ObjectiveTo explore the combined effects of multiple dietary nutrient intakes on the risk of type 2 diabetes mellitus.MethodsFrom May 2011 to February 2012, a 1∶2 matched case-control study was conducted to recruit participants who were aged 18-80 years and had resided in Guangzhou for five years or longer at endocrine clinics and wards of a Class A tertiary hospital in Guangzhou, China. According to the inclusion criteria, 384 patients with newly diagnosed type 2 diabetes were recruited into case group, and 768 participants without type 2 diabetes matched by sex and age (±3 years) were enrolled into control group. A general information questionnaire and food frequency questionnaire (FFQ) were used to collect the basic information and dietary profiles of the subjects. The intake of each nutrient was calculated, and energy intake was adjusted using the residual. A least absolute shrinkage and selection operator (Lasso) regression analysis was used to select key nutrients. A multivariable logistic regression analysis was used to assess the relationship between key nutrients and type 2 diabetes. A Bayesian kernel machine regression (BKMR) model was used to analyze the combined effect of mixed intake of multiple nutrients on the risk of type 2 diabetes.ResultsLasso regression models selected six key dietary nutrients associated with type 2 diabetes: dietary fiber, total fat, vitamin E, vitamin B2, zinc, and selenium. According to the multivariable logistic regression analysis, after adjusting for the basic information, physical activity, and other nutrients, compared with the lowest quartile intake groups, the risk of type 2 diabetes was increased in the highest quartile intake groups of total fat, vitamin E, and zinc, with the odds ratios (ORs) and 95% confidence intervals (CIs) being 2.23 (1.00, 4.99), 8.78 (4.52, 17.05), and 3.41 (1.55, 7.50), respectively, while the risk of type 2 diabetes was decreased in the highest quartile intake groups of dietary fiber, vitamin B2, and selenium, with the ORs and 95% CIs being 0.27 (0.16, 0.48), 0.25 (0.11, 0.56), and 0.39 (0.19, 0.82), respectively. The BKMR analysis showed that using the median intake of all nutrients as the reference, when the mixed nutrient intake level was at the 60th percentile (P₆₀) or above, the combined effect of nutrients was positively associated with the risk of type 2 diabetes. Single exposure-response relationships showed that total fat and vitamin E were positively associated with the risk of type 2 diabetes; dietary fiber, vitamin B2, and selenium were negatively associated with the risk of type 2 diabetes; and zinc had a U-shaped relationship with the risk of type 2 diabetes. The interaction model revealed the presence of interaction between the six nutrients.ConclusionThe intake levels of dietary fiber, total fat, vitamin E, vitamin B2, zinc, and selenium have effects on the risk of type 2 diabetes. The combined effect of mixed nutrient intake is positively associated with the risk of type 2 diabetes. Different nutrients have interacting effects on the risk of type 2 diabetes.