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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes mellitus is more frequently found in pateints with hepatic cirrhosis (about 10%) than in subjects without liver disease. Cirrhosis has been the main subject of interest in this respect. Very few studies have been made in viral hepatitis or steatosis. In about 40% of cases, the diabetes is identified before the cirrhosis. More often (in about 60% of cases) the diabetes is discovered at the same time as or after the finding of cirrhosis. This "post-cirrhosis diabetes" shows no clinical peculiarity. In about 80% of patients with liver cirrhosis when fasting blood glucose is normal, abnormalities of carbohydrate metabolism are to be found by the oral glucose tolerance test. Approximately 50% show an abnormal response to intravenous glucose and 30% to intravenous tolbutamide. The "mechanism" of these metabolic abnormalities in liver cirrhosis is unknown. The following abnormalities are observed: 1) With similar glycaemic response to a glucose challenge, plasma insulin levels are higher than in patients without liver disease, suggesting insulin unresponsiveness. Resistance to exogenous insulin can be demonstrated. 2) Plasma free fatty acid levels are often elevated. 3) Plasma growth hormone levels are often raised. 4) Plasma glucagon levels are high when porto-caval shunting is present. 5) Potassium is often depleted. These metabolic abnormalities, in association with porto-caval shunting and hepatocyte insufficiency may explain the insulin resistance which characterises liver cirrhosis, and the diabetes which it may precipitate in predisposed persons.
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PMID:[Diabetes mellitus secondary to liver diseases. A review (author's transl)]. 79 27

Glucagon is secreted not only by A2-cells of the pancreatic islets but also by A cells in the gastric fundus and duodenum. Several reports have demonstrated that the glucagon plasma concentration is increased in genetic diabetes as well as in many conditions associated with a decreased glucose tolerance such as hepatic cirrhosis, myocardial infarction, infectious diseases, burns, taumatic shock, glucagonomas, acute pancreatitis, acromegaly, pheochromacytoma and Cushing's syndrome. Hyperglucagonemia is particularly important in diabetic ketoacidosis and in non-ketotic hyperosmolar coma. The mechanisms responsible for the diabetic's hyperglucagonemia remain controversial. According to several authors, the increased glucagon secretion is, for its main part, secondary to a prolonged defect in insulin secretion and thus relatively insensitive to an acute insulin administration. According to others, the A cell abnormality is of primary origin, independant from insulin deficiency and its effects are cumulative with those of the insulin lack. Several reports dealing with induced or spontaneous experimental diabetes are in favor of the first or the second hypothesis. It appears likely that glucagon plays a role in the metabolic derangments of diabetes. Indeed, hepatic glucose production is closely related to the ratio of molar concentrations of insulin and glucagon. Finally, in insulin-dependant diabetics, somatostatin infusion reduces plasma glucagon concentration and blood glucose and prevents the development of ketosis after withdrawal of insulin therapy. These results illustrate the contribution of glucagon in the pathogenesis of hyperglycemia and ketosis. Several arguments have been accumulated in favor of the following concept: diabetes hyperglycemia results both from glucose under-utilization secondary to insulin lack and from hepatic glucose over-production due to glucagon excess. Although controversial, the role of glucagon in ketogenesis appears likely.
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PMID:[The role of glucagon in hyperglycemia. A review (author's transl)]. 79 28

Most forms of liver disease are probably associated with impaired gluconeogenesis, although hypoglycaemia is rarely an important clinical feature. Blood concentrations of the gluconeogenic precursors, lactate, glycerol and alanine are elevated although, in certain situations, alanine levels may be decreased. Abnormal glucose tolerance is present in both acute and chronic liver disease, but is usually not of clinical importance. The mechanism of glucose intolerance remains uncertain, with diminished hepatocyte mass, portal diversion and insulin resistance the major postulates. Indeed, the importance of the liver in disposing of an oral glucose load, is still questioned. Both hyperinsulinism and hypoinsulinism are found in liver disease, with hyperinsulinism common in cirrhosis and acute viral hepatitis. This is accompanied by insulin resistance. The hyperinsulinism is probably due to defective hepatic clearance of insulin rather that to over-production. The cause of the insulin resistance remains to be established. Glucagon levels are raised and may contribute to this resistance. Growth hormone levels are also increased but are associated with low somatomedin levels and the role of growth hormone in insulin resistance is therefore questionable. Future developments include use of new animal models, studies of biopsy specimens and studies of hepatic hormone receptors.
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PMID:Carbohydrate metabolism in liver disease. 79 84

The cholesterol-lowering effect of portacaval anastomosis in homozygous familial hypercholesterolemia suggested a study of lipid metabolism in cirrhotic patients after portasystemic anastomoses. Fasting serum cholesterol, triglycerides, insulin, and glucagon levels were obtained in 20 patients with alcoholic cirrhosis and portacaval anastomosis, and in 21 nonshunted subjects with cirrhosis. After 100 g of glucose, given orally, insulin and glucagon levels were measured. In the shunted patients serum cholesterol was higher than in the nonshunted subjects, 240 +/- 15 mg per 100 ml (mean +/- 1 SEM) versus 180 +/- 13 mg per 100 ml, P less than 0.01. Triglycerides were normal in both groups. Fasting insulin was elevated to a greater extent in the shunted patients with cirrhosis (36 +/- 5 muU per ml) than in the nonshunted patients (22 +/- 4 muU per ml), P less than 0.05. Two hours after glucose, insulin levels were also elevated to a greater extent in the shunted subjects (304 +/- 50 muU per ml) than in the nonshunted subjects (167 +/- 29 muU per ml), P less than 0.03. Fasting glucagon (corrected for interference factor) was elevated to a greater extent in the shunted subjects (204 +/- 35 pg per ml) than in the nonshunted subjects (80 +/- 19 pg per ml), P less than 0.01. The explanation for serum cholesterol elevation after surgical shunting in cirrhotics is unknown. Two possible hypotheses--the differential action of insulin and glucagon on cholesterol metabolism and the effects of shunting on the cirrhotic liver--are discussed.
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PMID:Serum lipids, insulin, and glucagon after portacaval shunt in cirrhosis. 83 May 79

Decreased increases in blood sugar by comparison with control subjects was noted in patients with cirrhosis of the liver after i.v. administration of 1 mg glucagon. Insulin secretion was similar to that observed in the controls. Basal GH values were higher in the liver patients, whereas after glucagon they displayed a gradual and progressive increase with a peak at 60'. No significant differences in GH pattern were noted in the two groups, however.
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PMID:[Changes in plasma insulin and growth hormone after intravenous glucagon in hepatic cirrhosis]. 99 78

Patients with liver cirrhosis develop marked abnormalities in small bowel motility and high plasma glucagon levels. Disturbances in small intestinal motor activity could be related to hyperglucagonemia. To investigate the relationship between fasting plasma glucagon levels and changes in small bowel motility in patients with liver cirrhosis, eighteen cirrhotic patients and ten controls were studied. Plasma glucagon was measured by RIA. Mouth to cecum transit time was estimated by lactulose hydrogen breath test. Fasting small bowel motility was investigated by means of intraluminal manometry. Plasma glucagon levels were significantly higher in patients with cirrhosis (61 +/- 5 pmol/l) than in controls (32 +/- 3 pmol/l); p < 0.01. In patients with liver disease, plasma glucagon levels were not significantly correlated to mouth to cecum transit time (r: -0.32), duration of migrating motor complex (r: -0.24), nor to the frequency of multiple clustered contractions (r: -0.26). The degree of small bowel dysmotility is not related to plasma glucagon levels in patients with hepatic cirrhosis. These results do not support the hypothesis that hyperglucagonemia plays an important pathogenic role in the abnormalities of gut motility in cirrhosis.
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PMID:[Are disturbances of small intestinal motility associated with hyperglucagonemia in patients with liver cirrhosis?]. 134 Sep 93

To investigate the renal effects of somatostatin in cirrhosis, renal function and plasma and urinary levels of endogenous neurohumoral vasoactive substances were measured in conditions of intravenous water overload (20 mL/kg body wt with 5% glucose) before and during the intravenous infusion of somatostatin (250-500 micrograms/h) in 6 cirrhotic patients without ascites and 17 nonazotemic cirrhotic patients with ascites. Somatostatin induced a significant reduction of renal plasma flow, glomerular filtration rate, and free water clearance in both groups of patients. In patients with ascites, somatostatin also reduced urinary sodium excretion. Changes in renal function were significantly more marked in patients with ascites than in those without ascites and occurred in the absence of changes in mean arterial pressure and plasma levels of renin, aldosterone, norepinephrine, antidiuretic hormone, and atrial natriuretic peptide. Somatostatin induced a significant reduction in the plasma concentration of glucagon and urinary excretion of prostaglandin E2 that was not related to changes in renal function. These findings indicate that somatostatin administration induces renal vasoconstriction and impairs glomerular filtration rate, free water clearance, and sodium excretion in cirrhosis by a mechanism unrelated to systemic hemodynamics and endogenous neurohumoral vasoactive systems.
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PMID:Effects of somatostatin on renal function in cirrhosis. 809 52

In patients with cirrhosis the renal response to amino acid infusion is controversial. In addition, the renal and systemic metabolic effects of amino acids are unknown. Therefore, the present study examined the effects of amino acids on renal hemodynamics, renal and systemic oxygen (O2) consumption, and hormones in patients with cirrhosis. Twelve patients received an 8% amino acid solution for 30 minutes at a rate providing 250 mg of amino acids/kg body wt. Renal blood flow increased by 45% (P less than 0.05) and the glomerular filtration rate by only 9% (P greater than 0.05). Renal vascular resistance decreased by 23% (P less than 0.05), and renal perfusion pressure did not change significantly. Renal and systemic O2 consumption and pulmonary artery plasma glucagon level significantly increased. There were no significant changes in plasma osmolality, plasma volume, and plasma atrial natriuretic peptide concentrations. In conclusion, the results show that amino acid-induced renal vasodilation caused hyperperfusion but not renal hyperfiltration in patients with cirrhosis. In addition, renal hyperemia was associated with renal and systemic hypermetabolism.
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PMID:Hemodynamic, neurohumoral, and metabolic responses to amino acid infusion in patients with cirrhosis. 850 Jul 52

Elevation of serum insulin and plasma glucagon have been reported during and immediately after clinical and experimental liver transplantation and in patients with cirrhosis and surgically created or spontaneous portacaval shunts. There is controversy about the relative roles of portal diversion and impaired liver function in the genesis of these elevated levels of pancreatic hormones. End-to-side portacaval shunt was made in normal pigs which were fitted with catheters which allowed transhepatic sampling during and for 4 hr after the operation. Within 5 min of opening the shunt, there was a sixfold increase in portal venous insulin concentrations but hepatic clearance of insulin and the arterial concentration were unaltered. The increase in insulin was sustained for 2 hr. A twofold increase occurred within 1 hr in portal venous glucagon concentration which appeared to be predominantly of pancreatic origin and which continued for the 4 hr of the study. Hepatic glucose uptake did not occur after portacaval shunting despite levels of glucose elevated two-fold by iv infusion. There were no changes in aspartate aminotransferase, hepatic tissue energy charge, or total adenine nucleotides, suggesting that hepatic function was intact. It is concluded that portal diversion results in an increase in insulin and glucagon secretion and in the absence of hepatic uptake of glucose. This is a novel observation with relevance especially in liver transplantation when portal diversion for at least 1 hr forms part of the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:How rapidly do hyperinsulinaemia and hyperglucagonaemia develop after portacaval shunting? 140 85

Cirrhosis of the liver is typically accompanied by low plasma levels of the three branched chain amino acids (BCAA). These patients also demonstrate increased concentrations of several hormones such as insulin, glucagon and catecholamines. Catecholamines have been shown to influence the plasma levels of amino acids in healthy subjects and diabetics. In the present study, amino acid concentrations were investigated before and up to 3 hours after beta blockade (Inderal, 40-80 mg, n = 10) or fasting (n = 8) in cirrhotic patients. In the basal state the patients had low levels of all three BCAA, as compared with healthy subjects. Norepinephrine was more than 3 times as high in the patients (3.65 +/- 0.6 vs. 0.84 +/- 0.08 nmol/l, p < 0.01) while epinephrine was only slightly raised (0.43 +/- 0.1 vs. 0.25 +/- 0.06 nmol/l, NS). Significant correlations were observed between the concentrations of norepinephrine and individual as well as the sum of the three BCAA (r = 0.43-0.62, p < 0.05-0.001), while no correlation was observed between the BCAAs and epinephrine or insulin. Three hours after beta blockade the concentrations of leucine (basal: 74 +/- 6, 180 min: 89 +/- 6 mumol/l, p < 0.05) and valine (basal: 110 +/- 10, 180 min: 132 +/- 11 mumol/l, p < 0.01) had increased significantly. A similar tendency was observed for isoleucine. No changes were observed after prolonged fasting. The results suggest that catecholamines, primarily norepinephrine, might contribute to the low levels of BCAA in cirrhotics.
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PMID:Influence of beta blockade on branched chain amino acid concentrations in cirrhosis. 145 31


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