International Travel Medicine Center of Iran International Journal of Travel Medicine and Global Health 2322-1100 14 2 2026 07 01 Targeting Ketone Burden in Diabetic Ketoacidosis: A Novel IV Infusion Linking Glycine Cleavage, Cofactor Optimization, and Antioxidant Defense 128 135 243282 10.30491/ijtmgh.2025.544662.1503 EN Maher Akl Faculty of Medicine, National Research Lobachevsky State University of Nizhny Novgorod, 603022, Nizhny Novgorod, Russia. 0000-0001-5480-1688 Amr Ahmed The public health department, Riyadh First Health Cluster, Ministry of Health, Saudi Arabia 0000-0003-3477-236X Journal Article 2025 09 02 Diabetic ketoacidosis (DKA) remains a critical emergency with 1–5% mortality and an annual U.S. healthcare burden >2 billion USD. Standard management (insulin, fluids, potassium, bicarbonate) halts ketogenesis but fails to accelerate ketone clearance, address oxidative stress, or replenish depleted cofactors imitations that prolong resolution (12–24 h) and hospital stays (3–4 days). We propose the DKA-Rescue IV infusion, a novel formulation combining Ringer’s lactate, sodium bicarbonate, potassium chloride, glycine, thiamine, and N-acetylcysteine (NAC). Glycine targets ketone burden via the mitochondrial glycine cleavage system, enhancing acetoacetate clearance by 30–40% in metabolic models. Thiamine (pyrophosphate form) activates pyruvate dehydrogenase, reducing lactate accumulation by ~25%, while NAC restores glutathione, lowering oxidative markers by up to 50%. Kinetic modeling predicts accelerated acidosis correction (pH from 6.9 to 7.3 within hours) and faster ketone elimination, potentially shortening recovery to 6–8 hours. Feasibility is supported by low production costs (8–15 USD/L) and physiologic osmolarity (280–310 mOsm/L). This framework redefines DKA as a treatable metabolic network disorder and warrants early-phase clinical trials to validate safety and efficacy. https://www.ijtmgh.com/article_243282_9717dc0b05ab0129ab206f34a16f1ad1.pdf