Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mallory bodies (MBs), which are common in alcoholic hepatitis, primary biliary cirrhosis and liver disease associated with Type II diabetes mellitus, are often difficult to find on liver biopsy specimens or to predict from clinical or biochemical studies. Immunofluorescence studies with anti-NMB-1, a Mallory body-specific monoclonal antibody, indicate that this is a sensitive method for recognizing Mallory bodies in cryostat sections of liver from griseofulvin-treated mice or patients with liver disease. Validity of the leukocyte migration test, which facilitates detection and monitoring of patients who harbor Mallory bodies, is confirmed by pretreatment of Mallory bodies with anti-NMB-1. Prevention of Mallory body-induced migration inhibition by addition of anti-NMB-1 indicates that this effect is not due to inactivation of leukocytes by a Mallory body contaminant. Anti-NMB-1, developed using standard hybridoma techniques, does not react with normal hepatocytes or other cells. Investigations with SDS polyacrylamide gel electrophoresis and western blotting reveal that it exhibits binding with 62, 55, 42 kd peptides, and four other bands in the range from 40 to 30 kd from the Mallory bodies. The NMB-1 epitope which facilitates morphologic and clinical detection of Mallory bodies is distinct from cytokeratin and appears to be responsible for its immunogenicity.
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PMID:Use of a specific monoclonal antibody to detect Mallory bodies in liver disease. 213 94

A 54-year-old woman with obesity, type II diabetes mellitus, hyperlipidemia, and massive hepatomegaly was found to have severe steatosis and cirrhosis on liver biopsy. Complete evaluation led to the diagnosis of fatty cirrhosis associated with obesity and diabetic mellitus. She underwent four months of fasting with a protein-carbohydrate and vitamin-mineral liquid supplement to control her weight and metabolic abnormalities and to evaluate the effect of this diet on her liver disease. She lost 40 pounds to ideal body weight, normalized her serum glucose and lipids, and decreased total liver height by one third. Liver biopsy at the completion of her diet showed inactive cirrhosis and complete resolution of steatosis. Supplemented fasting with only modest weight loss can safely resolve fatty liver in obese diabetics with nonalcoholic steatosis and cirrhosis. Aggressive dietary approaches to achieve long-term weight loss deserve study in this subgroup of diabetics with unexplained chronic liver disease.
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PMID:Steatosis and cirrhosis in an obese diabetic. Resolution of fatty liver by fasting. 382 84

The influence of two sulfonylureas on blood glucose and plasma immunoreactive insulin (IRI) and C-peptide responses to a standardized meal was investigated in a patient with type 2 diabetes and a liver disease with enhanced peripheral levels of liver enzymes. The very high fasting values of plasma IRI and C-peptide were further elevated by the meal. This response to the meal was markedly enhanced by both sulfonylureas, glipizide and glibenclamide. The blood glucose increment after the meal was diminished by sulfonylureas. Sulfonylureas thus seem to have beneficial effects in this diabetic patient, who had a liver disease and markedly elevated basal levels of plasma IRI and C-peptide concentrations.
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PMID:Effect of sulfonylurea on glucose, insulin and C-peptide responses to a meal stimulus in a patient with type 2 diabetes and liver disease. 643 37

Oral glucose tolerance was tested in a heterogeneous group of 108 patients with liver cirrhosis. Data were compared with those from 181 subjects without liver disease (44% normal, 35% impaired glucose tolerance and 21% type 2 diabetes mellitus). In cirrhosis, 27% of the patients had normal, 36% had impaired glucose tolerance, and 37% were diabetic. There was no association between glucose intolerance or diabetes and the aetiology of cirrhosis, the duration of the disease, the biochemical indicators of hepatocyte damage, cholestasis and/or liver function. Only weak associations were found between the results of quantitative liver functions tests (caffeine, xylocaine, indocyanine green) and basal and post load glucose and insulin concentrations. Cirrhotics with 1st degree relatives with type 2 diabetes mellitus (n = 16) did not show an increased prevalence of diabetes. Older and/or malnourished patients were more frequently glucose intolerant. Using the plasma glucose concentration 120 minutes after glucose load as the dependent variable, multivariate regression analysis showed that 54% of its variance is associated with the following variables: basal plasma glucose (36%) and free fatty acid concentration (5%), age (3%), basal glucose oxidation rate (3%), muscle mass (3%) and plasma free glycerol at 120 minutes after glucose load (3%). By contrast, the clinical state of the patients (i.e. the CHILD-Pugh score) accounted for only 2% of the variance. We conclude that glucose tolerance is variable in cirrhosis. After manifestation of liver disease, glucose intolerance or diabetes cannot be explained by the clinical, histological or biochemical signs of liver disease.
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PMID:Glucose intolerance in liver cirrhosis: role of hepatic and non-hepatic influences. 786 13

Increased energy needs, a reduced synthesis of endogenous substrates and a limited energy yield from exogenous substrates characterize the metabolic dilemma in patients with liver cirrhosis. The metabolic features observed in cirrhosis are highly variable and cannot be considered as clear-cut phenomena. They obviously differ in certain aspects from the metabolic situations known from starvation or type 2 diabetes mellitus. This is not contrary to the idea that cirrhosis may resemble certain aspects of these 'standard' situations. Cirrhosis-induced disturbances in fuel homeostasis cannot be predicted from clinical and biochemical parameters of the disease. Most of the metabolic picture is present at a very early stage of liver disease. Many metabolic features are independent of the clinical course of liver disease, suggesting that they are an early and extra-hepatic manifestation. A better understanding of the variance of cirrhosis-induced alterations in metabolism may come from characterization of the metabolic 'genotype' which adds to disease-related factors in the individual patient.
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PMID:Energy expenditure and substrate metabolism in liver cirrhosis. 812 90

A 60-year-old obese woman with type II diabetes mellitus and hepatomegaly exhibited progression of steatosis to hepatitis and cirrhosis. The patient was treated with large amounts of insulin combined with sulfonylurea, resulting in correction of the hyperglycemia. In the subsequent 9 months, weight loss did not occur, whereas insulin therapy could be discontinued. The liver decreased in size, and liver tests normalized. We suggest that intensive treatment of hyperglycemia may result in reversal of insulin resistance in patients with diabetic liver disease, while correction of hyperglycemia can lead to resolution of the hepatic abnormalities associated with diabetes mellitus.
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PMID:Remission of active diabetic hepatitis after correction of hyperglycemia. 837 94

The pharmacokinetics of the sulfonylurea, glimepiride, in risk groups of NIDDM patients are reviewed with regard to pharmacokinetic-effect relationships. A variety of factors, such as regulatory processes, glucose absorption, insulin sensitivity, might prevent the definition of a clear concentration-effect relationship for sulfonylureas. However, when these processes are minimized, as with the glucose clamp technique, such relationships can be defined. This is true for glibenclamide or glimepiride, for which saturation of effect is apparent in the upper therapeutic dose range in healthy subjects. However, pharmacokinetic-pharmacodynamic relationships are less readily defined during long-term treatment of NIDDM patients. In kidney or liver disease, the hypoglycemic effect of sulfonylureas can be increased and prolonged, mainly due to a decrease in insulin metabolism or of hepatic glucose output; the risk of hypoglycemia is increased. The pharmacokinetics of most sulfonylureas have not been well characterised in patients with kidney or liver disease. Generally, sulfonylureas are eliminated by renal excretion of metabolites, some of which have similar pharmacological activity to the parent drug e.g. glibenclamide, chlorpropamide, tolbutamide. In renal disease, elimination of these metabolites can be impaired. In 31 NIDDM patients with kidney disease, elimination of unchanged glimepiride was greater in patients with more severe renal disease, probably due to a decrease in the plasma protein-bound fraction. Elimination of the renally excreted metabolites was also impaired in the same group of patients. 12 of 16 NIDDM patients with kidney disease who continued glimepiride treatment for three months maintained fasting blood glucose levels of less than 9.99 mmol/l at a daily dose of 1-6 mg, the typical dose range for patients with normal renal function. Pharmacokinetic data on sulfonylureas are generally inconsistent in cirrhotic patients. In 11 patients with liver disease, the pharmacokinetics of glimepiride were similar to those of healthy volunteers. In conclusion, pharmacokinetics, pharmacodynamics and their relationships can be defined for glimepiride under controlled conditions. Such information is lacking for many commonly used sulfonylureas in risk group NIDDM patients. Studies described here show that the pharmacokinetics of glimepiride are altered in renal disease but may not be seriously affected in patients with liver disease.
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PMID:Pharmacokinetic basis for the safety of glimepiride in risk groups of NIDDM patients. 891 79

Investigations of liver function and histology were undertaken in thirty four patients with Fibrocalculous Pancreatic Diabetes (FCPD). The data obtained were compared with those of similarly aged members of a diabetic control group comprising twelve patients with Protein Deficient Diabetes Mellitus (PDDM), twelve with Type 1 diabetes or Insulin Dependent Diabetes Mellitus (IDDM) and four young patients with Type 2 Diabetes of Non-Insulin Dependent Diabetes Mellitus (NIDDM). None of them had apparent past or present liver disease. Elevations of serum ALT (SGPT) and alkaline phosphatase levels were fairly common and was often associated with mild fatty changes and occasionally with focal necrosis and inflammatory changes. Cirrhosis and inflammatory changes per se were infrequent and fatty changes per se did not occur. In contrast patients belonging to the other diabetic subsets were very occasionally afflicted with hepatic abnormalities or not afflicted at all. We propose that loss of hepatotrophic actions mediated by insulin and glucagon could initiate and/or enhance hepatic abnormalities in FCPD where deficiencies of insulin and glucagon coexist.
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PMID:Observations on hepatic structure and function in fibro-calculous pancreatic diabetes (FCPD) vis-a-vis other diabetic subtypes. 967 Jun 24

We characterized 70 consecutive patients with cryptogenic cirrhosis to assess major risks for liver disease. Each patient was reevaluated for past alcohol exposure, scored by the International Autoimmune Hepatitis (IAH) score and assessed for viral hepatitis risks and risks for nonalcoholic steatohepatitis (NASH). The results were compared with 50 consecutive NASH patients, 39 nonalcoholic patients age 50 and over with cirrhosis from hepatitis C, and 33 consecutive patients with cirrhosis caused by primary biliary cirrhosis (PBC). Among the cryptogenic group, 49 (70%) were female, and the mean age was 63 +/- 11 years. Although ascites and variceal bleeding were common, almost one half lacked major signs of complicated portal hypertension. A history of Type 2 diabetes mellitus and/or obesity was present in 51 (73%). Nineteen (27%) patients had a history of blood transfusions antedating the diagnosis of cirrhosis. No clinical or histological features distinguished this group from the other patients, and 14 (74%) of these had a history of obesity and/or diabetes. Nineteen of the remaining nontransfused patients had indeterminant IAH scores but were histologically and biochemically indistinguishable from the others. Twelve of these (63%) also had a history of obesity and/or diabetes. Both diabetes and obesity were significantly more common in the cryptogenic cirrhotic patients compared with the cirrhotic patients with PBC or hepatitis C. In contrast, the prevalence of obesity and diabetes was similar to the NASH patients who were, on average, a decade younger. Although there is some diversity that indicates more than one cause, our findings suggest that NASH plays an under-recognized role in many patients with cryptogenic cirrhosis, most of whom are older, type 2 diabetic and obese females.
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PMID:Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. 1005 66

The aim of the study was to detect a possible aetiological association between chronic hepatitis C virus (HCV) infection and diabetes mellitus (DM). Among the 591 HCV seropositive chronic liver disease (CLD) patients, 150 (25.4%) had associated diabetes mellitus while only 25 of 223 HCV seronegatives (11.2%) were diabetics. The HCV seropositive patients were three times more likely to suffer from diabetes mellitus than those who were HCV seronegative and the results were highly significant (odds ratio = 2.7, CI = 1.7-4.4, P < 0.0001). Liver biopsy showed cirrhosis in 24 out of 53 (45.3%) HCV seropositive diabetics and 9/20 (45%) of the HCV seronegative diabetics. The association between the degree of liver disease and the development of diabetes mellitus did not differ statistically between the two groups. Islet cell antibody (ICA) was present in 44.4% of HCV seropositives compared to 73.3% of seronegative diabetics, while NIDDM showed 40% ICA positivity. Although ICA level was highest in HCV seronegative diabetics, the difference between the various groups was not significant statistically. About 29% of HCV seropositive diabetics were on insulin therapy while only 16% of HCV seronegative diabetics received insulin therapy. HCV seropositives were about 2 times more prone to require insulin therapy than HCV seronegatives (odds ratio = 2.0, CI = 1.2-5.7, P = 0.010). We conclude that chronic hepatitis C patients in Egypt are three times more likely to develop DM than HCV seronegative patients. Pancreatic beta -cells might be an extrahepatic target of HCV.
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PMID:Association of chronic hepatitis C infection and diabetes mellitus. 1022 36


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