Post-Fasting Respiratory Quotient as a Marker of Metabolic Inflexibility in Severe Obesity

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Introduction Metabolic flexibility – the ability to shift between carbohydrate and fat oxidation – helps maintain energy balance. In severe obesity, this flexibility often declines, leading to higher respiratory quotient (RQ) and lower fat oxidation during fasting. Continuous glucose monitoring (CGM) may reveal how this inflexibility relates to altered glucose handling. We examined whether shifts in substrate oxidation correlate with CGM metrics during extended fasting in severe obesity. Methods This predefined subanalysis is part of an ongoing trial that characterizes metabolic phenotypes in severe obesity (BMI≥40 kg/m 2 , no type 2 diabetes). Thirteen participants (mean age 46.15±12.81 years, BMI 46.58±7.16, 38.5% male) wore CGM devices while on a standardized diet for three days (Day 1-3). On Day 4, after overnight fasting, resting metabolic rate (RMR) and RQ (3×20 min) were measured using indirect calorimetry; body composition was measured via BodPod. Participants then continued water-only fasting until Day 5, when RMR and RQ were reassessed. CGM data covered a 27-hour fast (06:00 Day 1 to 09:00 Day 2). We calculated average glucose, area under the curve (AUC), and other glycemic variables, relating them to RQ. Results Mean pre- and post-fasting RQ were 0.77±0.07 and 0.74±0.07, respectively. Glucose AUC was 148,832±17,139 mg×min/dL. Post-fasting RQ positively correlated with glucose AUC and other glycemic parameters (e.g., mean glucose, glucose variability). A larger drop in RQ from pre- to post-fasting showed a trend toward lower glucose AUC (r=0.497, p=0.08). Conclusion A higher post-fasting RQ – and thus a smaller shift in substrate oxidation – may be linked to less favorable glycemic profiles in severe obesity. These results highlight the potential importance of metabolic flexibility in glycemic control during prolonged fasting and support the need for larger studies to validate these findings. Publication History Article published online: 28 May 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

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