title: The alteration of aspart insulin pharmacodynamics when mixed with detemir insulin.
abstract: OBJECTIVE
  Mixing rapid acting insulin analogs with detemir insulin to minimize daily injections has been adopted as a common regimen, especially for some children with type 1 diabetes, despite the manufacturing company's caution against mixing these analogs in the same syringe. The effect of this practice on the pharmacodynamics (PD) of rapid-acting insulin has not been widely studied. This crossover, randomized study was undertaken to determine whether mixing aspart with detemir insulin has an adverse effect on the early glucodynamic action of rapid-acting insulin analog in humans.
  
  
  METHODS
  Eight adolescents with type 1 diabetes (age 17.3 ± 0.6 years and A1C 7.3 ± 0.3%) had two euglycemic glucose clamps during which 0.2 units/kg aspart and 0.4 units/kg detemir insulin were injected either as a separate or single mixed injection in random order.
  
  
  RESULTS
  Mixing the two insulins diminished the peak and overall early aspart insulin action with significantly lower maximum glucose infusion rate (GIR(max) separate 6.1 ± 0.7 mg/kg/min vs. mix 4.5 ± 0.5 mg/kg/min; P = 0.03) values and the area under curve for GIR during the first 3 h of the insulin action study (separate 757 ± 105 mg/kg vs. mix 491 ± 66 mg/kg; P = 0.04).
  
  
  CONCLUSIONS
  These data demonstrate that mixing aspart with detemir insulin markedly lowers the early PD action of aspart and prolongs its time-action profile as compared with the separate injection of these analogs. These changes in insulin PD should be weighed against the added convenience of mixing when considering such unlicensed use of these insulins in youth with type 1 diabetes.
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Yale School of Medicine, New Haven, Connecticut, USA. eda.cengiz@yale.edu
authors.forename: Eda
authors.initials: E
authors.lastname: Cengiz
authors.forename: Karena L
authors.initials: KL
authors.lastname: Swan
authors.forename: William V
authors.initials: WV
authors.lastname: Tamborlane
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Sherr
authors.forename: Melody
authors.initials: M
authors.lastname: Martin
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Weinzimer
mesh_terms: D000293:Adolescent; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D007260:Infusion Pumps; D061267:Insulin Aspart / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000069057:Insulin Detemir; D049528:Insulin, Long-Acting / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D013997:Time Factors; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D000069057:Insulin Detemir; D061267:Insulin Aspart; D005947:Glucose