Abstract

<b>OBJECTIVE </b>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. <p><b>RESEARCH DESIGN AND METHODS </b>We evaluated 2,731 participants without type 2 diabetes recruited between 2008-2013 in the Guangzhou Nutrition and Health Study, China. Type 2 diabetes cases 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.</p> <p><b>RESULTS </b>Over<b> </b>6.2 years of follow-up, 276 type 2 diabetes cases were identified (risk=0.10). Higher levels of erythrocyte <a>γ-linolenic acid</a> (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% confidence intervals: 1.21, 2.44) adjusted for potential confounders. Baseline GLA was inversely associated with gut microbial richness and diversity (α-diversity, both <i>p</i><0.05) during follow-up, and significantly associated with microbiota β-diversity (<i>p</i>=0.002). α-diversity acted as a potential mediator in the association between GLA and type 2 diabetes (<i>p</i><0.05). Seven genera (<i>Butyrivibrio</i>,<i> Blautia</i>,<i> Oscillospira</i>,<i> Odoribacter</i>,<i> S24-7 other</i>, <i>Rikenellaceae other</i>,<i> </i>and <i>Clostridiales other</i>) were enriched in quartile 1 of GLA, and in participants without type 2 diabetes.</p> <p><b>CONCLUSIONS </b>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.</p>

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