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Published online February 11, 2008
Diabetes Care 31:1021-1025, 2008
DOI: 10.2337/dc07-2185
© 2008 by the American Diabetes Association
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Cardiovascular and Metabolic Risk
Original Research

Effect of Insulin Glulisine on Microvascular Blood Flow and Endothelial Function in the Postprandial State

Clothilde Hohberg, MD1, Thomas Forst, MD1,2, Martin Larbig, PHD3, Michael Safinowski, PHD1, Stefan Diessel, MD1, Silvia Hehenwarter1, Matthias M. Weber, MD2, Thomas Schöndorf, PHD1 and Andreas Pfützner, MD, PHD1

1 Institute for Clinical Research and Development, Mainz, Germany
2 Department of Endocrinology, Johannes Gutenberg University, Mainz, Germany
3 sanofi-aventis, Berlin, Germany

Corresponding author: Thomas Forst, MD, Professor of Endocrinology, Institute for Clinical Research and Development, Parcusstrasse 8, D-55116 Mainz, Germany. E-mail: thomasf{at}ikfe.de

OBJECTIVE—To investigate the effect of insulin glulisine on postprandial microvascular blood flow in type 2 diabetes.

RESEARCH DESIGN AND 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 (AUC0–240 158 ± 9 vs. 180 ± 9 mg/dl; P < 0.05) and intact proinsulin (AUC0–240 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.

Abbreviations: ADMA, asymmetric dimethylarginine • AUC, area under the curve • IL, interleukin • LDF, laser Doppler fluxmetry • MMP-9, matrix metalloproteinase-9 • oxLDL, oxidized LDL


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