Associations of dietary diversity with type 2 diabetes in two Chinese cohorts: a multi-omics study

Background: The role of overall dietary diversity in type 2 diabetes (T2D) risk remains uncertain, and the potential associations involving the gut microbiota and metabolism are poorly understood. We therefore aimed to elucidate the associations between dietary diversity and T2D development and to explore the roles of gut microbiota and metabolism in two large-scale Chinese cohorts. Methods: This study included 8103 participants aged 18-80 years from the WELL-China cohort as the discovery cohort and 2020 from the Lanxi cohort as the validation cohort. Dietary diversity score (DDS) was calculated using a validated food frequency questionnaire and categorized as high-, medium-, or low-DDS groups. The primary outcome was incident T2D during a median follow-up period of 6.2 years. 16S rRNA sequencing was used to analyze the gut microbiota, while untargeted metabolomics was employed for plasma metabolite profiling. Cox regression was applied in all analyses. Results: High DDS was associated with a lower risk of T2D, with a hazard ratio of 0.71 [p = 0.039; 95% CI: 0.50 to 0.98] compared with low DDS. Eleven bacterial genera and 15 metabolites were identified between the high- and low- DDS groups. Among them, two genera (e.g., Blautia) and four metabolites, such as L-pipecolic acid, enriched in the high-DDS group were negatively correlated with incident T2D, whereas two genera and two metabolites depleted in the high-DDS group showed positive associations. Furthermore, most metabolites enriched in the high-DDS group were positively associated with high-DDS-enriched genera and linked to protective pathways (e.g., vitamin B6 metabolism); opposite associations were observed for depleted metabolites, which were linked to steroid hormone biosynthesis, a pathway whose dysregulation is closely linked to insulin resistance. Conclusions: Higher dietary diversity was associated with a lower risk of T2D, which might be partially due to the combined effects and interactions of beneficial bacteria and anti-inflammatory metabolites. Our findings position DDS as an easily modifiable lifestyle factor for T2D prevention, supporting its integration into public health guidelines.