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Dietary Protein Sources, Mediating Biomarkers, and Incidence of Type 2 Diabetes: Findings from the Women’s Health Initiative and the UK Biobank

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posted on 17.06.2022, 14:09 authored by Jie Li, Andrea J. Glenn, Qingling Yang, Ding Ding, Lingling Zheng, Wei Bao, Jeannette Beasley, Erin LeBlanc, Kenneth Lo, JoAnn E. Manson, Lawrence Philips, Lesley Tinker, Simin Liu



Whether and how dietary protein intake is linked to type 2 diabetes (T2D) remains unclear. This study aimed to investigate the associations of protein intake with the development of T2D and the potential mediating roles of T2D biomarkers. 

Research Design and Methods

We included 108,681 postmenopausal women without T2D at baseline from the Women’s Health Initiative (WHI) (primary cohort) and 34,616 adults without T2D from the UK Biobank (UKB) (replication cohort). Cox proportional hazard models were used to estimate the protein-T2D associations. Mediation analysis was performed to assess the mediating roles of biomarkers in case-control studies nested in the WHI. 


In the WHI, 15,842 incident T2D cases were identified during a median follow-up of 15.8 years. Intake of animal protein was associated with increased T2D risk (Hazard ratio, HR comparing the highest to the lowest quintile=1.31, 95% confidence interval [1.24–1.37]), while plant protein with decreased risk (HR: 0.82 [0.78–0.86]). Intakes of red meat, processed meat, poultry, and eggs were associated with increased T2D risk, while whole grains with decreased risk. Findings from the UKB were similar. These findings were materially attenuated after additional adjustment for body mass index. Substituting 5% energy from plant protein for animal protein was associated with 21% decreased T2D risk (HR: 0.79 [0.74–0.84]), which was mediated by levels of hs-CRP, interleukin-6, leptin, and SHBG.


Findings from these two large prospective cohorts support the notion that substituting plant protein for animal protein may decrease T2D risk mainly by reducing obesity-related inflammation.


J Li was supported by the National Natural Science Foundation of China (81673156, 82073528, and 81302417). S Liu was partly supported by the NIH R01DK125403, R01ES031391, and R01ES029082. J Beasley was supported by NIH R01DK127916. AJG was supported by the Canadian Institute of Health Research, CIHR Fellowship. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, 75N92021D00005. The funders had no role in the study design, data collection, data analysis, data interpretation, or writing of the manuscript.