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

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.

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).

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.

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%).

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.

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).