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Diabetes DOI:10.2337/db12-0754

Metabolite profiles during oral glucose challenge.

Publication TypeJournal Article
Year of Publication2013
AuthorsHo, JE, Larson, MG, Vasan, RS, Ghorbani, A, Cheng, S, Rhee, EP, Florez, JC, Clish, CB, Gerszten, RE, Wang, TJ
Date Published2013 Aug
KeywordsBlood Glucose, Female, Glucose Tolerance Test, Humans, Insulin, Insulin Resistance, Male, Metabolome, Middle Aged, Prediabetic State

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/m(2)) 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.


Alternate JournalDiabetes
PubMed ID23382451
PubMed Central IDPMC3717862
Grant ListN01HC25195 / HL / NHLBI NIH HHS / United States
R01 HL081572 / HL / NHLBI NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
R01-DK-HL-081572 / DK / NIDDK NIH HHS / United States