Counter-regulatory hormone responses to spontaneous hypoglycaemia during treatment with insulin Aspart or human soluble insulin: a double-blinded randomized cross-over study

Aims:  To compare insulin Aspart and human insulin with respect to glycaemic control, hypoglycaemic frequency and counter-regulatory responses to spontaneous hypoglycaemia. Methods:  Glycaemic control, hypoglycaemic frequency, p-insulin concentrations, insulin dosages and patients’ satisfaction were examined in a randomized, double-blinded cross-over study for two periods of 8 weeks. Sixteen patients with type 1 diabetes were subjected to three daily injections of human soluble insulin or Aspart in addition to Neutral Protamine Hagedorn (NPH) insulin twice daily. Each intervention period was followed by hospitalization where episodes of spontaneous hypoglycaemia and counter-regulatory hormone responses were evaluated from frequently obtained blood samples. Results:  No difference between soluble insulin and insulin Aspart was found regarding HbA1c (7.0 ± 0.2 vs. 7.0 ± 0.2%, ns), hypoglycaemic frequency (1.1 ± 0.2 vs. 0.9 ± 0.1 events per patient per week, ns), nocturnal hypoglycaemia, severe hypoglycaemic events, dosages of bolus insulin (31.8 ± 0.4 vs. 30.0 ± 0.6 IU day−1, ns), or NPH insulin (26.7 ± 1.8 vs. 26.0 ± 1.7 IU day−1, ns) or in patients satisfaction (ns). Modest differences existed in the counter-regulatory responses regarding growth hormone, glucagon and ghrelin whereas no differences were found in relation to free fatty acid, cortisol, insulin-like growth factor (IGF)-I, IGF-II and IGF-binding proteins 1 and 2. Treatment with insulin Aspart resulted in well-defined peaks in serum insulin concentrations as compared with more blunted insulin peaks using human soluble insulin. Conclusion:  Although insulin Aspart treatment was associated with clear postprandial insulin peaks, no improvement in glycaemic control was obtained and no difference in the hypoglycaemic frequency was observed. However, insulin Aspart elicited a slightly different physiological response to spontaneous hypoglycaemia compared with human insulin.