Peanuts-derived plasma lipids and lower risk of type-2 diabetes: Association mediated by body mass index. An intervention and case-cohort study.

BACKGROUND: Cardiometabolic risk can be modified by dietary factors, including fat quality. Peanuts have a distinctive fatty acid (FA) composition rich in very long-chain saturated fatty acids (VLCSFA), with potentially favorable effects on cardiometabolic health. OBJECTIVE: To characterize the effects of peanut consumption on the circulating lipidome and examine associations of the resulting changes with cardiovascular disease (CVD) and type-2 diabetes (T2D). METHODS: We integrated data from the clinical trial ARISTOTLE and the prospective, population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort. ARISTOTLE randomized 63 healthy young adults to 25g/d skin-roasted peanuts, 32g/d peanut butter, or 32g/d control butter with peanut oil for 6 months. EPIC-Potsdam included case-cohort samples for T2D (774 cases) and CVD (545 cases). Plasma lipids were measured pre- and post-intervention in ARISTOTLE and at baseline in EPIC-Potsdam. Linear mixed models identified within-class FA sums responsive to peanut fat ‒ pooling all participants ‒ in ARISTOTLE, which were combined to derive a peanut lipidomic signature (PeLS) in EPIC-Potsdam. Multivariable Cox models were used to estimate hazard ratios (HRs) for PeLS and individual lipids with incident T2D and CVD. Hypothesis-generating mediation by body mass index (BMI) was assessed. RESULTS: The ARISTOTLE intervention modified 51 within-class FA sums, predominantly VLCSFA-containing lipids, particularly sphingolipids. The resulting PeLS was modestly associated with lower risk of T2D (HR=0.89 per 1-SD increase in PeLS, 95%CI: 0.80, 0.99), but not CVD (HR=1.01 per 1-SD increase in PeLS, 95%CI: 0.90, 1.15), in EPIC-Potsdam, with BMI identified as a potential mediator of this association (proportion explainable of 89%, 95%CI: 57%, 100%). CONCLUSIONS: Peanut consumption induces changes in the circulating lipidome, largely involving VLCSFA-containing lipids, that are associated with lower T2D risk partly through BMI. These results highlight peanuts as a source of dietary fats that may be linked to lower risk of T2D. CLINICAL TRIAL REGISTRY: The ARISTOTLE study was conducted in accordance with the Declaration of Helsinki, approved by the Ethics Committee of Clinical Investigation of the University of Barcelona (Barcelona, Spain, on 1 October 2019), and registered at https://clinicaltrials.gov/study/NCT04324749 (accessed on 2 April 2026).