Physiological responses during hypoglycaemia induced by regular human insulin or a novel human analogue, insulin glargine

Aims: Glargine, a product of recombinant technology, has different structur al and physico-chemical properties compared with native human insulin. We d etermined whether such differences are associated with alterations in the r esponses to hypoglycaemia induced by glargine. Methods: Nineteen adults (six healthy and 13 with type 1 diabetes) underwen t a 5-h hyperinsulinaemic (2 mU/kg/min(-1)) stepped hypoglycaemic clamps (h ourly targets of 4.7, 4.2, 3.6, 3.1 and 2.5 mmol/l, respectively) on two oc casions using intravenous infusion of regular human insulin or glargine, in random sequence. Hypoglycaemic symptoms, counter-regulatory hormones and g lucose disposal rates were assessed at intervals throughout the clamps. A 1 -week 'wash out' period was observed between studies. Results: The peak total symptoms scores (mean +/- s.e.m.) at nadir blood gl ucose (2.5 mmol/l) were 18.83 +/- 2.68 (healthy) and 17.46 +/- 3.62 (diabet ic) during regular insulin, and 18.50 +/- 3.20 (healthy) and 19.08 +/- 3.83 (diabetic) during glargine infusion. The peak epinephrine levels during hy poglycaemia were 767.8 +/- 140.4 pg/ml (regular insulin) and 608.8 +/- 129. 9 pg/ml (glargine) among healthy subjects, and 332.5 +/- 54.8 pg/ml (regula r insulin) and 321.8 +/- 67.4 pg/ml (glargine) in diabetic patients. Diabet ic patients had blunted glucagon responses during hypoglycaemia with either insulin. Both insulins also elicited similar rates of glucose disposal. Conclusions: We conclude that insulin glargine and regular human insulin el icit comparable symptomatic and counter-regulatory hormonal responses durin g hypoglycaemia in healthy or diabetic subjects, and induce similar rates o f glucose disposal. Since glargine is designed for subcutaneous (s.c.) use, it is possible (though unlikely) that our findings obtained using an intra venous protocol could differ from responses to hypoglycaemia induced by the s.c. route.