Types of pediatric diabetes mellitus defined by anti-islet autoimmunity and random C-peptide at diagnosis

Objective To test the hypothesis that anti-islet autoantibody expression and random serum C-peptide obtained at diagnosis define phenotypes of pediatric diabetes with distinct clinical features. Subjects We analyzed 607 children aged <19 yr consecutively diagnosed with diabetes after exclusion of 13% of cases with secondary diabetes (e.g., cystic fibrosis related, steroid induced) and 7.3% of cases lacking measurement of C-peptide and/or autoantibodies. Methods Autoantibody positivity (A+) was defined as ≥1 positive out of GAD65, insulin, and ICA512 antibodies. Preserved beta-cell function (β+) was defined as random serum C-peptide at diagnosis ≥ 0.6 ng/mL. Body mass index (BMI) was measured at median 1.2 months after diagnosis. Characteristics at diagnosis and 2 yr (range 18–30 months) after diagnosis were compared among groups. Results Autoantibody expression and C-peptide at diagnosis defined the following groups: A+β− (52.1% of the children), A+β+ (32.8%), A−β+ (12.5%), and A−β− (2.6%). These four groups differed in gender, race/ethnicity, and clinical characteristics at diagnosis [i.e., age, pubertal development, obesity/overweight, diabetic ketoacidosis, glycemia, and hemoglobin A1c (HbA1c)] and at 2 yr (i.e., clinical diagnosis, treatment, and HbA1c) (all p  2 ng/mL was associated with lower HbA1c at onset (p = 0.0001) and, in the A+β+ subgroup, with higher frequency of achieving HbA1c < 7% at 2 yr (p = 0.03). All three patients (0.7% of total) with monogenic diabetes (maturity onset diabetes of the young, MODY) were A−β+ with C-peptide between 0.6 and 2 ng/mL. Conclusions Anti-islet autoantibodies status and serum random C-peptide at diagnosis define four distinct phenotypes of pediatric diabetes with prognostic value.