Autoimmunity and clinical course in children with type 1, type 2, and type 1.5 diabetes

Both type 1 (T1D) and type 2 diabetes (T2D) are increasing in incidence in children; often an admixture of T1D and T2D features are present at diagnosis. We examined the relationship between diabetes autoantibodies (DAA), human leukocyte antigen (HLA), and clinical course in subjects grouped by clinical diabetes type.

Subjects 8-18 years old with T1D, T2D, and mixed clinical features (T1.5D), were studied at diagnosis. DAA were measured in all subjects; a subset of subjects underwent HLA genotyping. Clinical course was followed in 84% of subjects for 47.9+8.7 months.

Eighty-nine percent of T1.5D subjects were positive for at least one DAA; 88% of HLA-typed subjects had risk HLA genotypes. Two subjects initially treated with oral agents were subsequently treated with insulin (50%); one had risk HLA, and the other was DAA positive. Thirty-three percent of T2D subjects were DAA positive and 93% were treated with oral agents at diagnosis. Three subjects were subsequently treated with insulin (21%); of these, two were DAA positive, and one had risk HLA. No subject who remained on diet therapy or oral agents had a combination of DAA-positivity and risk HLA genotype.

Children clinically classified with T1.5D or T2D have a high frequency of autoimmune markers and T1D-associated HLA alleles which appears to indicate a more aggressive diabetes disease process, as has been shown for DAA-positive adults with phenotypic T2D.