Roux-en-Y gastric bypass surgery (RYGB) alters postprandial glucose metabolism due to changes in gastrointestinal tract anatomy and large weight loss. Here, we propose a model quantifying postprandial hepatic and peripheral glucose fluxes in post-RYGB patients at steady weight loss and healthy controls (HC). Ten RYGB (2M, age=39.2±3.1 y, BMI=28±1 kg/m2 - mean±SE) and 10 HC (5M, age=36.4±3.2 y, BMI=26±1 kg/m2) underwent Deuterium Metabolic Imaging (DMI) at a 7 Tesla MR scanner before and after ingesting 60g of [6,6-2H2]-glucose (D-Glc). Venous blood was sampled to measure plasma insulin (I) and D-Glc (GP). Hepatic DMI was used to track liver D-Glc levels (GL) over 150min. Data was used to develop a model describing postprandial hepatic and peripheral glucose appearance (RaL and RaP) and disposal (RdL and RdP) as well as first-pass hepatic glucose extraction (ISE). Incremental Area Under the Curve (iAUC) of GL was greater in RYGB compared to HC (iAUC(GL)0-150min = 620±39 vs 467±41 mM·min, p=0.010), as was iAUC(I)0-150min (49.8±4.9 vs 29.2±3.4 nM·min, p=0.003), while iAUC(GP)0-150min was not significantly different (628±69 vs 520±26 mM·min). iAUCs of RaL and RaP normalized to 60g were higher in the first 60min in RYGB vs HC (63.0±3.0 vs 27.8±2.7 %; 60.5±3.1 vs 26.0±2.6 %, p<0.001), as were iAUCs of RdL and RdP after 150 min (24.6±1.1 vs 18.0±1.7 %, p=0.005; 53.6±2.9 vs 32.1±4.1 %, p<0.001). Conversely, model-derived ISE was similar (8.6±0.3 vs 8.8±0.7 %) in the two groups.<u></u> A model using stable isotope and liver DMI data was developed to quantify peripheral and organ-level glucose turnover without portal vein catheterization. Results showed that the difference in glucose time course in RYGB vs HC is explained by the faster rate of appearance in RYGB, while disposal, at both liver and periphery, appears to be intact. The model also suggests that no saturation arises in the first-pass extraction, despite the high glucose levels.

Disclosure

A. Brunasso: None. C. Dalla Man: None. S. Poli: None. D. Herzig: Speaker's Bureau; Ypsomed AG. R. Kreis: None. L. Bally: None. M. Schiavon: None.

Funding

PNRR Next Generation EU (ex DM 118/23)-Swiss National Science Foundation (PCEGP3_186978)

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