Impact of insulin antibodies on insulin aspart pharmacokinetics and pharmacodynamics after 12-week treatment with multiple daily injections of biphasic insulin aspart 30 in patients with type 1 diabetes

Objective: This study aimed to evaluate the impact of insulin antibodies on insulin aspart pharmacokinetics and pharmacodynamics after 12-week multiple daily injections of biphasic insulin aspart 30 (30% fast-acting and 70% protamine-crystallised insulin aspart, BIAsp30) in patients with type 1 diabetes. Methods: Twenty-three patients (8 women. 15 men) aged 44.8 (20.6-62.5) years (median and range) with diabetes duration of 19.5 (1.6-44.6) years and haemoglobin (Hb)A(1C) of 9.2% (8.1-12.3%) participated in the study, which consisted of 7.2-week treatment with multiple injections of BIAsp30. At the end of the treatment period, all patients attended two 24-h profile days 1 week apart for pharmacokinetic and pharmacodynamic assessments. HbA(1C) and insulin antibodies were also determined. Results: Patients were stratified into two groups depending on whether the level of insulin binding to insulin antibodies was below or above 75%> (moderate vs high (%, median and range): 62 (15-74) vs 80 (75-89)). High levels of insulin antibodies resulted in about threefold increase in AUC((0-24 h)) (the area under the concentration-time curve during 24 h) for total insulin aspart (analysis of variance, P < 0.05). The differences in free insulin aspart pharmacokinetics, insulin pharmacodynamics and HbA(1C) were not statistically significant between patients with different levels of insulin antibodies. Total daily insulin dosage was significantly lower in patients with high than moderate levels of insulin antibodies. Conclusions: In type 1 diabetic patients, high levels of circulating insulin antibodies result in elevated total, but not free, insulin aspart profiles. Consistent with the finding of similar insulin pharmacodynamics, the long-term glycaemic control is not significantly different between patients with different levels of insulin antibodies.