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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-alcoholic steatohepatitis (NASH) is a disease of emerging identity and importance, and is now considered as one of the commonest liver diseases in western countries. It is frequently associated with severe obesity, especially abdominal adiposity, and is intimately related to various clinical and biological markers of the insulin resistance syndrome. Especially, both the prevalence and the severity of liver steatosis are related to male sex, body mass index, waist circumference, hyperinsulinaemia, hypertriglyceridaemia and impaired glucose tolerance or type 2 diabetes. A substantial weight loss following gastroplasty is accompanied by a marked reduction in the prevalence and the severity of the various biological abnormalities of the metabolic syndrome and, concomitantly, by an important regression of liver steatosis in most obese patients. However, in some patients, this rapid and drastic weight loss may result in a mild increase in inflammatory lesions (hepatitis), despite the regression of steatosis, which might result from the rapid mobilization of fatty acids or cytokines from adipose tissue, especially visceral fat. The intimate relationship between NASH and obesity leads to the concept that NASH may be considered as another disease of affluence, as is the insulin resistance syndrome and perhaps being part of it.
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PMID:Non-alcoholic steatohepatitis: association with obesity and insulin resistance, and influence of weight loss. 1080 23

The definable causes of nonalcoholic steatohepatitis (NASH) include jejunoileal bypass surgery (JIB), other causes of rapid and profound weight loss in obese subjects, total parenteral nutrition, drugs, industrial toxins, copper toxicity, and disorders characterized by extreme insulin resistance. However, the etiopathogenesis in most cases of NASH appears multifactorial. Obesity, type 2 diabetes, and hypertriglyceridemia are often associated with hepatic steatosis, and although this does not invariably lead to NASH, the fatty liver is vulnerable to hepatocellular injury initiated by reactive oxygen species (ROS). It is critical to understand not only the triggers for hepatitis (injury and inflammation) in NASH but also how this is perpetuated as chronic liver disease. The present focus is on whether the biochemical processes that generate oxidative stress lead to hepatocyte injury and secondary recruitment of inflammation or whether inflammation is the primary mediator of liver cell injury. Insulin resistance is a reproducible pathogenic factor in NASH. It favors accumulation of free fatty acids in the liver and predisposes to oxidative stress by stimulating microsomal lipid peroxidases and by the direct effects of high insulin levels in decreasing mitochondrial beta-oxidation. CYP2E1 is normally suppressed by insulin but is invariably increased in the livers of patients with NASH. In rodent dietary models of steatohepatitis, CYP2E1 is the catalyst of microsomal lipid peroxidation, while in Cyp 2e1 nullizygous mice, CYP4A proteins are induced and function as alternative microsomal lipid peroxidases. Other studies implicate activation of peroxisome proliferator-activated receptor-alpha (PPAR alpha) as leading to NASH; PPAR alpha is a transcription factor that governs both microsomal (via CYP4A) and peroxisomal (beta-oxidation) pathways of lipid oxidation and ultimately production of ROS. Increased lipid peroxidation is a crucial difference between the livers of rodents with experimental NASH and those of ob/ob genetically obese mice that have uncomplicated steatosis. Administration of endotoxin, through the release of tumor necrosis factor-alpha (TNF-alpha), provokes liver inflammation with hepatocyte injury in the steatotic liver. This may be particularly relevant in JIB and has been suggested as a pathogenic mechanism in primary NASH. It has been proposed that inheriting one or more copies of the hemochromatosis gene, C282Y, promotes fibrotic progression in NASH because of increased hepatic iron deposition, but recent studies have failed to confirm this. The relationship between the severity of hepatitis in NASH and progression to cirrhosis implies that products of the inflammatory infiltrate play a role in fibrogenesis. In summary, NASH can be regarded as the hepatic consequence of the metabolic syndrome (or syndrome X). Attention should now shift from steatosis, a generally benign process that is less evident in the advanced stages of cirrhosis, to the mechanisms for hepatocellular injury, inflammation, and hepatic fibrosis. In particular, the genetic, molecular, and cellular factors that ordain and moderate fibrosis in the context of steatohepatitis will be of greatest relevance to effective therapy and clinical outcome.
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PMID:Etiopathogenesis of nonalcoholic steatohepatitis. 1129 94

Non-alcoholic liver steatosis is associated with metabolic syndrome and type 2 diabetes. The prevalence of this condition in type 2 diabetes is estimated to be between 28 and 55%. Non-alcoholic liver steatosis is not a benign disease because of its potential progression to liver fibrosis, cirrhosis and cancer. The Verona diabetes study, a population-based observational study, on 7148 type 2 diabetic patients after 5 years of follow-up has reported an increased risk of death from gastrointestinal diseases, particularly from chronic liver cirrhosis. Moreover, in the same population after 10 years of follow-up a higher risk of mortality from liver cancer was observed and this risk increased significantly in obese patients (body mass index >30 kg/m2). Of note is that obese diabetic patients suffer an even higher prevalence of non-alcoholic liver steatosis. In conclusion, the Verona diabetes study showed an increased risk of mortality from liver cirrhosis and liver cancer in type 2 diabetic patients. Diverse pathophysiological mechanisms can be responsible, i.e. higher alcohol consumption, hepatitis and others but, considering the high prevalence of non-alcoholic liver steatosis in these patients, it is plausible to hypothesize that non-alcoholic liver steatosis may play a significant role in predisposing the liver of diabetics to chronic diseases.
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PMID:Review article: type 2 diabetes and chronic liver disease in the Verona diabetes study. 1622 67

Changes in human behavior and lifestyle over the last century have resulted in a dramatic increase in the incidence of obesity, type 2 diabetes, and the metabolic syndrome. Differences in the reported overall prevalence of the metabolic syndrome, which is generally in the range of 10-30% depend on the diagnostic criteria and subjects of the study. Recently, Japanese criteria for diagnosis of the metabolic syndrome were defined. With these criteria, presence of visceral obesity is essential for the diagnosis and is simply determined by measurement of waist circumference. Reflecting a dramatic increase in the incidence of obesity and type 2 diabetes, the incidence of the metabolic syndrome is increasing in Japan as well as in Western countries, regardless of the criteria applied. Recently, the number of workers with elevated liver enzymes, in whom virus hepatitis, alcoholic liver disease, drug induced hepatitis, autoimmune hepatitis, and iron overload were ruled out as causal agents, has also be found to be increasing at workplace health checkups. Most of such workers have components of the metabolic syndrome and the presence of steatosis in the liver, this pathologic condition now being termed nonalcoholic fatty liver disease (NAFLD). In this review, we describe the relationship between NAFLD and the metabolic syndrome.
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PMID:Metabolic syndrome from the view point of public health: with special reference to nonalcoholic fatty liver disease. 1640 78

The farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily that is primarily expressed in the enterohepatic system where it functions as intracellular sensor for bile acids. Ligand dependent FXR activation induces transcriptional responses to coordinately regulate bile acid, cholesterol, triglyceride and glucose metabolism, and to protect the intestinal mucosa from bacterial overgrowth and inflammatory insults. Here we discuss the latest discoveries in FXR-driven metabolic pathways with relevance to pathophysiology and novel therapeutic approaches of several conditions such as hypertriglyceridemia, type 2 diabetes, cholesterol gallstone disease, steato-hepatitis and metabolic syndrome.
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PMID:Nuclear bile acid receptor FXR as pharmacological target: are we there yet? 1690 70

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins are the most successful cardiovascular drugs of all time. By interrupting cholesterol synthesis in the liver, they activate hepatocyte low-density lipoprotein (LDL) receptors and produce consistent and predictable reductions in circulating LDL cholesterol with resulting reproducible improvements in cardiovascular risk by retarding or even regressing the march of atherosclerosis in all major arterial trees (coronary, cerebral and peripheral). Clinical trials have demonstrated their capacity not only to extend life, but also to improve its quality by retarding the progression of diabetes mellitus and chronic renal disease and by enhancing central and peripheral blood flow. They are amongst the most extensively investigated pharmaceutical agents in current clinical use. In cardiovascular end-point trials they have proven ability to help prevent that first and all important myocardial infarction and to reduce the likelihood of a recurrence in those who do succumb. They are equally effective in men and women of all ages and at all levels of cardiovascular risk, whether caused by hypercholesterolaemia, hypertension, cigarette smoking, diabetes mellitus or the metabolic syndrome. In addition, they improve the outlook of patients with familial hypercholesterolaemia whose LDL receptor function is deficient or defective; and all of this comes at minimal risk to the recipient. Their most important potential side effect is myopathy, which on very rare occasions may lead to rhabdomyolysis. Clinical experience shows that myopathic symptoms with creatine kinase levels raised to more than 10 times the upper limit of normal is seen in <0.01% of recipients and progression to fatal rhabdomyolysis because of renal failure has been recorded in only 0.15 cases per million prescriptions. Liver function abnormalities are also, rarely, seen. Again, the frequency of raised aspartate or alanine aminotransferase to more than three times the normal limit is encountered in no more than 1-2% of all treated patients and is completely reversible upon withdrawal of treatment. Progression to hepatitis or liver failure does not occur. This constellation of benefits with little side effect penalty has resulted in the comparison of statins with antibiotics in the global battle against cardiovascular disease.
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PMID:Who should receive a statin these days? Lessons from recent clinical trials. 1696 68

Cochlospermum vitifolium (Willd.) Sprengel is a Mexican medicinal plant that is used in the folk medicine for the treatment of hypertension, diabetes, hepatitis and related diseases. The purpose of the present study was to assess the pharmacological properties of different extracts from Cochlospermum vitifolium bark as potential agent for the treatment of some factors related with metabolic syndrome (MS), a complex disease produced for several pathophysiological factors such as visceral fat obesity, insulin resistance, hypertension, dyslipidemia and liver steatosis. Hexane (HECv), dichloromethane (DECv) and methanol (MECv) extracts were subjected to some pharmacological assays to determine their vasorelaxant and hypoglycemic activity. On the other hand, MECv was also evaluated to determine its hepatoprotective effect on sub-chronic experimental assay. HECv showed a significant endothelium-independent relaxation on rat aorta rings (intact endothelium: IC(50)=14.42+/-5.90 microg/mL, E(max)=92.71+/-8.9%; denuded endothelium: IC(50)=27.94+/-4.0 microg/mL, E(max)=78.68+/-4.6%) and MECv produced an endothelium-dependent relaxation (IC(50)=21.94+/-6.87 microg/mL, E(max)=79.12+/-7.80%) on this tissue. Furthermore, HECv (at a dose of 120 mg/kg) also showed a significant decrease of blood glucose levels (p<0.05) on normoglycemic rats. Moreover, MECv (at a dose of 100 mg/kg) also was administered to bile duct-obstructed rats to determine its hepatoprotective activity, showing a statistically significant decrease of serum glutamic-pyruvic transaminase (PGT, 45%) and alkaline phosphatase (APh, 15%) (p<0.05). Finally, we obtained a crystalline polyphenolic compound from MECv by spontaneous precipitation. Those crystals were identified as (+/-)-naringenin by X-ray diffraction, NMR, IR and GC-MS techniques. Results suggest that Cochlospermum vitifolium could be used as a potential agent against MS since it shows hypoglycemic, vasorelaxant and hepatoprotective properties.
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PMID:Hypoglycemic, vasorelaxant and hepatoprotective effects of Cochlospermum vitifolium (Willd.) Sprengel: a potential agent for the treatment of metabolic syndrome. 1697 15

Essential hypertension is associated with the metabolic syndrome, insulin resistance and the development of fatty liver. Fatty liver disease is a spectrum of liver diseases ranging from simple hepatic steatosis through steato-hepatitis to cirrhosis and hepatoma. The purpose of this review is to discuss the evidence for an association between essential hypertension and non-alcoholic fatty liver disease, and to consider the diagnosis and management of non-alcoholic fatty liver disease. We conclude that it is important to consider the diagnosis of fatty liver disease in hypertensive patients, to measure the liver function tests at diagnosis and not to ignore minor elevations of serum aminotransferases. Hypertensive patients with raised liver enzymes should be referred for further assessment, particularly if risk factors for progressive liver disease, such as obesity and diabetes, are present.
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PMID:Hypertension and fatty liver: guilty by association? 1727 55

We evaluated the prevalence and the risk factors for gallstone disease in patients with chronic hepatitis C infection. We investigated 453 consecutively admitted patients with chronic infection with hepatitis C virus (HCV) (cirrhosis excluded) and 879 patients without liver disease (October 2006-April 2007). Gallstone disease was diagnosed if gallstones were present at ultrasonography or if there had been a previous cholecystectomy. Variables evaluated were age, gender, gallstone heredity, body mass index, waist circumference, parity, serum lipids, fatty liver, arterial hypertension, diabetes mellitus and metabolic syndrome (International Diabetes Federation criteria). Informed consent was obtained from all patients. We found that 88 of 453 (19%) patients with chronic HCV hepatitis (age 50.1 +/- 11.7 years) and 153 of 879 (17%) controls (age 60.6 +/- 12.6 years) had gallstone disease (GD). Abdominal obesity (OR = 2.108, 95% CI 1.287-3.452) and steatosis (OR = 3.699, 95% CI 2.277-6.008) were risk factors for GD in HCV patients. Gallstone heredity, dyslipidaemia, type 2 diabetes mellitus and metabolic syndrome increased the risk for GD in controls vs HCV patients. Our study shows that even HCV patients with chronic hepatitis but not cirrhosis have an increased prevalence of gallstones. Compared with controls, gallstones are present in HCV patients at a younger age and are associated with central obesity and liver steatosis, but not with gallstone heredity, dyslipidaemia, diabetes mellitus or metabolic syndrome. Although we could not establish a temporal relationship, the association between HCV infection and gall stone disease is real and appears to be causally linked, at least in predisposed individuals (obese and with liver steatosis).
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PMID:Hepatitis C virus infection is a risk factor for gallstone disease: a prospective hospital-based study of patients with chronic viral C hepatitis. 1948 79

Patients with the metabolic syndrome are at an increased risk of cardiovascular disease and might require intensive lipid therapy. Many patients remain at the starting dose of lipid therapy and might not be titrated up to a higher dose. The present double-blind, randomized, 6-week study assessed the lipid-lowering efficacy of ezetimibe/simvastatin 10/20 mg versus atorvastatin 10 or 20 mg, and ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg in 1,128 patients with hypercholesterolemia and the metabolic syndrome. The primary end point was the percentage of change from baseline in low-density lipoprotein (LDL) cholesterol. Additional end points included changes in other lipids, lipoprotein ratios, high-sensitivity C-reactive protein, and attainment of prespecified lipid levels. Significantly greater improvements in the levels of LDL cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B, and lipid/lipoprotein ratios resulted with ezetimibe/simvastatin compared with atorvastatin at all specified dose comparisons (p <0.001). The attainment of prespecified LDL cholesterol and non-high-density lipoprotein cholesterol levels was also significantly greater with ezetimibe/simvastatin than with atorvastatin at all dose comparisons (p <0.05). High-density lipoprotein cholesterol increases were significantly greater with ezetimibe/simvastatin 10/20 mg than with atorvastatin 10 mg (p <0.05) and ezetimibe/simvastatin 10/40 mg than with atorvastatin 40 mg (p <0.01). The changes in triglycerides, very low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein were similar for both treatments. The incidence of liver, muscle, and gastrointestinal-, hepatitis- and allergic reaction/rash-related adverse events were low and generally similar to those in previous studies of ezetimibe/simvastatin and/or atorvastatin. In conclusion, ezetimibe/simvastatin was more likely to result in lipid treatment end points than atorvastatin and was generally well tolerated at the doses compared in our patients.
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PMID:Lipid-altering efficacy and safety of ezetimibe/simvastatin versus atorvastatin in patients with hypercholesterolemia and the metabolic syndrome (from the VYMET study). 2042 79


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