Analytical and Bioanalytical Chemistry. 2015 Feb, 407 (6): 1641-50

Determination of Breath Acetone in 149 Type 2 Diabetic Patients Using a Ringdown Breath Acetone Analyzer

Meixiu Suna,b, Zhuying Chena, Zhiyong Gonga, Xiaomeng Zhaoa, Chenyu Jianga, Yuan Yuana, Zhennang Wanga, Yingxin Lia, and Chuji Wanga,b*

a Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China 300192

b Department of Physics and Astronomy, Mississippi State University, Starkville, MS 39759

 

Abstract

Over 90% of the diabetic patients are Type 2 diabetes. Although an elevated mean breath acetone concentration has been found to exist in Type 1 diabetes (T1D), information on breath acetone in Type 2 diabetes (T2D) remains to be further investigated. In this study, we first validated a ringdown breath acetone analyzer based on the cavity ringdown spectroscopy technique using gas chromatography-mass spectrometry (GC-MS) through comparing breath acetone concentrations in the range of 0.5 – 2.5 ppm measured using both methods. The linear fitting of R=0.99 suggests that the obtained acetone concentrations using both methods are consistent with the largest standard deviation of ± 0.4 ppm in the lowest concentration of the range. And then 620 breath samples from 149 T2D patients and 42 non-diabetic healthy subjects were collected and tested using the breath analyzer. Four breath samples were taken from each individual subject under each of the four different conditions: fasting, 2 hours (2h) post-breakfast, 2h post-lunch, and 2h post-dinner. Simultaneous blood glucose levels were also measured using a standard diabetic management blood glucose meter. For the 149 T2D subjects, their exhaled breath acetone concentrations ranged from 0.1 to 19.8 parts per million (ppm); and four different ranges of breath acetone concentrations were 0.1 – 19.8, 0.1 – 7.1, 0.1 – 6.3, and 0.1 – 9.5 ppm for the subjects under the four different conditions respectively. For the 42 non-diabetic healthy subjects, their breath acetone concentration ranged from 0.1 to 2.6 ppm; and four different ranges of breath acetone concentrations were 0.3 – 2.6, 0.1 – 2.6, 0.1 – 1.7 and 0.3 – 1.6 ppm for the four different conditions respectively. A mean breath acetone concentration of the 149 T2D subjects was determined to be 1.5 ± 1.5 ppm, which is 1.5 times of that in the 42 non-diabetic healthy subjects, 1.0 ± 0.6 ppm. No correlation was found between breath acetone concentration and blood glucose level in the T2D subjects and the healthy volunteers. This study using a relatively large number of subjects adds new data to breath acetone in diabetes (T1D and T2D) and suggests that an elevated mean breath acetone concentration also exists in T2D.

 

Supplement:

Breath analysis through testing exhaled breath components provides a potential option for nonintrusive disease diagnosis and metabolic status monitoring. Breath acetone has long been known as a biomarker for diabetes and the presence of abnormal (typically elevated) concentration is a good indicator of blood-hydrobutyrate (BHB) in diabetes mellitus (DM) (1-3).

More recently, we have constructed a ringdown breath acetone analyzer, as shown in Fig. 1, based on the cavity ringdown spectroscopy (CRDS) technique to pursue a large scale of clinical testing in near-real time, on-line toward higher data throughput as compared to use of the GC-MS method that is a well accepted analytical method for trace gas analysis for its high sensitivity and high accuracy, except for the drawbacks of high cost and long testing time.

 

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Fig. 1. Schematic diagram of the ringdown breath analyzer (a) and collection of an exhaled breath sample from a human subject (b).

 

The measured linear response along with the GC-MS validation test result shown in fig. 2 (a) and (b) ensured the functionality of the ringdown breath acetone analyzer that was ready for subsequent measurements of breath samples.

 

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Fig. 2. Linear response to various acetone concentrations measured by the ringdown acetone breath analyzer (a) and The ringdown breath analyzer’s performance validated by a certified GC-MS facility (b).

 

The mean values for all T2D subjects and for the T2D subjects under four conditions, fasting, 2 h after breakfast, 2 h after lunch, and 2 h after dinner, were all higher than the mean value of acetone concentration for the healthy subjects, as shown in Fig. 3.

 

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Fig. 3. Mean breath acetone concentrations from the 42 non-diabetic subjects and from the 149 T2D subjects. The error bar corresponds to one standard deviation.

 

The importance of this study is two-fold. First, the analytical application of the powerful enabling technique (real-time online) in breath analysis offers an advantage of improved statistically scientific significance compared with currently used data that either comes from a statistically small group of samples or from a long data-collection period (e.g. a month or longer) partially due to high costs of using the conventional analytical methods such as GC-MS and long testing time resulting from the sophisticated sample preparation such as the sample pre-concentration.

Second, this study using a relatively large number of subjects adds new data to breath acetone in diabetes (T1D and T2D) and suggests that an elevated mean breath acetone concentration also exists in T2D.

 

Reference:

  1. Wang, C. Wang, Is breath acetone a biomarker of diabetes—A historical review on breath acetone measurements, J. Breath Res. 7 (2013) 037109.
  2. H. Risby, S. F. Solga, Current status of clinical breath analysis, Appl. Phys. B 85 (2006) 421–426.
  3. R. Mccurdy, Y. Bakhirkin, G. Wysocki, R. Lewicki, F. K. Tittel, Recent advances of laser-spectroscopy-based techniques for applications in breath analysis, J. Breath Res. 1 (2007) 014001.

 

Acknowledgment: This work was supported by National Science Foundation of China (Grant No. 81471701). The authors thank the participation of numerous volunteers who provided breath gas samples.

 

Contact:

Chuji Wang, Ph.D.

Professor

Department of Physics and Astronomy

Mississippi State University

Starkville, MS 39759

Tel: 662-325-9455

cw175@msstate.edu

www.wang.physics.msstate.edu

 

 

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