The evidence on the association between long-term low-carbohydrate, high-fat and high-protein diets and type 2 diabetes (T2D) is controversial. Until now, data is limited for Chinese populations, especially in considering the influence of extra energy intake. In this paper, we aimed to investigate the association of low-carbohydrate, high-fat and high-protein diets with type 2 diabetes (T2D) risk in populations consuming extra calories and those with normal caloric intake, We also determined whether the association is mediated by insulin resistance (IR) or β-cell dysfunction. A total of 3644 subjects in the Harbin People's Health Study (Cohort 1, 2008-2012) and 7111 subjects in the Harbin Cohort Study on Diet, Nutrition and Chronic Non-Communicable Diseases (Cohort 2, 2010-2015) were analyzed, with a median follow-up of 4.2 and 5.3 years, respectively. Multivariate relative risks (RRs) and their 95% confidence intervals (95% CIs) were calculated to estimate the association between low-carbohydrate, high-fat and high-protein diet and T2D in logistic regression models. The multivariate RRs (95% CIs) were 1.00, 2.24 (1.07, 4.72) and 2.29 (1.07, 4.88) (Ptrend = 0.04), and 1.00, 1.45 (0.91, 2.31) and 1.64 (1.03, 2.61) (Ptrend = 0.04) across tertiles of low-carbohydrate, high-fat and high-protein diet scores in the population consuming extra calories in Cohort 1 and Cohort 2, respectively. The association was no longer significant after adjustment for livestock and its products, or poultry and its products. The mediation analysis discovered that this association in the population consuming extra calories was insulin resistance mediated, in both Cohort 1 and Cohort 2. However, the association was not significant among participants overall and participants with normal caloric intake. Our results indicated that long-term low-carbohydrate, high-fat and high-protein diets were associated with increased T2D risk among the population consuming extra calories, which may be caused by higher intake of animal-origin fat and protein as well as lower intake of vegetables, fruit and fiber. Additionally, the association was mediated by IR. In the population consuming extra calories, reducing the intake of livestock, poultry and their products and increasing the intake of vegetables, fruit and fiber might protect this population from developing T2D.
Keywords: extra energy intake; high-fat and high-protein diets; insulin resistance; low-carbohydrate; mediation analysis; prospective study; type 2 diabetes.