Ketoacidosis in the era of prediction

Abstract

Type 1 diabetes (T1D) is a common chronic autoimmune disease in childhood, often presenting abruptly and frequently complicated by diabetes ketoacidosis (DKA) at diagnosis. The natural history is currently conceptualized as a staged process reflecting progressive autoimmune and metabolic dysfunction.

Stage 1 is defined by the presence of multiple beta cell autoantibodies in individuals who remain normoglycemic and asymptomatic. Progression to stage 2 occurs when persistent multiple autoantibodies are associated with dysglycemia. Stage 3 corresponds to the onset of overt diabetes, defined by hyperglycemia meeting the glycemic and clinical diagnostic criteria of the American Diabetes Association. DKA frequently complicates the presentation of new-onset T1D in children, with reported rates of 15–70% in particularly among very young children and underserved populations.

Screening and monitoring strategies enable the identification of presymptomatic stages and early symptoms of T1D, thereby significantly reducing the incidence and severity of DKA at disease onset and hospitalization and promoting a more favorable metabolic trajectory following diagnosis. Beyond clinical benefits, screening enables children and families to engage in anticipatory guidance, a valuable opportunity for psychological preparation and appropriate educational training, improving acceptance of diagnosis and long-term disease management. It also allows the opportunity to receive potential immunomodulatory therapies, clinically or through research clinical trials, capable of delaying disease progression.

Participation in trials could not only potentially yield personal benefits for individuals receiving active study drug but also benefit the field, allowing for future clinical approval of other treatments or combination therapy approaches. However, implementation of structured early-stage T1D care pathways may be challenging due to a need for education among medical health providers, individuals, and caregivers, screening-related anxiety, and limited access to support teams. Addressing these barriers is essential to enable streamlined care delivery, reduce stress, and help maintain trust between individuals, families, and healthcare teams, ultimately reducing the risk of DKA and hospitalization.