Abstract

Background: High-quality carbohydrate sources, such as whole grains, have been associated with a lower risk of type 2 diabetes (T2D), whereas low-quality carbohydrate sources, such as refined grains and added sugar, have been associated with a higher T2D risk. However, few studies have considered how replacing dietary carbohydrate with other macronutrients may influence T2D risk. Objective: We examined whether isocaloric substitution of high- or low-quality carbohydrate for fat, protein, and their subtypes is associated with T2D risk. Methods: We included 75,430 women from the Nurses' Health Study (1984-2016), 85,630 women from the Nurses' Health Study II (1991-2017), and 40,261 men from the Health Professionals Follow-Up Study (1986-2016) who were free of T2D, CVD, and cancer at baseline. Dietary data were collected every 2-4 years using a validated, semi-quantitative food frequency questionnaire. High-quality carbohydrate was defined as carbohydrate from whole grains, fruits, vegetables, and legumes. Low-quality carbohydrate was defined as carbohydrate from refined grains, added sugars, and potatoes. We used Cox proportional hazards regression with time-varying covariates to model the substitution of 5% of energy intake from high- and low-quality carbohydrate for isocaloric amounts of fat, protein, and their subtypes [polyunsaturated fat (PUFA), animal and plant monounsaturated fat (MUFA), saturated fat, trans fat, and animal and plant protein]. Cohort-specific estimates were combined using inverse variance-weighted fixed effects meta-analyses. Results: During 4,859,845 years of follow-up, we documented 20,141 incident T2D cases. In multivariable-adjusted meta-analyses, isocaloric substitution of high-quality carbohydrate for total fat [HR (95% CI) 0.94 (0.93, 0.96)], total MUFA [0.95 (0.91, 0.98)], MUFA from animal sources [0.92 (0.88, 0.95)], total protein [0.91 (0.89, 0.94)], or animal protein [0.94 (0.91, 0.97] was associated with a lower T2D risk. On the other hand, the substitution of low-quality carbohydrate for plant MUFA [1.06 (1.02-1.10)] or plant protein [1.06 (1.02-1.11)] was associated with a higher risk of T2D. When we restricted high-quality carbohydrate sources to whole grains, the results were similar or stronger. Additionally, substitution of whole grain carbohydrate for saturated fat [0.87 (0.84, 0.91)], trans fat [0.87 (0.83, 0.92)], PUFA [0.88 (0.84, 0.92)], plant MUFA [0.92 (0.87, 0.96)], or plant protein [0.91 (0.86, 0.97)] was associated with lower T2D risk. Conclusions: The effect of carbohydrate substitution on T2D risk depends not only on the nutrient being substituted but also on the quality of the carbohydrate. Substitution of high-quality carbohydrate, especially carbohydrate from whole grains (i.e. whole wheat bread, oatmeal), for fat or protein, especially animal sources (i.e. beef, poultry), may lower T2D risk.

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