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

Glucose intolerance, overt diabetes mellitus, and insulin resistance are characteristic features of patients with cirrhosis. Insulin secretion, although increased in absolute terms, is insufficient to offset the presence of insulin resistance. The defect in insulin-mediated glucose disposal involves peripheral tissues, primarily muscle, and most likely reflects a disturbance in glycogen synthesis. Hepatic glucose production is normally sensitive to insulin; at present, it is unknown whether hepatic glucose uptake is impaired in cirrhosis. One of the more likely candidates responsible for the insulin-resistant state is insulin itself. The hyperinsulinemia results from three abnormalities: diminished hepatic extraction, portosystemic/intrahepatic shunting, and enhanced insulin secretion.
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PMID:Glucose and insulin metabolism in cirrhosis. 264 65

The liver participates in the turnover rate of free fatty acids (FFA) with a third. A severe disruption of liver function that occurs in cirrhosis leads therefore to a pathogenetic relevant hyperlipacidaemia respectively increases that. With regard to its clinical relevance a survey is given of the FFA metabolism of the liver. The factors are described which influence the FFA uptake by this organ. In this connection the metabolic fate of the FFA in dependence on the hormonal nutritive state is depicted. The author deals with the relation of the hepatic FFA metabolism to that of triglycerides, cholesterol, ketone bodies, carbohydrates, amino acids and insulin. The importance of these relatons for the caloric homeostasis and for the pathogenesis of various acute and chronic functional disturbances (ketoacidosis, negative nitrogen-balance, hyperlipoproteinaemia, hyperinsulinism, atherosclerosis) is described.
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PMID:[The metabolism of free fatty acids in the liver]. 266 56

The authors report preliminary data on the behavior of some lipid fractions in cirrhosis of the liver and correlate them with the changes in the insulin, glucagon and C-peptide levels. Elevated FFA (Free Fatty Acids) and normal cholesterol, triglyceride and total lipid values indicate a prevalent insulin induced effect and a reduction of liver metabolism of these fractions. This hypothesis is supported by the fact that L-carnitine, which reestablishes the carnitine-dependent intracellular transport system, reduces the levels of all the lipid fractions studied. The normal C-peptide values in these patients with liver cirrhosis show that hyperinsulinemia is caused by impaired metabolism of this hormone and not by hyperincretion. This hyperinsulinemia seems to react positively to the improvement of the intracellular transport systems. A fall in the hyperglucagonemia follows the decreased hyperinsulinemia leading to a hormone balance with lower values and a consequent reduction of the hormonal stimuli on the lipid metabolism. The possibility of administering drugs, which can act on the metabolic pathways responsible for the high FFA plasma levels, which seem to play a role in the physiopathology of encephalopathies and hepatic coma is clinically interesting.
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PMID:[Plasma lipids, insulin, C-peptide, and glucagon levels in cirrhosis: personal observations]. 267 5

Hyperinsulinemia and impaired glucose tolerance are associated with liver cirrhosis. To investigate whether insulin-degrading activity in liver tissue plays a role in hyperinsulinemia, we assayed this activity in biopsy tissue from healthy and cirrhotic subjects. There was no difference in insulin degradation between these two groups. Also glucagon-degrading activity in liver tissue, which is catalyzed by the same enzyme as insulin-degrading activity, did not differ between the two groups studied. Therefore, insulin-degrading activity does not appear to be involved in the hyperinsulinemia that occurs in liver cirrhosis. The study provides indirect evidence that hyperinsulinemia and impaired glucose metabolism in liver cirrhosis are due to different mechanisms (receptorial and post-receptorial defects, and altered feedback inhibition of insulin secretion).
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PMID:Insulin and glucagon degradation in liver are not affected by hepatic cirrhosis. 268 Jan 68

Altogether 155 patients with different clinical types of liver lesions were examined: 73 with chronic persistent hepatitis (CPH), 39 with chronic active hepatitis (CAH), and 43 with liver cirrhosis (LC). The patients with chronic liver diseases demonstrated hyperinsulinemia and a decrease in glucose tolerance, a frequency and degree of this decrease growing with the severity of a pathological process. It is postulated taking experiments with partial hepatectomy of rats by way of example that intolerance to glucose and hyperinsulinemia is caused by partial loss of glycogen synthetic function by the liver resulting from a decrease in the number of functionally active cell elements. Experience with 8 LC patients with secondary diabetes mellitus has shown that the addition of the latter is connected with the reduction of secretory capacity of pancreatic beta-cells and with the development of relative insulin insufficiency.
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PMID:[The relationship of disorders of glucose tolerance in patients with chronic hepatitis and liver cirrhosis to the severity of the pathological process]. 269 17

To clarify the clinical significance of specific plasma amino acid abnormalities occurring in liver disorders with portal-systemic shunting, plasma amino acids and insulin levels were measured in idiopathic portal hypertension (IPH), extrahepatic portal occulusion (EHPO), and liver cirrhosis (LC). Three branched chain amino acids (BCAA: valine + leucine + isoleucine) were decreased in all three diseases in comparison with controls. Since plasma insulin measured during oral glucose tolerance tests did not specifically rise in LC, reduction of BCAA is not merely ascribed to hyperinsulinemia. Either portal-systemic shunting or some extent of liver damage may contribute to a fall in BCAA. Two aromatic amino acids (AAA: phenylalanine + tyrosine), which were within the normal range in EHPO and IPH, showed a marked increase in LC. Thus, changes of AAA probably mainly reflect the severity of the liver disease. The molar ratio of BCAA/AAA (MR) significantly correlated with ICG k, ICG R15, PT and the sum of blood ammonia in an oral ammonia tolerance test which may reflect the degree of hepatic disorder. MR diminished in the following decreasing order: controls, EHPO, IPH and LC.
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PMID:Plasma amino acid abnormalities in liver disease: comparative analysis of idiopathic portal hypertension, extrahepatic portal occlusion and liver cirrhosis. 277 20

Fourteen normal controls, eleven patients with non-alcoholic cirrhosis, twenty-nine with hepatocellular carcinoma (HCC) and six with HCC and hypoglycemia were studied. The tests performed include iv glucose tolerance test (25 g) and glucagon challenge test (2 mg). In cirrhosis, glucose intolerance and insulin resistance were demonstrated. The fasting hyperinsulinemia in cirrhosis is the result of decreased degradation as shown by the normal fasting C-peptide. The increased insulin responses to glucose, despite a normal C-peptide response, further supports the importance of impaired degradation in the pathogenesis of hyperinsulinemia after challenge. Despite a strong etiological association between cirrhosis and HCC, patients with HCC do not have significant hyperinsulinemia or glucose intolerance. This provides metabolic evidence to support the clinico-pathological observation that HCC occurred when cirrhosis was not advanced or in a precirrhotic stage. In HCC patients with clinically overt hypoglycemia, the fasting glucose, insulin and C-peptide were very low. The C-peptide responses to glucose and glucagon challenges were suppressed despite pharmacologic stimulation. This can be explained by the suppression of insulin secretion by a circulating substance secreted by hepatoma. The results support the pathogenetic importance of insulin-like activities recently detected in HCC patients with hypoglycemia.
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PMID:C-peptide in non-alcoholic cirrhosis and hepatocellular carcinoma. 284 76

Carbohydrate intolerance was investigated in 8 alcoholics with liver cirrhosis and in controls. Indices of carbohydrate metabolism, glucose and insulin levels after glucose loading, were compared with glucose phosphorylating (glucokinase, hexokinase) and releasing (glucose-6-phosphatase) enzymes. Comparison was also made with pericellular collagen in liver biopsies and with insulin sensitivity assessed by the euglycemic clamp technique and with conventional liver function tests including oral antipyrine test. Glucokinase activity was low or absent, hexokinase activity increased and the GK/HK ratio reduced. Glucose-6-phosphatase activity was lowered and insulin sensitivity decreased. Pericellular collagen was increased (P less than 0.001) and related to the fasting glucose (r0.593) and insulin levels (r0.526). Blood glucose was related to antipyrine metabolism (r-0.727) but not to the other liver tests. Glucose intolerance in cirrhosis seems to be associated with reduced glucose phosphorylating and liberating enzyme activities. Hyperinsulinaemia, developing secondarily, may then lead to insulin resistance.
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PMID:Carbohydrate intolerance associated with reduced hepatic glucose phosphorylating and releasing enzyme activities and peripheral insulin resistance in alcoholics with liver cirrhosis. 299 23

To explore the insulin resistance state in liver cirrhosis and to assess the respective role of insulin sensitivity and cellular metabolism alterations, an euglycemic glucose clamp was performed in 12 cirrhotic patients and 6 healthy volunteers with 3 successive hyperinsulinemic periods of 90 mn (infusions of 7, 20 and Iu/h). An artificial beta-cell model allowed to quantify the amount of glucose needed to keep glycemia at 4.70 mmol/l. In 7 cirrhotic patients, insulin secretion was tested by an intravenous glucose tolerance test. The dose-response curves showed a significant (p less than 0.01) decrease of the theoretical maximal metabolic clearance rate of glucose (capacity). The insulin concentration corresponding to the half-maximal response (ED50) did not differ between cirrhotic and control subjects because of a very important dispersion of individual values in cirrhotics. The ED50 value was lower than the values of control subjects in five cirrhotic patients and normal or enhanced in seven other patients; the former showed the most reduced values for capacity, and the latter a more marked hyperinsulinemia during the intravenous glucose tolerance test. The two subgroups of patients did not differ for clinical or biological parameters of cirrhosis, or for glucose tolerance. These results 1) show a constant and marked impairment of glucose metabolism capacity in liver cirrhosis, 2) and suggest that the insulin resistance inconstantly observed in this state is a consequence of chronic hyperinsulinemia.
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PMID:[Study of insulin resistance in cirrhosis by the hyperinsulin euglycemia clamp]. 304 4

Impairments in pancreas incretory functions were detected in patients with chronic liver diseases of alcohol etiology (lipid dystrophy, cirrhosis) after radioimmunologic examination of immunoreactive insulin, C-peptide and glucagon in blood under these conditions and during glucose-tolerance test. Mechanisms of resistance to insulin and to hyperinsulinemia under conditions of these pathological states are considered. Role of liver tissue has been emphasized in maintaining of blood pancreatic hormones level.
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PMID:[Incretory function of the pancreas in alcoholic liver diseases]. 328 85


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