Human breath gas analysis in the screening of gestational diabetes mellitus.

BACKGROUND We present a pilot study on the feasibility of the application and advantages of online, noninvasive breath gas analysis (BGA) by proton transfer reaction quadrupole mass spectrometry for the screening of gestational diabetes mellitus (GDM) in 52 pregnant women by means of an oral glucose tolerance test (OGTT). SUBJECTS AND METHODS We collected and identified samples of end-tidal breath gas from patients during OGTT. Time evolution parameters of challenge-responsive volatile organic compounds (VOCs) in human breath gas were estimated. Multivariate analysis of variance and permutation analysis were used to assess feasibility of BGA as a diagnostic tool for GDM. RESULTS Standard OGTT diagnosis identified pregnant women as having GDM (n = 8), impaired glucose tolerance (n = 12), and normal glucose tolerance (n = 32); a part of this latter group was further subdivided into a "marginal" group (n = 9) because of a marginal high 1-h or 2-h OGTT value. We observed that OGTT diagnosis (four metabolic groups) could be mapped into breath gas data. The time evolution of oxidation products of glucose and lipids, acetone metabolites, and thiols in breath gas after a glucose challenge was correlated with GDM diagnosis (P = 0.035). Furthermore, basal (fasting) values of dimethyl sulfide and values of methanol in breath gas were inversely correlated with phenotype characteristics such as homeostasis model assessment of insulin resistance index (R = -0.538; P = 0.0002, P(corrected) = 0.0034) and pregestational body mass index (R = -0.433; P = 0.0013, P(corrected) = 0.022). CONCLUSIONS Noninvasive BGA in challenge response studies was successfully applied to GDM diagnosis and offered an insight into metabolic pathways involved. We propose a new approach to the identification of diagnosis thresholds for GDM screening.

[1]  A. Jawerbaum,et al.  The role of oxidative stress in the pathophysiology of gestational diabetes mellitus. , 2011, Antioxidants & redox signaling.

[2]  J. Pleil Non Invasive Biomedical Analysis. Breath Networking Session at PittCon 2011, Atlanta, Georgia , 2011, Journal of breath research.

[3]  Simone Meinardi,et al.  Noninvasive measurement of plasma glucose from exhaled breath in healthy and type 1 diabetic subjects. , 2011, American journal of physiology. Endocrinology and metabolism.

[4]  M. Hannemann,et al.  Special section on Breath Gas Analysis , 2011, Journal of breath research.

[5]  G. Teschl,et al.  A modeling-based evaluation of isothermal rebreathing for breath gas analyses of highly soluble volatile organic compounds , 2011, Journal of breath research.

[6]  David Smith,et al.  Can volatile compounds in exhaled breath be used to monitor control in diabetes mellitus? , 2011, Journal of breath research.

[7]  Julian King,et al.  Physiological modeling of isoprene dynamics in exhaled breath. , 2010, Journal of theoretical biology.

[8]  H. Paretzke,et al.  Differences in exhaled gas profiles between patients with type 2 diabetes and healthy controls. , 2010, Diabetes technology & therapeutics.

[9]  Julian King,et al.  A mathematical model for breath gas analysis of volatile organic compounds with special emphasis on acetone , 2010, Journal of mathematical biology.

[10]  K. Hayashi,et al.  Regulation of hepatic branched-chain alpha-keto acid dehydrogenase kinase in a rat model for type 2 diabetes mellitus at different stages of the disease. , 2010, Biochemical and biophysical research communications.

[11]  M. Fiegl,et al.  Noninvasive detection of lung cancer by analysis of exhaled breath , 2009, BMC Cancer.

[12]  D. Blake,et al.  Improved predictive models for plasma glucose estimation from multi-linear regression analysis of exhaled volatile organic compounds. , 2009, Journal of applied physiology.

[13]  J. Dungan,et al.  Hyperglycemia and Adverse Pregnancy Outcomes , 2009 .

[14]  G. Teschl,et al.  Isoprene and acetone concentration profiles during exercise on an ergometer , 2009, Journal of breath research.

[15]  K. Schwarz,et al.  Determining concentration patterns of volatile compounds in exhaled breath by PTR-MS , 2009, Journal of breath research.

[16]  K. Unterkofler,et al.  Breath acetone—aspects of normal physiology related to age and gender as determined in a PTR-MS study , 2009, Journal of breath research.

[17]  Bengt Persson,et al.  Hyperglycemia and Adverse Pregnancy Outcomes , 2009 .

[18]  Jens Herbig,et al.  Buffered end-tidal (BET) sampling—a novel method for real-time breath-gas analysis , 2008, Journal of breath research.

[19]  C. Marth,et al.  The impact of risk factors and more stringent diagnostic criteria of gestational diabetes on outcomes in central European women. , 2008, The Journal of clinical endocrinology and metabolism.

[20]  M. Brosnan,et al.  Homocysteine metabolism in diabetes. , 2007, Biochemical Society transactions.

[21]  D. Blake,et al.  Exhaled methyl nitrate as a noninvasive marker of hyperglycemia in type 1 diabetes , 2007, Proceedings of the National Academy of Sciences.

[22]  Anton Amann,et al.  Lung cancer detection by proton transfer reaction mass-spectrometric analysis of human breath gas , 2007 .

[23]  A. Ferrara Increasing Prevalence of Gestational Diabetes Mellitus , 2007, Diabetes Care.

[24]  E. Bonifacio,et al.  Predictors of postpartum diabetes in women with gestational diabetes mellitus. , 2006, Diabetes.

[25]  O. Kordonouri,et al.  Birth weight and parental BMI predict overweight in children from mothers with gestational diabetes. , 2005, Diabetes care.

[26]  R. Hamman,et al.  Increasing prevalence of gestational diabetes mellitus (GDM) over time and by birth cohort: Kaiser Permanente of Colorado GDM Screening Program. , 2005, Diabetes care.

[27]  Simone Meinardi,et al.  Breath ethanol and acetone as indicators of serum glucose levels: an initial report. , 2005, Diabetes technology & therapeutics.

[28]  M. Díaz-Flores,et al.  Glucose-stimulated acrolein production from unsaturated fatty acids , 2004, Human & experimental toxicology.

[29]  N. Magan,et al.  Electronic noses and disease diagnostics , 2004, Nature Reviews Microbiology.

[30]  M. Kalapos,et al.  On the mammalian acetone metabolism: from chemistry to clinical implications. , 2003, Biochimica et biophysica acta.

[31]  D. V. Vander Jagt,et al.  Methylglyoxal metabolism and diabetic complications: roles of aldose reductase, glyoxalase-I, betaine aldehyde dehydrogenase and 2-oxoaldehyde dehydrogenase. , 2003, Chemico-biological interactions.

[32]  C. Delahunty,et al.  Analysis of volatile flavour compounds by Proton Transfer Reaction-Mass Spectrometry: fragmentation patterns and discrimination between isobaric and isomeric compounds , 2002 .

[33]  Catherine Kim,et al.  Gestational diabetes and the incidence of type 2 diabetes: a systematic review. , 2002, Diabetes care.

[34]  M. Phillips,et al.  Variation in volatile organic compounds in the breath of normal humans. , 1999, Journal of chromatography. B, Biomedical sciences and applications.

[35]  A. Wisthaler,et al.  Proton-transfer-reaction mass spectrometry (PTR-MS): on-line monitoring of volatile organic compounds at volume mixing ratios of a few pptv , 1999 .

[36]  A. Hansel,et al.  Proton transfer reaction mass spectrometry (PTR-MS): propanol in human breath , 1996 .

[37]  K. Pickard,et al.  The regulation of transaminative flux of methionine in rat liver mitochondria. , 1994, Archives of biochemistry and biophysics.

[38]  R. Turner,et al.  Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man , 1985, Diabetologia.

[39]  M. Mehlman,et al.  Metabolic fate of 1,3-butanediol in the rat: conversion to -hydroxybutyrate. , 1971, The Journal of nutrition.

[40]  正雄 土居崎 Regulation of hepatic branched-chain α-keto acid dehydrogenase kinase in a rat model for type 2 diabetes mellitus at different stages of the disease , 2010 .

[41]  H. Blom,et al.  Transamination of methionine in humans. , 1989, Clinical science.