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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retinal vein occlusion (RVO) is a relatively common disease, often associated with the presence of diseases related to internal medicine. It is well known that RVO is associated with common systemic vascular disorders such as hypertension, arteriosclerosis and diabetes. Several studies using hospital-based controls have shown an increased risk of RVO in patients with arteriopathy, or high levels of plasma glucose and arterial blood pressure. Patients are categorized into six types of RVO based on the site of occlusion and on the type of consequent vascular damage. Central retinal vein occlusion (CRVO) is the most frequently-occurring and clinically relevant type of RVO. In addition to the well-known classical risk factors, new haemostasis-related ones have been investigated in patients affected by CRVO. While data concerning a number of parameters remain contradictory, high levels of type 1 plasminogen activator inhibitor (PAI-1) and hyperhomocysteinemia appear to play a significant role in the pathogenesis of this disease. Although based on a limited number of studies, this new knowledge could eventually provide important indications regarding prognosis and therapeutic strategies. There is no established treatment for CRVO. Treatment consists primarily of managing any identified underlying systemic disease. The increasing role of hypercoagulability in patients with CRVO supports the use of antithrombotic drugs in the treatment of this disease. Vitamin treatment to correct hyperhomocysteinemia should also be taken into consideration. However, the approach to CRVO treatment with antithrombotic drugs is not evidence-based yet. There is urgent need of intervention trials to evaluate the role of these drugs in CRVO patients.
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PMID:Retinal vein thrombosis: risk factors, pathogenesis and therapeutic approach. 1367 63

Cardiovascular disease is a major cause of death in diabetic subjects. Hyperglycaemia per se cannot explain this excess of risk. Several lines of evidence indicate that mild hyperhomocysteinemia is an independent atherosclerotic risk factor in general population. Hyperhomocysteinemia is not linked with diabetic disease per se, rather fasting homocysteine plasma levels largely depend on glomerular filtration rate (GFR). There is a great dial of controversy on the association between high homocysteine plasma levels and diabetic retinopathy and neuropathy. On the contrary, most of the studies confirm that hyperhomocysteinemia is an independent risk factor for cardiovascular disease associated with diabetes.
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PMID:[Hyperhomocysteinemia and cardiovascular risk in diabetes mellitus]. 1458 13

About half of all deaths are due to cardiovascular disease and its complications. The economic burden on society and the healthcare system from cardiovascular disability, complications, and treatments is huge and getting larger in the rapidly aging populations of developed countries. As conventional risk factors fail to account for part of the cases, homocysteine, a "new" risk factor, is being viewed with mounting interest. Homocysteine is a sulfur-containing intermediate product in the normal metabolism of methionine, an essential amino acid. Folic acid, vitamin B12, and vitamin B6 deficiencies and reduced enzyme activities inhibit the breakdown of homocysteine, thus increasing the intracellular homocysteine concentration. Numerous retrospective and prospective studies have consistently found an independent relationship between mild hyperhomocysteinemia and cardiovascular disease or all-cause mortality. Starting at a plasma homocysteine concentration of approximately 10 micromol/l, the risk increase follows a linear dose-response relationship with no specific threshold level. Hyperhomocysteinemia as an independent risk factor for cardiovascular disease is thought to be responsible for about 10% of total risk. Elevated plasma homocysteine levels (>12 micromol/l; moderate hyperhomocysteinemia) are considered cytotoxic and are found in 5 to 10% of the general population and in up to 40% of patients with vascular disease. Additional risk factors (smoking, arterial hypertension, diabetes, and hyperlipidemia) may additively or, by interacting with homocysteine, synergistically (and hence over-proportionally) increase overall risk. Hyperhomocysteinemia is associated with alterations in vascular morphology, loss of endothelial anti-thrombotic function, and induction of a procoagulant environment. Most known forms of damage or injury are due to homocysteine-mediated oxidative stress. Especially when acting as direct or indirect antagonists of cofactors and enzyme activities, numerous agents, drugs, diseases, and lifestyle factors have an impact on homocysteine metabolism. Folic acid deficiency is considered the most common cause of hyperhomocysteinemia. An adequate intake of at least 400 microg of folate per day is difficult to maintain even with a balanced diet, and high-risk groups often find it impossible to meet these folate requirements. Based on the available evidence, there is an increasing call for the diagnosis and treatment of elevated homocysteine levels in high-risk individuals in general and patients with manifest vascular disease in particular. Subjects of both populations should first have a baseline homocysteine assay. Except where manifestations are already present, intervention, if any, should be guided by the severity of hyperhomocysteinemia. Consistent with other working parties and consensus groups, we recommend a target plasma homocysteine level of <10 micromol/l. Based on various calculation models, reduction of elevated plasma homocysteine concentrations may theoretically prevent up to 25% of cardiovascular events. Supplementation is inexpensive, potentially effective, and devoid of adverse effects and, therefore, has an exceptionally favorable benefit/risk ratio. The results of ongoing randomized controlled intervention trials must be available before screening for, and treatment of, hyperhomocysteinemia can be recommended for the apparently healthy general population.
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PMID:DACH-LIGA homocystein (german, austrian and swiss homocysteine society): consensus paper on the rational clinical use of homocysteine, folic acid and B-vitamins in cardiovascular and thrombotic diseases: guidelines and recommendations. 1465 16

Homocysteine is a sulphur aminoacid with a free thiol group which is not present in dietary protein. This aminoacid is a secondary f methionine by-product from cysteine metabolism. The pathogenic mechanisms of homocysteine in vascular damage have not been clarified. At present, it is no possible to develop an atherogenic and thrombogenic hypothesis. Yet high levels of homocysteine can cause endothelial damage, with increased thrombosis and atherosclerosis. Hyperhomocysteinemia has been reported in patients with diabetes mellitus type 1 and type 2; the prevalence and secondary cardiovascular risk is higher in patients with diabetes type 2 than those with diabetes type 1. In patients with diabetes mellitus type 1, microvascular and macrovascular complications and neuropathy are found to be increased in those with hyperhomocysteinemia. In patients with diabetes mellitus type 2, the relationship between hyperhomocysteinemia, macrovascular complications and renal disease is unclear; however, a higher prevalence of macrovascular complications in diabetic patients with hyperhomocisteinemia is associated with a higher prevalence of renal disease. Moreover, patients with hyperhomocysteinemia have hypertension and dyslipemia. Multivariate regression analyses have shown an independent relationship between homocysteine and macrovascular complications. The relationship between retinopathy and homocysteine has not been clarified. In summary, hyperhomocysteinemia could be a risk factor accounting for chronic complications in diabetic patients. Nevertheless, it is necesary to perform more prospective and intervention studies to clarify the independent risk of homocysteine and thus assay alternative treatments.
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PMID:[Homocysteine in patients with diabetes mellitus]. 1473 72

Angiogenic brain damage and Alzheimer's disease caused by a progressing degenerative process are listed among the most frequent causes of dementia. These two processes are often concurrent and interrelated. Risk factors for vascular diseases including hypercholesteremia, arterial hypertension, and diabetes are also recognized risk factors for Alzheimer's disease. Results of many studies conducted in recent years suggest that the atheromatous process may be induced by elevated levels of homocysteine. Hyperhomocysteinemia first and foremost accelerates the onset of microangiopathic changes in small vessels. The mechanism underlying atherogenic action of homocysteine is still unclear. Hyperhomocysteinemia, generally assumed to have cytotoxic properties, damages endothelium in blood vessels, enhances thrombotic changes, and directly acts upon nitrogen oxide (NO), a vessel-dilating factor. Homocysteine is a metabolite of methionine. Homocysteine metabolism depends on current needs of the organism and involves either methionine reproduction (the reaction of remethylation, with such cofactors as B12 vitamin and folic acid), or cysteine synthesis (the transsulphuration reaction, with B6 vitamin as a cofactor). The normal range of plasma homocysteine concentration is assumed to be 5-14 mumol/L. The prevalence rates of hyperhomocysteinemia are 3-7% in the general population and 25% among those with vascular diseases. Elevated plasma homocysteine concentrations are due both to genetic and to environmental factors. In 2/3 of cases hyperhomocysteinemia is caused by decreased levels of folic acid, pyridoxine, and cobalamin. Deficiency of these vitamins is often seen in healthy elderly people.
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PMID:[Hyperhomocysteinemia in patients with dementia]. 1474 46

An increased level of total plasma homocysteine (tHcy) is a risk factor for poor cardiovascular outcome in the general population. However, a decreased, rather than an increased, tHcy concentration may predict poor outcome in maintenance hemodialysis (MHD) patients, a phenomenon referred to as reverse epidemiology. Associations were examined between tHcy level and markers of malnutrition-inflammation complex syndrome and 12-mo prospective hospitalization and mortality in 367 MHD patients, aged 54.5 +/- 14.7 (mean +/- SD) years, who included 199 men and 55% individuals with diabetes. tHcy was 24.4 +/- 11.8 micro mol/L, and 94% of the patients had hyperhomocysteinemia (tHcy >13.5 micro mol/L). tHcy had weak to moderate but statistically significant bivariate and multivariate correlations with some laboratory markers of nutrition (serum albumin, prealbumin, creatinine, and urea nitrogen) but no significant correlation with serum C-reactive protein or two proinflammatory cytokines (IL-6 and TNF-alpha). During 12 mo of follow-up, 191 MHD patients were hospitalized, 37 died, nine underwent renal transplantation, and 38 transferred out. Hospitalization rates were significantly higher in patients with lower tHcy levels. Mortality rate in the lowest tHcy quartile (17.4%) was significantly higher compared with other three quartiles (6.5 to 9.8%; Kaplan-Meier P = 0.04). Relative risk of death for the lowest tHcy quartile, even after adjustment for case-mix and serum albumin, was 2.27 (95% confidence interval, 1.14 to 4.53; P = 0.02). Hence, tHcy may be a more exclusive nutritional marker in MHD patients with no association with inflammatory measures. Despite a very high prevalence of hyperhomocysteinemia in MHD patients, lower values of tHcy are paradoxically associated with increased hospitalization and mortality. The lowest tHcy quartile confers a twofold increase in risk of death independent of hypoalbuminemia. The nutritional feature of tHcy in MHD patients may explain its reverse association with outcome.
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PMID:A low, rather than a high, total plasma homocysteine is an indicator of poor outcome in hemodialysis patients. 1474 92

Research over the past decade has shown that elevated levels of homocysteine have a strong association with all forms of atherothrombotic disease and venous thromboembolism. This association is particularly strong for coronary disease and newer data indicate that screening for homocysteine levels may be warranted in those with unexplained thrombotic tendencies and in young patients who develop coronary events or disease without the usual predisposing factors such as hypertension, smoking, hypercholesterolemia, or diabetes. Although the link between hyperhomocysteinemia and cardiac disease has not been conclusively shown to be causal as yet, data are emerging that lowering homocysteine levels may be beneficial in patients at high risk. Such lowering can be done safely and inexpensively with increased intake of fruits and vegetables and in those patients who are particularly at high risk using supplementation with folic acid and the B vitamins. Preliminary studies have shown that lowering homocysteine levels in this manner may slow the progression of atherosclerosis in coronary and carotid vessels. No mortality data exist yet showing that reducing homocysteine reduces cardiac or total mortality, although it is likely that ongoing and planned trials that are underway will shed light on these important questions soon.
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PMID:Homocysteine and cardiovascular disease. 1502 93

The vascular placental pathology (VPP) is associated with many etiologies. Some are the consequence of a maternal genetic or acquired predisposition. Others are associated with a chronic maternal disease (hypertension, lupus, obesity, diabetes, ...). Finally, some others are associated with placental implantation leading to fetal ischemia (multiple pregnancy, chorioangioma, primiparity, feto-placental hydrops) or to environmental (altitude) or nutritional factors (famine and specific alimentary depressions). We classify these factors into three categories according to the risk level (moderate, significant and elevated). While any of these factors can increase the risk of VPP, no one is sufficiently sensitive or specific in predict inevitable onset of VPP. In most cases VPP results from a combination of two (or more) risk factors. The risk factors of VPP classified as moderate include age (> or = 35 years), increased blood pressure during the second trimester of pregnancy, a new paternity, dietetic factors or environmental factors, smoking and controlled diabetes (class B, C), or inactive systemic diseases. Risk is significantly elevated among obese (BMI > or = 25), primiparous women, women with a past familial history (first degree) of preeclampsia or eclampsia, cocaine use or association of tobacco and caffeine use, increased placental mass (associated with twin pregnancy, fetal hydrops or molar pregnancy), uncontrolled diabetes, lupus, active scleroderma. Risk is considered to be high among patients with chronic hypertension, women with a past history of preeclampsia, diabetes (class D, F, R), patients with active systemic disease or with antiphospholipid antibodies or women with lupus or renal lesions and/or proteinuria as well as chronic kidney disease resulting in proteinuria, hypertension and renal insufficiency. Finally, the risk of VPP is considered to be increased in the presence of acquired thrombophilia. It remains moderate in the presence of isolated genetic thrombophilia, except in forms presenting with multiple genetic mutations or associated with an hyperhomocysteinemia. A "high-risk group" is defined among women with past history of deep venous thromboembolic events outside pregnancy, or with a past history of placental vascular pathology (intra-uterine death, placental abruptio, severe and precocious placental, intra-uterine growth retardation, early and repetitive fetal loss) and who, in addition, present with acquired thrombophilia (antiphospholipid antibodies, thrombocytemia), unique homozygous genetic thrombophilia, amultiple genetic thrombophilia or unique heterozygous genetic thrombophilia associated with hyperhomocysteinemia. Prophylactic treatment of acquired thrombophilia and of the multiple genetic forms or associated with hypercysteinemia is a logical rationale, particularly among women with a past history of placental vascular pathology, or with a past history of venous thromboembolic events. On the contrary, prophylaxis using low-molecular-weight heparin in the event of asymptomatic genetic thrombophilic mutations and for women without a past history of deep venous thromboembolism or vascular placental pathology remains controversial.
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PMID:[Vascular placental pathology in high-risk groups: definition and synopsis]. 1502 87

Deficiencies in vitamins or other factors (B6, B12, folic acid, betaine) and genetic disorders for the metabolism of the non-protein amino acid-homocysteine (Hcy) lead to hyperhomocysteinemia (HHcy). HHcy is an integral component of several disorders including cardiovascular disease, neurodegeneration, diabetes and alcoholic liver disease. HHcy unleashes mediators of inflammation such as NFkappaB, IL-1beta, IL-6, and IL-8, increases production of intracellular superoxide anion causing oxidative stress and reducing intracellular level of nitric oxide (NO), and induces endoplasmic reticulum (ER) stress which can explain many processes of Hcy-promoted cell injury such as apoptosis, fat accumulation, and inflammation. Animal models have played an important role in determining the biological effects of HHcy. ER stress may also be involved in other liver diseases such as alpha (1)-antitrypsin (alpha(1)-AT) deficiency and hepatitis C and/or B virus infection. Future research should evaluate the possible potentiative effects of alcohol and hepatic virus infection on ER stress-induced liver injury, study potentially beneficial effects of lowering Hcy and preventing ER stress in alcoholic humans, and examine polymorphism of Hcy metabolizing enzymes as potential risk-factors for the development of HHcy and liver disease.
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PMID:Hyperhomocysteinemia, endoplasmic reticulum stress, and alcoholic liver injury. 1518 90

Alzheimer's disease is a devastating condition that is increasing in prevalence. No known prevention or cure exists for Alzheimer's disease. Cardiovascular risk factors are prevalent and increase in the elderly, and there have been conflicting reports of associations between modifiable cardiovascular risk factors and Alzheimer's disease. The mechanisms for these associations are uncertain, but they are likely to be the result of a combination of direct and cerebrovascular disease-related mechanisms. From this standpoint, diabetes and hyperinsulinemia seem to have the strongest evidence from laboratory, clinical, and epidemiologic studies. Studies have also indicated that hypertension, hyperlipidemia, hyperhomocysteinemia, and smoking are potentially important risk factors for Alzheimer's disease.
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PMID:Cardiovascular risk factors and Alzheimer's disease. 1519 99


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