Predicting glycemic control in patients with impaired fasting glucose with fasting respiratory exchange ratio

Context: Impaired metabolic flexibility is associated with prediabetes. However, its assessment with reference methods is impractical in routine clinical practice. Objective: This study investigates the relationship between fasting respiratory exchange ratio (RER), measured through indirect calorimetry, and glucose metabolism in individuals with prediabetes. Methods: The study involved 2 cohorts: (1) a cross-sectional cohort of 10 176 individuals to assess the association between fasting RER and glucose metabolism parameters, and (2) a matched longitudinal cohort of 86 patients with impaired fasting glucose, categorized into fat oxidation (RER < 0.775) and glucose oxidation (RER > 0.925) groups, to evaluate the impact of fasting RER on impaired fasting glucose resolution and fasting glucose after a 1-year lifestyle intervention. Results: In the cross-sectional cohort, a higher fasting RER was associated with higher fasting glucose, insulin, and Homeostatic Model Assessment for Insulin Resistance. In the longitudinal cohort, the fat oxidation group showed a greater reduction in fasting glucose (+5.9; 95% CI 1.4, 10; P = .011) and a higher probability of achieving normal fasting glycemia (log(odds ratio) −0.89; 95% CI −1.8, −0.03; P = .046) after the intervention, despite similar weight loss between groups. Conclusion: Our findings suggest that fasting RER, a readily accessible clinical measure, can provide valuable insights into glucose metabolism and impaired fasting glucose resolution. A lower fasting RER, indicative of a greater capacity for fat oxidation, is associated with improved glycemic control after a lifestyle intervention.