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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

Dagogo-Jack S, Kazemi EJ, Doherty L, Srikanthan P, Echouffo-Tcheugui JB, Knowler WC, Kahn SE, Mudaliar S et al.

Diabetes care, 2025

3,072 participants · 1 citation

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…

How strong is the evidence?

Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 3,072 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

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