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

Abstract

<p> </p> <p><strong>Objective</strong> </p> <p>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. </p> <p><strong>Research Design and Methods</strong></p> <p>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. </p> <p><strong>Results</strong></p> <p>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.</p> <p><strong>Conclusions</strong> </p> <p>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.</p>