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Erythrocyte n-6 Polyunsaturated Fatty Acids, Gut Microbiota, and Incident Type 2 Diabetes: A Prospective Cohort Study.

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Miao, Zelei 
Lin, Jie-Sheng 
Mao, Yingying 
Chen, Geng-Dong 


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 γ-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 (α-diversity, both P < 0.05) during follow-up and significantly associated with microbiota β-diversity (P = 0.002). α-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, and Clostridiales 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.



Adult, Aged, Arachidonic Acid, Biomarkers, China, Diabetes Mellitus, Type 2, Erythrocytes, Fatty Acids, Omega-6, Fatty Acids, Unsaturated, Female, Gastrointestinal Microbiome, Humans, Incidence, Male, Middle Aged, Prospective Studies

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Diabetes Care

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American Diabetes Association


All rights reserved
Medical Research Council (MC_UU_12015/5)
MRC (MC_UU_00006/3)
This study was funded by the National Natural Science Foundation of China (81903316, 81773416), Zhejiang Ten-thousand Talents Program (101396522001), Westlake University (101396021801) and the 5010 Program for Clinical Researches (2007032) of the Sun Yat-sen University (Guangzhou, China). F.I. was funded by the United Kingdom Medical Research Council Epidemiology Unit core grant (MC_UU_12015/5). The funder had no role in study design, data collection and analysis, decision to publish, or writing of the manuscript.