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. 2022 Nov 14;12(11):2783.
doi: 10.3390/diagnostics12112783.

Divergent Effects of Glycemic Control and Bariatric Surgery on Circulating Concentrations of TMAO in Newly Diagnosed T2D Patients and Morbidly Obese

Marina Canyelles  1   2 , Antonio Pérez  2   3 , Alexandra Junza  2   4 , Inka Miñambres  2   3 , Oscar Yanes  2   4 , Helena Sardà  3 , Noemí Rotllan  1   2 , Josep Julve  1   2 , José Luis Sánchez-Quesada  1   2 , Mireia Tondo  2   5 , Joan Carles Escolà-Gil  1   2 , Francisco Blanco-Vaca  2   5   6
Affiliations

Divergent Effects of Glycemic Control and Bariatric Surgery on Circulating Concentrations of TMAO in Newly Diagnosed T2D Patients and Morbidly Obese

Marina Canyelles et al. Diagnostics (Basel). .

Abstract

High circulating concentrations of the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) are significantly associated with the risk of obesity and type 2 diabetes (T2D). We aimed at evaluating the impact of glycemic control and bariatric surgery on circulating concentrations of TMAO and its microbiota-dependent intermediate, γ-butyrobetaine (γBB), in newly diagnosed T2D patients and morbidly obese subjects following a within-subject design. Based on HbA1c concentrations, T2D patients achieved glycemic control. However, the plasma TMAO and γBB concentrations were significantly increased, without changes in estimated glomerular filtration rate. Bariatric surgery was very effective in reducing weight in obese subjects. Nevertheless, the surgery reduced plasma γBB concentrations without affecting TMAO concentrations and the estimated glomerular filtration rate. Considering these results, an additional experiment was carried out in male C57BL/6J mice fed a Western-type diet for twelve weeks. Neither diet-induced obesity nor insulin resistance were associated with circulating TMAO and γBB concentrations in these genetically defined mice strains. Our findings do not support that glycemic control or bariatric surgery improve the circulating concentrations of TMAO in newly diagnosed T2D and morbidly obese patients.

Keywords: glycemic control; liquid chromatography–mass spectrometry; obesity; trimethylamine N-oxide; type 2 diabetes; γ-butyrobetaine.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of the data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Serum TMAO (A) and γBB (B) levels in type 2 diabetic subjects at baseline and follow-up. Each pair of symbols with a line represents a participant before and after glycemic control. Wilcoxon matched-pairs signed rank test was performed to compare data.
Figure 2
Figure 2
Serum TMAO (A) and γBB (B) levels in morbidly obese subjects at baseline and one year after bariatric surgery. Each pair of symbols with a line represents a participant before and after bariatric surgery. Wilcoxon matched-pairs signed rank test was performed to compare data.
Figure 3
Figure 3
Weight and HOMA-IR (A) and serum TMAO and γBB (B) levels in C57BL6/6J mice fed with a Western-type diet. A Friedman test followed by a Dunn’s multiple comparisons test were performed in time-course analyses of mice. * p = 0.0002 (weight at 12 vs. 20 weeks) † p = 0.0005 (HOMA-IR at 12 vs. 20 weeks).
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