New Aspects in the Pathogenesis of Diabetic Ketoacidosis: Integration of Experimental and Clinical Data

The review highlights modern mechanisms underlying the pathogenesis of diabetic ketoacidosis (DKA) based on the analysis of experimental and clinical data. It describes molecular pathways involving activation of the nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome, followed by the release of pro-inflammatory cytokines interleukin-ie (IL-1P) and interleukin-18 (IL-18), as well as the initiation of в-cell pyroptosis in the pancreatic islets of Langerhans. Mitochondrial dysfunction and increased oxidative stress are discussed as contributors to cellular damage and amplification of the inflammatory response.

The dysregulation of pancreatic а-cells with enhanced glucagon secretion, stimulating gluconeogenesis and keto­genesis, is analyzed. The role of the kidneys in maintaining ketone body levels is considered, including filtration, reabsorption, and interactions with lipid signaling pathways that influence insulin resistance and inflammation. Central neurohumoral mechanisms involving the hypothalamic pituitary axis and the sympathetic nervous system are described, as well as the distinctive features of DKA developing during therapy with sodium-glucose cotrans­porter type 2 (SGLT2) inhibitors.

The importance of osmotic stress and its interplay with counter-regulatory hormones is emphasized. An integrative model is presented that unites inflammatory, metabolic, endocrine, and renal components, providing a deeper understanding of the clinical manifestations of DKA and offering prospects for the development of new diagnostic and therapeutic strategies.

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