title: Postprandial vascular effects of VIAject compared with insulin lispro and regular human insulin in patients with type 2 diabetes.
abstract: OBJECTIVE
  Recent studies suggested an impact of prandial insulin delivery on postprandial regulation of tissue blood flow. This study compared the effect of VIAject with human regular insulin and insulin lispro on postprandial oxidative stress and endothelial function in patients with type 2 diabetes.
  
  
  METHODS
  Fourteen patients (seven men; aged 61.5 +/- 1.8 years; duration of diabetes 6.6 +/- 4.6 years; A1C 7.2 +/- 0.5% [mean +/- SEM]) received a prandial injection of VIAject, human regular insulin, and insulin lispro. At baseline and after a standardized liquid meal test (Ensure Plus), the postprandial increases in asymmetric dimethylarginine (ADMA) and nitrotyrosine levels were investigated. In addition, the postprandial effects on microvascular blood flow, skin oxygenation, and vascular elasticity were measured.
  
  
  RESULTS
  Treatment with VIAject resulted in a significant reduction in the peak postprandial generation of ADMA compared with human insulin and insulin lispro (VIAject -27.3 +/- 22.6, human insulin 97.7 +/- 24.4, and insulin lispro 66.9 +/- 33.9 nmol/l; P < 0.05, respectively). The postprandial increases in nitrotyrosine levels were significantly less after VIAject than after human regular insulin (VIAject -0.22 +/- 0.17 vs. human insulin 0.25 +/- 0.15 microg/ml; P < 0.05), whereas nitrotyrosine after insulin lispro was in between (insulin lispro 0.09 +/- 0.07 microg/ml; NS). In parallel, earlier and more pronounced increases in microvascular blood flow and skin oxygenation were obtained after VIAject compared with those after human insulin or insulin lispro (P < 0.05, respectively). All insulin formulations resulted in comparable improvements in central arterial elasticity. CONCLUSIONS; Treatment with VIAject reduced postprandial oxidative stress and improved endothelial function compared with human regular insulin or insulin lispro.
authors.affiliation: Institute for Clinical Research and Development, Mainz, Germany. thomasf@ikfe.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Forst
authors.forename: Andreas
authors.initials: A
authors.lastname: Pfützner
authors.forename: Frank
authors.initials: F
authors.lastname: Flacke
authors.forename: Alan
authors.initials: A
authors.lastname: Krasner
authors.forename: Cloth
authors.initials: C
authors.lastname: Hohberg
authors.forename: Eda
authors.initials: E
authors.lastname: Tarakci
authors.forename: Philip
authors.initials: P
authors.lastname: Pichotta
authors.forename: Senait
authors.initials: S
authors.lastname: Forst
authors.forename: Solomon
authors.initials: S
authors.lastname: Steiner
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D001786:Blood Glucose / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007279:Injections, Subcutaneous / Q000379:methods*; D007328:Insulin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use*; D061268:Insulin Lispro; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D019518:Postprandial Period; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro; C002744:3-nitrotyrosine; D014443:Tyrosine; C018524:N,N-dimethylarginine; D001120:Arginine