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

About 80% of patients with chronic liver diseases such as cirrhosis are glucose intolerant and some 20-30% eventually develop frank diabetes mellitus. In a given individual it seems impossible to determine whether or not acquired liver diabetes or inherited non-insulin-dependent diabetes mellitus is present. The high prevalence, however, of impaired glucose tolerance and the finding that insulin sensitivity is reduced in nearly all cirrhotic patients before any impairment in glucose tolerance becomes manifest, make it likely that in the majority of patients the hepatic disease is the cause of the development of the hepatogenous diabetes. The insulin resistance resides in muscle and largely results from a defect in glycogen synthesis. Glucose intolerance ensues as a result of two abnormalities that occur simultaneously: insulin resistance of muscle and an inadequate response of the B-cell to appropriately secrete insulin to overcome the defect in insulin action. Diabetes mellitus in insulin-resistant cirrhotic patients develops as a result of a progressive impairment in insulin secretion together with the development of hepatic insulin resistance, leading to fasting hyperglycemia. Until recently, only little was known about the etiology of insulin resistance and impaired insulin secretion. However, most recent studies have shown that prolonged reduction of hyperinsulinemia in cirrhosis normalize insulin-mediated glucose uptake and glycogen synthesis in muscle. These results indicate that chronic hyperinsulinemia causes insulin resistance in cirrhosis and therefore plays a central role in the etiology of the hepatogenous diabetes.
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PMID:[Hepatogenic diabetes: pathophysiology, therapeutic options and prognosis]. 1044 11

The degree of glucose intolerance and diabetes mellitus in hemochromatosis is closely associated with the stage of iron overload and thus also the stage of the accompanying liver disease. Similar to other liver diseases glucose intolerance due to insulin resistance precedes diabetes mellitus also in hemochromatosis. Insulin resistance is probably caused by alterations of insulin or glucose metabolism in the liver and potentially also in extrahepatic peripheral tissue. Diabetes mellitus is found more frequently in iron overload when compared with other forms of chronic liver disease and cirrhosis, respectively. In advanced iron overload, iron accumulation in pancreatic B-cells deteriorates pancreatic insulin secretion and leads to insulin-dependent diabetes mellitus which cannot be reversed by iron removal. In contrast, early alteration of glucose intolerance and insulin resistance may partially be improved by phlebotomies. Thus, in the future we should aim to diagnose hemochromatosis in early stages which are not associated with diabetes mellitus or liver cirrhosis.
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PMID:[Diabetes mellitus in hemochromatosis]. 1044 12

Cirrhosis is often associated with insulin resistance and glucose intolerance. We evaluated if these alterations are restored by liver transplantation (LT). Glucose tolerance (oral glucose tolerance test [OGTT]), peripheral insulin sensitivity (euglycemic insulin clamp technique), glucose oxidation (indirect calorimetry), nonoxidative glucose disposal, and insulin secretion (hyperglycemic clamp technique) were measured in 6 patients (Group 1) before and 6 months after LT, in 12 patients (Group 2) who underwent LT 6 to 30 months previously, and in 6 healthy individuals (controls). In Group 1, glucose tolerance and insulin sensitivity (3.24 +/- 0.37 mg/kg/min) were normalized after LT (8.6 +/- 0.77 mg/kg/min; P <.0001; P = not significant vs. controls). The improved insulin-mediated glucose uptake was the result of a normalization of nonoxidative glucose disposal. Fasting insulin and C-peptide decreased from 24.6 +/- 3.3 microU/mL and 4.37 +/- 0.46 ng/dL, respectively, to 12.7 +/- 1.9 microU/mL and 2.46 +/- 0.5 ng/dL (controls: 10.0 +/- 3 microU/mL and 1.45 +/- 0.34 ng/dL). The glucose-induced increase of insulin concentration, which was higher before LT, showed a significant reduction, although the first phase of beta-cell secretion remained significantly higher compared with that of controls. All these findings were also confirmed in Group 2. The present data indicate that LT normalizes glucose tolerance and insulin sensitivity in cirrhotic patients through an improvement of both hepatic glucose clearance and the peripheral glucose disposal. The latter effect may be the result of the correction of chronic hyperinsulinemia. An increased first-phase beta-cell insulin secretion in response to high glucose levels persists, suggesting that a memory of previous insulin resistance is maintained.
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PMID:Glucose intolerance and insulin resistance in cirrhosis are normalized after liver transplantation. 1046 70

Seven patients with liver cirrhosis and five healthy subjects were studied over 4 hours after ingestion of a glucose meal to determine whether alterations of hepatic nonoxidative glucose disposal participate in the pathogenesis of impaired glucose tolerance. Hepatic uridyl-diphosphoglucose (UDPG) turnover was calculated from the isotopic enrichment of urinary acetaminophen glucuronide during continuous infusion of 13C-galactose and used as an index of hepatic glycogen synthesis. Patients with cirrhosis had postprandial hyperglycemia and decreased glucose clearance, but hepatic UDPG turnover was not altered (1.84 +/- 0.29 mg/kg fat-free mass min v 1.76 +/- 0.15 in controls, nonsignificant). It is concluded that hepatic postprandial glycogen synthesis is unaltered in patients with advanced cirrhosis, demonstrating important hepatic functional reserve.
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PMID:Hepatic nonoxidative disposal of an oral glucose meal in patients with liver cirrhosis. 1107 33

Impaired glucose tolerance or diabetes mellitus are frequent complications after organ transplantation, and are usually attributed to glucocorticoid and immunosuppressive treatments. Liver transplantation results in total hepatic denervation which may also affect glucoregulation. We therefore evaluated postprandial glucose metabolism in a group of patients with liver cirrhosis before and after orthotopic liver transplantation. Seven patients with liver cirrhosis of various etiologies, 6 patients having received a kidney transplant, and 6 healthy subjects were studied. Their glucose metabolism was evaluated in the basal state and over 4 hours after ingestion of a glucose load with 6.6 (2) H glucose dilution analysis. The patients with liver cirrhosis were studied before, and again 4 weeks (range 2-6) and 38 weeks (range 20-76, n=6) after orthotopic liver transplantation. Basal glucose metabolism was similar in liver and kidney transplant recipients. Impaired glucose tolerance was present in both groups, but postprandial hyperglycemia was exaggerated and lasted longer in liver transplant patients. Postprandial insulinemia was lower in liver transplant recipients, while C-peptide concentrations were comparable to those of kidney transplant recipients, indicating increased insulin clearance. Glucose turnover was not altered in both groups of patients during the initial 3 hours after glucose ingestion, but was higher in liver transplant early after transplantation during the fourth hour. Postprandial hyperglycemia remained unchanged in liver transplant recipients 38 weeks after liver transplantation, despite substantial reduction of immunosuppressive and glucocorticoid doses. We conclude that liver transplant recipients have severe postprandial hyperglycemia which can be attributed to insulinopenia (secondary, at least in part, to increased insulin clearance) and a late increased glucose turnover. These changes may be secondary to hepatic denervation.
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PMID:Mechanisms of postprandial hyperglycemia in liver transplant recipients: comparison of liver transplant patients with kidney transplant patients and healthy controls. 1070 4

Background: Careful nutritional support is required in patients with liver cirrhosis due to their glucose intolerance. To elucidate the mechanism of glucose intolerance in cirrhotics, we measured insulin secretion, whole body insulin sensitivity (SI), and glucose sensitivity (SG) in non-diabetic cirrhotics.Methods: Eight patients with compensated cirrhosis who showed normal fasting blood glucose levels and non-diabetic curves on a 75 g oral glucose tolerance test participated in this study. Four normal volunteers were selected as controls. After an overnight fast, glucose was injected intravenously at 300 mg kg(-1) in 2 min followed 20 min later by intravenous insulin at 0.02 U kg(-1) in 5 min. Sequential blood samples were drawn from 20 min before the glucose injection to 3 h post-injection, and plasma glucose and insulin levels were determined. Plasma glucose and insulin disappearance curves were analyzed using the minimal compartment model, and kinetic parameters, including glucose clearance (KG), insulin secretion, SI and SG, were estimated.Results: KG was slower in cirrhosis than in controls, although not significant (P=0.051). Insulin secretion was not different between the two groups. However, SI was significantly lower in cirrhotics (0.814x10(-4) min(-1) pM(-1); 0.572-1.403x10(-4) min(-1) pM(-1)) as compared to controls (1.643x10(-4) min(-1) pM(-1); 0.678-2.085x10(-4) min(-1) pM(-1)) (P=0.029). SG was also lower in the cirrhosis (0.0154 min(-1); 0.0071-0.0208 min(-1)) than in the control group (0.0211 min(-1); 0.0184-0.0260 min(-1)) (P=0.026).Conclusion: Both SI and SG are already impaired in non-diabetic cirrhotic patients even when KG is minimally delayed and insulin secretion has not yet been affected.
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PMID:Both insulin sensitivity and glucose sensitivity are impaired in patients with non-diabetic liver cirrhosis. 1070 3

Alterations in carbohydrate metabolism associated with liver cirrhosis are characterized by a high serum insulin level and prolonged hyperglycemia on oral glucose tolerance test (OGTT). We measured plasma glucose, immunoreactive insulin (IRI), and C-peptide immunoreactivity (CPR) levels during a 75-g OGTT before and after varices obliteration in 10 cirrhotic patients with gastric varices. After obliteration, the indocyanine green retention rate was decreased and the portal flow velocity was increased. A significant decline in plasma glucose and IRI levels was also noted on OGTT. Moreover, the plasma glucose and IRI levels declined at 90 and 120 min in OGTT while they increased progressively by 120 min before obliteration. The levels of CPR were similar before and after treatment. These results indicate that decreased portal flow due to extrahepatic shunt and consequent impairment of insulin metabolism play a role in glucose intolerance observed in cirrhotic patients and that shunt occlusion improves glucose metabolism.
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PMID:Effects of collateral vessel occlusion on oral glucose tolerance test in liver cirrhosis. 1074 36

The liver plays an important role in the pathogenesis of NIDDM. More importantly to the clinician is the myriad of situations in which the care of the patient with diabetes is affected by or causes an effect to the liver. Patients with underlying diabetes can present with abnormal liver chemistries, which can represent findings as benign as hepatic steatosis or as severe as cirrhosis of the liver. The medications used to treat diabetes can be potent hepatotoxins. Several primary liver diseases are associated with increased risk of the development of diabetes. Epidemiologically, there seems to be a correlation between diabetes mellitus, the most common endocrinologic disease, and hepatitis C, the leading cause of chronic liver disease in the United States. In the management of end-stage liver disease, both cirrhosis and orthotopic liver transplantation promote glucose intolerance and diabetes in a number of patients through various mechanisms including insulin resistance and impaired insulin secretion. These relationships highlight both the importance of the liver as an endocrine organ and the multisystem aspects of the patient with diabetes mellitus.
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PMID:Liver disease and diabetes mellitus. 1132 35

Although glucose intolerance and/or overt diabetes are common in cirrhotic subjects, the mechanism(s) that lead to post-prandial hyperglycemia in cirrhosis are not entirely known. To this aim, we measured whole-body rates of glucose appearance (Ra) and of disappearance (Rd) in cirrhotic-diabetic subjects and in controls, before and following a 4-hr administration of a mixed meal. In the post-prandial phase, endogenous and dietary glucose Ra, as well as first-pass splanchnic uptake of dietary glucose, were measured using a double (ie oral and intravenous) glucose tracer technique. In the fasting state, the cirrhotic patients were hyperglycemic (12.0 +/- 1.4 vs 4.4 +/- 0.2 mmol/l in controls, p < 0.001), had a higher glucose Ra (17.0 +/- 2.7 vs 10.2 +/- 0.5 micromol x kg(-1) x min(-1), p < 0.05) and a lower clearance rate (1.51 +/- 0.19 vs 2.32 +/- 0.06 ml x kg x min, p < 0.02). Following the meal, plasma glucose increased to greater values (p < 0.002) in the patients (to 16.8 +/- 2 mmol/l, mean values of the last 40 min) than in the controls (to 7.2 +/- 0.4 mmol/l). Insulin increased in both groups but it was 35% lower (p > 0.05) in the patients. Post-prandial total glucose Ra (cirrhotics: 21.3 +/- 2.6; controls: 19.2 +/- 1.4 pmol x kg(-1) x min(-1)), endogenous Ra (cirrhotics: 7.3 +/- 1.5; controls: 7.0 +/- 1.3 micromol x kg(-1) x min(-1)) and first-pass splanchnic uptake of dietary glucose (cirrhotics: 9.8 +/- 2.6; controls: 11.5 +/- 1.6 micromol x kg x min(-1)), were not different between the 2 groups, whereas glucose clearance remained lower (p<0.001) in the patients (1.31 +/- 0.25 ml x kg(-1) x min)-1)) than in the controls (2.72 +/- 0.26). These data demonstrate that, in cirrhotic-diabetic patients, post-pran-dial hyperglycemia is not due to a reduced extraction of dietary glucose nor to an increased endogenous production, but rather to a defect in peripheral glucose clearance, secondary to either insulin-resistance and/or relative insulin deficiency.
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PMID:Glucose kinetics and splanchnic uptake following mixed meal ingestion in cirrhotic-diabetic subjects. 1185 63

Non-alcoholic steatohepatitis (NASH) is a disease of emerging identity and importance. It is frequently associated with obesity, especially visceral fat, and is intimately related to fatty liver and markers of the insulin resistance syndrome. Both the prevalence and the severity of liver steatosis are related to body mass index, waist circumference, hyperinsulinaemia, hypertriglyceridaemia and impaired glucose tolerance or type 2 diabetes. The identification of obese patients who may progress from steatosis to NASH and from NASH to fibrosis/cirrhosis is an important clinical challenge. Substantial weight loss is accompanied by a marked attenuation of insulin resistance and related metabolic syndrome and, concomitantly, by a remarkable regression of liver steatosis in most patients, although increased inflammation may be detected in some subjects. Thus, NASH may be considered as another disease of affluence, as is the insulin resistance syndrome, and perhaps being part of it, especially in obese patients.
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PMID:Obesity and liver disease. 1246 16


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