Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperhomocysteinemia (HHcy) is a metabolic disorder frequently occurring in the elderly population. Recently several reports have suggested abnormalities in homocysteine (tHcy) metabolism implicating HHcy as a metabolic link in the multifactorial processes characterizing many geriatric illnesses-with special emphasis on atherosclerotic vascular diseases and cognitive impairment. The present study was undertaken in a large sample of elderly hospitalized subjects to determine (1) the prevalence of HHcy, (2) the association of HHcy with vascular and cognitive disorders, and (3) the factors independently predicting Hhcy. Six hundred elderly subjects (264 men and 336 women; mean age, 79 +/- 9 years) were randomly chosen from those admitted as inpatients over a period of 3 years. In all patients, body mass index (BMI), mid-upper arm muscle area (MUAMA), plasma cholesterol, triglycerides, total proteins, albumin, lymphocyte count, creatinine, homocysteine (fasting and 4 hours after methionine oral load), serum vitamin B(6), vitamin B(12), and folate concentrations were measured. The presence of disease or use of medications known to affect homocysteine plasma levels were also recorded. The mean fasting tHcy level was 16.8 +/- 12 micromol/L in the whole sample, 18.18 +/- 13.25 micromol/L in men, and 15.86 +/- 12.14 micromol/L in women (P =.005 men v women). The mean Hcy level 4 hours after methionine load was 37.95 +/- 20.9 in the whole sample. Prevalence of hyperhomocysteinemia (fasting Hcy > or = 15 micromol/L or 4 hours after methionine load > or = 35 micromol/L) was 61% (365/600) (67% in men and 56% in women, P <.05). HHcy was rarely (8%) an isolated disorder; in addition to diabetes (20%), renal failure (48.2%), and malnutrition (20.2%), it was often associated with heart failure (30%), malignancies (20.5%), and the use of diuretics (56%) and anticonvulsant drugs (13%). Plasma homocysteine progressively increases across subjects from those with no diabetes, malnutrition, renal failure, obesity, inflammatory bowel disease, heart failure to those with 1, 2, or more concurrent diseases. Multiple stepwise regression analysis showed that 72% of plasma total fasting tHcy variability was explained by age, serum folate, plasma albumin, use of diuretics, and renal function (measured as plasma creatinine clearance). In conclusion, the present study documents that hyperhomocysteinemia, in elderly hospitalized patients is (1) a common finding, (2) frequently associated with vascular and cognitive disorders, and (3) probably a secondary phenomenon in most cases. The major predictor of high plasma homocysteine levels were age, serum folate, plasma albumin, plasma creatinine clearance, and use of diuretic drugs. These variables explain a large proportion of plasma Hcy variability.
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PMID:Hyperhomocysteinemia and related factors in 600 hospitalized elderly subjects. 1173 95

Hyperhomocysteinemia is known to be associated with many of the occlusive vascular diseases including ischemic heart disease. Elevated plasma total homocysteine (t-Hcy) is also remarkably common among patients with moderate to severe renal failure. The purpose of this study was to investigate the role of homocysteine (Hcy) in the pathogenesis of diabetic nephropathy in the rat. Additionally, any effect of aminoguanidine (AG), an inhibitor of advanced glycation end product (AGE) formation, on the onset of nephropathic symptoms and on the concentrations of Hcy was searched for. Diabetes was induced in male Wistar albino rats (6 months old) by a single injection of 50 mg x kg (-1)streptozotocin (STZ) into the penile vein. Animals with blood glucose levels higher than 350 mg x dl (-1)72 h after STZ injection were included in the study. Age-matched rats receiving a single dose of citrate buffer served as controls. One half of the control and diabetic groups received AG via drinking water (1 g l (-1)). The experimental period lasted for ten weeks. Animals were killed by cardiac venipuncture after 24 hour urine samples were collected. Serum t-Hcy was quantified using HPLC, and urinary GAGs using the spectrophotometric 1,9-dimethyl methylene blue dye method. Serum glucose, protein, creatinine and total sulfydryl (t-SH) measurements, and urinary protein determinations were carried out spectrophotometrically. In diabetic rats, serum t-Hcy levels were significantly decreased (P< 0.001), and were negatively correlated with the urinary protein concentration (r= -0.67, P< 0.05). Urinary GAG levels were also increased in diabetic rats (P< 0.001). AG neither affected the t-Hcy levels, nor ameliorated the nephropathic symptoms. These results indicate that diabetic nephropathy is not linked to homocysteinemia in the rat.
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PMID:A study on the relationship between homocysteine and diabetic nephropathy in rats. 1188 23

Hyperhomocysteinemia is an independent risk factor for cardiovascular disease in human diabetes. Among the multiple factors that may account for the atherogenicity of homocysteine (Hcys) in patients with diabetes, macrophage (Mo) lipoprotein lipase (LPL) has unique features in that it is increased in human diabetes and acts as a proatherogenic factor in the arterial wall. In the present study, we determined the direct regulatory effect of Hcys on Mo LPL gene expression and secretion. Incubation of J774 Mo with Hcys increased, in a time- and dose-dependent manner, LPL mRNA expression and secretion. Induction of LPL gene expression was biphasic, peaking at 1 and 6 h. Whereas Hcys treatment increased protein kinase C (PKC) activity in Mo, pretreatment of Mo with PKC inhibitors totally suppressed Hcys-induced LPL mRNA expression. Hcys also increases the levels of c-fos mRNA in Mo and enhanced nuclear protein binding to the AP-1 sequence of the LPL gene promoter. Overall, these results demonstrate that Hcys stimulates Mo LPL at both the gene and protein levels and that Hcys-induced LPL mRNA expression requires PKC activation. They also suggest a possible role of c-fos in the stimulatory effect of Hcys on Mo LPL mRNA expression. These observations suggest a new mechanism by which Hcys may exert its proatherogenic effects in human diabetes.
Diabetes 2002 Apr
PMID:Homocysteine induces protein kinase C activation and stimulates c-Fos and lipoprotein lipase expression in macrophages. 1191 42

Management of the conventional cardiovascular risk factors is insufficient to prevent the dramatic increase in atherosclerotic cardiovascular morbidity and mortality in patients with renal failure. Folate recently received attention as a potential alternative treatment option to decrease the excess cardiovascular risk in the uremic population. Folate administration is the principal treatment modality for hyperhomocysteinemia. Hyperhomocysteinemia is prevalent in more than 85% of patients with end-stage renal disease (ESRD) and is independently associated with increased odds for atherosclerotic cardiovascular disease. Several attempts have been made to normalize homocysteine levels in uremic patients with folate-based vitamin regimens. Although supraphysiologic doses of folic acid afford greater reductions in homocysteine levels than standard doses, the response to treatment is generally only partial and the large majority of ESRD patients have residual hyperhomocysteinemia. Several defects in folate metabolism have been described in uremia, which may explain the relative folate resistance in patients with renal failure, but their clinical relevance remains uncertain. It appears unlikely that the hyperhomocysteinemia in ESRD can be cured solely with folic acid supplements, since folate does not affect the prolonged plasma elimination of homocysteine, which is the primary defect in homocysteine metabolism in uremia. Folate restores endothelial dysfunction, associated with hyperlipidemia, diabetes and hyperhomocysteinemia. The beneficial effect appears to be independent of its homocysteine-lowering capacity and is possibly related to an improved bioavailability of nitric oxide. However, folate has failed to improve endothelial dysfunction in uremic patients. In the ESRD population, multiple metabolic and hemodynamic abnormalities adversely affect endothelial function. In addition, irreversible structural vascular disease already may be present. Folate should, therefore, probably be an integral part of an "endothelial protective regimen," consisting of lipid-lowering agents, antihypertensives and antioxidant vitamins and started very early in patients with renal failure. Before large-scale folate administration can be recommended, effects on hard endpoints of cardiovascular disease need to be demonstrated in randomized trials. Such trials are currently underway in patients with normal renal function at high risk for cardiovascular disease, and one trial has recently been initiated in stable renal transplant recipients.
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PMID:Is folate a promising agent in the prevention and treatment of cardiovascular disease in patients with renal failure? 1263 Nov 53

Hyperhomocysteinemia is recognised as a risk factor of ischaemic heart disease and vascular complications of arterial hypertension. Methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism is associated with hyperhomocysteinaemia. The aim of the study was the assessment of an association of the above polymorphism with type 2 diabetes with special attention to myocardial infarction and arterial hypertension accompanying diabetes. The study group consisted of 172 type 2 diabetics. 172 control subjects with normal glucose tolerance were age and sex matched to patients with diabetes. C677T polymorphism in MTHFR gene locus was detected using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. CT and TT genotypes were found more often among diabetics (OR 1.83, 95% CI 1.16-2.89; p < 0.01). This finding may be secondary to the excess of T allele bearers among diabetics with myocardial infarction when compared to diabetics without infarction and to control group. Upon obtained results the potential role of genotypes CT and TT as risk factors of myocardial infarction among patients with type 2 diabetes could not be excluded (OR 2.33, 95% CI 0.93-5.8; p = 0.07). Genotypes containing T allele are not associated with diabetes type 2 and concomitant arterial hypertension (OR 1.45, 95% CI 0.89-2.57; p = 0.14). A confirmation in further studies is needed for the presented findings.
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PMID:[Methylenetetrahydrofolate reductase gene polymorphism in patients with type 2 diabetes]. 1192 64

Dialysis patients constitute a high-risk subset of patients for developing cardiovascular disease, which accounts for nearly 50% of deaths. After stratification for age, race and gender, cardiovascular mortality is 10-20 times higher in dialysis patients than in the general population. Cardiovascular disease in this population cannot be fully explained by the high prevalence of classical cardiovascular risk factors (age, hypertension, diabetes, hyperlipidemia, smoking, etc.). Thus, the involvement of "new" cardiovascular risk factors (hyperhomocysteinemia, hyperfibrinogenemia, high lipoprotein (a) levels, oxidative stress, inflammation, etc.), and uremia-related factors (anemia, impaired calcium-phosphorus metabolism, hyperparathyroidism, accumulation of endogenous inhibitors of nitric oxide synthesis, etc.) has been also invoked to play a role in the increased cardiovascular risk in these patients. Endothelial dysfunction is the initial event in the development of atherosclerosis. Uremic patients exhibit an endothelial dysfunction, even before starting dialysis, which persists o is even aggravated under dialysis treatment. Uremic patients must be considered at high risk of developing cardiovascular disease. Thus cardiovascular risk factors in these patients should be managed early, aggressive and multifactorially in order to reduce their high cardiovascular morbidity and mortality.
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PMID:[Cardiovascular risk in patients with chronic renal failure. Patients in renal replacement therapy]. 1198 73

The established risk factors for atherosclerosis such as hypertension, smoking, diabetes mellitus, hyperlipidemia, and hyperhomocysteinemia do not explain clinical and epidemiological features of coronary heart disease (CHD). The role of infectious disease as a CHD risk factor may partly explain these features. Chronic infection with various microorganisms, particularly, Chlamydia pneumoniae, Cytomegalovirus (CMV) and Helicobacter pylori may play a role in etiological factors, linking inflammation and atherogenesis. Results from epidemiological studies, pathology of atherosclerotic plaques, animal studies, molecular biology and clinical antibiotic trials indicated a positive association between C. pneumoniae infection and CHD. Chronic infection might also influence preexisting plaque by enhancing T cell activation, which participate in destabilization of intimal cap. However, the exact nature of pathophysiological link between the organisms and CHD remains to be elucidated. Future antibiotic interventional studies may help to further clarify the role of chronic infection and inflammation in CHD.
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PMID:Chronic infections and atherosclerosis. 1200 6

Retinal vein occlusion (RVO) is a relatively common disease that is often associated with a variety of systemic disorders including arterial hypertension, diabetes mellitus, dyslipidemia, and systemic vasculitis. There are various types of RVO, categorized on the basis of 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 hemostasis-related ones have been investigated in patients affected by CRVO. The data concerning a number of parameters remain contradictory; yet, 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.
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PMID:Cardiovascular and thrombophilic risk factors for central retinal vein occlusion. 1202 Jun 23

Hyperhomocysteinemia is a well-established risk factor for cardiovascular disease. Various factors, both modifiable and non-modifiable, interact with the homocysteine metabolism and determine the plasma homocysteine concentrations. These include genetic abnormalities, age, sex and various nutritional and hormonal determinants, all of which play a role in atherosclerosis and accelerated peripheral and cardio-vascular disease (CVD). Several hormones modulate homocysteine metabolism and hence may play a role in the pathogenesis of CVD. The mechanisms involved are unclear. The association of hyperhomocysteinemia with diabetes mellitus is complex and may explain some of the risk of CVD in diabetics not explained by traditional risk factors. Much conflicting data exists in the literature on the role of insulin on homocysteine metabolism, although insulin affects the enzymes regulating the homocysteine metabolism. Treatment of hyperhomocysteinemia with vitamins lowers plasma homocysteine concentrations. Little data is available on the effect of this intervention on cardiovascular outcomes. This review briefly outlines the homocysteine metabolism, summarizes its hormonal determinants, and discusses the role of hyperhomocysteinemia in diabetes, hyperlipidemia and other endocrine disorders.
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PMID:Hormones and homocysteine. 1209 90

Recent studies suggest that aggregation of platelets from patients with coronary artery and cerebrovascular disease may be resistant to low-dose aspirin (ASA) treatment, which may promote plaque-associated thrombus formation. However, the underlying mechanisms of platelet ASA resistance are poorly understood. ASA is thought to inhibit platelet aggregation primarily by inactivating the cyclooxygenase (COX), thus decreasing the synthesis of the pro-aggregatory arachidonic acid metabolite thromboxane A(2) (TxA(2)). However, recent studies also identified a non-enzymatic, oxidation-dependent pathway for the synthesis of the arachidonic acid derivative isoprostanes, which exhibit potent vasoconstrictor and pro-aggregatory effects similar to that of TxA(2). Because the pathophysiological conditions that promote arteriosclerotic vascular diseases (e.g. hypercholesterolemia, diabetes, hyperhomocysteinemia) are thought to be associated with an increased formation of reactive oxygen species and increased plasma isoprostane levels, it can be hypothesized that increased COX-independent isoprostane formation in platelets contribute to ASA resistance.
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PMID:Oxidative stress-induced isoprostane formation may contribute to aspirin resistance in platelets. 1214 79


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