| Title: | Nonlinear Associations and Isocaloric Substitution of Macronutrients With Incident Type 2 Diabetes |
| Journal: | Mayo Clinic Proceedings |
| Published: | 18 Sep 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40965384/ |
| DOI: | https://doi.org/10.1016/j.mayocp.2025.04.021 |
Publication 19462
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Abstract
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.</p>
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).</p>
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.</p>
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.</p>
15 Keywords
- Aged
- Body Mass Index
- Diabetes Mellitus, Type 2
- Diet
- Energy Intake
- Female
- Humans
- Incidence
- Male
- Middle Aged
- Nutrients
- Proportional Hazards Models
- Prospective Studies
- Risk Factors
- United Kingdom
7 Authors
- Jirapitcha Boonpor
- John C Mathers
- Naveed Sattar
- Jill P Pell
- Stuart R Gray
- Carlos Celis-Morales
- Frederick K Ho
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