To examine the contributions of hypersecretion and decreased insulin clearance to the hyperinsulinaemia of cirrhosis, insulin secretion was calculated over the day from serum C-peptide concentrations and C-peptide metabolic clearance rate. The latter was measured during infusions of recombinant human C-peptide. In cirrhotic patients (n = 9) insulin secretion rate was twice that of normal control subjects (n = 10), both in the basal state [02.00-07.00 hours, 15.7 +/- 2.1 (mean +/- SEM) nmol/h (2.6 +/- 0.4 units/h) versus 7.0 +/- 0.9 nmol/h (1.2 +/- 0.2 units/h), P < 0.002] and over 24 h [787 +/- 93 nmol (132 +/- 16 units) versus 346 +/- 34 nmol (58 +/- 6 units), P < 0.001]. However, the area under the serum insulin concentration curve was approximately six times greater in the cirrhotic patients (24 h basal, 6.3 +/- 1.0 versus 1.1 +/- 0.3 nmol l-1 h, P < 0.001; 24 h total, 21.7 +/- 3.2 versus 3.7 +/- 0.7 nmol l-1 h, P < 0.001). Thus, despite impairment of insulin clearance there is continuing hypersecretion of insulin in cirrhosis. 2. The relationship of carbohydrate and lipid metabolism with insulin secretion was assessed. In cirrhotic patients, 24 h blood glucose profiles showed a worsening of glucose tolerance over breakfast, despite greater insulin secretion compared with other meals, suggesting that the insulin insensitivity of cirrhosis is worse at this time. 3. Cirrhotic patients showed impaired suppression of blood glycerol levels after meals but normal suppression of serum non-esterified fatty acid concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
