Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diets with increased protein and reduced carbohydrates have been shown to improve body composition, lipid and lipoprotein profiles, and glycemic regulations associated with treatment of obesity and weight loss. Derived from these outcomes, high-protein, low-carbohydrate diets are also being examined for treatment of heart disease, metabolic syndrome, and type 2 diabetes. High-protein, low-carbohydrate diets have been found to have positive effects on reducing risk factors for heart disease, including reducing serum triacylglycerol, increasing HDL cholesterol, increasing LDL particle size, and reducing blood pressure. These diets appear particularly attractive for use with individuals exhibiting the atherogenic dyslipidemia of metabolic syndrome. High-protein, low-carbohydrate diets have also been investigated for treatment of type 2 diabetes with positive effects on glycemic regulation, including reducing fasting blood glucose, postprandial glucose and insulin responses, and the percentage of glycated hemoglobin. Specific effects of increasing protein compared with reducing carbohydrates have not been extensively investigated. Additional research is needed to determine specific levels of protein, carbohydrate, and fat for optimum health of individuals who differ in age, physical activity, and metabolic phenotypes.
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PMID:Protein in optimal health: heart disease and type 2 diabetes. 1846 90

Dietary carbohydrate restriction in the treatment of diabetes and metabolic syndrome is based on an underlying principle of control of insulin secretion and the theory that insulin resistance is a response to chronic hyperglycemia and hyperinsulinemia. As such, the theory is intuitive and has substantial experimental support. It has generally been opposed by health agencies because of concern that carbohydrate will be replaced by fat, particularly saturated fat, thereby increasing the risk of cardiovascular disease as dictated by the so-called diet-heart hypothesis. Here we summarize recent data showing that, in fact, substitution of fat for carbohydrate generally improves cardiovascular risk factors. Removing the barrier of concern about dietary fat makes carbohydrate restriction a reasonable, if not the preferred method for treating type 2 diabetes and metabolic syndrome. We emphasize the ability of low carbohydrate diets to improve glycemic control, hemoglobin A1C and to reduce medication. We review evidence that such diets are effective even in the absence of weight loss.
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PMID:Carbohydrate restriction as the default treatment for type 2 diabetes and metabolic syndrome. 1860 58

Endothelin plays an important role in the pathogenesis of atherosclerosis. The aim of the study was to evaluate the safety and hemodynamic and metabolic responses to 6 months treatment with atrasentan, the selective endothelin-A receptor antagonist. Seventy-two patients with multiple cardiovascular risk factors and nonobstructive coronary artery disease on coronary angiogram were randomly assigned in a double-blind manner to atrasentan or placebo. Mean aortic blood pressure decreased from 92+/-10 to 80+/-10 mm Hg (P<0.001) in the atrasentan group and did not change in the placebo group (93+/-10 and 92+/-11 mm Hg; P=0.84). The difference between the groups was significant (P<0.001). No effect on heart rate was observed. In a subgroup of patients not treated with angiotensin-converting enzyme inhibitor, creatinine level decreased in the atrasentan versus the placebo group (P=0.011). Fasting glucose (P=0.026), glycosylated hemoglobin level (P=0.041), triglyceride l (P=0.013), lipoprotein-A (P=0.046), and uric acid levels (P=0.048) decreased significantly in the atrasentan group compared with the placebo group. No progression of angiographic coronary disease was observed. The most common adverse effects with atrasentan were nasal stuffiness, headache, and edema. In conclusion, 6 months of treatment with atrasentan results in a reduction of blood pressure and improvement in glucose and lipid metabolism. These findings suggest the beneficial role of atrasentan in the treatment of hypertension and metabolic syndrome.
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PMID:Efficacy and safety of atrasentan in patients with cardiovascular risk and early atherosclerosis. 1869 43

Fetuin-A (alpha2-Heremans-Schmid glycoprotein), a circulating glycoprotein, can inhibit insulin signaling both in vivo and in vitro. Recently, we and another independent group have shown that fetuin-A is positively associated with insulin resistance in humans. Furthermore, it has been reported that higher fetuin-A levels are associated with metabolic syndrome and atherogenic lipid profiles. These data suggest that fetuin-A might be a regulator of insulin resistance and/or metabolic syndrome. However, it is not clear how fetuin-A levels are regulated. To address this, we investigated the effects of representative insulin-sensitizing therapies such as pioglitazone, metformin, and aerobic exercise on fetuin-A levels. Twenty-seven patients with type 2 diabetes mellitus were divided into pioglitazone-treated (Pio), metformin-treated (Met), and exercise-treated (Ex) groups. Ten patients in the Pio group and 9 patients in the Met group took 15 or 30 mg/d pioglitazone or 500 or 750 mg/d metformin, respectively, for 6 months. Eight patients in the Ex group underwent a 3-month aerobic exercise program. Serum fetuin-A levels were measured before and after each intervention. Intervention significantly decreased hemoglobin A(1c) in all groups. After treatment, serum fetuin-A levels significantly decreased in the Pio group (291.2 +/- 57.7 to 253.1 +/- 43.9 microg/mL, P = .006), whereas there were no changes in serum fetuin-A after intervention in either the Met or the Ex groups. We hypothesize that pioglitazone could partially ameliorate insulin resistance via modulating fetuin-A levels.
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PMID:Effects of pioglitazone on serum fetuin-A levels in patients with type 2 diabetes mellitus. 1870 51

Tsunan, Niigata is a non-westernized rural Japanese town, known for heavy snowfalls and as a rice-producing area, whose inhabitants have a long life expectancy. We investigated the prevalence of obesity, metabolic syndrome (MetS) and its components in Tsunan. A total of 1,155 men and women, 40-69 years of age were recruited from participants in the 2005 public-health program in Tsunan. Obesity was defined as body-mass index (BMI) >or= 25 kg/m(2). MetS was defined as BMI >or= 25 kg/m(2) as well as at least two of the following three items: (1) high glycosylated hemoglobin (HbA1c >or= 5.5%); (2) high blood pressure (HBP: systolic blood pressure >or= 130 mmHg or diastolic blood pressure >or= 85 mmHg), and (3) low high-density lipoprotein cholesterol (HDL-C < 40 mg/dL). If an individual was diagnosed with diabetes, hypertension, or dyslipidemia, each item was recorded as a positive finding. The prevalence of MetS and its components among Tsunan inhabitants were compared to the results of the 2005 Japanese nationwide survey. The prevalence of MetS was 4.6% in males and 4.2% in females. The prevalence of obesity, high HbA1c, HBP, and low HDL-C were 22.1/22.2%, 13.4/16.4%, 46.6/40.0%, and 9.2/3.9% in males/females, respectively. All values were significantly lower than the national results, except for the rate of female obesity. The lower prevalence of MetS and its components in Tsunan may be due to the consumption of traditional Japanese food, which is still commonly eaten there, and the higher levels of regular physical activity of farmers.
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PMID:Low prevalence of metabolic syndrome and its components in rural Japan. 1871 40

A considerable body of evidence exists suggesting a link among reduced testosterone plasma levels, type 2 diabetes (T2D), and insulin resistance (IR). Hypogonadal men are at higher risk for T2D. Here we evaluate the relationships between testosterone, metabolic syndrome (MetS), T2D, and IR and discuss the relationships among androgen deficiency and these factors, especially as it ultimately relates to the development of cardiovascular disease and erectile dysfunction (ED). Thus, a comprehensive literature search was carried out using PubMed, and relevant articles pertinent to androgen deficiency, T2D, IR, MetS, and ED were reviewed and discussed. Low testosterone precedes elevated fasting insulin, glucose, and hemoglobin A1c (HbA1C) values and may even predict the onset of diabetes. Treatment of prostate cancer patients with surgical or medical castration exacerbates IR and glycemic control, strengthening the link between testosterone deficiency and onset of T2D and IR. Androgen therapy of hypogonadal men improves insulin sensitivity, fasting glucose, and HbA1c levels. We suggest that androgen deficiency is associated with IR, T2D, MetS, and with increased deposition of visceral fat, which serves as an endocrine organ, producing inflammatory cytokines and thus promoting endothelial dysfunction and vascular disease.
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PMID:The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance. 1877 88

Obesity is reaching epidemic proportions worldwide and it is correlated with various comorbidities, among which the most relevant are diabetes mellitus, arterial hypertension, and cardiovascular diseases. Obesity management is a modern challenge because of the rapid evolution of unfavorable lifestyles and unfortunately there are no effective treatments applicable to the large majority of obese/overweight people. The current medical attitude is to treat the complications of obesity (e.g. dyslipidemia, hypertension, diabetes, and cardiovascular diseases). However, the potential of treating obesity is enormous, bearing in mind that a volitional weight loss of 10 kg is associated with important risk factor improvement: blood pressure -10 mmHg, total cholesterol -10%, LDL cholesterol -15%, triglycerides -30%, fasting glucose -50%, HDL cholesterol +8%. Drug treatment for obesity is an evolving branch of pharmacology, burdened by severe side effects and consequences of the early drugs, withdrawn from the market, and challenged by the lack of long-term data on the effect of medications on obesity-related morbidity and mortality, first of all cardiovascular diseases. In Europe three antiobesity drugs are currently licensed: sibutramine, orlistat, and rimonabant; important trials with clinical endpoints are ongoing for sibutramine and rimonabant. While waiting for their results, it is convenient to evaluate these drugs for their effects on body weight and cardiometabolic risk factors. Sibutramine is a centrally acting serotonin/noradrenaline reuptake inhibitor that mainly increases satiety. At the level of brown adipose tissue, sibutramine can also facilitate energy expenditure by increasing thermogenesis. The long-term studies (five) documented a mean differential weight reduction of 4.45 kg for sibutramine vs placebo. Considering the principal studies, attrition rate was 43%. This drug not only reduces body weight and waist circumference, but it decreases triglycerides and uric acid as well and it increases HDL cholesterol; in diabetics it improves glycated hemoglobin. Sibutramine has conflicting effects on blood pressure: in some studies there was a minimal decrease, in some others a modest increase. In all the studies this drug increased pulse rate. Sibutramine is not recommended in patients with uncontrolled hypertension, or in case of history of cardio- and cerebrovascular disease. Orlistat is a pancreatic lipase inhibitor that reduces fat absorption by partially blocking the hydrolysis of dietary triglycerides. A recent meta-analysis evaluated 22 studies lasting for at least 12 months, in obese patients with a mean body mass index of 36.7 kg/m2, where orlistat was associated with hypocaloric diet or behavioral interventions: the net average weight loss was 2.89 kg (confidence interval 2.27-3.51 kg). Considering the principal studies, attrition rate ranged from 33 to 57%. Orlistat significantly decreases waist circumference, blood pressure, total and LDL cholesterol, but has no effect on HDL and triglycerides. This drug significantly reduced the incidence of diabetes only in subjects with impaired glucose tolerance. The major adverse effects with orlistat are mainly gastrointestinal (fatty and oily stool, fecal urgency, oily spotting, fecal incontinence) and attenuate over time. Orlistat should be avoided in patients with chronic malabsorption and cholestasis. Rimonabant is a selective antagonist of cannabinoid type 1 receptor. This drug, by inhibiting the overactivation of the endocannabinoid system, produces anorectic stimuli at the central nervous level, but also has effects on the peripheral systems involved in metabolism control, such as liver, adipose tissue, skeletal muscles, endocrine pancreas, and gastrointestinal apparatus, influencing many processes partially unknown. An ample experimental program named RIO (Rimonabant In Obesity) involved about 6600 obese or overweight patients to identify the effects of rimonabant in weight loss and associated cardiometabolic abnormalities, over and beyond a caloric restriction of 600 kcal in the treatment and placebo arms. In the four double-blind RIO trials published (Rio-North America, RIO-Europe, RIO-Lipids, RIO-Diabetes), rimonabant 20 mg significantly (p <0.001) reduced weight by 6.3-6.9 kg in the non-diabetic groups vs placebo (-1.5-1.8 kg), whereas in the diabetic subjects enrolled in RIO-Diabetes, weight loss was 5.3 vs 1.4 kg in the placebo group. Attrition rate at 1 year ranged between 40 and 50%, similar to the studies with sibutramine or orlistat. Similarly to weight loss, also waist circumference was significantly reduced by rimonabant. As for cardiometabolic parameters, rimonabant induced a significant increase in HDL cholesterol and a significant decrease in triglycerides. Even if no significant LDL reduction was achieved, the RIO-Lipids study showed a significant decrease in small dense LDL particles, more atherogenic, in rimonabant-treated subjects. Non-diabetic treated patients improved basal insulin and indirect indexes of insulin resistance, while in the RIO-Diabetes study, the only one including diabetics, glycated hemoglobin improved by 0.7% in the active treatment arm vs placebo. The effects on HDL cholesterol and glycated hemoglobin seem in a large percentage unrelated to weight loss. These effects have been confirmed by another trial, named SERENADE, evaluating the treatment in naive diabetic patients. Rimonabant is not recommended in patients with a history of depressive disorders or suicidal ideation and with uncontrolled psychiatric illness, and is contraindicated in patients with ongoing major depression or ongoing antidepressive treatment. In conclusion, despite an enormous advancement in basic research to understand the pathogenetic mechanisms at the base of obesity, the pharmacological research did not reach the therapeutic opportunities available for other chronic conditions, like hypertension and dyslipidemia. However, the few molecules available for clinical practice (sibutramine, orlistat, rimonabant) have shown, when properly used, to contribute to reduce body weight and undoubtedly improve cardiometabolic risk factors. With this preamble, according to current guidelines and pharmacoeconomic studies, patients who might benefit from antiobesity treatment are those with a body mass index > or =30 or 27-29.9 kg/m2 with major obesity-related comorbidities such as hypertension, diabetes, dyslipidemia, obstructive sleep apnea, and metabolic syndrome.
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PMID:[Pharmacological therapy of obesity]. 1877 55

Recent studies have shown independent and opposite associations of hip circumference (HC) and waist circumference (WC) with glucose intolerance, insulin resistance, and type 2 diabetes mellitus. However, no studies have simultaneously considered the independent contributions of both markers to metabolic proinflammatory and atherosclerotic risk factors. In this study, we examine the independent associations of WC and HC with metabolic syndrome and with proinflammatory and atherothrombotic features. Independent associations of thigh muscle and adipose tissue (AT) compartments with metabolic features were also studied. Abdominal and thigh muscle and AT distributions were assessed by computed tomography in 140 overweight and obese women (mean +/- SD: age, 38.3 +/- 0.5 years; body mass index, 30.4 +/- 0.3 kg/m(2)). Blood lipids and inflammatory and atherothrombotic markers were measured. For a given WC, a larger HC was inversely associated with fasting insulin (beta = -0.288, P = .008), hemoglobin A(1c) (beta = -0.246, P = .041), and plasminogen activator inhibitor-1 concentrations (beta = -0.241, P = .023). Contrarily, WC was related with an unfavorable metabolic profile. For a given WC, higher total thigh AT and total thigh subcutaneous AT masses were associated with lower hemoglobin A(1c) (beta = -0.244, P = .049; beta = -0.233, P = .049) and low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (beta = -0.252, P = .040; beta = -0.245, P = .037). In addition, total thigh AT was related with leptin (beta = 0.310, P = .012), whereas total thigh subcutaneous AT revealed opposite associations with fasting insulin concentrations (beta = -0.239, P = .034). Total thigh muscular tissue mass was related with lower plasminogen activator inhibitor-1 (beta = -0.164, P = .049) and fibrinogen concentrations (beta = -0.222, P = .018). In conclusion, HC revealed independent and opposite associations with insulin resistance and atherothrombotic disturbances. Contrarily, a larger WC predicted an increased metabolic risk. These contrasting effects in diabetogenic and atherothrombotic disturbances were, respectively, mediated by gluteofemoral AT and thigh muscle tissue. Besides body mass index and WC screening relevance, HC can contribute to additionally predict health risk in overweight and obese women.
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PMID:Independent and opposite associations of hip and waist circumference with metabolic syndrome components and with inflammatory and atherothrombotic risk factors in overweight and obese women. 1880 32

We investigated the effect of body composition, nutrition, inflammation and iron status on insulin resistance in patients with long-term hemodialysis. We selected 43 stable end-stage chronic renal failure patients, on maintenance hemodialysis. We evaluated the nutritional status, body composition by subjective global assessment (SGA), anthropometric measurements (BMI and waist circumference), bioelectrical impedance analysis and biochemical parameters measurements [serum albumin, cholesterol, HDL-cholesterol, triglyceride, hematocrit, hemoglobin, iron, ferritin, calcium, phosphorus, intact parathormone (i-PTH), TNF-alpha, IL-6 and high sensitivity C-reactive protein]. All parameters were evaluated by comparisons between HOMA-IR tertiles, and after simple regression analysis, by backward multivariate regression analysis we identified independent variables for IR. As the tertile of HOMA-IR increased, serum level of glucose, insulin, and waist increascd, whereas HDL-cholesterol level decreased, or the prevalence of the metabolic syndrome increased across the tertiles of HOMA-IR. After adjustment for gender, age, hemodialysis duration, ferritin, phosphorus, waist and total fat percentages, multivariate regression analysis was performed and the association with HOMA-IR was still strong only for serum levels of iron and TNF-alpha. That explains 16% of the total variation in HOMA-IR. Our results suggest that the increase of IR in end-stage chronic renal failure patients on hemodialysis could be related to anemia and particularly to iron overload. Moreover, chronic inflammatory status with over-production of adipokine TNF-alpha participate in the pathogenesis of IR too. The present study demonstrated that adipokine TNF-alpha and serum iron participated as independent predictors in the pathogenesis of insulin resistance on long-term hemodialysis patients.
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PMID:The effect of nutritional status, body composition, inflammation and serum iron on the developement of insulin resistance among patients on long-term hemodialysis. 1892 54

Excess glycated hemoglobin (HbA(1c)), an indicator of long-term glucose homeostasis, is recognized as a risk factor for cardiovascular (CV) disease and mortality even among persons without diabetes. However, information is scant regarding its distribution and correlates of CV risk in nondiabetic younger adults. This aspect was examined in a biracial (black-white) community-based sample of 1111 younger adults (mean age: 36.2 years; 71% white, 43% male) enrolled in the Bogalusa Heart Study. Blacks vs whites and women vs men had higher HbA(1c) values (P < .0001). In bivariate analysis adjusted for age, race, sex, and smoking status, significant adverse trends were noted for body mass index, waist circumference, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), total cholesterol to HDL-C ratio, insulin, glucose, and homeostasis model assessment of insulin resistance across HbA(1c) quartiles; trends were not significant for mean arterial blood pressure, triglycerides, C-reactive protein, adiponectin, and estimated glomerular filtration rate. In multivariate analysis, besides race and sex, total cholesterol to HDL-C ratio and waist circumference were independent correlates of HbA(1c). Furthermore, the prevalence of excess (top decile) HbA(1c) was 1.6-fold (P < .05) higher among those with metabolic syndrome defined by the National Cholesterol Education Program Adult Treatment Panel III and 2.1-fold (P < .01) and 1.5-fold (P < .05) higher, respectively, among those with positive parental history of CV disease and type 2 diabetes mellitus. These findings underscore the potential value of HbA(1c) in risk assessments of CV disease and type 2 diabetes mellitus in nondiabetic, apparently "healthy" younger adults.
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PMID:Distribution and cardiovascular risk correlates of hemoglobin A(1c) in nondiabetic younger adults: the Bogalusa Heart Study. 1894 Mar 83


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