title: Effect of a local heating device on insulin and glucose pharmacokinetic profiles in an open-label, randomized, two-period, one-way crossover study in patients with type 1 diabetes using continuous subcutaneous insulin infusion.
abstract: BACKGROUND
  Reducing postprandial hyperglycemia and hypoglycemia is a major challenge in the treatment of patients with diabetes. Studies suggest that heating the insulin injection site may accelerate insulin absorption. InsuPatch (InsuLine Medical Ltd., Petach-Tikva, Israel) is a device intended to accelerate subcutaneous insulin delivery using an insulin pump by locally warming the infusion site.
  
  
  OBJECTIVE
  The aim of this study was to assess the effect of the InsuPatch device on the pharmacokinetics of short-acting insulin analogues and on postprandial glycemia.
  
  
  METHODS
  This was an open-label, randomized, 2-period, 1-way crossover study using a meal tolerance test (MTT) protocol in subjects with type 1 diabetes mellitus aged 18 to 65 years with glycosylated hemoglobin (HbA(1c)) of 6% to 12%, who were using continuous subcutaneous insulin infusion (CSII) therapy (insulin lispro or aspart). A bolus of insulin 0.15 U/kg was delivered immediately before a standardized liquid meal. The effect of the device on insulin absorption and postprandial glucose excursions was tested by measuring blood glucose and insulin concentration profiles with and without the operation of the device. Adverse events (AEs) were monitored during the 2 study visits. The infusion site was visually inspected at the end of each study. All AEs were recorded in the case-report form.
  
  
  RESULTS
  The MTT protocol was performed in 17 white patients with type 1 diabetes (sex, male/female, 7/10; mean age, 31.8 years [range, 18-53 years]; mean body mass index, 25.6 kg/m(2) [range, 20.0-39.4 kg/m(2)]; and mean HbA(1c), 7.1% [range, 5.8%-9.3%]). The mean (SD) postprandial glucose excursion AUC at 120 minutes after the meal was significantly reduced in the group that used the device compared with the group that did not (104 [65] vs 155 [56] mg/dL/h; P < 0.005). Plasma insulin was measured randomly in 9 of the 17 subjects. Use of the device was associated with significant reductions in mean (SD) T(max) (45 [28] vs 78 [35] minutes) and time to half-maximum concentration (T(50%max)) (20 [11] vs 28 [10] minutes; both, P < 0.05). Insulin AUC increased significantly in the group that used the device compared with the group that did not at 30 (21 [6] vs 33 [16] mU/L/h), 60 (55 [12] vs 80 [28] mU/L/h), and 90 (93 [19] vs 118 [31] mU/L/h) minutes after administration (all, P < 0.05). Cmax also increased significantly (118 [35] vs 86 [16] mU/L [38%]; P < 0.05).
  
  
  CONCLUSIONS
  In this pilot study, use of the InsuPatch was associated with significant decreases in T(max) and T(50%max) and increases in insulin AUC and C(max) of subcutaneous infused rapid-acting insulin analogues, resulting in a lower postprandial glucose excursion in these patients with type 1 diabetes mellitus treated with CSII.
authors.affiliation: The Diabetes Center, Hadassah Hebrew University School of Medicine, Jerusalem, Israel. ntv502@netvision.net.il
authors.forename: Itamar
authors.initials: I
authors.lastname: Raz
authors.forename: Ram
authors.initials: R
authors.lastname: Weiss
authors.forename: Yevgeny
authors.initials: Y
authors.lastname: Yegorchikov
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bitton
authors.forename: Ron
authors.initials: R
authors.lastname: Nagar
authors.forename: Benny
authors.initials: B
authors.lastname: Pesach
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004864:Equipment and Supplies; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics*; D006358:Hot Temperature / Q000627:therapeutic use*; D006801:Humans; D055104:Infusions, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D007332:Insulin Infusion Systems; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005947:Glucose