Accuracy of the 13C-glucose breath test to identify insulin resistance in non-diabetic adults

  • Jorge Maldonado-Hernández
  • Azucena Martínez-Basila
  • Mario Enrique Rendón-Macías
  • Mardia López-AlarcónEmail author
Original Article



To assess the validity of the 13C-glucose breath test (13C-GBT) to identify insulin resistance (IR) in non-diabetic individuals, using hyperinsulinemic–euglycemic clamps as gold standard. This validity was compared with that of other IR surrogates.


Non-diabetic adults were studied in a cross-sectional design. In a first appointment, oral glucose tolerance tests were conducted simultaneously with 13C-GBTs. Oral 75 g glucose dissolved in 150 ml water, followed by 1.5 mg/Kg body weight U-13C-glucose dissolved in 50 ml water, was administered. Breath and blood samples were collected at baseline and at 30-min intervals. The percentages of glucose-oxidized dose at given periods were calculated. Clamps were conducted a week later. A clamp-derived M value ≤ 6.0 mg/kg*min was used as cut-off. ROC curves were constructed for 13C-GBT, fasting insulin, HOMA, and ISI-composite.


Thirty-eight subjects completed the study protocol. The correlation coefficient between the 13C-GBT derived glucose-oxidized dose at 180 min and M values was 0.524 (p = 0.001). The optimal value to identify IR with the 13C-GBT was 4.23% (AUC 0.81; 95CI 0.66, 0.96; accuracy 0.82, 95CI 0.66, 0.92). The 13C-GBT sensitivity (0.88) was higher than HOMA and fasting insulin sensitivities (0.83 and 0.75 respectively), while their specificities were comparable (0.71, 0.71, and 0.79, respectively). The sensitivity of ISI-C was higher (0.92) than that of the 13C-GBT, but its specificity was poor (0.36). The accuracy of the 13C-GBT was superior to that of the other studied surrogates.


The 13C-GBT is a valid and accurate method to detect IR in non-diabetic adults. Therefore, it is potentially useful in clinical and community settings.


Insulin resistance 13C-glucose breath test Hyperinsulinemic–euglycemic clamp ISI-composite Accuracy ROC curve 



This study was supported with grants from: Consejo Nacional de Ciencia y Tecnología (CONACYT): 068915, and from the Instituto Mexicano del Seguro Social: FIS/IMSS/PROT 2007-3603-18.

Compliance with ethical standards

Conflict of interest

Authors declare that no competing financial interests exist.

Ethical approval

The protocol was approved by the Ethics Committee of the Instituto Mexicano del Seguro Social and with the 1964 Helsinki declaration (Approval Number: R-2007-3603-18).

Informed consent

Informed consent was obtained from all individual participants included in the study before the study protocol initiated.


  1. 1.
    Ogurtsova K, da Rocha Fernandes JD, Huang Y, Linnenkamp U, Guariguata L, Cho NH, Cavan D, Shaw JE, Makaroff LE (2017) IDF Diabetes Atlas: global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract 128:40–50CrossRefGoogle Scholar
  2. 2.
    Wilcox G (2005) Insulin and insulin resistance. Clin Biochem Rev 26:19–39Google Scholar
  3. 3.
    Petersen KF, Shulman GI (2006) Etiology of insulin resistance. Am J Med 119:10S–16SCrossRefGoogle Scholar
  4. 4.
    Abdul-Ghani MA, Williams K, DeFronzo RA, Stern M (2007) What is the best predictor of Type 2 Diabetes? Diabetes Care 30:1544–1548CrossRefGoogle Scholar
  5. 5.
    Song Y, Manson JE, Tinker L, Howard BV, Kuller LH, Rifai LNN, Liu S (2007) Insulin sensitivity and insulin secretion determined by homeostasis model assessment and risk of diabetes in a multiethnic cohort of women. Diabetes Care 30:1747–1752CrossRefGoogle Scholar
  6. 6.
    DeFronzo RA, Tobin JD, Andrews R (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237:E214–E223Google Scholar
  7. 7.
    Trout KK, Homko C, Tkacs NC (2007) Methods of measuring insulin sensitivity. Biol Res Nurs 8:305–318CrossRefGoogle Scholar
  8. 8.
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419CrossRefGoogle Scholar
  9. 9.
    Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing. Diabetes Care 22:1462–1470CrossRefGoogle Scholar
  10. 10.
    Mooy JM, Grootenhuis PA, de Vries H, Kostense PJ, Popp-Snidders C, Bouter LM, Heine RJ (1996) Intra-individual variation of glucose, specific insulin and proinsulin concentrations measured by two oral glucose tolerance tests in a general caucasian population: the hoorn study. Diabetologia 39:298–305CrossRefGoogle Scholar
  11. 11.
    Uwaifo GI, Fallon EM, chin J, Elberg J, Parikh SJ, Yanovski JA (2002) Indices of insulin action, disposal, and secretion derived from fasting samples and clamps in normal glucose-tolerant black and white children. Diabetes Care 25:2081–2087CrossRefGoogle Scholar
  12. 12.
    Gungor N. Saad R. Janosky J. Arslanian S (2004) Validation of surrogate estimates of insulin sensitivity and insulin secretion in children and adolescents. J Pediatr 144:47–55CrossRefGoogle Scholar
  13. 13.
    Libman IM, Barinas-Mitchell E, Bartuccil A, Robertson R, Arslanian S (2008) Reproducibility of the oral glucose tolerance test in overweight children. J Clin Endocrinol Metab 93:4231–4237CrossRefGoogle Scholar
  14. 14.
    Abdul-Ghani MA, Matsuda M, Balas B, DeFronzo RA (2007) Muscle and liver insulin resistance indexes obtained from the oral glucose tolerance test. Diabetes Care 30:89–94CrossRefGoogle Scholar
  15. 15.
    Sonko BJ, Murgatroyd PR, Goldberg GR, Coward WA, Ceesay SM, Prentice AM (1993) Non-invasive techniques for assessing carbohydrate flux: II. Measurement of deposition using 13C-glucose. Acta Physiol Scand 147:99–108CrossRefGoogle Scholar
  16. 16.
    Lewanczuk RZ, Paty BW, Toth EL (2004) Comparison of the [13C] glucose breath test to the hyperinsulinemic–euglycemic clamp when determining insulin resistance. Diabetes Care 27:441–447CrossRefGoogle Scholar
  17. 17.
    Ziakun AM, Maevskiĭ EI, Sokolov EI, Starkova NT, Davydov AL, Grishina EV, Kudriavtseva AI, Zakharchenko VN, Peshenko VP, Shidlovskiĭ M (2004) Evaluation of glucose utilization in patients with insulin-independent diabetes mellitus by using breathing test. Biofizika 49:948–957Google Scholar
  18. 18.
    Dillon EL, Janghorbani M, Angel JA, Casperson SL, Grady JJ, Urban RJ, Volpi E, Sheffield-Moore M (2009) Novel noninvasive breath test method for screening individuals at risk for diabetes. Diabetes Care 32:430–435CrossRefGoogle Scholar
  19. 19.
    Singal P, Janghorbani M, Schuette SA, Chisholm R, Mather KJ (2010) Intra-individual variability of CO2 breath isotope enrichment compared to blood glucose in the oral glucose tolerance test. Diabetes Technol Ther 12:947–953CrossRefGoogle Scholar
  20. 20.
    Maldonado-Hernández J, Martínez-Basila A, Matute González MG, López-Alarcón MG (2014) The [13C] glucose breath rest is a reliable method to identify insulin resistance in Mexican adults without diabetes: comparison with other insulin resistance surrogates. Diabetes Technol Ther 16:1–7CrossRefGoogle Scholar
  21. 21.
    Ibarra-Pastrana E, Candia Plata MC, Álvarez G, Valencia ME (2012) Estimation of insulin resistance in Mexican adults by the [13C] glucose breath test corrected for endogenous total CO2 production. Intl J Endocrinol 2012:907818. CrossRefGoogle Scholar
  22. 22.
    Ghosh C, Mukhopadhyay P, Ghosh S, Pradhan M (2015) Insulin sensitivity index (ISI0, 120) potentially linked to carbon isotopes of breath CO2 for pre-diabetes and type 2 diabetes. Sci Rep. Google Scholar
  23. 23.
    Salas Fernández A, Maldonado Hernández J, Martínez Basila A, Martínez Razo G, Jasso-Saavedra F (2015) The 13C-glucose breath test is a valid non-invasive screening tool to identify metabolic syndrome in adolescents. Clin Chem Lab Med 53:133–138CrossRefGoogle Scholar
  24. 24.
    Tam CS, Xie W, Johnson WD, Cefalu WT, Redman LM, Ravussin E (2012) Defining insulin resistance from hyperinsulinemic–euglycemic clamps. Diabetes Care 35:1605–1610CrossRefGoogle Scholar
  25. 25.
    Braden B, Lembcke B, Kuker W, Caspary WF (2007) 13C-breath tests: current state of the art and future directions. Dig Liver Dis 39:795–805CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2019

Authors and Affiliations

  1. 1.Unidad de Investigación Médica en Nutrición, Hospital de PediatríaCentro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro SocialMéxico CityMexico
  2. 2.Unit of Research in Clinical EpidemiologyCentro Médico Nacional “Siglo XXI”, Instituto Mexicano del Seguro SocialMexico CityMexico

Personalised recommendations