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)

1. Oral glucose-tolerance tests (100 g) were carried out in six patients with stable well-compensated cryptogenic cirrhosis and in 12 control subjects. 2. In confirmation of previous studies, patients with cirrhosis had high post-glucose serum insulin levels and were glucose intolerant (mean incremental glucose area 954 +/- 186 compared with 482 +/- 35 mmol 3 h-1 l-1 in controls; P < 0.05). 3. Forearm arteriovenous differences of glucose and forearm blood flow were measured to estimate the proportion of the glucose load metabolized in peripheral tissues. Values in cirrhotic patients and control subjects (5614 +/- 1630 compared with 5344 +/- 672 mumol of glucose min-1 l-1 of forearm in 3 h) were similar despite higher glucose levels and sustained high insulin levels in the cirrhotic patients. 4. Peak lactate concentrations after glucose were of similar magnitude in the two groups (0.66 +/- 0.12 compared with 0.62 +/- 0.75 mmol/l) but in the patients with cirrhosis the peak occurred later and was more sustained. 5. The glucose intolerance of cirrhosis is primarily due to impaired hepatic retention of the glucose load. Insulin resistance in peripheral tissues may also be important since the higher insulin concentrations found in cirrhotic patients failed to enhance peripheral glucose uptake.
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PMID:Forearm glucose uptake in cirrhosis and its relationship to glucose tolerance. 700 Apr 17

Plasma levels of immunoreactive insulin (IRI), C-peptide and glucagon were assayed in 16 patients with liver cirrhosis and 9 control subjects after an oral glucose load (OGTT). Nine of the cirrhotics showed glucose intolerance, the remaining 7 cases showed normal OGTT. Both groups of cirrhotics showed high IRI and C-peptide values in basal conditions; peaks of these parameters, higher than those observed in the control subjects, were found during the OGTT. The C-peptide/IRI ratio, which was lower than normal both during fasting and after glucose load, presented the lowest values in patients with normal OGTT. In the conditions adopted for this study, glucagon showed higher plasma levels in all the cirrhotics studied than those found in the controls, but the highest levels were found in patients with normal OGTT. It can be concluded that the high levels of insulin found in liver cirrhosis are due to a beta-pancreatic hypersecretion (high C-peptide levels) but are also maintained by a decreased hepatic degradation of the hormone (C-peptide/IRI ratio below normal). Hyperglucagonemia is not the chief factor in determining the insulin-resistance observed in liver cirrhosis.
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PMID:Plasma levels of insulin, C-peptide and glucagon in liver cirrhosis. 701 66

Abnormalities of carbohydrate metabolism, including hyperinsulinaemia and insulin resistance, are well recognised complications of cirrhosis. While diabetes mellitus can be explained in many instances on the basis of coincident pancreatic disease, in most the characteristic glucose intolerance of cirrhosis is not readily explicable. A previous clinical observation that hepatitis C virus infection and diabetes mellitus appeared to be associated was formally tested by a retrospective review of 100 consecutive adult patients with cirrhosis undergoing assessment for liver transplantation. Hepatitis C virus was diagnosed by conventional serological and histological criteria. Twenty-three patients had diabetes mellitus, of whom 18 were being treated with insulin. Of the 34 patients with hepatitis C virus-related cirrhosis, 17 (50%) had diabetes mellitus, in contrast to just six (9%) of the 66 patients with cirrhosis unrelated to hepatitis C virus (chi2 = 19.1, p < 0.0001) with an odds ratio for hepatitis C virus by diabetes mellitus status 10.0 (95% confidence interval 3.4 to 29.3). Hierarchical loglinear model analysis of those factors of potential relevance to the development of diabetes mellitus revealed that only hepatitis C virus interacted significantly with diabetes mellitus while the relation between diabetes mellitus and origin, sex, body mass index and severity of cirrhosis was conditional. By multiple logistic regression analysis of diabetes mellitus status in relation to the same variables, only hepatitis C virus status was statistically significant (p < 0.0001). Origin, sex, severity of cirrhosis, body mass index and therapy were not significantly associated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evidence for a link between hepatitis C virus infection and diabetes mellitus in a cirrhotic population. 877 23

A blunted initial insulin secretory response may contribute to oral glucose intolerance in cirrhosis. Oral glucose is a better stimulant to insulin secretion than intravenous (IV) glucose in part because of release of gut peptides, notably glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 [7-36 amide] (GLP-1 [7-36 amide]). Because impaired release of or resistance to these gut peptides could explain impaired insulin secretion after oral glucose, we measured insulin secretion, plasma GIP, and GLP-1 [7-36 amide] levels, basally and after 75 g oral glucose, in 10 cirrhotics and 10 controls. Insulin secretion was calculated from a two-compartment analysis of serum C-peptide levels using kinetic parameters derived from IV injection of recombinant human C-peptide. C-peptide metabolic clearance rate, and the fractional rate constants for C-peptide (using the two-compartment model) were not significantly different, but the volume of the central compartment was 15% greater in cirrhotics (P < .01). Fasting blood glucose levels were similar (cirrhotics, 4.9 +/- 0.2; controls, 4.6 +/- 0.1 mmol/L) but serum insulin was six times higher in cirrhotics (P < .001). Cirrhotics had higher fasting GIP (215 +/- 72 vs. 42 +/- 18 pmol/L) and GLP-1 [7-36 amide] levels (25 +/- 3 vs. 16 +/- 1 pmol/L) (both P < .05). After oral glucose, blood glucose levels were significantly higher in cirrhotics. The timing of the gut peptide response to oral glucose was similar in the two groups, but peak levels of both peptides were approximately x2 higher in the cirrhotics.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin secretion and plasma levels of glucose-dependent insulinotropic peptide and glucagon-like peptide 1 [7-36 amide] after oral glucose in cirrhosis. 770 3

Liver cirrhosis is characterized by an increased incidence of glucose intolerance, diabetes and insulin resistance. We report a cirrhotic man (41 years old) who developed glucose intolerance and diabetes with insulin resistance over a period of six years. This patient suffered from severe portal hypertension with oesophageal varices and a enormously increased spleen volume. The subject underwent prophylactic endoscopic sclerotherapy of oesophageal varices. Splenectomy was performed because of severe piastrinopenia with recurrent nose bleeding. During laparotomy, multiple liver biopsies confirmed diagnosis of liver cirrhosis. Intra-operatory exploration revealed a splenic vein thrombosis. For this reason the planned spleno-renal shunting was not performed and the patient was only submitted to splenectomy. Liver function improved in the month following splenectomy and concomitant decrease of insulin resistance was observed (with a reduction in daily insulin dosage from 126 to 10 I.U.). We propose the following explanations of this event: 1) A decrease of portal and pancreatic vein pressure may have induced a proportional decrease (as already reported) of glucagon secretion. 2) The ameliorated liver function may have induced an improvement of liver glucose, insulin and glucagon metabolism. 3) A reduction of insulin circulating level (proved by a decrease of C Peptide value) may have lessened the insulin receptor down-regulation.
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PMID:[Decrease of insulin resistance after splenectomy in a diabetic patient with liver cirrhosis and portal hypertension. Physiopathologic evaluation]. 784 51

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

To study the mechanisms of glucose intolerance and hyperinsulinism in liver cirrhosis, we compared the plasma glucose, insulin, and C-peptide levels during a frequently sampled i.v. glucose tolerance test (0.3 g glucose/kg BW) in nine compensated cirrhotic patients and nine healthy volunteers well matched for age, sex, and body weight. The insulin secretion rate was derived by the deconvolution of plasma C-peptide levels, insulin sensitivity was calculated using Bergman's minimal model method, and insulin clearance was estimated by dividing the 0-180 min area under the curve of insulin secretion rate by that of peripheral plasma insulin levels. The cirrhotic patients were characterized during the frequently sampled i.v. glucose tolerance test by a 60% greater insulin secretion rate (P < 0.05), a markedly reduced insulin sensitivity index (SI; 2.82 +/- 0.75 vs. 5.86 +/- 0.68 x 10(-4) min/mU.L; P < 0.01) and a 40% reduced insulin clearance (725 +/- 169 vs. 1165 +/- 99 mL/min.m-2; P < 0.05). The reduction of insulin clearance was significantly correlated with the amplitude of the portosystemic shunt, measured using an isotopic method (r = 0.75; P < 0.02). In conclusion, cirrhosis is characterized by an important peripheral hyperinsulinism, resulting from both a higher insulin secretion rate and a reduced insulin hepatic clearance; the severe insulin resistance explains the glucose metabolism alterations.
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PMID:Insulin secretion, clearance, and action on glucose metabolism in cirrhotic patients. 807 19

The site of impaired glucose uptake in cirrhosis is uncertain. We therefore performed hyperglycemic clamps (glucose 10 mmol/L) in 10 patients with compensated alcoholic cirrhosis and impaired glucose tolerance and in six control subjects. Muscle glucose uptake was estimated in patients and controls with the forearm technique. In the cirrhotic subjects splanchnic glucose uptake was measured with hepatic vein catheterization and primed continuous infusions of indocyanine green and [6-3H]glucose. To assess insulin-independent glucose uptake and the effects of elevated nonesterified fatty acid levels on glucose uptake, we repeated the study with somatostatin to induce insulin deficiency and a nicotinic acid analog, acipimox, to inhibit lipolysis. Substrate disposal was assessed on indirect calorimetry. Despite similar stimulated insulin levels, total glucose utilization was lower in the cirrhotic subjects (3.9 +/- 0.3 vs. 8.8 +/- 1.7 mg/kg/min, p = 0.006). This deficiency was accounted for by lower nonoxidative glucose disposal (1.2 +/- 0.2 vs. 5.8 +/- 1.6 mg/kg/min, p = 0.002). Forearm glucose uptake was lower in the cirrhotic subjects (0.39 +/- 0.06 vs. 1.21 +/- 0.3 mg/100 ml/min, p = 0.001). However, splanchnic glucose uptake at 1.59 +/- 0.14 mg/kg/min was similar to that reported in other studies of normal subjects. Insulin-independent glucose uptake was normal, and acipimox had no effect on total or forearm glucose utilization. Glucose intolerance in cirrhosis is characterized by impaired peripheral insulin-stimulated non-oxidative glucose disposal. The high nonesterified fatty acid levels seen in cirrhosis most likely do not contribute to this defect. Splanchnic glucose uptake is normal in cirrhosis.
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PMID:Normal splanchnic but impaired peripheral insulin-stimulated glucose uptake in cirrhosis. 810 Jul 99

Glucose intolerance and diabetes mellitus are both prevalent in cirrhosis, yet the pathogenesis of impaired glucose metabolism remains unknown. Therefore insulin secretion (hyperglycemic clamp, +125 mg/dl), insulin sensitivity (euglycemic hyperinsulinemic insulin clamp, +10 microU/ml and +50 microU/ml), whole-body glucose oxidation (indirect calorimetry) and glucose turnover ([6,6-2H2]glucose isotope dilution) were evaluated in a homogenous group of cirrhotic patients with glucose intolerance (n = 7) or frank diabetes mellitus (n = 6). The results were compared with those obtained in control subjects (n = 8). In glucose-intolerant patients, whole-body glucose uptake (mainly reflecting glucose utilization by muscle) was significantly impaired in patients during both insulin infusions as a result of decreased stimulation of the two major intracellular pathways of glucose disposal--nonoxidative glucose disposal (i.e., glycogen synthesis) and glucose oxidation. Hepatic glucose production was normal in the basal state and was normally suppressed during stepwise insulin infusion (by 65% and 85%, respectively, p = NS vs. controls). Hyperglycemia-induced increases of plasma C-peptide concentrations were comparable to those in controls (p = NS). In diabetic patients, insulin-mediated glucose uptake was significantly reduced, mainly because of impaired non-oxidative glucose disposal. Glucose oxidation appeared to be reduced, too. Hepatic glucose production was significantly increased in the basal state (3.03 +/- 0.24 vs. 2.34 +/- 0.10 mg/kg min, p < 0.02) and during insulin infusion (+50 microU/ml: 0.67 +/- 0.17 vs. 0.13 +/- 0.08 mg/kg min, p < 0.05) compared with that in controls. Both the first and second phases of beta-cell secretion were significantly reduced in response to steady-state hyperglycemia (both p < 0.01 vs. control values). In conclusion, glucose intolerance in cirrhosis results from two abnormalities that occur simultaneously: (a) insulin resistance of muscle and (b) an inadequate response (even when comparable to that of controls) of the beta-cells to appropriately secrete insulin to overcome the defect in insulin action. Diabetes mellitus in insulin-resistant cirrhotic patients develops as the result of progressive impairment in insulin secretion together with the development of hepatic insulin resistance leading to fasting hyperglycemia and a diabetic glucose tolerance profile.
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PMID:Pathogenesis of glucose intolerance and diabetes mellitus in cirrhosis. 811 86

The pathogenetic mechanism underlying glucose intolerance in pancreatic cancer is still unclear. We studied the pattern of three glucose regulating hormones (C-peptide, glucagon and GH) in pancreatic cancer patients with (N = 34) and without (N = 8) hyperglycemia, and compared the findings made with those from subjects with other hyperglycemic conditions of well-known origin [type I diabetes mellitus (8 cases) and diabetes mellitus secondary to chronic pancreatitis (13 cases) or liver cirrhosis (4 cases)]. In hyperglycemic pancreatic cancer patients, C-peptide was absent in 26% of the cases, reduced in 24%, elevated in 29% and within the normal range in the remaining 21%. In normoglycemic pancreatic cancer this hormone was reduced in two cases (25%) and within the normal range in all the others. GH was within the normal range in all cases: glucagon was below the normal range in some hyperglycemic pancreatic cancer patients (41%) or within the normal range in all the remaining patients. No correlations were found between the three hormones when findings from subjects were considered all together. However, in pancreatic cancer C-peptide and glucagon presented consensual variations. C-peptide, glucagon and GH levels were not related to tumor volume; glucagon was found to be associated with liver metastases. C-peptide was correlated with serum ALT and ALP. We may conclude that hyperglycemia associated with pancreatic cancer may be caused by different mechanisms. In some cases a reduced secretion of both insulin and glucagon was observed, as occurs in chronic pancreatitis. In the majority of patients, beta cell function appears normal, and the hyperglycemic state may depend on an altered peripheral sensitivity to insulin due to the pancreatic pathology itself or to consensual liver involvement.
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PMID:C-peptide pattern in patients with pancreatic cancer. 813 97


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