Mechanisms of hyperinsulinaemia in Child’s disease grade B liver cirrhosis investigated in free living conditions

Aims: Human liver cirrhosis is commonly associated with increased fasting and glucose induced insulin concentrations. However, whether the hyperinsulinaemia is a consequence of increased pancreatic insulin secretion, decreased hepatic insulin removal, or impaired feedback regulation of insulin secre... Full description

Aims: Human liver cirrhosis is commonly associated with increased fasting and glucose induced insulin concentrations. However, whether the hyperinsulinaemia is a consequence of increased pancreatic insulin secretion, decreased hepatic insulin removal, or impaired feedback regulation of insulin secretion is still doubtful. To investigate these issues, insulin secretion—during 24 hours of standardised living conditions—insulin sensitivity, and hepatic insulin extraction were assessed in cirrhotic patients compared with matched healthy subjects. Patients: Nine Child’s disease grade B cirrhotic patients and seven healthy volunteers, participated in the study. The subjects were studied on two separate days, one for the assessment of insulin secretion during a standardised 24 hour life period (calorimetric chamber), and one for the determination of insulin sensitivity. Methods: Insulin secretion rates were reconstructed from plasma C peptide concentrations by deconvolution, and indices of β cell function were derived using a mathematical model describing the functional dependence of insulin secretion on plasma glucose concentrations. Insulin sensitivity was determined using the euglycaemic hyperinsulinaemic clamp technique. Results: Cirrhotic patients showed a marked hypersecretory response, both in absolute terms (mean (SEM) 295 (53) versus 138 (11) nmol/m2, p