The entero-endocrine response following a mixed-meal tolerance test with a non-nutritive pre-load in participants with pre-diabetes and type 2 diabetes: A crossover randomized controlled trial proof of concept study

Mirthe Muilwijk, Joline W. J. Beulens, Lenka Groeneveld, Femke Rutters, Marieke T. Blom, Valeria Agamennone, Tim van den Broek, Bart J. F. Keijser, Femke Hoevenaars

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Abstract

Introduction This crossover randomized controlled trial (RCT) investigated differences in short-term entero-endocrine response to a mixed-meal tolerance test preceded by nutrient sensing between participants with pre-diabetes (pre-T2D) and type 2 diabetes (T2D). Additionally, differences in gut and oral microbiome composition between participants with a high and low entero-endocrine response were investigated. Research design and methods Ten participants with pre-T2D and ten with T2D underwent three test days with pre-loads consisting of either swallowing water (control), or rinsing with a non-nutritive sweetener solution, or swallowing the sweetener solution before a mixed-meal tolerance test. Blood glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), glucagon, glucose, insulin and peptide YY (PYY) were determined at t = -20, 0, 15, 30, 60, 120 and 240 minutes. The composition of the oral and gut microbiome at baseline were also determined. Results The entero-endocrine response differed by pre-loads, e.g. a lower PYY response after swallowing the non-nutritive sweetener (-3585.2pg/mL [95% CI: -6440.6; -729.8]; p = 0.01). But it also differed by T2D status, e.g. a higher glucose, glucagon and PYY response was found in participants with T2D, compared to those with pre-T2D. Evidence for associations between the oral and gut microbiome composition and the entero-endocrine response was limited. Still, the level of entero-endocrine response was associated with several oral microbiome measures. Higher oral anterior α-diversity was associated with a lower PYY response (e.g. Inverse Simpson index -1357pg/mL [95% CI -2378; -336; 1.24]), and higher oral posterior α-diversitywith a higher GIP response (e.g. Inverse Simpson index 6773pg/mL [95% CI 132; 13414]) in models adjusted for sex, age and T2D status. Conclusions Non-nutritive pre-loads influence the entero-endocrine response to a mixed-meal, and this effect varies based on (pre-)T2D status. The entero-endocrine response is likely not associated with the gut microbiome, and there is limited evidence for association with the α-diversity of the oral microbiome composition.

Original languageEnglish
Article numbere0290261
Pages (from-to)e0290261
JournalPLOS ONE
Volume18
Issue number8 August
DOIs
Publication statusPublished - Aug 2023

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