title: Improved pharmacokinetic and pharmacodynamic profiles of insulin analogues using InsuPatch, a local heating device.
abstract: BACKGROUND
  Previous studies have shown that heating the insulin injection site may accelerate insulin absorption. We investigated the pharmacological profile of insulin administered with InsuPatch, a local skin-heating device.
  
  
  METHODS
  In this randomized, crossover study carried out in 56 subjects with type 1 diabetes treated with insulin pump [mean age 32 ± 13.5 years; 23 women; HbA1c :7.8 ± 0.9% (62 ± 10 mmol/mol) (mean+/-standard deviation)]. Euglycemic glucose clamps were performed after administration of 0.15 units/kg of short-acting insulin analogues. Each subject underwent three clamp procedures: two with the InsuPatch device (day 1 and day 3) and one without the device (day 1 control). The primary endpoints were the following: (1) the change in the area under the curve (AUC) of insulin during the first 60 min post-insulin bolus on day 1 with the InsuPatch device versus day 1 control and (2) parameters to assess the safety of using the device.
  
  
  RESULTS
  The area under the curve of insulin during the initial 60 min (insulin AUC(0-60)) after insulin bolus was increased by 29.7 ± 7% on day 1 InsuPatch versus day 1 control (p < 0.01). Maximal post-insulin bolus concentration was 57 mU/L on day 1 InsuPatch versus 47.6 mU/L on day 1 control (p < 0.01). On day 3 InsuPatch, insulin AUC(0-60) was increased by 27.9 ± 72% versus day 1 InsuPatch (p < 0.01). Maximal insulin concentration was 70.4 mU/L versus 57 mU/L, respectively (p = 0.05).
  
  
  CONCLUSIONS
  The use of the heating device upon administration of short-acting insulin analogues in pump-treated type 1 diabetic patients was found to enhance insulin absorption. This heating device may therefore serve to achieve better meal insulin coverage.
authors.affiliation: Diabetes Unit, E. Wolfson Medical Center, Holon, Israel.
authors.forename: Zohar
authors.initials: Z
authors.lastname: Landau
authors.forename: David
authors.initials: D
authors.lastname: Klonoff
authors.forename: Irina
authors.initials: I
authors.lastname: Nayberg
authors.forename: Dmitry
authors.initials: D
authors.lastname: Feldman
authors.forename: Shmuel Boris
authors.initials: SB
authors.lastname: Levit
authors.forename: Dan
authors.initials: D
authors.lastname: Lender
authors.forename: Ofri
authors.initials: O
authors.lastname: Mosenzon
authors.forename: Itamar
authors.initials: I
authors.lastname: Raz
authors.forename: Julio
authors.initials: J
authors.lastname: Wainstein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D016503:Drug Delivery Systems / Q000009:adverse effects; D005260:Female; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000032:analysis; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D061267:Insulin Aspart / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D007332:Insulin Infusion Systems; D061268:Insulin Lispro / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012881:Skin Temperature; D065566:Subcutaneous Absorption; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D061267:Insulin Aspart; D061268:Insulin Lispro; C517652:hemoglobin A1c protein, human
keywords: insulin; pharmacodynamic; pharmacokinetic