Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a cross-sectional study of 293 nondiabetic patients (169 men and 124 women) referred for the diagnosis and treatment of hyperlipidemia, our specific aim was to determine whether fasting serum insulin independently contributes to the prediction of atherosclerotic cardiovascular disease (ASCVD) status. Of the 169 men and 124 women, 65 (38%) and 44 (35%), respectively, had ASCVD with at least one of the following: unstable angina, myocardial infarction (MI), angioplasty, coronary artery bypass graft (CABG), claudication, transient ischemic attack, or ischemic stroke. In addition, 42% and 38% had fasting hyperinsulinemia (> or =20 microU/mL). Fasting serum insulin of 20 microU/mL or higher was very common in women (59% to 100%) and men (67% to 88%) when hypertension, obesity, top-decile triglyceride (TG), and bottom-decile high-density lipoprotein cholesterol (HDLC) were concurrent in various combinations. ASCVD events (present or absent) were dependent variables in a stepwise logistic regression model with explanatory variables including age, gender, race, hypertension, cigarette smoking, ASCVD in first-degree relatives at age 55 years or less, Quetelet Index, fasting serum insulin, a gender x insulin interaction term, anticardiolipin antibodies (ACLAs) IgG and IgM, total cholesterol to HDLC ratio, TG, lipoprotein(a) [Lp(a)], and homocysteine. The risk odds ratio for ASCVD (109 events and 184 nonevents) for subjects with top-decile insulin (vthe bottom nine deciles) was 3.71, with a 95% confidence interval (CI) of 1.62 to 8.9 (P = .002). For patients with MI and/or CABG and/or angioplasty ([MCA] 63 events and 184 nonevents), the risk odds ratio for top-decile insulin versus the rest was 5.07 (95% CI, 1.83 to 14.8, P = .002). For patients with MCA at age 55 or less, the gender x insulin interaction term was significant (P = .0004); the risk odds ratio for men with top-decile insulin was 13.28 (95% CI, 3.82 to 51.65, P = .0001). Hyperinsulinemia is very common in nondiabetic hyperlipidemic women and men. Fasting serum insulin, a crude, simple, practical, and inexpensive measure, independently and uniformly improved the prediction of ASCVD status beyond traditional risk factors and lipid variables in patients referred for treatment of hyperlipidemia.
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PMID:Contribution of fasting hyperinsulinemia to prediction of atherosclerotic cardiovascular disease status in 293 hyperlipidemic patients. 1058 54

Evidence suggests that isolated intracranial hypertension (iIH) is often associated with cerebral venous thrombosis (CVT). In eight patients referred to our Institution for iIH who were later shown to harbor CVT we have performed a comprehensive coagulation work-up, including genetic tests for inherited predisposition to thrombophilia, to clarify the etiology of sinus venous thrombosis. All subjects were women. All but one were overweight. There were high plasma concentrations of D dimer, thrombin-anti-thrombin complexes or prothrombin fragments 1 and 2, further supporting the neuroimaging diagnosis of CVT. Importantly, seven of eight cases had a raised level of plasminogen activator inhibitor 1, a well known inhibitor of fibrinolysis related to obesity. Tissue plasminogen activator levels were elevated accordingly. Factor V gene mutation was present in one subject, and the 20,210 prothrombin gene mutation was found in another individual. Three patients had elevated plasmatic levels of homocysteine. In conclusion, the present study provides solid evidence that impaired fibrinolysis probably related to overweight, acting in concert with other prothrombotic abnormalities, is involved in the pathogenesis of CVT presenting as iIH.
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PMID:A hypofibrinolytic state in overweight patients with cerebral venous thrombosis and isolated intracranial hypertension. 1063 43

Coronary artery disease (CAD) is a major cause of morbidity and mortality in SLE, including the Hopkins Lupus Cohort. Currently, 9% of the cohort have had clinical evidence (angina or myocardial infarction) of CAD. In our initial prospective study we found that duration of prednisone, hypertension, hyperlipidemia and obesity were risk factors for later CAD. We can now extend that list to include age, male sex, elevated homocysteine, renal insufficiency and antiphospholipid antibodies. Many of the risk factors are amenable to intervention, but the timing of intervention, and the effectiveness of intervention, must be determined.
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PMID:Detection of coronary artery disease and the role of traditional risk factors in the Hopkins Lupus Cohort. 1080 83

Hyperhomocysteinemia (HH) and hyperinsulinemia are both risk factors for cardiovascular disease. To examine the effects of hyperinsulinemia on homocysteine metabolism, we fed rats a high-fat-sucrose (HFS) diet and then measured the hepatic mRNA and activity of 2 key enzymes involved in this metabolic pathway: 5,10-methylenetetrahydrofolate reductase (MTHFR) and cystathionine-beta-synthase (CbetaS). Fischer rats made insulin-resistant by a HFS diet were examined at 6 months and 2 years of age and compared with control rats fed a low-fat, complex-carbohydrate (LFCC) diet. At the end of 6 months, the HFS rats were heavier than the LFCC rats (214 +/- 3.4 v 188 +/- 1.4 g, P < .01). There were no differences in blood glucose between HFS and LFCC rats; however, plasma insulin and homocysteine concentrations were elevated in HFS rats (insulin, 56 +/- 12 v 14.5 +/- 2.9 microU/mL; homocysteine, 10.77 +/- 0.9 v 6.89 +/- 0.34 micromol/L, P < .01). Hepatic CbetaS enzyme activity was significantly lower in HFS compared with LFCC rats (0.45 v 0.64 U/mg, P = .0001), and this decrease was reflected in a decrease of the CbetaS mRNA concentration. In contrast, hepatic MTHFR enzyme activity and mRNA concentration were significantly elevated in the HFS group compared with controls (HFS and LFCC, 8.62 and 4.8 nmol/h/mg protein, respectively, P = .0001). These changes in plasma homocysteine, CbetaS, and MTHFR were significantly correlated with the degree of obesity and hyperinsulinemia. Fasting plasma insulin correlated significantly and positively with plasma homocysteine (r = .51, P < .01) and MTHFR activity (r = .48, P < .01) and negatively with CbetaS activity (r = -.54, P < .001). CbetaS and MTHFR activities were inversely correlated with each other (r = -.58, P < .001). In conclusion, rats fed a HFS diet are hyperinsulinemic, and the hyperinsulinemia is associated with an elevated homocysteine concentration and changes in 2 key enzymes in homocysteine metabolism.
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PMID:Effects of a high-fat-sucrose diet on enzymes in homocysteine metabolism in the rat. 1087 98

Observational studies support the role of modifying lifestyle-related risk factors such as diet, physical activity and alcohol use in stroke prevention. For example, increased Na intake is associated with hypertension, and reduction in salt consumption may significantly lower blood pressure and may reduce stroke mortality. Moderately elevated homocysteine levels may be associated with stroke and are associated with deficiency of dietary intake of folate, vitamin B6 and vitamin B12. Consumption of a diet rich in fruits, vegetables, folate, K, Ca, Mg, dietary fibre, fish and milk may protect against stroke. Regular physical activity may also protect against stroke through its role in controlling various risk factors such as hypertension, diabetes mellitus and obesity. The role of fat intake as a risk factor for stroke remains uncertain, whereas the association between stroke and cholesterol has more convincingly been demonstrated by the recent intervention trials using statins. There is also evidence that a low serum albumin may be causally linked to stroke risk and outcome and that a significant number of stroke patients are undernourished on admission and their nutritional status deteriorates further whilst in hospital. Undernutrition is associated with increasing morbidity and mortality and nutritional supplements may have some beneficial effect on some outcome measures.
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PMID:Nutritional factors in stroke. 1096 Nov 55

Liver transplant recipients have an increased risk for cardiovascular disease because of a high incidence of obesity, arterial hypertension, diabetes mellitus, and hyperlipidemia. Hyperhomocysteinemia has been found to be an important risk factor for cardiovascular disease in large studies. Fasting serum levels of homocysteine were measured in 105 liver transplant recipients, and hyperhomocysteinemia was defined as a fasting serum homocysteine level greater than 13 micromol/L. Patients with versus without hyperhomocysteinemia were compared. The possible association of hyperhomocysteinemia with age, sex, cause of liver disease, time elapsed since liver transplantation, immunosuppressive therapy, folic acid level, liver function test results, renal function, and other cardiovascular risk factors was investigated. Patients with serum homocysteine levels greater than 15 micromol/L were treated with folic acid, 10 mg/d, and serum homocysteine levels were measured again 1 to 3 months later in 10 patients. Hyperhomocysteinemia was detected in 28 patients (27%). In univariate analysis, it was associated with hepatitis C virus infection, treatment with mycophenolate mofetil, and greater serum levels of alkaline phosphatase, gamma-glutamyl transpeptidase, urea, and creatinine. In multivariate analysis, only greater serum levels of creatinine (P =.006) were associated with hyperhomocysteinemia. Treatment with folic acid resulted in a decrease in fasting serum homocysteine levels in 9 of the 10 patients tested (P =.01). Hyperhomocystinemia, associated with renal dysfunction, is a frequent finding in liver transplant recipients. Treatment with folic acid may reduce fasting homocysteine levels.
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PMID:Hyperhomocysteinemia in liver transplant recipients: prevalence and multivariate analysis of predisposing factors. 1098 61

Nitric oxide (NO) produced by the endothelium of cerebral arterioles is an important mediator of endothelium-dependent vasodilation (EDV), and also helps to prevent thrombosis and vascular remodeling. A number of risk factors for ischemic stroke are associated with impaired EDV, and this defect is usually at least partially attributable to a decrease in the production and/or stability of NO. These risk factors include hypertension, high-sodium diets, homocysteine, diabetes, visceral obesity, and aging. Conversely, many measures which may provide protection from ischemic stroke - such as ample dietary intakes of potassium, arginine, fish oil, and selenium - can have a favorable impact on EDV. Protection afforded by exercise training, estrogen replacement, statin drugs, green tea polyphenols, and cruciferous vegetables may reflect increased expression of the endothelial NO synthase. IGF-I activity stimulates endothelial NO production, and conceivably is a mediator of the protection associated with higher-protein diets in Japanese epidemiology and in hypertensive rats. These considerations prompt the conclusion that modulation of NO availability is a crucial determinant of risk for ischemic stroke. Multifactorial strategies for promoting effective cerebrovascular NO activity, complemented by measures that stabilize platelets and moderate blood viscosity, should minimize risk for ischemic stroke and help maintain vigorous cerebral perfusion into ripe old age. The possibility that such measures will also diminish risk for Alzheimer's disease, and slow the normal age-related decline in mental acuity, merits consideration. A limited amount of ecologic epidemiology suggests that both stroke and senile dementia may be extremely rare in cultures still consuming traditional unsalted whole-food diets. Other lines of evidence suggest that promotion of endothelial NO activity may decrease risk for age-related macular degeneration.
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PMID:Up-regulation of endothelial nitric oxide activity as a central strategy for prevention of ischemic stroke - just say NO to stroke! 1105 18

Various lifestyle factors have been associated with increasing the risk of stroke. These include lack of exercise, alcohol, diet, obesity, smoking, drug use, and stress. Guidelines endorsed by the Centers for Disease Control and Prevention and the National Institutes of Health recommend that Americans should exercise for at least 30 minutes of moderately intense physical activity on most, and preferably all, days of the week. Recent epidemiologic studies have shown a U-shaped curve for alcohol consumption and coronary heart disease mortality, with low-to-moderate alcohol consumption associated with lower overall mortality. High daily dietary intake of fat is associated with obesity and may act as an independent risk factor or may affect other stroke risk factors such as hypertension, diabetes, hyperlipidemia, and cardiac disease. Homocysteine is another important dietary component associated with stroke risk, while other dietary stroke risk factors are thought to be mediated through the daily intake of several vitamins and antioxidants. Smoking, especially current smoking, is a crucial and extremely modifiable independent determinant of stroke. Despite the obstacles to the modification of lifestyle factors, health professionals should be encouraged to continue to identify such factors and help improve our ability to prevent stroke.
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PMID:Lifestyle factors and stroke risk: exercise, alcohol, diet, obesity, smoking, drug use, and stress. 1112 40

Cardiovascular disease (CVD) is the main cause of death. Atherosclerosis of coronary arteries is responsible for almost all cases of CVD. The term 'risk factor' describes all those characteristics found in healthy individuals that are independently related to subsequent development of CVD. It includes modifiable biochemical and physiological characteristics, such as hypercholesterolaemia, hypertension, cigarette smoking, diabetes mellitus, obesity and low HDL cholesterol levels, as well as non-modifiable personal characteristics, such as age, gender and family or personal history of early onset CVD. In addition to the 'classic' risk factors mentioned above, several other variables have been implicated as predictors of CVD: left ventricular hypertrophy; infectious agents; markers of inflammation; oxidative stress; and increased levels of fibrinogen, triglycerides, homocysteine and Lp(a)]. However, controversy exists regarding the exact role of these variables in the pathogenesis of atherosclerosis. Furthermore, there are no conclusive data showing that the modification of these variables is associated with a decrease in the incidence of cardiovascular events. Nevertheless, these 'new' risk factors should be taken into account in patients with CVD without established risk factors.
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PMID:The treatment of coronary heart disease: an update. Part 1: An overview of the risk factors for cardiovascular disease. 1146 41

Plasma homocysteine levels have been shown to be associated with indexes of obesity and insulin resistance in obese children and adolescents. We, therefore, investigated the contribution of changes in body composition, markers of insulin resistance, folate, and vitamin B(12) to changes in homocysteine during a weight reduction program in obese children and adolescents. Thirty-seven obese white girls (mean SD; age, 12 +/- 1.8 years, body mass index [BMI], 26.9 +/- 5.25) and 19 obese white boys (age, 11.9 +/- 1.7 years; BMI, 26.2 +/- 5.2) were investigated for body composition, fasting total plasma homocysteine (tHcy), insulin, C-peptide, folate, and vitamin B(12) before and after a 3-week weight reduction program including physical activities. During weight reduction BMI, fat mass (FM), percentage fat mass, insulin, and C-peptide decreased significantly, whereas homocysteine and vitamin B(12) showed a significant increase. Folate and lean body mass (LBM) remained unchanged. tHcy concentration before weight reduction was a function of age, folate, and C-peptide, whereas tHcy concentration after weight reduction was a function of folate and baseline LBM. Changes in tHcy during weight reduction correlated significantly with baseline LBM and were related inversely to changes in LBM during weight reduction. Children who increased LBM showed lower increases in tHcy compared with children who lost LBM. In multiple linear regression analysis, only baseline LBM contributed independently and significantly to changes in tHcy. Our study suggests that LBM has a significant impact on tHcy metabolism during weight reduction.
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PMID:Determinants of homocysteine during weight reduction in obese children and adolescents. 1158 97


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