The carbon dioxide production rate assumption biases gastric emptying parameters in healthy adults

Rationale An altered gastric emptying (GE) rate has been implicated in the aetiology of obesity. The ¹³C-octanoic acid breath test (OBT) is frequently used to measure GE, and the cumulative percentage of ¹³C recovered (cPDR) is a common outcome measure. However, true cPDR in breath is dependent on accurate measurement of carbon dioxide production rate (V̇CO₂). The current study aimed to quantify differences in the ¹³C OBT Results obtained using directly measured V̇CO₂ (V̇CO₂DM) compared with (i) predicted from resting V̇CO ₂ (V̇CO₂PR) and (ii) predicted from body surface area V̇CO₂ (V̇CO₂BSA). Methods The GE rate of a high-fat test meal was assessed in 27 lean subjects using the OBT. Breath samples were gathered during the fasted state and at regular intervals throughout the 6-h postprandial period for determination of ¹³C- isotopic enrichment by continuous-flow isotope-ratio mass spectrometry. The V̇CO₂ was measured directly from exhaled air samples and the PDR calculated by three Methods. The bias and the limits of agreement were calculated using Bland-Altman plots. Results Compared with the V̇CO ₂DM, the cPDR was underestimated by V̇CO₂PR (4.8%; p = 0.0001) and V̇CO₂BSA (2.7%; p = 0.02). The GE T_half was underestimated by V̇CO₂PR (13 min; p = 0.0001) and V̇CO₂BSA (10 min; p = 0.01), compared with V̇CO ₂DM. Conclusions The findings highlight the importance of directly measuring V̇CO₂ production rates throughout the ¹³C OBT and could partly explain the conflicting evidence regarding the effect of obesity on GE rates.