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Archived Comments for: Intensive insulin treatment improves forearm blood flow in critically ill patients: a randomized parallel design clinical trial

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  1. Dependence of endothelial function and blood flow on insulin and glucose levels

    IVAN ZURAN, General Hospital Celje, Oblakova ul. 5,3000 Celje

    21 September 2010

    Dependence of endothelial function and blood flow on insulin and glucose levels
    Pavel Poredoš1 and Ivan Žuran2
    1Clinical Department of Vascular Diseases, University Medical Centre Ljubljana, Zaloška c. 2,1000 Ljubljana, Slovenia
    2 Department of Angiology, Endocrinology and Rheumatology, General Hospital Celje, Oblakova ul.5, 3000 Celje, Slovenia


    In the commentary published in Critical Care, 2010, 14: 122 related to the article by Žuran and collaborators [1], Van den Berghe highlighted the involvement of insulin and glucose levels in the regulation of blood flow, and the clinical relevance of changes in forearm blood flow in critically ill patients [2]. In the study conducted by Žuran and co-workers it was found that intensive insulin treatment of critically ill patients increases forearm blood flow. The blood flow increase was related to the insulin dose and not to blood glucose concentration. We agree with Van den Berghe’s remark that the absence of correlation between the forearm blood flow and blood glucose levels found in our study does not generally exclude the influence of glucose levels on blood flow. We acknowledge that in our small and complex study various factors could hide the involvement of glucose levels in regulation of blood flow.

    Most probably both glucose levels and insulin concentration are important regulators of the arterial dilatory function and are related to the changes in blood flow. The capability of vessel vasodilation on a macro- as well as on a micro level is regulated by the endothelial function, which deteriorates with increased blood glucose levels. Endothelium-dependent vasodilation in both macro- and micro circulation was shown to be impaired during acute hyperglycaemia [3]. The study by Dengel and colleagues also confirmed the deteriorating effect of oral glucose loading on the endothelial function in children [4]. Further, the effect of glucose levels on the endothelial function has been confirmed in interventional studies. These studies showed that glucose-lowering drugs or endurance exercise along with the decrease in glucose levels improved the endothelial function [5, 6]. Hyperglycaemia probably causes endothelial dysfunction by inducing oxidative stress [7], leading to a decrease of nitric-oxide (NO) production and to increased bio-availability of NO. In one of our studies it was shown that the flow-mediated dilation of the brachial artery is related to glucose levels [8].

    Most likely insulin is also directly involved in the functional capability of endothelium and in the regulation of the blood flow. It has been shown that insulin influences the endothelial function through the activation of eNOS and consequently increases its bio-availability [9]. The increase of flow in skeletal muscles is probably selective. In the study by Rosdahl and co-workers it was shown that insulin infusion resulted in increased blood flow in the calf and forearm but not in other studied muscles of the limbs [10]. This could mean that during the administration of insulin a redistribution of blood flow occurs. This presumption is supported by the results of our study – in spite of increased blood flow in the forearm there were no differences in global hemodynamic parameters. Considering these results, it is therefore impossible to conclude that improved blood flow in skeletal muscles indicates better perfusion of vital organs, and that the positive effect of insulin is based on the improvement of blood flow in overall circulation. However, in spite of these somehow contradictory results, there is strong evidence that endothelial dysfunction is related to the increased risk of cardiovascular events, and that procedures which improve endothelial functions have a beneficial effect on the outcome [11]. In our study, the increased forearm blood flow was most probably the consequence of improved endothelial function. As forearm blood flow was followed only for a short period (three days), it is difficult to presume its long-term effect. Notwithstanding the lack of hard evidence-based data on the influence of blood glucose and insulin levels on the survival of the critically ill patients, it is expected that lower glucose levels as well as optimal insulin availability (which improve endothelial function) also have long-term positive effects. Normal endothelial function thus represents one of the basic protective mechanisms that maintain cardiovascular homeostasis.


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    Competing interests

    There are no competing interests