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

Akl, Maher; Ahmed, Amr

doi:10.30491/ijtmgh.2025.544662.1503

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

Document Type : Perspective

Authors

Maher Akl ¹

Amr Ahmed ²

¹ Faculty of Medicine, National Research Lobachevsky State University of Nizhny Novgorod, 603022, Nizhny Novgorod, Russia.

² The public health department, Riyadh First Health Cluster, Ministry of Health, Saudi Arabia

10.30491/ijtmgh.2025.544662.1503

Abstract

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.

Keywords

Diabetic ketoacidosis

intravenous infusion

glycine cleavage system

thiamine pyrophosphate

N-acetylcysteine

ketone metabolism