Family history of type 2 diabetes delays development of type 1 diabetes in TEDDY children with islet autoimmunity.

Summary

In the TEDDY cohort (n=8676), having a first-degree relative with type 1 diabetes increased the risk of islet autoimmunity, whereas having type 2 diabetes in a second-degree relative significantly delayed progression from autoantibody positivity to type 1 diabetes (HR 0.61). This demonstrates that familial factors differentially influence initiation versus progression of type 1 diabetes.

Key Findings

• First-degree relative with T1D increased risk of developing islet autoimmunity (HR 2.2).
• Second-degree relative with T2D delayed progression from autoantibody positivity to T1D (HR 0.61).
• No associations with other diabetes types or autoimmune diseases were observed for progression.

Clinical Implications

Risk counseling and monitoring of autoantibody-positive children may incorporate detailed family history: FDR T1D flags higher seroconversion risk, while SDR T2D may indicate slower progression, informing surveillance intensity and trial stratification.

Limitations

• Family history obtained via questionnaire; potential misclassification
• Findings generalize to HLA high-risk children, not necessarily to general population

Future Directions

Elucidate genetic/environmental mediators linking SDR T2D to slower progression; integrate metabolic traits and microbiome; test risk-adapted monitoring and prevention strategies in autoantibody-positive children.