Lack of glucagon response in glucose counter-regulation in type 1 (insulin-dependent) diabetics: absence of recovery after prolonged optimal insulin therapy.

Mild hypoglycaemia was induced using an artificial pancreas in five normal subjects (from 5.00 +/- 0.15 to 2.83 +/- 0.15 mmol/l) by infusing 28 mU/m2 per min soluble insulin for 60 min. Six Type 1 (insulin-dependent) diabetic patients were stabilized for 14h using an artificial pancreas. They were then rendered hypoglycaemic (from 4.94 +/- 0.09 to 2.89 +/- 0.11 mmol/l) by infusing 28 mU/m2 per min plus 16 +/- 3.8 mU/min insulin for 60 min. Before the study, the diabetic patients were in optimal blood glucose control (mean blood glucose 6.72 +/- 0.11 mmol/l over the previous 14-20 days; HbA1 8.3 +/- 0.1%). During the insulin infusion test, blood glucose decrement was slower in the diabetic patients than in the control subjects. The blood glucose nadir was delayed in the diabetics until 75 min compared with 55 min in the control subjects. Blood glucose recovery rate in the diabetic subjects was severely impaired. In Type 1 diabetes, the counter-regulatory hormonal response to insulin induced hypoglycaemia is similar to that of non-diabetics, except for that of glucagon, the blunted response of which is not reversed by prolonged optimisation of blood glucose control. This impaired response of the A cell does not seem to be a consequence of insulin deficiency.