Introduction: Type 1 diabetes (T1D) and type 2 diabetes (T2D) polygenic risk scores (PGST1D and PGST2D) can differentiate T1D and T2D, but it remains unclear whether PGST1D and PGST2D can inform T2D treatment and disease severity.

Methods: Among T2D patients in the Genomic Health Initiative (GHI) (N=2,716) and UK Biobank (UKB) (N=39,957), PGST1D and PGST2D were examined for association with anti-diabetes medications (ADM), number of ADM classes ever used, metabolic (BMI>30, triglycerides>150mg/dL, hypertension diagnosis) and autoimmune (hypothyroidism, celiac disease) phenotypes, and diabetic ketoacidosis with adjustment for HbA1c, age of recruitment and top 4 principal components.

Results: We confirmed previous UKB findings in the GHI that PGST1D and PGST2D differentiate T1D and T2D diagnoses. Among T2D patients in the GHI and UKB, a high vs. low PGST2D associated with more prevalent usage of insulin and non-insulin ADM, a greater number of ADM classes ever used, earlier age of T2D onset, and higher mean HbA1c. In the UKB, high PGST1D wasassociated with insulin treatment and number of ADM classes ever used (Table 1). Lastly, PGST1D associated with autoimmune phenotype and diabetic ketoacidosis, while the PGST2D associated with metabolic phenotype.

Conclusion: These findings emphasize the potential of polygenic risk scores to inform diabetes treatment and provide insights into disease onset and severity in T2D.

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Disclosure

L.K. Billings: Advisory Panel; Novo Nordisk, Pfizer Inc. Z. Shi: None. A. Mulford: None. A. Ashworth: None. J. Xu: None. A.R. Sanders: None.

Funding

NorthShore Auxiliary Scholars Award (internal)

© 2024 by the American Diabetes Association
2024
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