ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2019) 16 10.10 | DOI: 10.1530/ey.16.10.10

Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland


To read the full abstract: Pediatr Diabetes. 2018 Nov;19(7):1221–1228

Despite good metabolic control some patients with type 1 diabetes (T1D) may develop comorbidities early while others despite high HbA1c levels remain free of complications for long durations. Risk factors for T1D complications are both of intrinsic (e.g. genetic) and extrinsic (e.g. environmental) origin. Amongst the intrinsic risk factors for progressive disease, ethnicity, gender and age at T1D onset are debated.

This study tested the hypothesis that girls have a more aggressive disease process than boys at the very beginning of T1D. Sociodemographic and clinical characteristics, autoantibody expression, and the genetic risk as assessed by the presence of HLA DR-DQ haplotypes were analyzed in relation to sex of the patients in a large cohort of 4993 children and adolescents diagnosed with T1D between January 2003 and December 2016 in Finland. Interestingly, the cohort comprised a prominent male preponderance (56.6%) and boys were significantly older than girls at T1D onset (mean 8.3 vs 7.7 years, P<0.001).

Age-adjusted analyses showed a worse metabolic decompensation in girls than boys at T1D diagnosis. Boys tested more often positive for anti-insulin autoantibodies, anti-islet antigen-2 autoantibodies, and anti-zinc transporter 8 autoantibodies, whereas girls had a higher frequency of anti-glutamic acid decarboxylase autoantibodies (GADA) and higher GADA and islet cell antibody titers. No difference in the genetic risk profile between girls and boys was detected.

These data show that metabolic derangement was more severe in girls already at diagnosis of T1D. Importantly, this difference was independent of age. The immunologic aggressiveness of the disease is more variable as the predominance of different autoantibodies varies between the sexes with a higher frequency of GADA in girls, while the 3 other autoantibodies were more common in boys. This study very clearly points to genetic factors that are responsible for the progression of T1D and strengthen the view that sex is an important factor that contributes to the aggressiveness of autoimmune disease.

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