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

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

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.