Increased activity of inflammasomes as osmosensors as cause of cerebral edema in diabetic ketoacidosis

Diabetic ketoacidosis (DKA) related cerebral edema (CE) is associated with a high mortality and rate of neurodisability and neurocognitive difficulties. In 54% of children with DKA there is subclinical evidence of CE on MRI studies. It is known that DKA is accompanied by a systemic inflammatory response characterized by elevated cytokine levels including interleukin-1 (IL-1) and interleukin-6. IL-1 has been linked to the pathogenesis of CE. Inflammasomes like nucleotide binding domain and leucine-rich repeat containing proteins 3 (NRLP3) are multiprotein complexes generating the active form of IL-1 in response to high glucose levels. The resulting hypothesis is that increased activity of inflammasomes as osmosensors is the cause of CE in diabetic ketoacidosis. Confirmation of the hypothesis could be achieved by correlation of IL-1 and NRLP3 levels and expression with degree of subclinical CE on MRI imaging and peripheral blood glial fibrillary acidic protein levels (a marker of brain injury). If confirmed future randomized controlled trials could use NRLP3 inhibitors and IL-1 antagonists as auxiliary treatment in DKA and measure neurocognitive outcome. Correspondence to: Michael Eisenhut, Luton and Dunstable University Hospital NHS Foundation Trust, Lewsey Road, Luton, LU4ODZ, United Kingdom, E-mail: [email protected]