Insulin glargine metabolite 21^A-Gly-human insulin (M1) is the principal component circulating in the plasma of young children with type 1 diabetes: Results from the PRESCHOOL study

Background and Aims: Insulin glargine metabolite 21A-Gly-human insulin (M1) is the principal component circulating in plasma of adults with type 1 diabetes. The objective of this study was to confirm this finding in young children and to rule out accumulation of parent insulin glargine. Design and Methods: Children with type 1 diabetes from the PRESCHOOL study, aged 2-6 yr, were treated with insulin glargine for 24 wk (n = 62). Blood samples were drawn at weeks 1, 2, and 4 approximately 24 h after the last dose and analyzed for glargine, M1, and Thr30B-des-M1 (M2) using immunoaffinity purification and liquid chromatography with mass spectrometry. The lower limit of quantification was 33 pmol/L for all analytes. Results: M1 was the principal active component circulating in plasma. Mean (SD) plasma Ctrough values were 101 (138), 80 (122), and 79 (102) pmol/L following glargine doses of 0.33 (0.02), 0.34 (0.02), and 0.38 (0.03) U/kg at weeks 1, 2, and 4, respectively. Parent insulin glargine and M2 concentrations were below the level of quantification. These results are in line with those observed in adults and indicate no accumulation of the parent compound in this patient population. Conclusion: In young children with type 1 diabetes, the principal component circulating in plasma after subcutaneous injection of insulin glargine is M1, the pharmacologically active component. No accumulation of the parent insulin glargine was observed. These data provide additional evidence on the safety profile of insulin glargine in young children (Clinical trial identifier: NCT00993473).