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Abstract P163: Gut Microbiome And Stages Of Diabetes In Middle-aged Adults: CARDIA Microbiome Study


 Background:
 Animal and human studies suggest the gut microbiome may be linked to insulin resistance and to diabetes. Results from population-based studies are limited and different stages of diabetes in relation to the gut microbiome have not been investigated.
 
 
 Objective:
 Examine cross-sectional associations of insulin resistance (IR), duration of diabetes, and 4 stages of diabetes (normoglycemic, prediabetes, and diabetes with (+) and without (-) anti-diabetic medication) with gut microbiome community composition in the Coronary Artery Risk Development in Young Adults (CARDIA).
 
 
 Method:
 The analysis is based on 605 Black and White participants who attended CARDIA’s Year 30 follow-up examination (2015-2016; aged 48-60 years). Using previously described methods, DNA from stool samples was sequenced using 16S rRNA method. We included 3 genus-level gut microbiome composition measures: alpha-diversity (Shannon index and richness), beta-diversity (Bray-Curtis dissimilarity matrix, PERMANOVA test), and taxonomy. For the analysis, the HOMA-IR levels at Years 25 and 30 were averaged; and diabetes duration was calculated as the sum of years starting at the Year 2 exam. Multivariable-adjusted regressions were used to assess associations of diabetes-related exposures with microbial features, adjusting for socio-demographics, clinical measures, health behaviors, and medication use. Genus-specific analysis was adjusted for multiple comparisons using a false discovery rate (FDR), with significance set to q-value <0.1.
 
 
 Results:
 Among 605 participants, 20% had prediabetes, and 15% had diabetes (9% on anti-diabetic medication treatment) at Year 30. Compared to those without diabetes, richness and Shannon index were inversely associated with diabetes duration and diabetes with treatment but not with HOMA-IR or prediabetes. PERMANOVA tests were significant for all diabetes-related exposures (p-values<0.05). After multivariable and FDR adjustment, 3 genera (all negative associations) were associated with HOMA-IR, 22 genera (2 positive associations) with diabetes duration, and 4 genera (1 positive association) with diabetes+. No genera were associated with prediabetes. There was reduced abundance of several butyrate producers in participants with higher HOMA-IR (ex.,
 Lachnospiraceae_UGG.004
 and
 Veillonella
 ), longer diabetes duration (ex.,
 Agathobacter
 and
 Ruminococcus
 ), or diabetes+ (ex.,
 Agathobacter and Romboutsia)
 .
 
 
 Conclusion:
 This study indicates significant associations of the gut microbiota composition with glycemic control and insulin resistance, which can contribute to our understanding of diabetes pathophysiology and its prevention and management. Certain butyrate-producing bacteria may play a beneficial role in glucose metabolism and insulin regulation. Future studies with longer-term follow-ups are warranted to explore the relevant mechanisms.
