Prevalence, clinical characteristics and HLA genotypes of idiopathic type 1 diabetes: A cross-sectional study.

ABSTRACT

AIMS: Idiopathic type 1 diabetes (T1D) is a neglected subtype of T1D. Our aim was to investigate the frequency, clinical characteristics, and human leucocyte antigen (HLA) genotypes of idiopathic T1D. METHODS: We enrolled 1205 newly diagnosed T1D patients in our analysis. To exclude monogenic diabetes in autoantibody-negative patients, we utilised a custom monogenic diabetes gene panel. Individuals negative for autoantibodies and subsequently excluded for monogenic diabetes were diagnosed with idiopathic T1D. We collected clinical characteristics, measured islet autoantibodies by radioligand assay and obtained HLA data. RESULTS: After excluding 11 patients with monogenic diabetes, 284 cases were diagnosed with idiopathic T1D, accounting for 23.8% (284/1194) of all newly diagnosed T1D cases. When compared with autoimmune T1D, idiopathic T1D patients showed an older onset age, higher body mass index among adults, lower haemoglobin A1c, higher levels of fasting C-peptide and 2-h postprandial C-peptide, and were likely to have type 2 diabetes (T2D) family history and carry 0 susceptible HLA haplotype (all p < 0.01). A lower proportion of individuals carrying 2 susceptible HLA haplotypes in idiopathic T1D was observed in the adult-onset subgroup (15.7% vs. 38.0% in child-onset subgroup, p < 0.001) and in subgroup with preserved beta-cell function (11.0% vs. 30.1% in subgroup with poor beta-cell function, p < 0.001). Multivariable correlation analyses indicated that being overweight, having T2D family history and lacking susceptible HLA haplotypes were associated with negative autoantibodies. CONCLUSIONS: Idiopathic T1D represents about 1/4 of newly diagnosed T1D, with adult-onset and preserved beta-cell function patients showing lower HLA susceptibility and more insulin resistance.