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Critical Care

, 17:P454 | Cite as

Multiscale modeling of acute insulin resistance in critical care

  • A Pritchard-Bell
  • G Clermont
  • B Yegneswaran
  • R Parker
Poster presentation
  • 385 Downloads

Keywords

Insulin Resistance Insulin Sensitivity Insulin Signaling Insulin Receptor Substrate Multiscale Model 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Introduction

Stress hyperglycemia in the critically ill is a complex process in which insulin signaling is systematically hijacked to provide energy substrate for metabolic priorities such as cell healing or infection containment. Fluctuating levels of plasma glucose are associated with increased mortality in the ICU [1]. We develop a multiscale mathematical model that can characterize the severity of stress hyperglycemia based on a fundamental understanding of the signaling molecules involved.

Methods

Insulin resistance following insult has been shown to be driven primarily by the immune response via the cytokine IL-6 [2]. We created a multiscale mathematical model that links circulating glucose and insulin concentration dynamics from the extended minimal model [3] to a cellular insulin response model [4] that captures insulin-mediated glucose uptake in an insulin-responsive cell.

Results

Inhibitory dynamics driven by IL-6 were incorporated into the cellular model to attenuate an insulin signaling intermediate (insulin receptor substrate 1) according to the proposed biological mechanisms. The percentage reduction in glucose uptake as a function of IL-6 concentration was fit to data from patients who underwent elective abdominal surgery [2], shown in Figure 1. The overall multiscale model captures decreased insulin signaling as a result of increased IL-6 levels and the subsequent hyperglycemia that may ensue.
Figure 1

Reduced glucose uptake driven by increased plasma IL-6 levels.

Conclusion

A multiscale model has been developed to describe the inhibitory effects of IL-6 on insulin-mediated glucose uptake. Cellular inhibitory dynamics were shown to capture reduced insulin sensitivity on the macroscale, which could then be used to characterize insulin sensitivity and to provide insulin treatment advice to reduce glucose variability.

References

  1. 1.
    Van den Berghe G: N Engl J Med. 2001, 345: 1359-1367. 10.1056/NEJMoa011300CrossRefPubMedGoogle Scholar
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    Thorell A: Clin Nutr. 1996, 15: 75-79. 10.1016/S0261-5614(96)80023-9CrossRefPubMedGoogle Scholar
  3. 3.
    Roy A: Diabetes Technol Ther. 2006, 8: 617-626. 10.1089/dia.2006.8.617CrossRefPubMedGoogle Scholar
  4. 4.
    Sedaghat A: Am J Physiol Endocrinol Metab. 2002, 283: E1084-E1101.CrossRefPubMedGoogle Scholar

Copyright information

© Pritchard-Bell et al.; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Authors and Affiliations

  • A Pritchard-Bell
    • 1
  • G Clermont
    • 2
  • B Yegneswaran
    • 2
  • R Parker
    • 1
  1. 1.University of PittsburghUSA
  2. 2.University of Pittsburgh Medical CenterPittsburghUSA

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