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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is becoming increasingly clear that suboptimal blood glucose control results in adverse effects on large blood vessels, thereby accelerating atherosclerosis and cardiovascular disease, manifested as myocardial infarction, stroke, and peripheral vascular disease. Cardiovascular disease is accelerated by both type 1 and type 2 diabetes. In type 1 diabetes, hyperglycemia generally occurs in the absence of elevated blood lipid levels, whereas type 2 diabetes is frequently associated with dyslipidemia. In this review article, we discuss hyperglycemia versus hyperlipidemia as culprits in diabetes-accelerated atherosclerosis and cardiovascular disease, with emphasis on studies in mouse models and isolated vascular cells. Recent studies on LDL receptor-deficient mice that are hyperglycemic, but exhibit no marked dyslipidemia compared with nondiabetic controls, show that diabetes in the absence of diabetes-induced hyperlipidemia is associated with an accelerated formation of atherosclerotic lesions, similar to what is seen in fat-fed nondiabetic mice. These effects of diabetes are masked in severely dyslipidemic mice, suggesting that the effects of glucose and lipids on lesion initiation might be mediated by similar mechanisms. Recent evidence from isolated endothelial cells demonstrates that glucose and lipids can induce endothelial dysfunction through similar intracellular mechanisms. Analogous effects of glucose and lipids are also seen in macrophages. Furthermore, glucose exerts many of its cellular effects through lipid mediators. We propose that diabetes without associated dyslipidemia accelerates atherosclerosis by mechanisms that can also be activated by hyperlipidemia.
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PMID:Do glucose and lipids exert independent effects on atherosclerotic lesion initiation or progression to advanced plaques? 1752 72

This study aimed to further analyse the potential role of oxidative stress in children and adolescents with type 1 diabetes at clinical onset, during disease progression and when early microvascular complications ( + DC) appeared. Compared with age-matched controls, diabetic patients had greater oxidative damage to lipids, proteins and DNA demonstrated by analysis of plasma and erythrocyte malondialdehyde, carbonyl proteins and leukocyte 8-hydroxy-deoxyguanosine, all of which were significantly raised at onset, decreased during the first 1.5 years of evolution and rose progressively thereafter. Plasma lipid levels were significantly associated with lipid and protein oxidation products. Erythrocyte glutathione and glutathione-peroxidase activity were significantly decreased with the lowest values at onset and in + DC sub-groups. Insulin therapy in the first year improved metabolic and oxidant-antioxidant status and, consequently, hyperglycaemia-derived biomolecular oxidative damage. Diabetes-associated hyperlipidaemia is related to lipid and protein oxidation, thereby supporting the concept of glucotoxicity and lipotoxicity being inter-related. The overall increase in lipid, protein and DNA oxidative damage in diabetic patients with microangiopathy could be pathogenetically relevant in the early development of diabetes-related complications.
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PMID:Oxidative stress in childhood type 1 diabetes: Results from a study covering the first 20 years of evolution. 1765 49

Type I (T1) diabetes, also called insulin dependent diabetes mellitus (IDDM), is characterized by little or no insulin production and hyperglycemia. One of the less well known complications of T1-diabetes is bone loss which occurs in humans and animal models. This complication is receiving increased attention because T1-diabetics are living longer due to better therapeutics, and are faced with their existing health concerns being compounded by complications associated with aging, such as osteoporosis. Both male and female, endochondrial and intra-membranous, and axial and appendicular bones are susceptible to T1-diabetic bone loss. Exact mechanisms accounting for T1-diabetic bone loss are not known. Existing data indicate that the bone defect in T1-diabetes is anabolic rather than catabolic, suggesting that anabolic therapeutics may be more effective in preventing bone loss. Potential contributors to T1-diabetic suppression of bone formation are discussed in this review and include: increased marrow adiposity, hyperlipidemia, reduced insulin signaling, hyperglycemia, inflammation, altered adipokine and endocrine factors, increased cell death, and altered metabolism. Differences between T1-diabetic- and age-associated bone loss underlie the importance of condition specific, individualized treatments for osteoporosis. Optimizing therapies that prevent bone loss or restore bone density will allow T1-diabetic patients to live longer with strong healthy bones.
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PMID:Understanding the pathology and mechanisms of type I diabetic bone loss. 1797 93

The creation of mouse models that recapitulate human diabetic cardiovascular disease remains a significant challenge. Part of the problem relates to the lack of a clear understanding of the human phenotype. Although improved insulin-treat of hyperglycemia reduces cardiovascular events in patients with type 1 diabetes, similar data are not available in type 2 diabetes. Moreover, whether human vascular disease is increased by hyperglycemia, defective insulin actions, or other factors is not known. Significant progress has been made in developing models of both type 1 and type 2 diabetes in mouse that can be used to study the relationship between hyperglycemia and atherosclerosis. This review describes mouse models that recapitulate specific aspects of diabetic dyslipidemia, hyperglycemia/insulin resistance, and diabetic vascular disease. Overall, the studies have clearly demonstrated that hyperlipidemia is a major driver of atherosclerotic vascular disease in the mouse. The effects of hyperglycemia and insulin resistance on murine atherosclerosis remain uncertain.
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PMID:Effects of diabetes on murine lipoproteins and vascular disease. 1804 98

A case of a 26-year-old patient with acute myocardial infarction and hypertension, hyperlipidaemia as well as type 1 diabetes from 18 years complicated by background retinopathy and nephropathy in the state of proteinuria is described. State of metabolic compensation of the diabetes was poor. The patient did not perform regular self-monitoring of glycaemia, smoked, and used oral contraception. Early diagnosis of vascular lesions in young persons with long-lasting of type 1 diabetes as well as the introduction of proper preventive and treatment methods may improve prognosis in these high-risk patients.
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PMID:[Myocardial infarction in a 26-year-old patient with diabetes type 1]. 1805 87

Responses of platelets from diabetic and diabetic-hyperlipidemic pigs were studied. Pigs were made diabetic with single dose of alloxan, which acts by selectively destroying insulin-producing pancreatic beta cells thus inducing type 1 diabetes. Pigs were kept for 1 or 12 wk, during which thrombin-induced aggregation was monitored in washed platelets. The platelets showed increased sensitivity to aggregation within 1 wk of induction of diabetes. Hyperlipidemia alone for 12 wk did not increase platelet hypersensitivity, but hyperlipidemia together with diabetes significantly increased thrombin-induced platelet aggregation. Because this hypersensitivity occurred in washed platelets, this characteristic appears to be independent of any contribution by plasma factors or other blood cells. The hypersensitivity of platelets from diabetic pigs correlated with decreased activity of mitogen-activated protein kinase. These studies offer the first evidence that platelet hyperactivity occurs during the early stages (within a week) of induction of diabetes in pigs and before manifestation of other cardiovascular problems.
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PMID:Platelets from diabetic pigs exhibit hypersensitivity to thrombin. 1900 74

Recent work shows a high prevalence of low testosterone and inappropriately low LH and FSH concentrations in type 2 diabetes. This syndrome of hypogonadotrophic hypogonadism (HH) is associated with obesity, and other features of the metabolic syndrome (obesity and overweight, hypertension and hyperlipidemia) in patients with type 2 diabetes. However, the duration of diabetes or HbA1c were not related to HH. Furthermore, recent data show that HH is also observed frequently in patients with the metabolic syndrome without diabetes but is not associated with type 1 diabetes. Thus, HH appears be related to the two major conditions associated with insulin resistance: type 2 diabetes and the metabolic syndrome. CRP concentrations have been shown to be elevated in patients with HH and are inversely related to plasma testosterone concentrations. This inverse relationship between plasma free testosterone and CRP concentrations in patients with type 2 diabetes suggests that inflammation may play an important role in the pathogenesis of this syndrome. This is of interest since inflammatory mechanisms may have a cardinal role in the pathogenesis of insulin resistance. It is relevant that in the mouse, deletion of the insulin receptor in neurons leads to HH in addition to a state of systemic insulin resistance. It has also been shown that insulin facilitates the secretion of gonadotrophin releasing hormone (GnRH) from neuronal cell cultures. Thus, HH may be the result of insulin resistance at the level of the GnRH secreting neuron. Low testosterone concentrations in type 2 diabetic men have also been related to a significantly lower hematocrit and thus to an increased frequency of mild anemia. Low testosterone concentrations are also related to an increase in total and regional adiposity, and to lower bone density. This review discusses these issues and attempts to make the syndrome relevant as a clinical entity. Clinical trials are required to determine whether testosterone replacement alleviates symptoms related to sexual dysfunction, and features of the metabolic syndrome, insulin resistance and inflammation.
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PMID:Hypogonadotrophic hypogonadism in type 2 diabetes, obesity and the metabolic syndrome. 1907 78

Oxidative stress damages DNA in experimental diabetes, and in vitro studies have suggested that it is linked to lipid peroxidation. The objective of the study was to determine whether lipid peroxidation, as assessed with malondialdehyde excretion in recent-onset type 1 diabetes mellitus, is associated with oxidative damage to DNA, as assessed from 8-hydroxydeoxyguanosine excretion. A 3-year longitudinal study of recent-onset type 1 diabetes mellitus was performed. Age- and sex-matched control subjects were studied once. Patients were studied as inpatients at West Virginia University Hospitals. Thirty-seven patients with recent-onset (2-22 months) type 1 diabetes mellitus (male, 10; female, 27) were enrolled in a longitudinal study of oxidative stress. The mean age of the patients was 20 years. None of the patients had hyperlipidemia or were treated with lipid-lowering drugs. Only 1 patient had hypertension and was being treated with beta-adrenergic blocking therapy. Thirty-six patients completed the study; one withdrew after the second evaluation. Lipid peroxidation was assessed by measuring malondialdehyde excretion. Oxidative damage to DNA was assessed from 8-hydroxydeoxyguanosine excretion. Malondialdehyde excretion was increased in the diabetic patients at the first evaluation (2.43 +/- 0.31 micromol/g creatinine), second evaluation (2.34 +/- 0.24), and third evaluation (1.93 +/- 0.15) compared with control subjects (1.51 +/- 0.11) (P < .005). 8-Hydroxydeoxyguanosine excretion, however, was not increased in the diabetic patients. There was no correlation between malondialdehyde and 8-hydroxydeoxyguanosine excretion. We confirmed the presence of oxidative stress in early diabetes as assessed from malondialdehyde excretion. We were unable, however, to confirm oxidative damage to DNA in this cohort of patients; and there was no evidence of a correlation between lipid peroxidation and DNA damage.
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PMID:Lipid peroxidation in early type 1 diabetes mellitus is unassociated with oxidative damage to DNA. 1937 99

Diabetic lipaemia, severe hypertriglyceridaemia associated with diabetic ketoacidosis, is a well recognised, but rare condition. Why this occurs in some patients and not others is unknown. We report a case of extreme lipaemia in a 20-year-old woman with type 1 diabetes who presented to hospital with diabetic ketoacidosis (DKA). At admission the patient's blood was grossly lipaemic and plasma lipid analyses showed triglyceride and cholesterol concentrations of 379 mmol/L and 52 mmol/L, respectively. She had no peripheral stigmata of chronic hyperlipidaemia and 1 year previously her plasma triglyceride and total cholesterol concentrations were 2.5 mmol/L and 4.4 mmol/L respectively. She was treated with insulin and the hypertriglyceridaemia resolved over several days. Because of the marked hypertriglyceridaemia, lipoprotein lipase (LPL) genetic testing was performed. Sequencing of the LPL gene revealed that she was heterozygous for the common S447X LPL variant and heterozygous for a novel missense mutation in exon five (I225N). Ile(225) is highly conserved among species and this mutation is predicted to impair function of the mature LPL protein. We conclude that heterozygosity for LPL mutations may predispose to transient severe hypertriglyceridaemia, when combined with insulin deficiency.
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PMID:Extreme diabetic lipaemia associated with a novel lipoprotein lipase gene mutation. 1944

Insulin deficiency in type 1 diabetes leads to disruptions in glucose, lipid, and ketone metabolism with resultant hyperglycemia, hyperlipidemia, and ketonemia. Exogenous insulin and hepatic insulin gene therapy cannot mimic the robust glucose-stimulated insulin secretion (GSIS) from native pancreatic islets. Gene therapy of streptozotocin-diabetic mice with neurogenin 3 (Ngn3) and betacellulin (Btc) leads to the induction of periportal oval cell-derived neo-islets that exhibit GSIS. We hence hypothesized that this gene therapy regimen may lead to a complete correction of the glucose and lipid metabolic abnormalities associated with insulin deficiency; we further hypothesized that the neo-islets formed in response to Ngn3-Btc gene delivery may display an ultrastructure and transcription profile similar to that of pancreatic islets. We injected streptozotocin-diabetic mice with helper-dependent adenoviral vectors carrying Ngn3 and Btc, which restored GSIS and reversed hyperglycemia in these animals. The treatment also normalized hepatic glucose secretion and reversed ketonemia. Furthermore, it restored hepatic glycogen content and reinstated hepatic lipogenesis-related gene transcripts back to nondiabetic levels. By transmission electron microscopy, the neo-islets displayed electron-dense granules that were similar in appearance to those in pancreatic islets. Finally, using RNA obtained by laser capture microdissection of the periportal neo-islets and normal pancreatic islets, we found that the neo-islets and pancreatic islets exhibited a very similar transcription profile on microarray-based transcriptome analysis. Taken together, this indicates that Ngn3-Btc gene therapy corrects the underlying dysregulated glucose and lipid metabolism in insulin-deficient diabetic mice by inducing neo-islets in the liver that are similar to pancreatic islets in structure and gene expression profile.
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PMID:Gene therapy with neurogenin 3 and betacellulin reverses major metabolic problems in insulin-deficient diabetic mice. 1981 64


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