Glucoregulation in acute liver failure

Five patients with fatal acute liver failure, given 5 g h-1 of glucose for the previous 12 h, were investigated by the hyper- and euglycaemic glucose 'clamp' technique, and the results compared with reported control values. Initial average blood glucose concentration was normal (6.0 mmol l-1, range 5.0-8.8). Plasma insulin and C-peptide concentrations were increased about tenfold (1450 pmol l-1, range 330-4021, and 3000 pmol l-1, range 670-7650, respectively). The whole body glucose metabolic rate was decreased to about half control values (21 mumol min-1 kg-1, range 6-28) and the insulin sensitivity of the glucose metabolism was decreased to about 15% (9.4 m3 min-1 kg-1, range 3.6-14.4). The calculated metabolic clearance of insulin was normal (520 ml min-1 (m2)-1, range 305-1027) and the calculated systemic delivery rate of insulin was about sixfold increased (1135 pmol min-1 (m2)-1, range 474-2010). The initial glucagon concentrations were fifty-fold increased (550 pmol 1, range 72-1309) and not suppressible by glucose and insulin. The patients thus exhibited pronounced insulin insensitivity and hyperinsulinaemia, attributable primarily to pancreatic hypersecretion. The reason for the relation between, and the pathogenetic importance of, these findings is not known.