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.
Publication/Presentation Date
10-1-2025
Abstract
OBJECTIVE: To determine the effects of first-degree family history of diabetes on diabetes incidence in Diabetes Prevention Program (DPP) and Diabetes Prevention Program Outcomes Study (DPPOS) participants.
RESEARCH DESIGN AND METHODS: In the DPP, adults with prediabetes were randomized to an intensive lifestyle intervention, metformin, or placebo and followed for incident diabetes. On study completion 88% of eligible DPP participants reenrolled in DPPOS for long-term follow-up. The present analysis includes all 3,072 participants with family history information through DPPOS, with a median follow-up of 21 years (1,975 had parental history of diabetes [PH] [312 biparental, 947 maternal, 716 paternal], 226 had only sibling history [SH], and 871 denied any family history). The primary outcome is incident diabetes based on American Diabetes Association criteria, with adjustment for demographic and clinical variables, DPP randomization arm, and polygenic risk score (PRS).
RESULTS: Adjusted hazard ratio (HR) was 1.21 (95% CI 1.06, 1.38) for any family history, 1.19 (1.04, 1.35) for PH, and 1.15 (0.91, 1.44) for SH. Biparental history conferred greater hazard (HR 1.44 [95% CI 1.22, 1.69]) than maternal (1.22 [1.08, 1.38]) or paternal (1.22 [1.08, 1.39]) diabetes history alone. PRS explained 32% of the association of any family history with diabetes risk.
CONCLUSIONS: 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.
Volume
48
Issue
10
First Page
1695
Last Page
1703
ISSN
1935-5548
Published In/Presented At
Dagogo-Jack, S., Kazemi, E. J., Doherty, L., Srikanthan, P., Echouffo-Tcheugui, J. B., Knowler, W. C., Kahn, S. E., Mudaliar, S., Temprosa, M., & DPP Research Group (2025). 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, 48(10), 1695–1703. https://doi.org/10.2337/dc25-0633
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
40882001
Department(s)
Administration and Leadership
Document Type
Article