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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A limited number of studies have reported associations of markers of liver injury, including elevated concentrations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), with prospective risk of type 2 diabetes. However, only one study has adjusted for a detailed measure of insulin sensitivity (insulin sensitivity index [S(i)]), which is important given associations of obesity and S(i) with nonalcoholic fatty liver disease (NAFLD). Our objective was to investigate the associations of elevated AST and ALT with incident type 2 diabetes among 906 participants in the Insulin Resistance Atherosclerosis Study who were nondiabetic at baseline. S(i) and acute insulin response (AIR) were measured directly from the frequently sampled intravenous glucose tolerance test among black, Hispanic, and non-Hispanic white participants aged 40-69 years. After 5.2 years, 148 individuals had developed type 2 diabetes. Baseline AST and ALT were positively correlated with fasting insulin (r = 0.22 and r = 0.35, respectively), waist circumference (r = 0.18 and r = 0.34), and fasting glucose (r = 0.13 and r = 0.29) and inversely with S(i) (r = -0.18 and r = -0.30; all P < 0.0001). In separate logistic regression models adjusting for age, sex, ethnicity, clinical center, and alcohol consumption, participants in the highest quartiles (Q4) of AST and ALT were at significantly increased risk of incident type 2 diabetes compared with those in the lowest three quartiles (Q1-Q3): AST: odds ratio (OR) 1.73 (95% CI 1.17-2.57); ALT: OR 2.32 (1.36-3.75). After further adjustment for smoking, waist circumference, triglyceride, HDL, impaired glucose tolerance, S(i), and AIR, both AST and ALT remained significantly associated with incident type 2 diabetes: AST, Q4 vs. Q1-Q3: OR 1.98 (1.23-3.17); ALT, Q4 vs. Q1-Q3: OR 2.00 (1.22-3.28). There were no interactions of sex, ethnicity, obesity, impaired glucose tolerance, or S(i) with AST or ALT in the prediction of type 2 diabetes. When entered into the same model with adjustment for demographic variables, both C-reactive protein and ALT independently predicted type 2 diabetes. In addition, AST and ALT were positively associated with incident type 2 diabetes after excluding former and moderate to heavy drinkers. In conclusion, AST and ALT independently predict type 2 diabetes. Baseline elevations of these markers may reflect NAFLD or related pathologies.
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PMID:Elevations in markers of liver injury and risk of type 2 diabetes: the insulin resistance atherosclerosis study. 1544 93

The objective of the study was to determine whether plasma migration inhibitor factor (MIF) concentration and mononuclear cell (MNC) mRNA are elevated in obesity and whether treatment with metformin reduces plasma MIF concentration. Forty obese subjects [body mass index (BMI), 37.5 +/- 4.9 kg/m(2)] and 40 nonobese healthy subjects (BMI, 22.6 +/- 3.4 kg/m(2)) had their plasma MIF, glucose, insulin, free fatty acids (FFAs) and C-reactive protein (CRP) concentrations measured. Sixteen obese patients and 16 nonobese healthy subjects had RNA prepared from MNCs. Eight obese subjects with normal glucose concentration were treated with metformin 1 g (Glucophage XR; 1000 mg twice daily) twice daily for 6 wk. Eight obese subjects were used as controls. Plasma concentration of glucose, insulin, FFAs, and MIF was measured by appropriate assays. mRNA for MIF was measured by real-time PCR. Forty obese subjects had a fasting concentration of MIF of 2.8 +/- 2.0 ng/ml, whereas 40 nonobese subjects had a fasting MIF concentration of 1.2 +/- 0.6 ng/ml (P < 0.001). Plasma MIF concentrations were significantly related to BMI (r = 0.52; P < 0.001). mRNA for MIF was correlated to plasma FFAs (r = 0.40; P < 0.05) and plasma CRP (r = 0.42; P < 0.05) concentrations. Eight obese subjects had their fasting blood samples taken before and after taking a slow-release preparation of metformin at 1, 2, 4, and 6 wk. The mean plasma concentration fell from 2.3 +/- 1.4 to 1.6 +/- 1.2 ng/ml at 6 wk (P < 0.05). Obese subjects not on treatment with metformin showed no change. During the period of treatment with metformin, the body weight did not change and the plasma concentration of glucose, insulin, and FFAs did not alter. We conclude that: 1) plasma MIF concentrations and MIF mRNA expression in the MNCs are elevated in the obese, consistent with a proinflammatory state in obesity; 2) these increases in MIF are related to BMI, FFA concentrations, and CRP; 3) metformin suppresses plasma MIF concentrations in the obese, suggestive of an antiinflammatory effect of this drug; and 4) this action of metformin may contribute to a potential antiatherogenic effect, which may have implications for the reduced cardiovascular mortality observed with metformin therapy in type 2 diabetes mellitus.
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PMID:Increased plasma concentration of macrophage migration inhibitory factor (MIF) and MIF mRNA in mononuclear cells in the obese and the suppressive action of metformin. 1547 3

In the present study, we examined (i) whether C3 (complement C3) was an independent marker of prevalent CHD (coronary heart disease), and (ii) which preferential associations existed between C3 and some cardiovascular risk factors when jointly analysed with CRP (C-reactive protein) and fibrinogen. In a cohort of 756 unselected adults, 39% of whom had the metabolic syndrome, C3 and other risk variables were evaluated in a cross-sectional manner. In a logistic regression model for the likelihood of CHD, a significant OR (odds ratio) of 3.5 [95% CI (confidence intervals), 1.27 and 9.62)] for C3 was obtained after adjustment for smoking status, TC (total cholesterol) and usage of statins. A similar model, also comprising systolic blood pressure, with a cut-off point of >or=1.6 g/l C3 exhibited a 1.9-fold risk (95% CI, 1.01 and 3.58) compared with individuals below the cut-off point. Both analyses displayed an adjusted OR of 1.37 for each S.D. increment in C3. The significant relationship of C3 with a likelihood of CHD also proved to be independent of CRP. In multiple linear regression models, associations were tested for each acute-phase protein with measures of obesity, fasting insulin, triacylglycerols (triglycerides), TC, HDL (high-density lipoprotein)-cholesterol, physical activity, smoking status, diagnosis of metabolic syndrome and family income. When both genders were combined, C3 was independently associated with serum triacylglycerols, waist circumference, BMI (body mass index) and TC. CRP was independently associated with waist circumference, TC, family income (inversely) and physical activity, and fibrinogen with BMI, TC, smoking status and metabolic syndrome. In summary, elevated levels of complement C3 are associated with an increased likelihood of CHD independent of standard risk factors and regardless of the presence of acute coronary events, suggesting that C3 might be actively involved in coronary atherothrombosis. Unlike CRP and fibrinogen, C3 was preferentially associated with waist girth and serum triacylglycerols.
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PMID:Cross-sectional study of complement C3 as a coronary risk factor among men and women. 1548 75

Adipose tissue expression of tumor necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of obesity-linked insulin resistance and the dyslipoproteinemia of insulin resistance. This study has two aims: (1) to compare select inflammatory mediators in non-smoking, normoglycemic male subjects with and without the atherogenic dyslipoproteinemia (ADL), and (2) to determine the effects of statin therapy on select inflammatory mediators. ADL subjects had higher levels of insulin (16.7 +/- 7.5 versus 11.6 +/- 5.9 microIU/mL, P=0.008), soluble TNF receptor superfamily 1B (sTNFRSF1B) (3.3 +/- 0.7 versus 2.7 +/- 0.5 ng/mL, P=0.005), and interleukin-6 (IL-6) (2.6 +/- 2.2 versus 1.3 +/- 1.8 pg/mL, P=0.006) as compared to those of the non-ADL subjects. After adjustment for age, sTNFRSF1B (P=0.003) was more predictive of ADL than high-sensitivity C-reactive protein (hs-CRP) (P=0.047). Statin therapy did not change sTNFRSF1B, TNF-alpha, IL-6, hs-CRP, whereas soluble TNF receptor superfamily 1A (sTNFRSF1A) increased slightly (P=0.048). A high level of sTNFRSF1B is a strong marker of the pro-inflammatory state in this sample of male ADL subjects.
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PMID:Elevated soluble tumor necrosis factor receptor levels in non-obese adults with the atherogenic dyslipoproteinemia. 1548 68

Acute phase reactants have been implicated for their involvement as proinflammatory molecules in various inflammatory diseases. However, little is known regarding their role in the allergic airway disease. The aim of the present study was to examine the blood concentrations of three acute-phase proteins, namely C-reactive protein (CRP), serum amyloid A (SAA) and fibrinogen in patients with allergic rhinitis and asthma. Three study groups include: non-smoker allergic rhinitis (n = 50), non-smoker asthma (n = 20), and non-allergic, non-smoker healthy control subjects (n = 20). Patients who have had recent upper or lower respiratory tract infection and trauma, any rheumatological illnesses, malignancy or obesity were excluded. Blood samples were obtained from all the patients and control subjects and were analyzed for serum CRP, SAA and plasma fibrinogen. The mean CRP and fibrinogen values in the rhinitis and asthma groups were not significantly different when compared to the control group. However, the mean SAA levels of both groups were found to be significantly higher than those of the control group (p = 0.002 for rhinitis, p = 0.02 for asthma). There was no significant correlation between the FEV(1) values and the levels of the serum markers. This study demonstrates that acute phase reactant SAA rises in patients with allergic rhinitis and patients with asthma. We therefore suggest that SAA may have a role in the inflammatory airway disease.
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PMID:Acute phase reactants in allergic airway disease. 1550 20

Metabolic alterations such as insulin resistance are thought to underlie the endothelial dysfunction and low grade inflammation found in morbid obesity. Twenty-six morbidly obese patients, aged 39.0 +/- 10.0 (mean +/- sd), were evaluated before and 4.2 +/- 0.8 months after bariatric surgery. A marked increment in the insulin sensitivity index (S(I)) and the endothelium-dependent vasodilatory response in a dorsal hand vein was observed after weight loss following bariatric surgery. Circulating levels of E-selectin, P-selectin, plasminogen activator inhibitor-1, and von Willebrand factor, which were higher than those in the control group, decreased significantly after surgery. Plasma vascular cell adhesion molecule-1, angiotensin-converting enzyme, intercellular adhesion molecule-1, thrombomodulin, and plasma and intraplatelet cGMP levels did not change after weight loss. All inflammatory markers were higher in morbidly obese patients. After surgery, C- reactive protein and sialic acid diminished, whereas circulating levels of IL-6, TNF-alpha, and its soluble receptors did not. Positive correlations were found between changes in adiposity and S(I) and changes in C-reactive protein and between changes in sialic acid and changes in endothelial function. In conclusion, a marked improvement in S(I), endothelial function, and low grade inflammation was observed in the weight-losing, morbidly obese patients after bariatric surgery. S(I) and adiposity appear to play roles in obesity-related, low grade inflammation that contribute to the endothelial dysfunction observed in morbid obesity.
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PMID:Effects of changes in body weight and insulin resistance on inflammation and endothelial function in morbid obesity after bariatric surgery. 1550 18

Metabolic syndrome is a cluster of cardiovascular risk factors. Pathogenesis of metabolic syndrome implies 3 potential etiological mechanisms: obesity and adipose tissue disorders, insulin resistance, and a constellation of independent factors. Clinical recognition of the metabolic syndrome is based on finding several well-recognized signs in clinical practice: abdominal obesity, elevated triglycerides, reduced HDL cholesterol, raised blood pressure, and elevated plasma glucose. In addition, other components commonly aggregate with the major components: elevated apolipoprotein B, small LDL particles, insulin resistance and hyperinsulinemia, impaired glucose tolerance (IGT), elevated C-reactive protein (CRP), and variation in coagulation factors (plasminogen activator inhibitor [PAI]-I and fibrinogen). Cardiovascular disease (CVD) is the primary clinical outcome of metabolic syndrome. Additionally, risk for type 2 diabetes is higher. Diabetes is itself a major risk factor for CVD. ATP III criteria for diagnosis of metabolic syndrome provide a practical tool to identify patients at increased risk for CVD. World Health Organization (WHO) and American Association of Clinical Endocrinologists (AACE) criteria require further oral glucose testing if IFG and diabetes are absent. IGT on OGTT denotes greater risk for diabetes than does metabolic syndrome without elevated fasting glucose.
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PMID:Metabolic syndrome--new insights into a growing entity. 1552 16

Lipid and non-lipid cardiovascular risk parameters (cholesterol, HDL- and LDL-cholesterol, triglycerides, homocysteine, C-reactive protein, insulin resistance) and data about blood pressure, smoking, body mass index were assessed in two ethnic groups aged 19-35 years--the Gypsy group (n=122) and the Slovak group (n=137) of two regions with a high density of Gypsy population. In the Gypsy group, the values of triglycerides, atherogenic index, insulin, insulin resistance were significantly increased and the level of HDL-cholesterol was significantly decreased. The risk value of atherogenic index was found in 27 % of Gypsy vs 13 % of majority subjects, and 28 % vs 24 % of subjects had hypertriglyceridemia. Risk value of insulin resistance (HOMA) was presented in 11 % of the Gypsy vs 5 % of the majority group. More obese subjects (20 % vs 8 %), more smokers (55 % vs 25 %) and more subjects with low education (85 % vs 27 %) were recorded in the minority group. The greater occurrence of dyslipidemia, obesity and insulin resistance in young Gypsy subjects is influenced with lifestyle (nutrition /prevalence of animal fat consumption, low consumption of food with low glycemic index and soluble fibre/, smoking, low physical activity) as well as low educational status. (Tab. 2, Ref. 22.).
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PMID:Cardiovascular risk factors in young Gypsy population. 1554 46

The prevalence of the metabolic syndrome is increasing owing to lifestyle changes leading to obesity. This syndrome is a complex association of several interrelated abnormalities that increase the risk for cardiovascular disease and progression to diabetes mellitus (DM). Insulin resistance is the key factor for the clustering of risk factors characterizing the metabolic syndrome. The National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III defined the criteria for the diagnosis of the metabolic syndrome and established the basic principles for its management. According to these guidelines, treatment involves the improvement of the underlying insulin resistance through lifestyle modification (eg, weight reduction and increased physical activity) and possibly by drugs. The coexistent risk factors (mainly dyslipidemia and hypertension) should also be addressed. Since the main goal of lipid-lowering treatment is to achieve the NCEP low-density lipoprotein cholesterol (LDL-C) target, statins are a good option. However, fibrates (as monotherapy or in combination with statins) are useful for the treatment of the metabolic syndrome that is commonly associated with hypertriglyceridemia and decreased high-density lipoprotein cholesterol (HDL-C) levels. The blood pressure target is < 140/90 mm Hg. The effect on carbohydrate homeostasis should possibly be taken into account in selecting an antihypertensive drug. Patients with the metabolic syndrome commonly have other less well-defined metabolic abnormalities (eg, hyperuricemia and raised C-reactive protein levels) that may also be associated with an increased cardiovascular risk. It seems appropriate to manage these abnormalities. Drugs that beneficially affect carbohydrate metabolism and delay or even prevent the onset of DM (eg, thiazolidinediones or acarbose) could be useful in patients with the metabolic syndrome. Furthermore, among the more speculative benefits of treatment are improved liver function in nonalcoholic fatty liver disease and a reduction in the risk of acute gout.
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PMID:Prevention and treatment of the metabolic syndrome. 1554 46

It is now well documented that obesity is associated with a chronic low-grade inflammatory state. Levels of high-sensitivity C-reactive protein, a marker of systemic inflammation and a mediator of atherothrombotic disease, have been shown to correlate with cardiovascular disease risk. Our objective was to evaluate the effect of fenofibrate on the levels of high-sensitivity C-reactive protein in dyslipidemic obese patients. We selected 30 dyslipidemic obese patients (body mass index > or = 30 kg/m2) and 20 normolipidemic, nonobese healthy subjects. Dyslipidemic obese patients were treated with fenofibrate 200 mg/day for 3 months. Serum high-sensitivity C-reactive protein and metabolic parameters were evaluated at baseline in both groups and after fenofibrate treatment in dyslipidemic obese patients. At baseline, significantly higher high-sensitivity C-reactive protein levels were found in dyslipidemic obese patients than normal subjects (0.58+/-0.3 vs 0.14+/-0.1 mg/dL, P < 0.01). Total cholesterol, low-density lipoprotein cholesterol, and triglyceride decreased significantly (P < 0.05, P < 0.05, and P < 0.01, respectively), and levels of high-density lipoprotein cholesterol significantly increased (P < 0.05) after treatment with fenofibrate in the dyslipidemic obese group. Levels of high-sensitivity C-reactive protein decreased significantly (approximately 74.1%) after fenofibrate treatment from a mean of 0.58+/-0.3 mg/dL to 0.15+/-0.2 mg/dL, P < 0.01. Our findings suggest that fenofibrate may be used as a first-line therapy for improving the plasma lipids profile, as well as the chronic low-grade inflammatory state in dyslipidemia and obesity.
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PMID:The effect of fenofibrate on the levels of high sensitivity C-reactive protein in dyslipidemic obese patients. 1555 50


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