. Various studies also implicate the nucleoside analogues stavudine, didanosine and lamivudine in the pathogenesis of HARS, especially fat atrophy. It is uncertain whether the changes described in HARS represent a single syndrome or a group of related syndromes. Reports have noted differences between morphologic and metabolic changes. More recently, it has been suggested that fat atrophy and fat accumulation may also be separate entities. There are several potential pathogenic theories for HARS that implicate both protease inhibitors and nucleoside analogues as causative agents. However, long term HIV infection rather than any specific agent or class of agent may be the source. Recombinant human growth hormone (rhGH) is a mammalian cell-derived product, which has been useful in a variety of human disorders ranging from pituitary dwarfism to septic shock. It has anabolic, immunological and metabolic properties that restore normal functioning to many aberrant disease pathways. The lipolytic properties of rhGH have been especially beneficial in the diminution of localised fat accumulation in the dorsocervical area (buffalo humps) and truncal region. This has been observed in various reports where rhGH has been administered at doses of 5 to 6 mg/day in patients with HARS for periods ranging from 3 months to >2 years. Relapses after discontinuation of rhGH occurred in most patients. Adverse effects included carpal tunnel syndrome, facial swelling, arthralgias and myalgias and worsening or onset of hyperglycaemia. The small uncontrolled studies conducted to date suggest that the most notable effect of rhGH treatment is the reduction of truncal adiposity and buffalo humps and that the agent has little effect on restoring the adiposity of the appendicular muscles, buttocks or face. Although most patients with HARS have associated hyperlipidaemia, rhGH has no notable effect on serum cholesterol and triglyceride levels. However, blood glucose levels can increase and pre-existent diabetes mellitus may worsen. A short term confirmatory placebo-controlled trial in patients with HARS is urgently needed, as are comparative trials using other anabolic agents such as oxandrolone and testosterone.
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PMID:Potential of recombinant human growth hormone in HIV-associated adipose redistribution syndrome. 1803 60

Diabetes is currently one of the leading causes of end-stage renal failure requiring renal replacement therapy in the Western World. About 15% to 20% of type 1 diabetic patients and 30% to 40% of type 2 diabetic patients will eventually develop end-stage renal failure. To prevent the development or progression of diabetic kidney disease, good glycaemic control remains the cornerstone in the management of diabetic patients. Beyond glycaemic control, other metabolic factors have been shown to be involved in the development of diabetic kidney disease, i.e. advanced glycation endproducts (AGEs) and the aldose reductase pathway. Furthermore, an adequate control of high blood pressure and treatment of microalbuminuria are major therapeutic targes. To achieve adequate blood pressure control, a combination therapy with different classes of antihypertensive agents is often necessary, especially including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Other vasoactive factors involved in diabetic nephropathy such as endothelin and nitric oxide will be covered briefly. Besides hyperglycaemia and high blood pressure, other risk factors have been identified in the development or progression of diabetic kidney disease: smoking, hyperlipidaemia, obesity and high protein intake. Their impact on renal function will be highlighted. Finally, recent research has also identified intracellular pathways such as the diacylglycerol-protein kinase C pathway and several growth factors, such as growth hormone, insulin-like growth factor, transforming growth factor-beta, vascular endothelial growth factor, and platelet derived growth factor as players in diabetic kidney disease.
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PMID:Novel insights in the treatment of diabetic nephropathy. 1822 60


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