A new study presented at this year's European Society for the Study of Diabetes Annual Congress (September 9-13, Madrid, Spain) finds that after the age of 10, girls' risk of developing type 1 diabetes (T1D) drops significantly, while boys' risk remains the same.
Furthermore, boys with only one autoantibody were at significantly higher risk of T1D than girls, suggesting that gender may be associated with autoantibody development and highlighting the importance of considering gender in risk assessment.The study was by Erin L. Templeman and Richard Oram, PhD, of the University of Exeter Medical School in Exeter, UK, and colleagues.
Autoantibodies (AB) are proteins produced by the body's immune system that attack other proteins in autoimmune diseases such as type 1 diabetes.
In contrast to most autoimmune diseases, being male is a risk factor for type 1 diabetes (T1D). This raises the hypothesis that immune, metabolic, or other differences between the sexes may affect the risk or progression of each stage of T1D. In this study, the authors aimed to assess risk and progression rates in participants of the TrialNet Pathway to Prevention study, which tests for the presence of autoantibodies in relatives of T1D patients.
Authors The study included 235,765 relatives of people with type 1 diabetes. Using computers and statistical models, the researchers calculated the risk of type 1 diabetes as a 5-year estimated risk for women and men, after adjusting for confounding factors.
The proportion of people with a positive AB test was higher in men (women: 5.0%, men: 5.4%). Of these people, men were more likely to have multiple positive AB tests (women: 1.8%, men: 2.6%). The absolute 5-year risk of progression to type 1 diabetes among people with a single AB positive test was significantly higher in men (women: 14%, men: 21%).
However, men and women showed similar risks for stage 1 (at least two ABs) (women: 38%, men: 38%) or stage 2 (AB and abnormal glycemic stability) (women: 57%, men: 59%). When taking into account the presence of a first-degree relative with T1D and age, the risk for AB-positive men was still significantly higher (27% higher risk for AB-positive men compared to AB-positive women).
Females who were screened after age 10 years and tested positive for autoantibodies have been shown to have a significantly reduced 5-year T1D risk compared with those screened before age 10 years (see Figure 1 in the overview). In contrast, males have been shown to have a steadily decreasing 5-year T1D risk with increasing age at screening.
The authors conclude: “With only one autoantibody, men are at significantly higher risk for type 1 diabetes than women. Boys and girls are at similar risk during childhood, but the risks differ at age 10 years. Thereafter, women's risk decreases significantly, while men's risk persists. This suggests that sex is associated with autoantibody development and highlights the importance of incorporating sex into risk assessment.“
Regarding the difference in risk between boys and girls, the authors add:“We don't know, but this is an interesting area that needs further study. The change in risk around age 10 raises the hypothesis that puberty-related hormones may play a role.”
They added: “The greatest differences in risk of T1D were seen in individuals who had not progressed to stage 1 T1D, with similar rates and risks of progression to stage 1 and stage 2 T1D. Thus, explaining the mechanisms of sex differences is likely to help us understand the underlying etiology of T1D and potential intervention targets, as well as impact how we screen, diagnose, and intervene.”