Diabetic ketoacidosis and oxidative stress: pathophysiological mechanisms

Abstract

Diabetes mellitus (DM) is a common endocrine disease with a large number of acute and chronic complications, among which diabetic ketoacidosis (DKA) is the most frequent and severe, especially in children and adolescents with type 1 DM. Oxidative stress (OS) is a pathological condition that develops due to an imbalance between free radicals formation and inefficiency of the antioxidant system. OS is a strong risk factor for the development of numerous diabetic complications. Recently OS has been considered as an important component of DKA, the pathophysiological mechanisms of which have not yet been fully elucidated. This paper describes hypotheses according to which OS not only triggers and exacerbates manifestations of DKA, but itself represents a severe consequence of DKA, leading to the progression of numerous micro- and macroscopic diabetic complications. The formation of glycation end products, activation of protein kinase C, polyol and hexosamine pathways are considered among the key pathophysiologic mechanisms of OS development in DKA. Achieving a better understanding of OS pathogenesis in DKA will optimize the diagnosis of OS and approaches to DKA correction through timely prescription of antioxidants.