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. 2024 May 1:15:1360989.
doi: 10.3389/fendo.2024.1360989. eCollection 2024.

Metabolic trajectories of diabetic ketoacidosis onset described by breath analysis

Mo Awchi  1   2 , Kapil Dev Singh  1   2 , Sara Bachmann Brenner  1   3 , Marie-Anne Burckhardt  1   3 , Melanie Hess  1   3 , Jiafa Zeng  1   2 , Alexandre N Datta  1   3 , Urs Frey  1   3 , Urs Zumsteg  1 , Gabor Szinnai  1   3 , Pablo Sinues  1   2
Affiliations

Metabolic trajectories of diabetic ketoacidosis onset described by breath analysis

Mo Awchi et al. Front Endocrinol (Lausanne). .

Abstract

Purpose: This feasibility study aimed to investigate the use of exhaled breath analysis to capture and quantify relative changes of metabolites during resolution of acute diabetic ketoacidosis under insulin and rehydration therapy.

Methods: Breath analysis was conducted on 30 patients of which 5 with DKA. They inflated Nalophan bags, and their metabolic content was subsequently interrogated by secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS).

Results: SESI-HRMS analysis showed that acetone, pyruvate, and acetoacetate, which are well known to be altered in DKA, were readily detectable in breath of participants with DKA. In addition, a total of 665 mass spectral features were found to significantly correlate with base excess and prompt metabolic trajectories toward an in-control state as they progress toward homeostasis.

Conclusion: This study provides proof-of-principle for using exhaled breath analysis in a real ICU setting for DKA monitoring. This non-invasive new technology provides new insights and a more comprehensive overview of the effect of insulin and rehydration during DKA treatment.

Keywords: ICU; breath analysis; diabetic ketoacidosis; mass spectrometry; metabolomics.

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Conflict of interest statement

PS is co-founder of Deep Breath Intelligence AG Switzerland, which develops breath-based diagnostic tools. KDS and JZ are consultants for Deep Breath Intelligence AG Switzerland. The University Children’s Hospital Basel is a shareholder of Deep Breath Intelligence AG Switzerland. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Overview of patient measurements. Small dot indicates single breath measurement, big dot indicates multiple breath measurements. Red numbers indicate DKA, blue in control and green non-diabetic. The breath samples were collected and measured within 15 minutes after collection. The total measurements were the base excess was below -2 totaled 24, whereas 64 measurements were made when diabetic participants were in control and 19 measurements of non-diabetic control measurements. Image was generated with the use of BioRender.
Figure 2
Figure 2
Time traces of (A) breath acetone (left y-axis); (B) and acetoacetate (left y-axis); in comparison with BE (right y-axis in a and b) for five DKA participants admitted to ICU after start of insulin administration and rehydration therapy. X-axis represents time after start of iv insulin. Breath timepoints were linearly interpolated to match with the clinical time-points.
Figure 3
Figure 3
Breath analysis captures generally accepted DKA-altered pathways. Participants with T1D with BE < -2 show a significant partial up-regulation of pyruvate, and significant upregulation acetone and acetoacetate vs participants with T1D with normal BE values (i.e. +/- 2) and participants without T1D. In contrast, exhaled free fatty acids are downregulated. Y-axis in the boxplots represent: Log10(signal intensity) [a.u.]. Figure adapted from Wallace et al. (18).
Figure 4
Figure 4
(A) PCA plot of all patients (B) Participant 073 shows trajectory towards in-control state as it progresses towards homeostasis.
See this image and copyright information in PMC

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