<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>
Funding
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). The funder had no role in study design, data collection and analysis, decision to publish, or writing of the manuscript.