Abstract 17285: Metabolite-Derived Network Reveals Cluster of Acylcholine Metabolites Associated With Better Diet Quality and Lower Prevalence of Type 2 Diabetes: Findings From the Boston Puerto Rican Health Study

Abstract

Introduction: Puerto Rican (PR) adults living on the US mainland are at high risk for developing type 2 diabetes (T2D), and dietary factors may contribute to this increased risk. Network analysis is a data-reduction tool that can identify correlated clusters of co-regulated metabolites that reflect mechanisms underlying diet-T2D associations. Hypothesis: Diet quality will associate with T2D-associated metabolite clusters among PR adults. Methods: We used LC/MS to measure fasting plasma metabolites (>700) among Boston PR Health Study participants, aged 45-75 years, with (n=258) and without (n=421) T2D. We applied an unsupervised correlation network-based method to identify metabolite clusters within a global metabolite network and calculated a score for each cluster using a weighted sum of metabolite concentrations. To estimate diet quality, we calculated a modified version of a previously validated American Heart Association diet score (AHA-DS). Logistic regression was used to assess cross-sectional associations between metabolite clusters and prevalent T2D, and linear regression was used to assess associations between the continuous AHA-DS and T2D-associated metabolite clusters among controls, adjusting for potential confounders and correcting for multiple testing. Results: We identified 7 metabolite clusters that were associated with prevalent T2D ( p <0.05). For every 1-standard deviation (SD) increase in cluster score, the odds ratios for prevalent T2D and 95% confidence intervals were as the follows: acylcholines [0.40 (0.31, 0.50)], aromatic hydrocarbon derivatives [0.33 (0.22, 0.47)], sphingolipids [0.46 (0.33, 0.64)], tricarboxylic acid (TCA) cycle amino acids/peptides [0.39 (0.25, 0.62)], branched-chain amino acid metabolites [4.1 (2.9, 6.0)], acylcarnitines [1.8 (1.3, 2.5)], and TCA cycle/energy metabolites [2.0 (1.4, 3.0)]. The AHA-DS was only significantly associated with the acylcholine metabolites cluster [β (standard error) = 0.01 (0.004) SD increase in cluster score, p=0.02]. Conclusions: In individuals of PR descent, we identified a cluster of acylcholine metabolites where concentrations are higher among those with better diet quality and lower among those with prevalent T2D.