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
Year: 2025
Type: other
Abstract: OBJECTIVE To determine the effects of first-degree family history of diabetes on diabetes incidence in Diabetes Prevention Program (DPP)/DPP Outcomes Study (DPPOS) participants. RESEARCH DESIGN AND METHODS The DPP randomized adults with prediabetes to an intensive lifestyle intervention or metformin or placebo and followed them for incident diabetes. Upon study completion, 88% of eligible DPP participants re-enrolled in DPPOS for long-term follow-up. The present analysis includes all 3072 participants with family history information through DPPOS, with a median follow-up of 21 years (1975 had parental history {PH} [312 biparental, 947 maternal, 716 paternal]), 226 had only sibling history {SH}, and 871 denied any family history of diabetes {No-FH}). The primary outcome is incident diabetes based on American Diabetes Association criteria, adjusted for demographic and clinical variables, DPP randomization arm, and polygenic risk score (PRS). RESULTS The adjusted hazard ratio (HR) and 95% confidence interval [95% CI] were 1.21 [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 (1.44 [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 Parental history increased type 2 diabetes risk after controlling for DPP treatment groups. 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.
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4413818079