Metabolite profiles during oral glucose challenge

Jennifer E. Ho, Martin G. Larson, Ramachandran S. Vasan, Anahita Ghorbani, Susan Cheng, Eugene P. Rhee, Jose C. Florez, Clary B. Clish, Robert E. Gerszten, Thomas J. Wang

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

To identify distinct biological pathways of glucose metabolism, we conducted a systematic evaluation of biochemical changes after an oral glucose tolerance test (OGTT) in a community-based population. Metabolic profiling was performed on 377 nondiabetic Framingham Offspring cohort participants (mean age 57 years, 42% women, BMI 30 kg/m2) before and after OGTT. Changes in metabolite levels were evaluated with paired Student t tests, cluster-based analyses, and multivariable linear regression to examine differences associated with insulin resistance. Of 110 metabolites tested, 91 significantly changed with OGTT (P ≤ 0.0005 for all). Amino acids, β-hydroxybutyrate, and tricarboxylic acid cycle intermediates decreased after OGTT, and glycolysis products increased, consistent with physiological insulin actions. Other pathways affected by OGTT included decreases in serotonin derivatives, urea cycle metabolites, and B vitamins. We also observed an increase in conjugated, and a decrease in unconjugated, bile acids. Changes in β-hydroxybutyrate, isoleucine, lactate, and pyridoxate were blunted in those with insulin resistance. Our findings demonstrate changes in 91 metabolites representing distinct biological pathways that are perturbed in response to an OGTT. We also identify metabolite responses that distinguish individuals with and without insulin resistance. These findings suggest that unique metabolic phenotypes can be unmasked by OGTT in the prediabetic state. Diabetes 62:2689-2698, 2013.

Original languageEnglish (US)
Pages (from-to)2689-2698
Number of pages10
JournalDiabetes
Volume62
Issue number8
DOIs
StatePublished - Aug 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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  • Cite this

    Ho, J. E., Larson, M. G., Vasan, R. S., Ghorbani, A., Cheng, S., Rhee, E. P., Florez, J. C., Clish, C. B., Gerszten, R. E., & Wang, T. J. (2013). Metabolite profiles during oral glucose challenge. Diabetes, 62(8), 2689-2698. https://doi.org/10.2337/db12-0754