Modeling Hepatic Glucose Tracer Kinetics from Isotope Dilution Technique and Deuterium Metabolic Imaging in Post-Bariatric-Surgery and Non-Operated Individuals.

Abstract

Despite extensive research on liver metabolism, mathematical models describing hepatic glucose kinetics are currently limited due to the lack of organ-level data. Here, we propose a model of postprandial hepatic glucose kinetics exploiting liver Deuterium Metabolic Imaging (DMI) data combined with plasma isotope dilution analysis in humans. We used data from 10 individuals who had previously undergone Roux-en-Y Gastric Bypass surgery (RYGB) and 10 healthy controls (HC). The experimental setting included a labeled Oral Glucose Tolerance Test consisting of 60g of [6,6'-2H2]-glucose in combination with liver DMI at 7T. The hepatic glucose tracer signal was frequently quantified over 150 min, while peripheral plasma insulin and glucose tracer concentrations were measured in venous blood. The model was able to describe both liver and peripheral glucose tracer data well and provided estimates of postprandial glucose appearance and disposal in both the liver and the systemic circulation. The model predicted that almost all the ingested glucose had appeared in the liver in RYGB, but not in HC (89.0% vs. 64.0%, p=0.008) after 150 min, while total hepatic disposal (RYGB=26.4% vs. HC=29.7%) and first-pass extraction (RYGB=10.7% vs. HC=11.4%) were similar between populations. The fraction of glucose eliminated in the periphery was greater in RYGB (49.9% vs. 25.3%, p=0.003). Lastly, no differences were observed in hepatic blood flow and GLUT2 transport rates. Although further studies are needed to validate and extend the model to include endogenous glucose production and disposal, it can be used to quantify parameters, and possibly reveal defects, of hepatic glucose handling.