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Volume 3 Supplement 1

ESICM LIVES 2015

Relation of Resting Membrane Polarization and Insulin Resistance in Critically Ill Patients

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Introduction

Critically ill patients feature depolarization of the resting membrane potential and reduced membrane excitability in motor nerve and muscle [1, 2], which is correlated to ICU-acquired weakness and an increased insulin resistance [3].

Objectives

Since insulin is one agonist of the Na-K-pump, controlling resting membrane potential in muscle and nerve, we hypothesized that insulin resistance is linked to motor nerve resting membrane depolarisation in critically ill patients.

Methods

We recorded compound motor action potential from the abductor pollicis brevis muscle in ICU patients to test excitability measures of the median-nerve at baseline and during euglycemic-hyperinsulinemic clamp, proving resting membrane polarization. the recovery-of-excitability following a supra-maximal conditioning stimulus was tested at 18 conditioning test intervals, decreasing from 200 to 2 ms in geometric progression.

Insulin sensitivity index (ISI), as marker of myocellular insulin resistance, was calculated during steady state condition of euglycemic-hyperinsulinemic clamp.

Results

10 ICU patients and 31 healthy controls were enrolled in this trial. Compared to control group, ICU-patients exhibited depolarization of resting membrane potential (superexcitability in healthy controls -25 + 6.1% versus -18.5 + 4.5% in ICU patients; p = 0.003). the resting membrane depolarization was significantly correlated to ISI (R² = 0.858; p = 0.003), where pronounced insulin resistance correlates with pronounced resting membrane depolarization (Figure 1), indicating that membrane repolarization after insulin stimulation of Na-K-pump is reduced in patients with severe insulin resistance. K+ plasma levels were not correlated with membrane depolarization.

Figure 1
figure1

Correlation between resting membrane polarisation and insulin resistance (ISI = Insulin sensitivity index; indicates ratio of glucose infusion rate to the serum insulin concentration during steady state). Less negative Superexcitability indicates resting membrane depolarization; lower ISI values indicate higher insulin resistance.

Conclusions

Resting membrane depolarization in critically ill patients is correlated to insulin resistance. Patients with severe insulin resistance reveal a failure of repolarization, so that high dosage of insulin administration does not facilitate rectification of membrane polarization.

Grant Acknowledgment

DFG / DGAI supported this work.

References

  1. 1.

    Rich MM, Pinter MJ: Crucial role of sodium channel fast inactivation in muscle fibre inexcitability in a rat model of critical illness myopathy. J Physiol. 2003, 547 (Pt 2): 555-566.

  2. 2.

    Koch S, Bierbrauer J, et al: Motor-nerve excitability in critically ill patients. Neurology. under review

  3. 3.

    Weber-Carstens S, Schneider J, Wollersheim T, Assmann A, Bierbrauer J, Marg A, et al: Critical illness myopathy and GLUT4: significance of insulin and muscle contraction. Am J Respir Crit Care Med. 2013, 187 (4): 387-396. 10.1164/rccm.201209-1649OC.

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Author information

Correspondence to S Koch.

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Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0), which permits use, duplication, adaptation, distribution, and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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Koch, S., Wollersheim, T., Mai, K. et al. Relation of Resting Membrane Polarization and Insulin Resistance in Critically Ill Patients. ICMx 3, A520 (2015) doi:10.1186/2197-425X-3-S1-A520

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Keywords

  • Insulin Resistance
  • Conditioning Stimulus
  • Motor Nerve
  • Rest Membrane Potential
  • Insulin Sensitivity Index