Abstract

Introduction: Diet and exercise are key prevention strategies for type 2 diabetes (T2DM). Few longitudinal studies have examined separate effects of animal and plant proteins on T2DM risk and results are conflicting. The goal of this study was to evaluate the association between usual intake of dietary protein (total, animal, and plant) and T2DM risk. Methods: Data from middle-aged men and women in the longitudinal Framingham Offspring Study (FOS) with approximately 20 years of follow-up were used. Diet was assessed using three-day diet records (exams 3 and 5); protein intake was adjusted for body weight using the residuals from a linear regression model. Glucose was measured after an overnight fast; impaired fasting glucose (IFG) was defined as a FG >100; diabetes was diagnosed using a standardized and validated FOS protocol. To estimate the hazards ratios) (HR) for IFG or T2DM, Cox proportional hazards models were used to adjust for confounding by age, sex, education level, physical activity, cigarette smoking, height, energy intake, and weight-adjusted carbohydrate intake. Results: Subjects with the highest total protein intakes (≥100 g, men, ≥90 g women) had 34% reduced risks of IFG/T2DM (HR: 0.66; 95% CI: 0.51, 0.85). In this cohort, intakes of animal protein were more than double those of plant protein. The highest intakes of animal protein (≥65 g, men; ≥55 g, women) vs. lower intakes (<55 g, men; <40 g, women) were linked with 33% reduced risks of IFG/T2DM (95% CI: 0.55, 0.82) while intermediate levels of intake were linked with 29% lower risks. In contrast, moderate and higher intakes of plant protein (20-25 g and ≥25 g vs. <20 g) led to non-statistically significant 6-12% risk reductions. Beneficial effects of total protein were stronger for women (HR: 0.53; 95% CI: 0.36, 0.80) than for men (HR: 0.80; 95% CI 0.57, 1.13). In secondary analyses, we evaluated effect modification by other dietary and lifestyle factors. In particular, both men and women with higher intakes of protein and higher levels of physical activity had statistically significant reductions in long-term risk of IFG/T2DM (31%, 39%, and 22% risk reductions among active adults with higher intakes of total, animal, and plant protein, respectively) compared with more sedentary adults who had lower intakes of protein. In contrast, higher physical activity levels alone (among those with lower protein intakes) were associated with non-statistically significant 13-14% lower risks of IFG/T2DM. Conclusions: This prospective study of middle-aged men and women provides important evidence to suggest that dietary protein when combined with an active lifestyle, may be a strategy for lowering long-term risk of diabetes. In this study, animal protein had stronger beneficial effects, but future studies are needed in population groups with higher intakes of plant protein to determine whether these effects would be comparable.

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