Characterisation of islet antibody‐negative type 1 diabetes mellitus in Indian children

Abstract

AimsIslet antibody‐negative type 1 diabetes mellitus (T1DM) has not been well characterised. We determined the frequency of antibody‐negative T1DM and compared it with antibody‐positive T1DM in a cohort of north Indian children.MethodsIn a multi‐centre, prospective, observational study, 176 Indian children (age 1–18 years) were assessed within 2 weeks of diagnosis of T1DM. Antibodies against GAD65 (GADA), islet antigen‐2 (IA‐2A) and zinc transporter 8 (ZnT8A), were estimated using validated ELISA. HLA‐DRB1, DQA1 and DQB1 alleles were studied by Luminex‐based typing. Monogenic diabetes was determined by targeted next‐generation sequencing using the Illumina platform.ResultsAfter excluding 12 children with monogenic diabetes, GADA, IA‐2A and ZnT8A were present in 124 (76%), 60 (37%) and 62 (38%) o children, respectively, while 24 (15%) were negative for all antibodies. A single antibody (most frequently GADA) was present in 68 (41%) of children, while all three antibodies were found in 34 (21%). Islet antibody‐negative T1DM (n = 24, 15%) did not differ from antibody‐positive children in their clinical features, HbA1c or plasma C‐peptide, both at onset or after 1 year follow‐up (available in 62 children). The frequency of other organ‐specific antibodies or high‐risk HLA‐DR and DQ alleles were also similar. Children with a single islet antibody did not differ from those with multiple antibodies.ConclusionsThe frequency of various islet‐antibodies, in isolation and combination, differed considerably from studies among children of European descent with T1DM. Children with T1DM who were islet antibody‐negative were indistinguishable from those who were antibody‐positive.