Impact of Parental or First-Degree Family History of Diabetes on Diabetes Incidence and Progression During Long-term Follow-up in the Diabetes Prevention Program Outcomes Study
Authors' conclusion
PH increased type 2 diabetes risk after DPP treatment group was controlled for. That effect was only partially explained by PRS, suggesting that rare gene variants, familial, and environmental factors may contribute to type 2 diabetes risk in people with prediabetes.
Study context
- Population
- Adults with prediabetes in DPP (randomized to intensive lifestyle intervention, metformin or placebo) with family history information through DPPOSwith family history information
- Participants
- 3,072 adults
- Comparison
- First-degree family history of diabetes vs no family history
- PHn = 1,975
- SHn = 226
- No family historyn = 871reference
- Primary endpoint
- Incident diabetes (ADA criteria), adjusted for demographic and clinical variables, DPP randomization arm and polygenic risk score (PRS)
- Follow-up
- Median 21 years
Methodological detailslong-term follow-up, adjusted for demographic and clinical variables, DPP randomization arm and polygenic risk score (PRS)
- Long-term follow-up
- Adjusted for demographic and clinical variables, DPP randomization arm and PRS
Primary result
As reported in the abstract
Incident diabetes
Each group vs no family historyEstimate (95% CI)
Any family history
adjusted HR 1.21(1.06–1.38)
PH
adjusted HR 1.19(1.04–1.35)
SH
adjusted HR 1.15(0.91–1.44)
Biparental history
HR 1.44(1.22–1.69)
Maternal history
HR 1.22(1.08–1.38)
Paternal history
HR 1.22(1.08–1.39)
Further findings
- PRS explained share of the association of any family history with diabetes risk
- 32%
Original publication
Impact of Parental or First-Degree Family History of Diabetes on Diabetes Incidence and Progression During Long-term Follow-up in the Diabetes Prevention Program Outcomes Study. Diabetes Care. Published 29 August 2025. doi:10.
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