Comorbidity between neurodevelopmental disorders and childhood-onset type 1 diabetes

Childhood-onset type 1 diabetes and neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, and intellectual disability, globally represent substantial health challenges. Each condition places a substantial challenge on the individuals, their families, and healthcare systems. The comorbidity between these two types of disorders has been a research focus, with findings suggesting a higher prevalence of neurodevelopmental disorders among individuals with childhood-onset type 1 diabetes. However, the underlying mechanism of this comorbidity remains largely unknown, and the potential alteration in the health and socio-economic outcomes due to this comorbidity remains unexplored. This thesis aimed to elucidate the potential mechanisms behind the comorbidity between childhood-onset type 1 diabetes and neurodevelopmental disorders and explore its impact on health and education outcomes, with the goal of improving early detection, prevention, and management strategies to enhance the quality of life for the affected children and adolescents.

In Study I, we examined the impact of childhood-onset type 1 diabetes and the role of glycemic control on the risk of subsequent neurodevelopmental disorders. We found that individuals with childhood-onset type 1 diabetes had a higher risk of developing neurodevelopmental disorders than the general population. Notably, this risk was highest among those with less optimal glycemic control. These findings provided insight into the role of glycemic control, a crucial diabetes-related factor, in the occurrence of comorbidity between childhood-onset type 1 diabetes and neurodevelopmental disorders.

In Study II, we investigated the potential contribution from shared familial liability to the comorbidity between childhood-onset type 1 diabetes and neurodevelopmental disorders. We found that the elevated risk of neurodevelopmental disorders did not only appear in individuals with childhood-onset type 1 diabetes but also in their full-siblings. The general family co-aggregation pattern and the results of the quantitative genetic modeling, however, did not conclusively show that familial liability contributes to the comorbidity. This ambiguity underscores the need for subsequent research to further elucidate the underlying causes of this comorbidity.

In Study III, we explored the impacts of neurodevelopmental disorders on long-term glycemic control and the risk of diabetic complications in individuals with childhoodonset type 1 diabetes. We found that neurodevelopmental disorders, particularly ADHD and intellectual disability, were associated with increased risk of poor glycemic control and diabetic complications such as nephropathy and retinopathy. These observations highlight that taking neurodevelopmental aspects into account can be crucial when designing interventions and follow-ups for individuals with childhood-onset type 1 diabetes.

In Study IV, evaluated the interplay between childhood-onset type 1 diabetes, ADHD, and academic outcomes, spanning from compulsory education to university levels. We found that children and adolescents with both type 1 diabetes and ADHD were significantly less likely to achieve educational milestones, crossing different education levels, and had less favorable compulsory school performances compared to their peers without these conditions. These results underline the importance of providing targeted support to minimize the educational gap between the affected children and adolescents and their peers.

List of scientific papers

I. Liu S, Kuja-Halkola R, Larsson H, Lichtenstein P, Ludvigsson JF, Svensson AM, Gudbjörnsdottir S, Tideman M, Serlachius E, Butwicka A. Poor glycaemic control is associated with increased risk of neurodevelopmental disorders in childhood-onset type 1 diabetes: a population-based cohort study. Diabetologia. 2021 Apr;64:767-77.
https://doi.org/10.1007/s00125-020-05372-5

II. Liu S, Kuja-Halkola R, Larsson H, Lichtenstein P, Ludvigsson JF, Gudbjörnsdottir S, ... & Butwicka A. Childhood-onset type 1 diabetes and neurodevelopmental disorders: a genetically informative register-based cohort study. [Manuscript]

III. Liu S, Kuja-Halkola R, Larsson H, Lichtenstein P, Ludvigsson JF, Svensson AM, Gudbjörnsdottir S, Tideman M, Serlachius E, Butwicka A. Neurodevelopmental disorders, glycemic control, and diabetic complications in type 1 diabetes: a nationwide cohort study. The Journal of Clinical Endocrinology & Metabolism. 2021 Nov 1;106(11):e4459-70.
https://doi.org/10.1210/clinem/dgab467

IV. Liu S, Larsson H, Lichtenstein P, Ludvigsson JF, Gudbjörnsdottir S, Serlachius E, Kuja‐Halkola R, Butwicka A. Childhood‐onset type 1 diabetes and attention-deficit/hyperactivity disorder with educational attainment: A population‐based sibling‐comparison study. Acta Paediatrica. 2022 Nov;111(11):2131-41.
https://doi.org/10.1111/apa.16500