Abstract 43: Prevalence of islet-autoantibodies and monogenic diabetes in children with recent onset type 1 diabetes mellitus: A multicenter study

Background: Previous smaller studies have shown higher prevalence of islet-antibody negative Type 1 diabetes mellitus (T1DM) among Indians compared to Caucasians. Islet-antibody negative (Type 1B) diabetes is not well characterized. Aims and Objectives: To study the prevalence of islet-autoantibodies, characterize type 1B diabetes, and determine the role of enterovirus infections and monogenic diabetes in children and adolescents with recent onset T1DM. Results: Among 111 patients, frequency of islet-autoantibody positivity were: GAD65-73%, IA2-35% and ZnT8-34%. 20 (18%) were negative for all 3 islet-autoantibodies. There were no significant clinical, biochemical or HLA allelic frequency differences between antibody negative and positive group. None of the ninety subjects tested showed evidence of enterovirus infection in serum by RT-PCR. Of the seven Type 1B patients without ketoacidosis tested, 2 had pathogenic mutations: one each in WFS 1 [homozygous c.2006A>G (p.Tyr669Cys)] and HNF4a [heterozygous c.998G>A (p.Arg333His)] loci. An additional 2 subjects had mutations of uncertain significance: one each in WFS 1 [heterozygous c.1522_1523del (p.Tyr508CysfsTer34)] and ABCC 8 [Heterozygous c.3784G>A (p.Ala1262Thr)] loci. Conclusions: A significant proportion of patients with T1DM were negative for islet antibodies at onset, but did not differ clinically or biochemically. Monogenic diabetes was found in a proportion of patients with type 1B diabetes.