LUND UNIVERSITY

 

Heterogeneity in Paediatric Type 1 Diabetes

Hedlund, Emma

 

• Disputation 14/11 13.oo
• Lund

 

 

 

 

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https://lup.lub.lu.se/search/files/230413138/Avhandling_Emma_Hedlund_LUCRIS.pdf

 

 

 

Abstract

 

Background and aim:

Children with type 1 diabetes (T1D) represent a heterogeneous group of children with varying genetic backgrounds and different numbers of autoantibodies at diagnosis. The latter may reflect an interaction between genetic susceptibility and environmental triggers that contribute to the onset of the disease. However, the specific triggers remain unknown. The overall aim of this thesis was to increase our understanding of the heterogeneity of T1D in children.

 

Methods:

To address our specific research questions, we used data from the Better Diabetes Diagnosis (BDD) cohort in combination with the Swedish National Diabetes Register (NDR). The overall study cohort, used for all papers, comprised 3,647 children diagnosed between 2005 and 2010. Blood samples, clinical data, and family history information were collected at diagnosis. Analyses included age at diagnosis, sex, autoantibodies (GAD65, IAA, IA-2, ZnT8A), and HLA genotype (Papers I-IV), as well as month of birth (Paper I), family history, body mass index (BMI), diabetes ketoacidosis (DKA) and HbA1c (Papers II-IV), and c-peptide (Papers III-IV). Paper IV also included follow-up data on BMI and HbA1c after diagnosis.

 

Results:

In Paper I, boys diagnosed before the age of 5 were more often born in May. In Paper II, a family history of T1D or T2D was more common among children with T1D than among those without, and clinical presentation varied by family history. A family history of T1D was associated with younger age at diagnosis and lower HbA1c, whereas a family history of T2D was associated with higher BMI. In Paper III, children without autoantibodies at diagnosis differed from those with autoantibodies: they were more often boys, had higher HbA1c, less DKA, and more frequently a family history of T2D, suggesting a more slowly progressing disease. In Paper IV, follow-up data showed that differences in HbA1c and BMI observed at diagnosis persisted over time.

 

Conclusion:

These findings suggest that there are subgroups of children with T1D that differ according to family history, sex, and autoantibody status. Understanding this heterogeneity may be crucial for improving risk prediction for poorer metabolic management and long-term complications, ultimately supporting the development of precision medicine approaches for children with T1D.

 

 

 

Link to publications

https://portal.research.lu.se/en/publications/exploring-heterogeneity-in-paediatric-type-1-diabetes/

 

Exploring Heterogeneity in Paediatric Type 1 Diabetes. [Doctoral Thesis (compilation),

Department of Clinical Sciences, Lund]. Lund University, Faculty of Medicine

 

 

 

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