The plasma C-peptide and insulin responses to stimulation with intravenous glucagon and a mixed meal in well-controlled type 2 (non-insulin-dependent) diabetes mellitus: dependency on acutely established hyperglycaemia.

Abstract

The dose-response relationships between acutely established hyperglycaemia and the plasma C-peptide and insulin responses to i.v. stimulation with 1 mg of glucagon and a standard mixed meal were investigated in 10 patients with well-controlled Type 2 (non-insulin dependent) diabetes mellitus. Hyperglycaemia was maintained for 90 min before stimulation using a hyperglycaemic clamp technique. Each test was performed on different steady state blood glucose levels of approximately 6 mmol/l, approximately 12 mmol/l, and approximately 20 mmol/l, respectively. The plasma C-peptide and insulin responses after glucagon and the meal were potentiated markedly at each level of prestimulatory hyperglycaemia. After glucagon injection, the relative glucose potentiation of the insulin response was significantly higher than the relative glucose potentiation of the C-peptide response at each level of hyperglycaemia (p less than 0.01). This difference may be explained by a higher fractional hepatic removal of insulin at normoglycaemia, since the molar ratio between the incremental C-peptide and insulin responses after glucagon stimulation was higher at prestimulatory normoglycaemia (4.85 (3.65-12.05] than at the prestimulatory blood glucose concentrations approximately 12 mmol/l (2.41 (2.05-4.09] (p less than 0.01) and approximately 20 mmol/l (2.24 (1.37-3.62] (p less than 0.01). In conclusion, the islet B-cell responses to glucagon and a standard mixed meal are potentiated to a high degree by acutely established prestimulatory hyperglycaemia in patients with well-controlled Type 2 diabetes. Acute prestimulatory hyperglycaemia is also associated with a markedly reduced incremental C-peptide/insulin ratio after glucagon stimulation in such patients.(ABSTRACT TRUNCATED AT 250 WORDS)