Postprandial vascular effects of VIAject compared with insulin lispro and regular human insulin in patients with type 2 diabetes.
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.
Forst
Thomas
T
Institute for Clinical Research and Development, Mainz, Germany. thomasf@ikfe.de
Pfützner
Andreas
A
Flacke
Frank
F
Krasner
Alan
A
Hohberg
Cloth
C
Tarakci
Eda
E
Pichotta
Philip
P
Forst
Senait
S
Steiner
Solomon
S
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
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro; C002744:3-nitrotyrosine; D014443:Tyrosine; C018524:N,N-dimethylarginine; D001120:Arginine