Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin resistance is a characteristic feature of glucose-intolerant and diabetic cirrhotic patients. The pathogenic factors, however, that are responsible for the development of impaired glucose tolerance in cirrhosis, remain unclear. To examine whether the ability of hyperglycemia per se to enhance glucose uptake (by means of mass-action effect) is impaired in cirrhosis, we measured (insulin-independent) whole-body glucose disposal during hyperglycemia (hyperglycemic clamp studies, +125 mg/dl, in combination with an infusion of somatostatin (500 micrograms/hr), insulin (0.1 mU/kg min) and glucagon (0.5 ng/kg min) to "clamp" hormone levels at baseline), whole-body glucose oxidation (indirect calorimetry) and glucose turnover (prime-continuous infusion of [6,6-2H2-]glucose in a clinically homogeneous group of cirrhotic patients with glucose intolerance (n = 7) or frank diabetes mellitus (n = 7) and in control individuals (n = 7). Fasting plasma glucose concentrations were normal in glucose-intolerant patients but were significantly increased in diabetic patients (158 +/- 19 vs. 87 +/- 2 mg/dl in controls; p < 0.01). Plasma glucose concentrations were clamped at 214 +/- 4 mg/dl in controls, at 212 +/- 4 mg/dl in glucose-intolerant patients and at 287 +/- 19 mg/dl in diabetic patients; plasma insulin and glucagon concentrations were maintained at baseline levels. In the basal state, total-body glucose disposal (which equals basal hepatic glucose output) was normal in glucose-intolerant patients (2.25 +/- 0.11 mg/kg min) but was increased in diabetic patients compared with controls (3.32 +/- 0.26 mg/dl vs. 2.45 +/- 0.10 mg/dl; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Glucose resistance contributes to diabetes mellitus in cirrhosis. 780 65

We used a dual-isotope method (oral [1-14C]glucose and intravenous [6-3H]glucose) to examine whether the oral glucose intolerance of cirrhosis is due to (a) a greater input of glucose into the systemic circulation (owing to a lower first-pass hepatic uptake of ingested glucose, or to impaired inhibition of hepatic glucose output), (b) a lower rate of glucose removal, or (c) a combination of these mechanisms. Indirect calorimetry was used to measure oxidative and nonoxidative metabolism. Basal plasma glucose levels (cirrhotics, 5.6 +/- 0.4[SE], controls, 5.1 +/- 0.2 mmol/liter), and rates of glucose appearance (Ra) and disappearance (Rd) were similar in the two groups. After 75 g of oral glucose, plasma glucose levels were higher in cirrhotics than controls, the curves diverging for 80 min despite markedly higher insulin levels in cirrhotics. During the first 20 min, there was very little change in glucose Rd and the greater initial increase in plasma glucose in cirrhotics resulted from a higher Ra of ingested [1-14C]glucose into the systemic circulation, suggesting a reduced first-pass hepatic uptake of portal venous glucose. The continuing divergence of the plasma glucose curves was due to a lower glucose Rd between 30 and 80 min (cirrhotics 236 +/- 17 mg/kg in 50 min, controls 280 +/- 17 mg/kg in 50 min, P < 0.05, one-tailed test). Glucose metabolic clearance rate rose more slowly in cirrhotics and was significantly lower than in controls during the first 2 h after glucose ingestion (2.24 +/- 0.17 vs 3.30 +/- 0.23 ml/kg per min, P < 0.005), in keeping with their known insulin insensitivity. Despite the higher initial glucose Ra in cirrhotics, during the entire 4-h period the quantity of total glucose and of ingested glucose (cirrhotics 54 +/- 2 g [72% of oral load], controls 54 +/- 3 g) appearing in the systemic circulation were similar. Overall glucose Rd (cirrhotics 72.5 +/- 3.8 g/4 h, controls 77.2 +/- 2.2 g/4h) and percent suppression of hepatic glucose output over 4 h (cirrhotics, 53 +/- 10%, controls 49 +/- 8%) were also similar. After glucose ingestion much of the extra glucose utilized was oxidized to provide energy that in the basal state was derived from lipid fuels. Glucose oxidation after glucose ingestion was similar in both groups and accounted for approximately two-thirds of glucose Rd. The reduction in overall nonoxidative glucose disposal did not reach significance (21 +/- 5 vs. 29 +/- 3 g/4 h, 0.05 < P < 0.1). Although our data would be compatible with an impairment of tissue glycogen deposition after oral glucose, glucose storage as glycogen probably plays a small part part in overall glucose disposal. Our results suggest that the higher glucose levels seen in cirrhotics after oral glucose are due initially to an increase in the amount of ingested glucose appearing in the systemic circulation, and subsequently to an impairment in glucose uptake by tissues due to insulin insensitivity. Impaired suppression of hepatic glucose output does not contribute to oral glucose intolerance.
 ...
PMID:Metabolic handling of orally administered glucose in cirrhosis. 845 36

Insulin has been shown to be vasodilatory and antinatriuretic and to stimulate sympathetic nervous activity independent of hypoglycemia in healthy normal subjects. It is hypothesized that hyperinsulinemia, which is commonly observed in cirrhosis, may in part be responsible for the systemic vasodilatation, sympathetic activation, and sodium retention in these patients. The aims of this study, in preascitic cirrhotics, were as follows: (1) to document baseline hyperinsulinemia and its effects on sodium handling, forearm and renal circulations, and sympathetic nervous activity; (2) to determine if pharmacological increases in plasma insulin levels would result in an exaggeration of these physiological effects. Seven male, nonobese, well-compensated, preascitic cirrhotic patients were studied, after being maintained on a 150 mmol sodium per day diet for 7 days, firstly at baseline level, followed by increasing doses of insulin from 10 to 1,200 mU/m2/min using the euglycemic clamp technique. Systemic and renal hemodynamics, urinary sodium excretion, plasma norepinephrine, and forearm blood flow (FBF) were measured at the end of baseline and each hyperinsulinemic period. Baseline measurements in the cirrhotics, when compared with our laboratory standards obtained from a comparable group of male healthy normals, showed significant hyperinsulinemia (P=.01), associated with significantly higher FBF (P=.02), and glomerular filtration rate (GFR) (P=.02), as well as significantly reduced urinary volume (P=.04) and fractional excretion of sodium (P=.04). Insulin infusions in the cirrhotics produced no further sodium retention, but further forearm vasodilatation occurred at doses > or = 10 mU/m2/min. In contrast, there was no further renal vasodilatation except at very high pharmacological levels of insulin together with an unchanged GFR, natriuresis, and diuresis. Hyperinsulinemia produced no significant effects on the sympathetic nervous activity. In conclusion, these results suggest that hyperinsulinemia may be implicated in the glomerular hyperfiltration and sodium retaining tendency of preascitic cirrhotic patients with glucose intolerance. The ability of the kidneys to escape from the sodium retaining effects may serve as an in-built physiological regulatory mechanism on sodium homeostasis.
 ...
PMID:Hyperinsulinemia in preascitic cirrhosis: effects on systemic and renal hemodynamics, sodium homeostasis, forearm blood flow, and sympathetic nervous activity. 861 19

Glucose intolerance is a common consequence of transfusion therapy in patients with thalassemia major (TM), but the relative contribution of pancreatic damage and insulin resistance to glucose intolerance is unclear. We have investigated oral (OGTT) and intravenous (IVGTT) glucose tolerance, insulin sensitivity, and fasting concentrations of insulin, proinsulin, and des 31,32 proinsulin in 12 patients with TM (seven hepatitis C virus [HCV] antibody-negative and five-positive), eight patients with hepatic cirrhosis, and nine healthy controls. Two-hour plasma glucose concentrations were marginally higher in anti-HCV-negative (median, 7.4 mmol/ L; range, 4.0 to 8.2) and significantly so in anti-HCV-positive thalassemics (median, 8.5 mmol/L; range, 6.4 to to 23.0) and cirrhotics (median, 8.0 mmol/L; range, 4.7 to 17.6) than in controls (median, 5.5 mmol/L; range, 3.0 to 6.3). Insulin sensitivity was also reduced in the three patient groups (P < .05). Insulin resistance was the main determinant of oral glucose intolerance in all patient groups (partial r2 = .49, P < .0001, n = 28). In turn, the main determinants of insulin insensitivity in TM patients were liver damage (albumin, r = .67, P = .02) and serum ferritin concentration (r = -.62, P = .03). There was no relationship of either 2-hour or incremental insulin concentrations with ferritin levels or with HCV status in TM subjects. Moreover, these patients showed no elevation of concentrations of proinsulin and des 31,32 proinsulin, markers of pancreatic beta-cell damage, in excess of those observed in cirrhotic patients. In conclusion, the glucose intolerance of TM, like that of cirrhosis, is associated with insulin resistance, not insulin deficiency, and may be a direct or indirect consequence of hepatic damage.
 ...
PMID:Glucose intolerance in thalassemia major is related to insulin resistance and hepatic dysfunction. 862 11

Historically, alcohol use by the diabetic patient has been controversial. Recent studies in the general population have shown an improvement in mortality with moderate alcohol intake (one to three drinks per day). This improved mortality is greatest in those individuals who have a higher risk of ischemic heart disease. The mechanisms of the beneficial effects of alcohol include positive effects on insulin resistance, HDL cholesterol, platelet aggregation, and fibrinolysis. Since the diabetic patient has an especially high risk of ischemic heart disease because of these factors, the use of a moderate amount of alcohol should not be discouraged. The short-term risks of heavy or continuous alcohol intake include hypoglycemia, glucose intolerance, and ketone and lactate accumulation. In the long term, heavy alcohol intake is associated with an increased prevalence of cancer, hypertension, cirrhosis of the liver, and symptomatic neuropathy. Moderate alcohol intake taken with a meal has been shown to have little or no effect on postprandial glycemic excursions.
 ...
PMID:Alcohol and the NIDDM patient. 873 20

Glucose intolerance is associated with chronic liver disease, particularly cirrhosis, and overt diabetes mellitus is two to four times more common than in the general population. Little attention has been paid to the relationship between the cause of cirrhosis and the development of glucose intolerance or whether cirrhosis is a prerequisite. We found glucose intolerance to be particularly common in patients with chronic hepatitis C, and in this retrospective study we attempt to confirm this possible association. To investigate this question we reviewed the files of 128 patients with chronic hepatitis C and 40 with chronic hepatitis B and active liver disease. Demographic, laboratory, imaging and pathology data were abstracted. The mean fasting blood glucose (+/-SD) in the hepatitis C and B groups was 160 +/- 83 and 103 +/- 18 mg/dl (P < 0.0001) with 2.5% and 39.1% respectively being overtly diabetic (P < 0.00001). However, the mean age of the hepatitis C group was much higher (45.6 +/- 12.5 vs. 60.1 +/- 12.3 years, P < 0.00001). The prevalence of diabetes was much higher among the hepatitis C patients than in the general population. Cirrhosis was not more frequent in biopsies from hepatitis C diabetic patients compared with non-diabetic or hepatitis B patients. Multivariate analysis showed that type of hepatitis and age were significant and independent predictors for developing diabetes. We conclude that there appears to be an association between diabetes mellitus and chronic hepatitis C that is not present in patients with chronic hepatitis B.
 ...
PMID:Diabetes mellitus is associated with chronic hepatitis C but not chronic hepatitis B infection. 875 86

We studied the effect of percutaneous ethanol injection therapy (PEI) on glucose tolerance in liver cirrhosis patients with hepatocellular carcinoma. All of 10 patients underwent PEI and aspiration biopsy of the tumor on separate day. Two-time oral glucose tolerance tests (OGTT), before and after PEI, were performed in all patients. There were no significant changes in blood glucose and insulin chronologically measured on aspiration biopsy and PEI. To detect changes in glucose tolerance, we compared the results of OGTT before PEI with those of OGTT after PEI. On the basis of results of OGTT before PEI, patients were classified to impaired glucose tolerance group (4) and diabetes mellitus group (6). Blood glucose at 180 minutes on OGTT after PEI showed significantly higher value than that of OGTT before PEI, but insulin response was not suppressed. From these experiments we speculate that exaggerated insulin resistance due to injected ethanol may be one of the factors influencing glucose tolerance after PEI.
 ...
PMID:[Glucose intolerance after percutaneous ethanol injection therapy (PEI) in liver cirrhosis patients with hepatocellular carcinoma]. 886 48

Impaired glucose tolerance(IGT) frequently occurs in patients with liver diseases. Because of the central role of the liver in carbohydrate metabolism, it is generally assumed that impaired hepatic metabolism plays a major role in the pathogenesis of IGT in liver disease. However, recent observation using glucose clamp techniques has demonstrated that the majority of patients with cirrhosis are characterized by peripheral hyperinsulinemia and insulin resistance of muscle tissues. Glucose intolerance in patients with chronic pancreatitis in related to impaired glucose-mediated insulin secretion, which is induced by the loss of B-cell mass in the pancreas. Patients with hemochromatosis have insulin resistance in the precirrhotic stage. The mechanism of insulin resistance, produced by iron overload, remains unknown.
 ...
PMID:[Impaired glucose tolerance in liver and pancreas disease]. 891 34

Glucose intolerance and diabetes mellitus are both prevalent not only in alcoholic liver cirrhosis, but also in chronic alcoholics without cirrhosis. Nutritional properties, pharmacological effects, and metabolic alterations produced by alcohol intake due to excessive production of reducing equivalents play significant roles in the pathogenesis of ethanol-induced glucose intolerance. Gluconeogenesis from glycogen, fatty acids, amino acids, and lactate are also impaired during ethanol metabolism. Thus, ethanol-induced hypoglycemia is closely related to depressed hepatic gluconeogenesis produced by ethanol, whereas ethanol-induced hyperglycemia or diabetes is due to hepatic and tissue insulin resistance and impairment of pancreatic endocrine system.
 ...
PMID:[Pathogenesis of glucose intolerance in alcoholics]. 891 36

More than 30% of the end stage liver cirrhosis was complicated by the impared glucose tolerance, in some of which insulin supplements may be required to control the blood glucose level. However, there are many unsolved issues on the cause and cares of hyperglycemia in cirrhotic men. Here, we presented a case of liver cirrhosis and hepatocellular caricnoma complicated by the severe glucose intolerance, and summarized our recent insulin therapy on the glucose intolerance of the decompensated liver cirrhosis in Fukuoka City Hospital, Department of Internal Medicine.
 ...
PMID:[Pathogenesis and treatments of glucose intolerance with liver cirrhosis in men--lessons from the clinical cases of Fukuoka City Hospital, Department of Internal Medicine, Fukuoka, Japan]. 894 Aug


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>