First-emerging islet autoantibody and glucose metabolism: search for type 1 diabetes subtypes

Endocr Connect. 2022 Jul 1;EC-21-0632. doi: 10.1530/EC-21-0632. Online ahead of print.


Objective: Subtypes in type 1 diabetes pathogenesis have been implicated based on the first appearing autoantibody (primary autoantibody). We set out to describe the glucose metabolism in preclinical diabetes in relation to the primary autoantibody in children with HLA-conferred disease susceptibility.

Design and methods: Dysglycemic markers were defined as 10% increase in HbA1c in a 3-12 months interval or HbA1c ≥5.9% (41mmol/mol) in two consecutive samples, impaired fasting glucose or impaired glucose tolerance, or a random plasma glucose value ≥7.8mmol/l. A primary autoantibody could be detected in 295 children who later developed at least one additional biochemical autoantibody. These children were divided into groups: IAA multiple (n=143), GADA multiple (n=126) and IA-2A multiple (n=26). Another 229 children seroconverted to positivity only for a single biochemical autoantibody and were grouped: IAA only (n=87), GADA only (n=114) and IA-2A only (n=28).

Results: No consistent differences were observed in selected autoantibody groups during the preclinical period. At diagnosis, children with IAA only showed the highest HbA1c (P<0.001 between groups) and the highest random plasma glucose (P=0.005 between groups). Children with IA-2A only progressed to type 1 diabetes as frequently as those with IA-2A multiple (46% vs 54%, P=0.297) whereas those with IAA only or GADA only progressed less often than children with IAA multiple or GADA multiple (22% vs 62% (P<0.001) and 7% vs 43% (P<0.001)), respectively.

Conclusions: The phenotype of preclinical diabetes defined by the primary autoantibody is not associated with any discernible differences in glucose metabolism before the clinical disease manifestation.