Glucagon, in the setting of absolute or relative insulin deficiency, is thought to contribute to the pathogenesis of hyperglycaemia in diabetes, but much of the evidence is extrapolated from short-term studies to the long-term condition. In the present issue of Clinical Science , Li and co-workers report that infusion of glucagon raised fasting plasma glucose concentrations and impaired glucose tolerance over 4 weeks in mice, thus demonstrating a sustained glycaemic effect of hyperglucagonaemia. Nonetheless, compelling evidence that glucagon contributes to the pathogenesis of hyperglycaemia in diabetes awaits long-term selective reduction of glucagon secretion or action in humans.
1. To test the hypothesis that patients with insulin-dependent diabetes mellitus perceive the symptoms of hypoglycaemia to a greater extent when they are in the standing position than when they are in the lying position, we assessed symptoms of hypoglycaemia, as well as heart rate and plasma noradrenaline and adrenaline concentrations, in both positions during hyperinsulinaemic glucose clamps on three occasions in seven patients. 2. Plasma glucose concentrations were clamped at 5.0 mmol/l (90 mg/dl) and 5.0 mmol/l on one occasion, at 5.0 mmol/l and 3.9 mmol/l (70 mg/dl) on another occasion, and at 5.0 mmol/l and 2.8 mmol/l (50 mg/dl) on yet another occasion. 3. During euglycaemia there was no effect of position on the symptom panels used to assess the symptomatic response to hypoglycaemia. However, at the plasma glucose concentration of 2.8 mmol/l, total ( P < 0.003) and neurogenic ( P < 0.005), but not neuroglycopenic, hypoglycaemic symptom scores were higher with the patients in the standing than in the lying position. Increments in total hypoglycaemic symptom scores, over those during the corresponding euglycaemic phase, were 5 ± 2 in the lying position and 11 ± 2 in the standing position (means ± sem , P < 0.01). 4. Thus patients with insulin-dependent diabetes mellitus perceive symptoms of hypoglycaemia to a greater extent when they are in the standing position than when they are in the lying position because of enhanced neurogenic symptoms.