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

Whether and how dietary protein intake is linked to type 2 diabetes (T2D) remains unclear. The aim of this study was to investigate the associations of protein intake with development of T2D and the potential mediating roles of T2D biomarkers. 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 U.K. Biobank (UKB) (replication cohort). Cox proportional hazard models were used for estimation of 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 in comparing the highest to the lowest quintile = 1.31 [95% CI 1.24-1.37]) and plant protein with decreased risk (0.82 [0.78-0.86]). Intakes of red meat, processed meat, poultry, and eggs were associated with increased T2D risk and whole grains with decreased risk. Findings from the UKB were similar. These findings were materially attenuated after additional adjustment for BMI. Substituting 5% energy from plant protein for animal protein was associated with 21% decreased T2D risk (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.