title: Faster in and faster out: accelerating insulin absorption and action by insulin infusion site warming.
abstract: OBJECTIVE
  This study was undertaken to investigate the effect of an insulin infusion site warming device, the InsuPatch(40)(™) (IP(40)) (InsuLine Medical Ltd., Petach-Tikvah, Israel), on insulin aspart pharmacodynamics (PD) and pharmacokinetics (PK) in adolescents with type 1 diabetes.
  
  
  METHODS
  Seventeen subjects with type 1 diabetes (age, 15±1 years; hemoglobin A1c, 7.5±0.2% [58±2.2 mmol/mol]) underwent two euglycemic clamps performed on separate mornings with and without IP(40) activation with warming temperature at 40°C. On both days, the basal infusion was suspended, and glucose levels were maintained between 90 and 100 mg/dL by a variable rate dextrose infusion for up to 5 h after a 0.2 U/kg bolus of insulin aspart.
  
  
  RESULTS
  Time to peak insulin action and time to half-maximal action occurred earlier with a greater early glucodynamic effect (area under the curve [AUC] for glucose infusion rate from 0 to 30 min) with IP(40) than without the IP(40), whereas the AUC for the time-action profile and the peak action did not differ with and without infusion site warming. PK parameters were in agreement with PD parameters, namely, a significantly earlier time to reach the maximum increment in insulin concentrations and greater early bioavailability (AUC for the change in insulin concentration from 0 to 30 min) with the IP(40). The tail of the plasma insulin response curve was also shortened with infusion site warming, with the time to reach baseline insulin concentration occurring significantly earlier (P=0.04).
  
  
  CONCLUSIONS
  Our data demonstrate that skin warming around the infusion site to 40°C with the IP(40) is an effective means to accelerate absorption and action of rapid-acting insulin. These improvements in time-action responses have the potential to enhance the performance of open- and closed-loop insulin delivery systems.
authors.affiliation: Division of Pediatric Endocrinology, Yale School of Medicine , New Haven, Connecticut.
authors.forename: Eda
authors.initials: E
authors.lastname: Cengiz
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Weinzimer
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Sherr
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Tichy
authors.forename: Lori
authors.initials: L
authors.lastname: Carria
authors.forename: Darryll
authors.initials: D
authors.lastname: Cappiello
authors.forename: Amy
authors.initials: A
authors.lastname: Steffen
authors.forename: William V
authors.initials: WV
authors.lastname: Tamborlane
mesh_terms: D000042:Absorption; D000293:Adolescent; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics*; D061267:Insulin Aspart / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics*; D007332:Insulin Infusion Systems; D008297:Male; D012039:Regional Blood Flow; D012881:Skin Temperature; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D061267:Insulin Aspart; C517652:hemoglobin A1c protein, human