High Prevalence of A-β+ Ketosis-Prone Diabetes in Children with Type 2 Diabetes and Diabetic Ketoacidosis at Diagnosis: Evidence from the Rare and Atypical Diabetes Network (RADIANT)

Background. A(-)beta(+) ketosis-prone diabetes (KPD) in adults is characterized by presentation with diabetic ketoacidosis (DKA), negative islet autoantibodies, and preserved beta-cell function in persons with a phenotype of obesity-associated type 2 diabetes (T2D). The prevalence of KPD has not been evaluated in children. We investigated children with DKA at "T2D" onset and determined the prevalence and characteristics of pediatric A(-)beta(+) KPD within this cohort. Methods. We reviewed the records of 716 children with T2D at a large academic hospital and compared clinical characteristics of those with and without DKA at onset. In the latter group, we identified patients with A(-)beta(+) KPD using criteria of the Rare and Atypical Diabetes Network (RADIANT) and defined its prevalence and characteristics. Results. Mean age at diagnosis was 13.7 +/- 2.4 years: 63% female; 59% Hispanic, 29% African American, 9% non-Hispanic White, and 3% other. Fifty-six (7.8%) presented with DKA at diagnosis and lacked islet autoantibodies. Children presenting with DKA were older and had lower C-peptide and higher glucose concentrations than those without DKA. Twenty-five children with DKA (45%) met RADIANT A(-)beta+ KPD criteria. They were predominantly male (64%), African American or Hispanic (96%), with substantial C-peptide (1.3 +/- 0.7 ng/mL) at presentation with DKA and excellent long-term glycemic control (HbA1c 6.6%+/- 1.9% at follow-up (median 1.3 years postdiagnosis)). Conclusions. In children with a clinical phenotype of T2D and DKA at diagnosis, approximately half meet criteria for A(-)beta(+) KPD. They manifest the key characteristics of obesity, preserved beta-cell function, male predominance, and potential to discontinue insulin therapy, similar to adults with A(-)beta(+) KPD.