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

A follow-up study of 1939 diabetic patients with a mean observation period of 9.4 years was carried out in Osaka, Japan. The mortality rates per 1000 person-years were 31.35 for males and 21.99 for females, and the ratios of observed to expected number of deaths were 1.69 for males and 1.74 for females, indicating an excess mortality for diabetic patients of both sexes and higher mortality in males than in females in Japan. Factors related to the prognosis of the patients were age, elevated fasting glucose level, lower obesity index, hypertension, diabetic retinopathy, and albuminuria at entry to the study. Insulin treatment was also associated with poor prognosis. Cerebro-cardiovascular and renal disease were the major causes of death in diabetic patients; heart disease killed 19.5%, cerebrovascular disease 16.7% and renal disease 13.1%. The relatively high frequency of renal disease as a cause of death in type 2 diabetes, especially in patients with a lower age of onset, was noteworthy, suggesting some difference in the clinical manifestations of diabetes between Japan and Western countries. Malignant neoplasms accounted for 25% of deaths, and cirrhosis of the liver for 6.4%.
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PMID:Mortality and causes of death in type 2 diabetic patients. A long-term follow-up study in Osaka District, Japan. 275 88

Plasma insulin, glucagon, somatostatin, and glucose concentrations were measured in the fasting state as well as after mixed meals (breakfast, lunch, and dinner) in 10 cirrhotic patients and 10 control subjects during a 24-hour period. Cirrhotic patients had fasting glucose values higher than controls (at -15 min: 5.2 +/- 0.2 mmol/L v 3.9 +/- 0.5 mmol/L, P less than 0.05; at 0 min: 5.5 +/- 0.3 mmol/L v 4.3 +/- 0.5 mmol/L, P less than 0.01). After meals blood glucose values remained higher in cirrhotics than in controls. Insulin levels did not differ between the groups in the fasting state, but cirrhotics showed a lower response to meals. Corresponding glucagon concentrations were greater in cirrhotics than in controls before and after meals throughout the 24-hour period (from -15 min to 24 hour: P less than 0.01). BAsal plasma somatostatin levels in the cirrhotic group were significantly higher than in control subjects (at -15 min and at 0 min: P less than 0.05) and further increased after meals. Plasma somatostatin was heterogeneous in normal and cirrhotic group, but the increase in its concentrations in patients with chronic liver disease was for the most part a consequence of elevations in the 1600 and 3500 molecular weight components. The half-life of exogenously infused somatostatin in cirrhotics was comparable to that of controls. These results indicate that in liver cirrhosis elevated levels of circulating somatostatin are associated with hyperglucagonemia and impaired insulin release. The high plasma somatostatin levels observed in cirrhotic patients are the result of hypersecretion of the D cell rather than impaired removal of the peptide.
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PMID:Circulating somatostatin concentrations in healthy and cirrhotic subjects. 286 81

The influence of a long-acting somatostatin octapeptide analogue (SMS 201-995) on splanchnic circulation and metabolism has been studied in healthy subjects and in patients with liver cirrhosis. In healthy subjects doses of 5, 10, 50, or 100 micrograms SMS and in the cirrhotic patients 25 micrograms SMS were infused intravenously during 1 h. Measurements were obtained before, during, and for 1 h after SMS infusion. SMS infusion in healthy subjects resulted in a 25-35% reduction in hepatic blood flow. This effect was largely independent of the dose used. Splanchnic oxygen uptake was unchanged before and during SMS infusion. Insulin and glucagon levels fell markedly in response to SMS administration, and the blood concentration and splanchnic output of glucose decreased transiently. Patients with liver cirrhosis responded to SMS infusion similarly to the healthy subjects. Hepatic blood flow decreased by 25-35% and remained suppressed for at least 1 h after infusion. Wedge hepatic venous pressure was 18 +/- 2 mm Hg in the basal state and decreased progressively during and after SMS infusion (60 min after infusion, 15 +/- 2 mm Hg; P less than 0.01). The marked hyperinsulinaemia and hyperglucagonaemia seen in the basal state decreased significantly during SMS administration. As in the case of the controls, blood concentration and splanchnic output of glucose fell transiently during and after SMS infusion. It is concluded that SMS exerts a marked and prolonged suppressive effect on hepatic blood flow in both healthy subjects and patients with liver cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The influence of a long-acting somatostatin analogue on splanchnic haemodynamics and metabolism in healthy subjects and patients with liver cirrhosis. 287 92

Pancreatic endocrine function in liver cirrhosis was examined in rats both in vivo and in vitro. Experimental liver cirrhosis was induced by subcutaneous injections of 50% carbon tetrachloride in a dose of 2 mL/kg body weight twice a week for 16 weeks. Control rats received a similar dose of olive oil during the same period. In cirrhotic rats, immunoreactive insulin contents in the pancreas were significantly lower, whereas immunoreactive glucagon contents were about threefold higher than those of control rats. In the first part of this study, insulin and glucagon concentrations in both jugular and portal venous blood at basal conditions and after oral glucose loading were simultaneously determined in vivo. Peripheral insulin levels, both before and after glucose loading, were higher, whereas portal insulin concentrations were lower in cirrhotic rats than in the control rats. In contrast, glucagon levels in both the peripheral and portal veins were significantly higher in cirrhotic rats than in control rats. In the second part, isolated perfused pancreata were prepared from cirrhotic and control rats to further characterize the endocrine function of cirrhotic rat pancreas. Insulin secretion in response to 16.7 mmol/L glucose and 100 pmol/L cholecystokinin-octapeptide both were 40% lower in cirrhotic rats than in controls. In contrast, there was no significant difference in arginine-stimulated insulin release between the two groups. However, glucagon secretion in response to 20 mmol/L arginine was 40% higher in cirrhotic rats. If sensitivity is defined as the hormone release proportional to the pancreatic contents, then A and B cells in the cirrhotic rats had normal sensitivity to both glucose and cholecystokinin-octapeptide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pancreatic endocrine function in cirrhotic rats. 304 24

Insulin (IRI) and C-peptide dynamics were studied after iv glucagon in 5 nondiabetic patients with ascites due to cirrhosis of the liver. Plasma and ascitic fluid samples for glucose, IRI and C-peptide determinations were obtained before and 6, 10, 15, 20 and 30 min after glucagon injection. Ascitic fluid volumes, estimated by dilution of ip injected PAH, were 6.2 to 20.5 L. The mean fasting plasma glucose [88 +/- 6.7 mg/dl (SE)] and C-peptide (1.40 +/- 0.42 ng/ml) levels were normal; mean plasma insulin was increased (17.4 +/- 3.0 microU/ml). After glucagon injection, there was a subnormal rise in plasma glucose (PG) compared to 5 mild diabetic patients without liver disease (8.4 +/- 3.5 vs 76 +/- 7.4 mg/dl). The plasma C-peptide rise was less than that of plasma IRI (54% vs 192%). The mean basal ascitic fluid concentration of glucose was 86 +/- 9.4 mg/dl, IRI 13.2 +/- 2.9 microU/ml and C-peptide 3.09 +/- 0.49 ng/ml. Total calculated basal ascitic fluid contents of glucose was 5.2-23.3 g, IRI 47, 120-290,000 microU and C-peptide 15,750-66,420 ng. These were 3-10 times the quantity of these substances circulating in the plasma volume. After glucagon injection, there was no significant increase in ascitic fluid glucose or IRI, but there was a 43% increase in C-peptide concentration at 10 min. In ascitic fluid, the molar concentration of IRI was lower and C-peptide higher than plasma, resulting in a C-peptide: IRI molar ratio of 11.31, markedly higher than the published normal plasma ratio of 4.63.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin and C-peptide in ascitic fluid and plasma and their relative responses to glucagon in patients with cirrhosis. 306 13

In order to evaluate the relationship between nutritional status and insulin secretion in cirrhosis, the following parameters of caloric (tricipital skin fold, prealbumin) and proteic (arm muscle size, transferrin, 24 h-urinary creatinine excretion) nutritional status were compared in 20 alcoholic cirrhotics and 10 normal subjects. Insulin secretion was evaluated in both groups by insulin and C-peptide response to an intravenous glucose tolerance test and by 24 h urinary excretion of C-peptide. When compared to normals, cirrhotics have lower values for all nutritional status parameters and individually for at least three of those in 14 (70 p. 100) patients. In cirrhotics there is a significant decrease of the 4-min poststimulative response of insulin and C-peptide, contrasting with higher basal and late poststimulative values than in normals. This contrast could be explained by a reduced metabolic clearance rate of insulin (consistent with insulin resistance) and of C-peptide (the urinary clearance of which is 2.5 times lower in cirrhotics than in normals). The 24-h urinary excretion of C-peptide, probably weakly dependent of this reduced clearance, is 50 p. 100 lower in cirrhotics: 12.9 +/- 1.6 nM/24 h than in normals: 26.0 +/- 2.4 nM/24 h (p less than 0.001). In cirrhotics there is a significant linear correlation between 24 h urinary C-peptide excretion and all the nutritional status parameters but one (prealbumin). These results indicate that in cirrhosis: 1) urinary C-peptide excretion rate is a good index of insulin secretion; 2) urinary C-peptide indicates a marked deficit in insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Malnutrition and deficiency of insulin secretion in alcoholic cirrhosis. Study by the assay of urinary C-peptide]. 308 65

We have examined the hypothesis that insulin insensitivity in hepatic cirrhosis is related to abnormalities of glycogen deposition and skeletal muscle enzyme activities. Otherwise well patients with biopsy-proven hepatic cirrhosis secondary to previous excess alcohol intake were studied. Prior to study, in basal state, patients had identical blood glucose concentrations but raised serum insulin concentrations (cirrhotic: 8.5 +/- 0.8 mU per liter; matched control subjects: 5.7 +/- 0.5 mU per liter, p less than 0.01). Muscle glycogen content, glycogen synthase activity and pyruvate dehydrogenase activity were normal in the basal state. The cirrhotic patients required less glucose to maintain the clamp in response to 0.1 unit per kg per hr insulin (6.7 +/- 0.5 vs. control 8.3 +/- 0.4 mg per kg per min, p less than 0.05) and deposited less glycogen in muscle during the clamp (8.6 +/- 0.5 vs. 12.0 +/- 1.4 mg per gm protein, p less than 0.05). Glycogen deposition correlated with clamp glucose requirement in the cirrhotic patients (r = 0.78, p less than 0.05). The expressed activity of glycogen synthase activity was significantly lower in cirrhotic patients at the end of the clamp (26.5 +/- 1.1% vs. 30.9 +/- 1.6%) and again correlated with clamp glucose requirement (r = 0.82, p less than 0.05). Skeletal muscle pyruvate dehydrogenase activity was not different in patients and control subjects. Insulin insensitivity in hepatic cirrhosis appears to be related to abnormalities of glucose deposition as glycogen in skeletal muscle.
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PMID:The relationship between insulin sensitivity and skeletal muscle enzyme activities in hepatic cirrhosis. 314 11

Clearance of porcine insulin, glucagon, and human growth hormone was measured in intact perfused cirrhotic and normal rat livers. Binding and degradation of 125I-insulin by hepatocytes isolated from cirrhotic and normal livers were also studied. The half-lives (t1/2) of immunoreactive insulin and glucagon were 14.0 +/- 3.1 and 9.6 +/- 2.1 min in normal livers and 26.0 +/- 6.1 and 25.0 +/- 7.1 min in cirrhotic livers (P less than 0.001). Insulin binding and degradation by hepatocytes from control and cirrhotic livers showed no significant differences. Intraportal insulin infusion in perfusion studies suppressed glucagon-stimulated increases in glucose output from control livers but failed to suppress glucose production by cirrhotic livers, suggesting the presence of hepatic insulin resistance in cirrhosis. Impaired clearance of insulin and glucagon by the intact cirrhotic liver and normal binding and degradation of insulin by isolated hepatocytes suggest that factors such as intrahepatic fibrosis and shunting and postbinding defects may be responsible for the impaired hormone clearance and hepatic insulin resistance.
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PMID:Insulin resistance and delayed clearance of peptide hormones in cirrhotic rat liver. 329 81

Coexistence of hyperinsulinemia and normal or impaired carbohydrate tolerance indicates insulin resistance which is frequently observed in patients with liver diseases such as liver cirrhosis, fatty liver, acute and chronic hepatitis and idiopathic haemochromatosis. Insulin resistance in liver diseases can be due to circulating insulin antagonists or a target tissue defect in insulin action, either due to changes in the state of the insulin receptor or due to a postreceptor defect, that means any abnormality in the insulin action sequence following the initial binding step. High insulin levels in liver diseases are caused by diminished degradation of insulin by the liver whereas hypersecretion only plays a minor role under basal conditions. High levels of glucagon, free fatty acids and growth hormone are well known in liver diseases but until now there is no evidence of the pathogenetic importance of these factors. Conflicting results on insulin binding, methodological criticism on binding data and the question whether or not diminished insulin binding on peripheral blood cells plays any physiological role make it unlikely that studies on insulin receptors of peripheral blood cells contribute to the revelation of insulin resistance in liver diseases. The clamp technique allows to quantify the sensitivity of the body to exogenous insulin. The results on liver cirrhosis in connection with studies on glucose metabolism show that under basal conditions insulin insensitivity is due to peripheral resistance (primarily muscle) according to a postreceptor defect. Finally the causes of insulin resistance in liver diseases are still not known.
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PMID:[Insulin resistance in liver diseases]. 353 94

In the fasting state the mean portal blood flow demonstrated by the pulsed Doppler system with the Octoson in liver cirrhosis (LC) patients (velocity (PV), 10.2 +/- 3.5 (mean +/- SD) cm/sec, 7.0 +/- 2.6 cm/sec/m2; flow (PF), 579 +/- 262 ml/min, 383 +/- 184 ml/min/m2 (n = 40)) was significantly lower than that in control subjects (PV, 21.2 +/- 5.2 cm/sec, 14.7 +/- 3.9 cm/sec/m2; PF, 966 +/- 344 ml/min, 667 +/- 220 ml/min/m2 (n = 40)). Food intake increased PV by 15% and PF by 15% in LC (n = 8) and increased PV by 56%, PF by 125% in controls (n = 8). Glucagon increased PV by 30% and PF by 52% in LC (n = 10) and increased PV by 50% and PF by 120% in controls (n = 8). Secretin increased PV by 44% and PF by 75% in LC (n = 9) and increased PV by 66% and PF by 142% in controls (n = 8). Vasopressin decreased PV by 42% and PF by 54% in LC (n = 9) and decreased PV by 48% and PF by 62% in controls (n = 8). Insulin, gastrin, and prostaglandin E1 had no effect in either group.
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PMID:Effects of food intake and various extrinsic hormones on portal blood flow in patients with liver cirrhosis demonstrated by pulsed Doppler with the Octoson. 354 85


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