Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The liver plays an important role in the pathogenesis of NIDDM. More importantly to the clinician is the myriad of situations in which the care of the patient with diabetes is affected by or causes an effect to the liver. Patients with underlying diabetes can present with abnormal liver chemistries, which can represent findings as benign as hepatic steatosis or as severe as cirrhosis of the liver. The medications used to treat diabetes can be potent hepatotoxins. Several primary liver diseases are associated with increased risk of the development of diabetes. Epidemiologically, there seems to be a correlation between diabetes mellitus, the most common endocrinologic disease, and hepatitis C, the leading cause of chronic liver disease in the United States. In the management of end-stage liver disease, both cirrhosis and orthotopic liver transplantation promote glucose intolerance and diabetes in a number of patients through various mechanisms including insulin resistance and impaired insulin secretion. These relationships highlight both the importance of the liver as an endocrine organ and the multisystem aspects of the patient with diabetes mellitus.
 ...
PMID:Liver disease and diabetes mellitus. 1132 35

The metabolic syndrome is strongly associated with insulin resistance and has been recognized as a cluster of risk factors for cardiovascular diseases such as visceral obesity, hypertension, and diabetes. There is a growing body of evidence to show that nonalcoholic steatohepatitis (NASH) is the hepatic manifestation of insulin resistant patients with the metabolic syndrome. Indeed, insulin resistance increases adipocyte lipolysis and subsequently elevates circulating free fatty acids, thus stimulating the accumulation of fatty acids in the liver (hepatic steatosis). Fatty acids elicit reactive oxygen species generation, thereby promoting disease progression to NASH by both lipid peroxidation and inflammatory cytokine production. Postprandial hyperglycemia, one of the characteristic features of insulin resistance, also induces oxidative stress generation, being involved in dysfunction of pancreatic beta cells and vascular wall cells in the metabolic syndrome. Recently, STOP-NIDDM trial revealed that acarbose (Glucobay), an alpha-glucosidase inhibitor, improved postprandial hyperglycemia and subsequently reduced the risk of development of type 2 diabetes and newly diagnosed hypertension in patients with impaired glucose tolerance. In this study, acarbose treatment was also found to reduce body mass index and waist circumference in these patients. Furthermore, a meta-analysis of seven long-term studies has also shown that intervention with acarbose improved triglyceride levels, body weight and systolic blood pressure and subsequently prevented myocardial infarction in type 2 diabetic patients. Since acarbose improves postprandial hyperglycemia by delaying the release of glucose from complex carbohydrates in the absence of an increase in insulin secretion, the beneficial aspects of acarbose could be ascribed to improvement of insulin sensitivity in these patients. Given the pathological link between NASH and insulin resistance, we would like to hypothesize here that acarbose may become a promising therapeutic strategy for the treatment of patients with NASH. Does acarbose treatment improve steatohepatitis histologically? Is the extent of histological improvement by acarbose parallel to that of insulin sensitivity in these patients? Large clinical trials will provide us with more definite information whether acarbose treatment can improve insulin sensitivity and resultantly reduce the risk of progression of liver diseases in patients with NASH.
 ...
PMID:Acarbose is a promising therapeutic strategy for the treatment of patients with nonalcoholic steatohepatitis (NASH). 1592 16

In-vivo 1H magnetic resonance (MR) spectra of the liver were obtained in 8 patients admitted for liver biopsy. These patients had abnormal liver function and the presumptive diagnosis of fatty liver prior to biopsy. Two patients with NIDDM were also studied but liver biopsies were not performed as liver function was normal. The MR spectra, obtained on a 60 cm clear-bore 1.9 tesla superconducting magnet showed two 1H resonances, one from water and the other from repeating methylene protons - (CH2)n - in triglyceride. The lipid: water signal ratio was used to characterize tissues as subcutaneous fat (high lipid:water ratio), normal liver (low lipid: water ratio) and fatty liver (intermediate lipid: water ratio). The spectra obtained at the greatest depth from the probe surface ~4.5 cm) was used as it was most likely to represent liver tissue. Although all 8 patients were expected to have fatty liver only 2 had evidence of significant fatty changes on microscopy. This was assessed by counting the vacuoles of fat over the area of the biopsy specimen and quantitated as 'fat vacuoles per high power field' (f/hpf). In the 2 patients with NIDDM, unusual stack plots suggested technical difficulties with 1H MR spectroscopy for in-vivo assessment of fatty liver. The first patient, PT had a significant increase in lipid:water ratio on the spectra thought to represent liver (lipid:water ~ 65% cf levels <3% in norma liver and 12.6% + 26.5% in those patients subsequently found to have fat on biopsy). This was later found on MR imaging to represent omental fat lying between the liver and muscle layer. The second patient, OM had a large amount of subcutaneous fat overlying the area assessed. As seen on the stack plot, the probe depth was not great enough to pass through the subcutaneous fat and muscle layer to penetrate liver tissue. There was a significant correlation between the lipid:water signal ratio and visible fat on biopsy in those patients who underwent liver biopsy. Difficulties experienced with probe depth suggests imaging would be necessary prior to spectroscopy to ensure liver tissue is actually assessed.
...
PMID:Problems associated with using in vivo proton (1H) magnetic resonance spectroscopy to quantify liver fat. 2439 82

Hepatic steatosis, a hallmark of non-alcoholic fatty liver diseases (NAFLD), is an early marker as well as a cause of the cardiometabolic syndrome, prediabetes and NIDDM. Its high prevalence in the general population and its many causes and complex mechanisms make it a pathology which must be treated and requires careful diagnosis also in terms of underlying causes, which may strongly vary among subjects. The recent awareness of the commonness of NAFLD has prompted intensive research which unraveled many different mechanisms causing hepatic steatosis, from diet to intestinal diseases and liver receptors. Epigenetic factors must be added to this list. A variety of causes and mechanisms open many different potential therapeutic approaches. This review aims at summarizing the effects of a selected series of old and new treatments for which there exist at least a reasonable amount of data. Many show efficacy in animals but human data are less convincing largely because of poor amount of data and generally they lack histological confirmation. Many drugs either induce undesirable side-effects or have tight therapeutic dose windows. The recent recognition of a key role of intestinal microbiota in NAFLD and metabolic syndrome may represent a major therapeutic breakthrough by the modulation of bacteria in the gut. Performing randomized long-term clinical studies including liver biopsies appears as prerequisite to determine which treatment is the most valuable, however not ignoring that the therapeutic choice may require individualization among subjects as a function of the origins of NAFLD.
...
PMID:Treatment strategies for fatty liver diseases. 2551 15