Erythrocyte N-6 Polyunsaturated Fatty Acids, Gut Microbiota, And Incident Type 2 Diabetes: A Prospective Cohort Study

OBJECTIVE To examine the association of erythrocyte n-6 polyunsaturated fatty acid (PUFA) biomarkers with incident type 2 diabetes and explore the potential role of gut microbiota in the association. RESEARCH DESIGN AND METHODS We evaluated 2,731 participants without type 2 diabetes recruited between 2008 and 2013 in the Guangzhou Nutrition and Health Study (Guangzhou, China). Case subjects with type 2 diabetes were identified with clinical and biochemical information collected at follow-up visits. Using stool samples collected during the follow-up in the subset (n= 1,591), 16S rRNA profiling was conducted. Using multivariable-adjusted Poisson or linear regression, we examined associations of erythrocyte n-6 PUFA biomarkers with incident type 2 diabetes and diversity and composition of gut microbiota. RESULTS Over 6.2 years of follow-up, 276 case subjects with type 2 diabetes were identified (risk 0.10). Higher levels of erythrocyte gamma-linolenic acid (GLA), but not linoleic or arachidonic acid, were associated with higher type 2 diabetes incidence. Comparing the top to the bottom quartile groups of GLA levels, relative risk was 1.72 (95% CI 1.21, 2.44) adjusted for potential confounders. Baseline GLA was inversely associated with gut microbial richness and diversity (alpha-diversity, bothP< 0.05) during follow-up and significantly associated with microbiota beta-diversity (P= 0.002). alpha-Diversity acted as a potential mediator in the association between GLA and type 2 diabetes (P< 0.05). Seven genera (Butyrivibrio,Blautia,Oscillospira,Odoribacter,S24-7 other,Rikenellaceae other, andClostridiales other) were enriched in quartile 1 of GLA and in participants without type 2 diabetes. CONCLUSIONS Relative concentrations of erythrocyte GLA were positively associated with incident type 2 diabetes in a Chinese population and also with gut microbial profiles. These results highlight that gut microbiota may play an important role linking n-6 PUFA metabolism and type 2 diabetes etiology.