Early expression of neuroinflammation in an untreated fatal case of diabetic ketoacidosis

Abstract

SUMMARY We present the case of a young adult who had lethargy and significant weight loss for the three weeks before his death. The history of the present illness suggested a prodrome of several weeks, with progressive weakness indicating an advancing metabolic decompensation. To our knowledge, this is the first study performed on human brain tissue with type 1 diabetes (T1D) and likely diabetic ketoacidosis (DKA) before treatment. We studied neuroinflammatory markers in an insulin-deficient state without treatment compared with those found in a treated patient with T1D/DKA of similar age and race who died shortly after treatment. The frontal cortex and hippocampus were stained for tight junction proteins, RAGE, NLRP3, and HMGB1. Other markers that can disrupt the blood-brain barrier, such as IL-17, IL-6, IL-1β, GFAP, and IL-10 were also tested. This case study reveals that neuroinflammatory markers are expressed in the DKA brain at a lower level before treatment than those found to be expressed in the brain after treatment. These findings suggest that in DKA, dehydration minimizes inflammation which could be exacerbated with fluids promoting neuroinflammation and cognitive deficits. These findings require further studies and could identify therapeutic targets to reduce the progression of neuroinflammation and brain edema.