The prevalence of insulin autoantibodies at the onset of Type 1 diabetes is higher in males than females during adolescence

Aims/hypothesis The incidence of Type 1 diabetes shows little sex bias up to age 15 years, but more males are diagnosed in early adult life. Humoral responses to the beta cell antigen insulin could help to reveal the mechanism underlying this difference. We therefore determined the influence of sex on the prevalence of insulin autoantibodies (IAA) at diagnosis.Methods IAA were measured by radiobinding assay in 598 patients with newly diagnosed Type 1 diabetes (aged 10.5, range 0.8–20.7 years, 333 male), and analysed according to age, sex and HLA class II genotype.Results Overall, 74% of males and 65% of females had IAA above the 97.5^th centile of 2860 schoolchildren (p=0.028). IAA prevalence was similar in males and females under the age of 15 (0–4 yr, 95% vs 88%; 5–9 yr, 76% vs 73%; 10–14 yr, 67% vs 58%), but male excess was seen between 15 and 21 years (66% vs. 32%, p_corr=0.016). HLA class II genotype was available for 426 patients. IAA prevalence in DR4 homozygous patients was 87%, in DR4 heterozygous patients 72% and in DR4 negative patients 55% (p<0.001). Multivariate analysis showed independent association of IAA with age (p<0.001), number of DR4 alleles (p<0.001) and male sex (p=0.002).Conclusions/interpretation The prevalence of IAA in patients with newly diagnosed Type 1 diabetes is higher in males than females between 15 and 21 years of age. The lower prevalence of IAA in adolescent females implies sex-specific modulation of the autoimmune process during puberty.Abbreviations IAA Insulin autoantibodies - IA-2 protein tyrosine phosphatase IA-2 - ICA islet cell antibodies