Targeting Ketone Burden in Diabetic Ketoacidosis: A Novel IV Infusion Linking Glycine Cleavage, Cofactor Optimization, and Antioxidant Defense

Diabetic ketoacidosis (DKA) remains a critical emergency with ۱–۵% mortality and an annual U.S. healthcare burden >۲ 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 (۱۲–۲۴ h) and hospital stays (۳–۴ 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 ۳۰–۴۰% in metabolic models. Thiamine (pyrophosphate form) activates pyruvate dehydrogenase, reducing lactate accumulation by ~۲۵%, while NAC restores glutathione, lowering oxidative markers by up to ۵۰%. Kinetic modeling predicts accelerated acidosis correction (pH from ۶.۹ to ۷.۳ within hours) and faster ketone elimination, potentially shortening recovery to ۶–۸ hours. Feasibility is supported by low production costs (۸–۱۵ USD/L) and physiologic osmolarity (۲۸۰–۳۱۰ mOsm/L). This framework redefines DKA as a treatable metabolic network disorder and warrants early-phase clinical trials to validate safety and efficacy.

کلیدواژه ها:

Diabetic ketoacidosis ، intravenous infusion ، glycine cleavage system ، thiamine pyrophosphate ، N-acetylcysteine ، ketone metabolism