Abstract

Objective - Recent studies suggested an impact of prandial insulin delivery on postprandial (pp) 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 mellitus.

Reseaerch Design And Methods - Fourteen patients (7 male; age 61.5±1.8 years; duration of diabetes 6.6±4.6 years; HbA1c 7.2±0.5 %; mean±SEM) received a prandial injection of Viaject™, human regular insulin and insulin lispro. At baseline and after a standardised liquid meal test (Ensure Plus™) the pp increase in asymmetric dimethylarginine (ADMA) and nitrotyrosine levels were investigated. In addition, the pp effects on microvascular blood flow, skin oxygenation, and vascular elasticity were measured.

Results - Treatment with Viaject™ (VJ) resulted in a significant reduction in the peak pp generation of ADMA compared with human insulin (HI) and insulin lispro (LI) (VJ: −27.3±22.6; HI: 97.7±24.4; LI: 66.9±33.9 nmol/L; p<0.05 respectively). The pp increase in nitrotyrosine levels were significant less after Viaject™ compared with human regular insulin (VJ: −0.22±0.17, HI: 0.25±0.15 μg/ml; p<0.05), while nitrotyrosine after insulin lispro was in between (LI: 0.09±0.07 μg/ml; n.s.). In parallel, earlier and more pronounced increases in microvascular blood flow and skin oxygenation were obtained after Viaject™ compared to HI or insulin lispro (p<0.05 respectively). All insulin formulations resulted in comparable improvements in central arterial elasticity.

Conclusions - Treatment with Viaject™ reduced pp oxidative stress and improved endothelial function compared to human regular insulin or insulin lispro.