637-P: Longitudinal Metabolic and Microbial Responses to Habitual Dietary Changes in Individuals at Risk for Type 2 Diabetes

Introduction & Objective: Despite normal glucose levels, individuals with insulin resistance (IR) are more likely to develop Type 2 diabetes as compared to those with insulin sensitivity (IS). Moreover, the gut microbiome changes in response to diet and is associated with glucose regulation. Nonetheless, it is unclear whether and how metabolic and microbial responses to longitudinal changes in habitual diet would differ by one’s insulin resistance status.

Methods: We utilized biological samples obtained from a cohort study where 71 healthy adults (mean 53.4y) were longitudinally followed every quarter for one year. At each visit, participants completed dietary assessments using food records. They also provided blood and stool samples for plasma metabolomics and gut microbiome analyses using untargeted liquid chromatography-mass spectrometry and 16S rRNA sequencing, respectively. Furthermore, the insulin suppression test determined the insulin resistance status of the participants.

Results: We found that 22 nutrients, including total fiber and soluble fiber, significantly changed over the study period and/or differed between IS and IR individuals (p<0.05). Notably, our correlation analysis showed fewer and weaker associations between longitudinal changes in nutrients and metabolites in participants with IR than those with IS (q<0.05). The pathway enrichment analysis further confirmed that dietary change-related metabolites were associated with several metabolic pathways in IS participants, which were not as observed in those with IR. The pathways include steroid hormone biosynthesis, sphingolipid metabolism, and pyrimidine metabolism. Similarly, the numbers and degree of correlations between changes in nutrients and gut microbiome were reduced in IR compared to IS.

Conclusion: People with insulin resistance might need careful dietary interventions likely due to compromised nutrient signaling related to microbial and metabolic processes.