Dietary cholesterol consumption and incidence of type 2 diabetes mellitus: A dose-response meta-analysis of prospective cohort studies

Background and aim: The purpose of this meta-analysis was to evaluate the dose-response relationship between dietary cholesterol (DC) consumption and the incidence of type 2 diabetes mellitus (T2DM). Methods and results: Prospective studies with the endpoint of T2DM were included. The Random-effect model weighted by inverse variance was used. Meta-regression and subgroup an-alyses were conducted to explore the potential sources of heterogeneity by specified study char-acteristics. Restricted cubic splines regression models were used to estimate the dose-response relationship. 11 prospective studies comprising of 355 230 subjects were included. Compared to lowest DC consumption, highest DC consumption was associated with an increased risk of T2DM (RR 1.15, 95% CI 1.03 to 1.28, P = 0.012; chi-squared = 31.41, I-squared 58.6%, P heterogeneity = 0.003). Subgroup analyses have shown that this positive association was more evident in western countries than in eastern countries (RR 1.19, 95% CI 1.06 to 1.36 VS 1.34, 95% CI 0.84 to 1.29; P subgroup difference = 0.02). For 100 mg/d increment in DC intake, the pooled RR was 1.05, (95% CI 1.04 to 1.07, Plinearity = 0.000, Pnonlinearity = 0.02), 1.06 (95% CI 1.04 to 1.07, Plinearity=0.000), and 1.01 (95% CI 0.98 to 1.05, Plinearity = 0.525) for the incidence of T2DM, in western and eastern countries, respectively. Conclusions: Our study suggests that there is a positive dose-response association between DC consumption and the incidence of T2DM, especially in western countries. Systematic review registration: PROSPERO CRD42020216318. & COPY; 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Ital-ian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.