Plasma C-peptide and insulin responses to intravenous glucagon stimulation in idiopathic haemochromatosis

Beta-cell reserve was investigated in 15 patients with proven idiopathic haemochromatosis (IHC) (7 normoglycaemic haemochromatotic patients, 4 non-insulin-requiring diabetics and 4 insulin-requiring diabetics) by measuring the response of plasma C-peptide, insulin and glucose to a 2 mg intravenous bolus of glucagon, and compared with that in 5 lean normal subjects. The corresponding C-peptide/insulin molar ratios were also calculated. Despite the significant fasting hyperglycaemia in the insulin-requiring haemochromatotic diabetics, mean fasting C-peptide concentrations were similar in all four groups. However, after glucagon stimulation the C-peptide response was significantly reduced in the insulin-requiring group over the whole period of observation. A trend in insulin response to glucagon was noted, with the highest values in the non-diabetic haemochromatotic patients, followed by the controls and then by the non-insulin-requiring diabetics, although there were no significant differences. In contrast, C-peptide/insulin molar ratios after glucagon were significantly reduced in the normoglycaemic IHC group. These results suggest the presence of at least two abnormalities of insulin metabolism in IHC--a progressive reduction in beta-cell function and a diminished rate of removal of insulin by the liver.