Glucose intolerance and insulin resistance in cirrhosis are normalized after liver transplantation

Abstract

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 F .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 U/mL and 4.37 ؎ 0.46 ng/dL, respectively, to 12.7 ؎ 1.9 U/mL and 2.46 ؎ 0.5 ng/dL (controls: 10.0 ؎ 3 U/mL and 1.45 ؎ 0.34 ng/dL). The glucoseinduced increase of insulin concentration, which was higher before LT, showed a significant reduction, although the first phase of ␤-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 ␤-cell insulin secretion in response to high glucose levels persists, suggesting that a memory of previous insulin resistance is maintained. (HEPATOLOGY 1999;30:649-654.)

Study of prevalence and pattern of peripheral neuropathy in patients with liver cirrhosis

“…The prevalence of DM in cirrhosis has been reported from 20-60%. [16][17][18][19] In our study, the prevalence of DM was 15.3%. Apart from a higher prevalence in cirrhotic, DM is also associated with more incidence of hypoglycemia, especially with oral hypoglycemic agents (OHA) and hence insulin is recommended for its control.…”

Effect of hepatic denervation on peripheral insulin sensitivity in conscious dogs

“…This peripheral insulin resistance is related to a defect in nonoxidative glucose disposal, i.e., muscle glycogen storage (22,29,37,38). On the other hand, insulin sensitivity was restored to normal in nondiabetic cirrhotic individuals that underwent hepatic transplantation and thus had little or no extrinsic liver innervation (22,32). These findings imply that the extrinsic hepatic innervation is not essential for an effect of the liver on insulin-stimulated glucose uptake in nonhepatic tissues.…”

“…In humans, cirrhosis of the liver, a disorder associated with a high incidence of autonomic (particularly parasympathetic) dysfunction (12), is also associated with peripheral insulin resistance (22,29,32,37,38). This peripheral insulin resistance is related to a defect in nonoxidative glucose disposal, i.e., muscle glycogen storage (22,29,37,38).…”

Dextrose in the banked blood products does not seem to affect the blood glucose levels in patients undergoing liver transplantation

“…Impaired gluconeogenesis and glucogenolysis, glucose intolerance or insulin resistance may occur in patients with end stage liver disease, predisposing these patients to fasting hypoglycemia or postprandial hyperglycemia [13][14][15][16][17] . In view of the complexity of glucose regulation and disease-specific anesthetic management [18] , our study primarily focuses on pediatric biliary atresia patients, who have had Kasai operation.…”