1132-OR: Effects of Ketogenic and Low-Carbohydrate Diet on Glucose and Weight Control in T2DM Patients along with Metabolome Change

Introduction and Objective: Few trials have explored associations between diets, diet-induced metabolomic changes, and metabolic outcomes in Type 2 diabetes (T2DM), especially weight-stratified management. This study aimed to identify diet-specific metabolomic signatures by defining ketogenic diet (KD) and low-carbohydrate diet (LCD) applicability in T2DM patients with varying body mass index (BMI). Methods: 611 T2DM patients were enrolled, 505 were included after excluding ineligible ones. All received metformin and were randomly assigned to LCD or KD. BMI-stratified medical phenotype analysis was performed, with clinical/serum profiles measured at baseline and 3 months. High-throughput untargeted chromatography-mass spectrometry analyzed serum metabolome. Associations between metabolites and diet intake were examined, and diet-induced metabolomic changes vs. diabetes prognosis were analyzed via correlation. Results: Of 611 randomized participants, 505 completed 12-week treatment. Weight-stratified analysis: Obese patients in KD group had most significant HbA1c (8.1±2.2 vs. 5.8±0.9%) and weight (88.5±15.8vs. 80.5±15.3kg) reductions. Overweight patients benefited from both diets for weight and glucose control. LCD had no weight loss effect in normal BMI patients. Metabolomic analysis identified 2410 markers post-intervention: KD group (279 vs.259, up and downregulated); LCD group (300 vs. 288). Correlation regression: for LCD group, weight negatively with Histidinyl Hydroxyproline; HbA1c positively with 4-hydroxyphenylacetylglutamic acid. As for KD group, HbA1c positively with Glutamyl Isoleucine, negatively with Diethanolamine. Conclusion: KD is most effective for obese patients, both diets are suitable for overweight patients, while LCD shows no weight loss benefits for patients with normal BMI. Metabolomic signatures sensitively reflect the effects of different diets and are closely associated with clinical metabolic improvements in T2DM, which is crucial for optimizing dietary strategies. Disclosure K. Zeng: None. Y. Wang: None. Y. Huang: None. G. Xu: None. Funding This work was supported by Distinguished Young Scientists projects (Siqing Talent project) by Guangdong Second Provincial General Hospital (Award number: 2024E005) to Kejing Zeng and the National Natural Science Foundation of China (81902004) and Basic and Applied Basic Research Foundation of Guangdong Province (2023A1515012575) to Kejing Zeng.