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Lookup NU author(s): Emeritus Professor John Mathers, Dr Carlos Celis Morales
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2025 The Authors. Published by Elsevier Inc on behalf of Mayo Foundation for Medical Education and Research. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/. Objective: To investigate the associations between dietary intake of macronutrient components and incident type 2 diabetes, potential mediation via adiposity, and isocaloric substitution of macronutrients associated with higher risk. Participants and Methods: A prospective cohort study of 176,057 UK Biobank participants was conducted, following up participants registered from March 13, 2006, to November 30, 2022. Dietary intake of macronutrient components was expressed as a percentage of total energy intake (%E). Cox proportional hazards models with penalized cubic splines, adjusting for major confounders, were used to examine nonlinear associations. The mediating roles of body mass index and waist to height ratio were tested using a g-formula approach, which simulates potential outcomes for various exposure values. Isocaloric substitution analysis was conducted for macronutrients that were statistically significantly associated with higher type 2 diabetes risk (hazard ratio >1; P<.05). Results: Over a median follow-up of 11 years, 5078 (2.9%) of the 176,057 participants had development of type 2 diabetes. Higher risk of type 2 diabetes was observed in people with higher intake of free sugar (>12%E; free sugar included any added sugar and sugar in honey, syrup, and juices), starch (>25%E), and animal protein, and in people with lower intake of non–free sugar (<10%E; any sugar that is not free sugar), omega-3 (<1.5%E) and omega-6 PUFA (<6%E), and plant protein (<5%E). Waist to height ratio explained 31% and 25% of the excess type 2 diabetes risk associated with free sugar and starch, respectively, and fully explained that with animal protein. Substituting free sugar, starch, and animal protein with non–free sugar or plant protein was associated with 16%, 18%, and 12% lower type 2 diabetes risk, respectively. Conclusion: In this study, excess free sugar, starch, and animal protein were associated with higher type 2 diabetes risk. People at risk of diabetes who have a high intake of these macronutrients should consider substitution with non–free sugar and plant protein.
Author(s): Boonpor J, Mathers JC, Sattar N, Pell JP, Gray SR, Celis-Morales C, Ho FK
Publication type: Article
Publication status: Published
Journal: Mayo Clinic Proceedings
Year: 2026
Volume: 101
Issue: 3
Pages: 403-415
Print publication date: 01/03/2026
Online publication date: 18/09/2025
Acceptance date: 02/04/2018
Date deposited: 03/03/2026
ISSN (print): 0025-6196
ISSN (electronic): 1942-5546
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/j.mayocp.2025.04.021
DOI: 10.1016/j.mayocp.2025.04.021
Data Access Statement: Data can be requested from the UK Biobank: https://www.ukbiobank.ac.uk/
PubMed id: 40965384
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