Pharmacokinetics of diluted (U20) insulin aspart compared with standard (U100) in children aged 3–6 years with type 1 diabetes during closed-loop insulin delivery: a randomised clinical trial
MetadataShow full item record
Ruan, Y., Elleri, D., Allen, J., Tauschmann, M., Wilinska, M., Dunger, D., & Hovorka, R. (2014). Pharmacokinetics of diluted (U20) insulin aspart compared with standard (U100) in children aged 3–6 years with type 1 diabetes during closed-loop insulin delivery: a randomised clinical trial. Diabetologia, 58 687-690. https://doi.org/10.1007/s00125-014-3483-6
Aims/hypothesis The aim of this study was to compare the pharmacokinetics of two different concentrations of insulin aspart (B28Asp human insulin) in children aged 3–6 years with type 1 diabetes. Methods Young children with type 1 diabetes underwent an open-label, randomised, two-period crossover study in a clinical research facility, 2–6 weeks apart. In random order, diluted (1:5 dilution with saline [154 mmol/l NaCl]; 20 U/ml) or standard strength (100 U/ml) insulin aspart was administered via an insulin pump as a meal bolus and then overnight by closed-loop insulin delivery as determined by a model predictive algorithm. Plasma insulin was measured every 30–60 min from 17:00 hours on day 1 to 8:00 hours on day 2. We measured the time-to-peak insulin concentration (tmax), insulin metabolic clearance rate (MCRI) and background insulin concentration (insc) using compartmental modelling. Results Eleven children (six male; age range 3.75–6.96 years, HbA1c 7.6%±1.3% [60±14 mmol/mol], BMI standard deviation score 1.0±0.8, duration of diabetes 2.2±1.0 years, total daily dose 12.9 [10.6–16.5] U, fasting C-peptide concentration 5 [5–17.1] pmol/l; mean±SD or median [interquartile range]) participated in the study. No differences between standard and diluted insulin were observed in terms of tmax (59.2±14.4 vs 61.6±8.7) min for standard vs diluted, p=0.59; MCRI (1.98×10−2±0.99×10−2 vs 1.89×10−2±0.82×10−2 1/kg/min, p=0.47), and insc (34 [1–72] vs 23 [3–65] pmol/l, p=0.66). However, tmax showed less intersubject variability following administration of diluted aspart (SD 14.4 vs 8.7 min, p=0.047). Conclusions/interpretation Diluting insulin aspart does not change its pharmacokinetics. However, it may result in less variable absorption and could be used in young children with type 1 diabetes undergoing closed-loop insulin delivery. Trial registration: Clinicaltrials.gov NCT01557634 Funding: Funding was provided by the JDRF, 7th Framework Programme of the European Union,Wellcome Trust Strategic Award and the National Institute for Health Research Cambridge Biomedical Research Centre.
Aspart, Insulin absorption, Insulin concentration, Pharmacokinetics, Rapid-acting insulin, Type 1 diabetes, Young children
Funding was provided by the JDRF (grant number 22-2011- 668), 7th Framework Programme of the European Union (Spidiman project; grant agreement number 305343), Wellcome Trust Strategic Award (100574/Z/12/Z) and the National Institute for Health Research Cambridge Biomedical Research Centre.
Wellcome Trust (100574/Z/12/Z)
EC FP7 CP (305343)
External DOI: https://doi.org/10.1007/s00125-014-3483-6
This record's URL: https://www.repository.cam.ac.uk/handle/1810/246832
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/
Recommended or similar items
The following licence files are associated with this item: