Salivary molecular spectroscopy: a sustainable, rapid and non-invasive monitoring tool for diabetes mellitus during insulin treatment

Douglas C. Caixeta; Emília M. G. Aguiar; Léia Cardoso-Sousa; Líris M. D. Coelho; Stephanie W. Oliveira; Foued S. Espindola; Leandro Raniero; Karla T. B. Crosara; Matthew J. Baker; Walter L. Siqueira; Robinson Sabino-Silva

doi:10.1371/journal.pone.0223461

Salivary molecular spectroscopy: a sustainable, rapid and non-invasive monitoring tool for diabetes mellitus during insulin treatment

Douglas C. Caixeta, Emília M. G. Aguiar, Léia Cardoso-Sousa, Líris M. D. Coelho, Stephanie W. Oliveira, Foued S. Espindola, Leandro Raniero, Karla T. B. Crosara, Matthew J. Baker, Walter L. Siqueira, Robinson Sabino-Silva^*

^*Corresponding author for this work

Pure And Applied Chemistry

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Abstract

Monitoring of blood glucose is an invasive, painful and costly practice in diabetes. Consequently, the search for a more cost-effective (reagent-free), non-invasive and specific diabetes monitoring method is of great interest. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy has been used in diagnosis of several diseases, however, applications in the monitoring of diabetic treatment are just beginning to emerge. Here, we used ATR-FTIR spectroscopy to evaluate saliva of non-diabetic (ND), diabetic (D) and insulin-treated diabetic (D+I) rats to identify potential salivary biomarkers related to glucose monitoring. The spectrum of saliva of ND, D and D+I rats displayed several unique vibrational modes and from these, two vibrational modes were pre-validated as potential diagnostic biomarkers by ROC curve analysis with significant correlation with glycemia. Compared to the ND and D+I rats, classification of D rats was achieved with a sensitivity of 100%, and an average specificity of 93.33% and 100% using bands 1452 cm^-1 and 836 cm^-1, respectively. Moreover, 1452 cm^-1 and 836 cm^-1 spectral bands proved to be robust spectral biomarkers and highly correlated with glycemia (R² of 0.801 and 0.788, P < 0.01, respectively). Both PCA-LDA and HCA classifications achieved an accuracy of 95.2%. Spectral salivary biomarkers discovered using univariate and multivariate analysis may provide a novel robust alternative for diabetes monitoring using a non-invasive and green technology.

Original language	English
Article number	e0223461
Number of pages	18
Journal	PLoS ONE
Volume	15
Issue number	3
DOIs	https://doi.org/10.1371/journal.pone.0223461
Publication status	Published - 17 Mar 2020

Funding

This research was supported by a grant from CAPES/CNPq (#458143/2014), FAPEMIG (#APQ-02872-16), Federal University of Uberlandia and National Institute of Science and Technology in Theranostics and Nanobiotechnology (CNPq Process N.: 465669/2014-0). Canadian Institutes of Health Research (CIHR grants #106657 and # 400347). CAIXETA, D.C.; AGUIAR, E. M. G.; and CARDOSO-SOUSA, L. received a fellowship from FAPEMIG, CNPq e CAPES, respectively. Sabino-Silva, R received a fellowship from PrInt CAPES/ UFU. We would like to thank our collaborators at the Rodent Vivarium Network (REBIR-UFU) and Dental Research Center in Biomechanics, Biomaterials and Cell Biology (CPbio-UFU). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Keywords

diabetes mellitus
saliva
insulin
glucose
biomarkers

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Caixeta, D. C., Aguiar, E. M. G., Cardoso-Sousa, L., Coelho, L. M. D., Oliveira, S. W., Espindola, F. S., Raniero, L., Crosara, K. T. B., Baker, M. J., Siqueira, W. L., & Sabino-Silva, R. (2020). Salivary molecular spectroscopy: a sustainable, rapid and non-invasive monitoring tool for diabetes mellitus during insulin treatment. PLoS ONE, 15(3), Article e0223461. https://doi.org/10.1371/journal.pone.0223461

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abstract = "Monitoring of blood glucose is an invasive, painful and costly practice in diabetes. Consequently, the search for a more cost-effective (reagent-free), non-invasive and specific diabetes monitoring method is of great interest. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy has been used in diagnosis of several diseases, however, applications in the monitoring of diabetic treatment are just beginning to emerge. Here, we used ATR-FTIR spectroscopy to evaluate saliva of non-diabetic (ND), diabetic (D) and insulin-treated diabetic (D+I) rats to identify potential salivary biomarkers related to glucose monitoring. The spectrum of saliva of ND, D and D+I rats displayed several unique vibrational modes and from these, two vibrational modes were pre-validated as potential diagnostic biomarkers by ROC curve analysis with significant correlation with glycemia. Compared to the ND and D+I rats, classification of D rats was achieved with a sensitivity of 100%, and an average specificity of 93.33% and 100% using bands 1452 cm-1 and 836 cm-1, respectively. Moreover, 1452 cm-1 and 836 cm-1 spectral bands proved to be robust spectral biomarkers and highly correlated with glycemia (R2 of 0.801 and 0.788, P < 0.01, respectively). Both PCA-LDA and HCA classifications achieved an accuracy of 95.2%. Spectral salivary biomarkers discovered using univariate and multivariate analysis may provide a novel robust alternative for diabetes monitoring using a non-invasive and green technology.",

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Caixeta, DC, Aguiar, EMG, Cardoso-Sousa, L, Coelho, LMD, Oliveira, SW, Espindola, FS, Raniero, L, Crosara, KTB, Baker, MJ, Siqueira, WL & Sabino-Silva, R 2020, 'Salivary molecular spectroscopy: a sustainable, rapid and non-invasive monitoring tool for diabetes mellitus during insulin treatment', PLoS ONE, vol. 15, no. 3, e0223461. https://doi.org/10.1371/journal.pone.0223461

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T2 - a sustainable, rapid and non-invasive monitoring tool for diabetes mellitus during insulin treatment

AU - Caixeta, Douglas C.

AU - Aguiar, Emília M. G.

AU - Cardoso-Sousa, Léia

AU - Coelho, Líris M. D.

AU - Oliveira, Stephanie W.

AU - Espindola, Foued S.

AU - Raniero, Leandro

AU - Crosara, Karla T. B.

AU - Baker, Matthew J.

AU - Siqueira, Walter L.

AU - Sabino-Silva, Robinson

PY - 2020/3/17

Y1 - 2020/3/17

N2 - Monitoring of blood glucose is an invasive, painful and costly practice in diabetes. Consequently, the search for a more cost-effective (reagent-free), non-invasive and specific diabetes monitoring method is of great interest. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy has been used in diagnosis of several diseases, however, applications in the monitoring of diabetic treatment are just beginning to emerge. Here, we used ATR-FTIR spectroscopy to evaluate saliva of non-diabetic (ND), diabetic (D) and insulin-treated diabetic (D+I) rats to identify potential salivary biomarkers related to glucose monitoring. The spectrum of saliva of ND, D and D+I rats displayed several unique vibrational modes and from these, two vibrational modes were pre-validated as potential diagnostic biomarkers by ROC curve analysis with significant correlation with glycemia. Compared to the ND and D+I rats, classification of D rats was achieved with a sensitivity of 100%, and an average specificity of 93.33% and 100% using bands 1452 cm-1 and 836 cm-1, respectively. Moreover, 1452 cm-1 and 836 cm-1 spectral bands proved to be robust spectral biomarkers and highly correlated with glycemia (R2 of 0.801 and 0.788, P < 0.01, respectively). Both PCA-LDA and HCA classifications achieved an accuracy of 95.2%. Spectral salivary biomarkers discovered using univariate and multivariate analysis may provide a novel robust alternative for diabetes monitoring using a non-invasive and green technology.

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KW - diabetes mellitus

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KW - insulin

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Salivary molecular spectroscopy: a sustainable, rapid and non-invasive monitoring tool for diabetes mellitus during insulin treatment

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