The Clinic Research On Breath Acetone In Type 2 Diabetic Patients Using CRDS Breath Acetone Analyzer

Objective:Owing to the improved living standard, lifestyle changes and ageing population, the world can no longer ignore the inexorable rise in prevalence of diabetes. China in particular has a large burden of diabetes, where 11.6% of adults had diabetes and 50.1% had prediabetes. Much attention has been focused on the non-invasive diabetes diagnosis and monitoring. Acetone in exhaled breath is a potential biomarker of diabetes. Studies of the potential of noninvasive disease diagnosis and monitoring through breath analysis have proliferated in recent years. We utilized a pilot-scale breath acetone analyzer based on the cavity ringdown spectroscopy (CRDS) technique to conduct clinical breath tests on the type 2 diabetic (T2D) patients. It explores the quantitative correlation between diabetes and breath acetone and analyzes the factors influencing breath acetone concentration, which aims to provide reference values for the application of breath analysis in diabetic diagnosis and monitoring.Methods:First, a series of instruments performance of the cavity ringdown breath acetone analyzer is tested, including the baseline stability, the theoretical detection limit, the reproducibility, the response time, the linear response and the validation of gold standard gas chromatography-mass spectrometry (GC-MS). And then we utilized this cavity ringdown breath acetone analyzer to conduct breath tests with 997 breath samples from 312 T2D patients (178 male,134 female, age 14-83 years) and 119 breath samples from 68 healthy individuals (39 male,29 female, age 20-49 years). The distribution difference of acetone concentrations between T2D patients and healthy controls were discussed. And the relations between breath acetone and blood glucose (BGL) and glycohemoglobin A1C (HbAlc) and several other clinical indices, such as gender, age, body mass index (BMI), years of diabetes and breath samples’collection conditions were investigated. The multi-variation linear regression model was also constructed to explore the influencing factors of breath acetone concentration. Simultaneously, logistic regression analysis was performed to build a predictive model for diabetic ketoacidosis (DKA).Results:l.The cavity ringdown breath acetone analyzer has high sensitivity (57 ppb), high data throughput (one data per second), good baseline stability (0.16%), good reproducibility, good linearity (R=0.9998) and good measurement accuracy (R=0.943).2. For the 312 T2D patients, the range of breath acetone concentrations is 0.1 to 19.8 ppmv. The results suggest that T2D subjects have elevated mean breath acetone concentrations and a much wider breath acetone range than that in 68 healthy controls.3.(1)For the healthy controls:Fasting breath acetone concentration (1.29±0.51 ppmv) was significantly higher than post-2 h breath acetone concentration (1.06±0.53 ppmv); Breath acetone concentration was significantly correlated inversely with BGL (R=-0.34); No correlations were observed between breath acetone and gender, age or BMI. (2)For the 312 T2D subjects:Fasting breath acetone concentration (1.69±1.67 ppmv) was significantly higher than post-2 h breath acetone concentration (1.47±1.13 ppmv); No correlations were observed between breath acetone concentration and BGL, however the breath acetone concentration was positively correlated with HbAlc levels (R=0.1); Breath Acetone concentration was significantly higher in male subjects (1.80 ±1.58 ppmv) than female subjects (1.20±0.71 ppmv); And the breath acetone was both negatively correlated with age and BMI (R=-0.1, R=-0.07. respectively); Besides, breath acetone concentration was significantly higher in subjects with DKA (1.90±1.48 ppmv) than subjects without DKA (1.47±1.27 ppmv). Furthermore, there was no correlations between breath acetone and years of diabetes.4.Multi-variation analysis showed that gender (β=0.5)、 DKA (β=0.33)、 breath samples’collection conditions (β=-0.16)、BMI (β=-0.04) and age (β=-0.01) affect breath acetone concentrations.5. With the model accuracy of 88.71%, breath acetone testing appears to be a noninvasive method for the diagnosis of DKA.Conclusion:The ringdown breath acetone analyzer can be used for reliable, real-time, online breath acetone analysis in clinic. And there is an elevated mean breath acetone concentration in T2D. Moreover, breath acetone concentration in T2D was correlated with breath samples’ collection conditions, gender, age, BMI and whether the patients have DKA. Besides, the DKA prediction accuracy is high, and the results are promising because it does provide a possibility of non-invasive diabetes monitoring. The findings indicate the potential value of understanding the relationship between breath acetone and various clinical indices for non-invasive diabetic monitoring and diagnosis.