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

Aims: Islet 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.

Methods: In 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.

Results: After 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.

Conclusions: The 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.