Effect of insulin glulisine on microvascular blood flow and endothelial function in the postprandial state.
OBJECTIVE
To investigate the effect of insulin glulisine on postprandial microvascular blood flow in type 2 diabetes.


METHODS
A total of 15 patients with type 2 diabetes received insulin glulisine or human insulin before a liquid meal test. Thereafter, skin microvascular blood flow was measured by laser Doppler fluxmetry and blood samples were taken for measurement of plasma levels of glucose, insulin, intact proinsulin, asymmetric dimethylarginine, nitrotyrosine, interleukin-18, matrix metalloproteinase-9, oxidized LDL, and free fatty acids.


RESULTS
Insulin glulisine injections resulted in higher postprandial insulin levels (means +/- SEM area under the curve [AUC](0-120) 51.0 +/- 6.8 vs. 38.2 +/- 5.4 mU/l; P = 0.004), while plasma glucose (AUC(0-240) 158 +/- 9 vs. 180 +/- 9 mg/dl; P < 0.05) and intact proinsulin (AUC(0-240) 26.2 +/- 3.5 vs. 31.2 +/- 4.3 pmol/l; P = 0.002) were lower. Microvascular blood flow increased after insulin glulisine injection (27.9 +/- 3.1 to 51.7 +/- 9.9 arbitrary units [AU]; P < 0.05), while only a minor increase was found during human insulin (27.9 +/- 3.1 to 34.4 +/- 7.8 AU; not significant). Asymmetric dimethylarginine and nitrotyrosine levels were reduced after insulin glulisine (P < 0.05).


CONCLUSIONS
Insulin glulisine is superior to human insulin in restoring postprandial metabolic and microvascular physiology.
Hohberg
Clothilde
C
Institute for Clinical Research and Development, Parcusstrasse 8, D-55116 Mainz, Germany.
Forst
Thomas
T
Larbig
Martin
M
Safinowski
Michael
M
Diessel
Stefan
S
Hehenwarter
Silvia
S
Weber
Matthias M
MM
Schöndorf
Thomas
T
Pfützner
Andreas
A
D000328:Adult; D000368:Aged; D001783:Blood Flow Velocity / Q000187:drug effects*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D018579:Patient Selection; D019518:Postprandial Period; D011384:Proinsulin / Q000097:blood; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood
D007004:Hypoglycemic Agents; D007328:Insulin; C002744:3-nitrotyrosine; D014443:Tyrosine; C479079:insulin glulisine; D011384:Proinsulin