TY - JOUR T1 - Associations of network-derived metabolite clusters with prevalent type 2 diabetes among adults of Puerto Rican descent JF - BMJ Open Diabetes Research & Care JO - BMJ Open Diab Res Care DO - 10.1136/bmjdrc-2021-002298 VL - 9 IS - 1 SP - e002298 AU - Danielle E Haslam AU - Liming Liang AU - Dong D Wang AU - Rachel S Kelly AU - Clemens Wittenbecher AU - Cynthia M Pérez AU - Marijulie Martínez AU - Chih-Hao Lee AU - Clary B Clish AU - David T W Wong AU - Laurence D Parnell AU - Chao-Qiang Lai AU - José M Ordovás AU - JoAnn E Manson AU - Frank B Hu AU - Meir J Stampfer AU - Katherine L Tucker AU - Kaumudi J Joshipura AU - Shilpa N Bhupathiraju Y1 - 2021/08/01 UR - http://drc.bmj.com/content/9/1/e002298.abstract N2 - Introduction We investigated whether network analysis revealed clusters of coregulated metabolites associated with prevalent type 2 diabetes (T2D) among Puerto Rican adults.Research design and methods We used liquid chromatography-mass spectrometry to measure fasting plasma metabolites (>600) among participants aged 40–75 years in the Boston Puerto Rican Health Study (BPRHS; discovery) and San Juan Overweight Adult Longitudinal Study (SOALS; replication), with (n=357; n=77) and without (n=322; n=934) T2D, respectively. Among BPRHS participants, we used unsupervised partial correlation network-based methods to identify and calculate metabolite cluster scores. Logistic regression was used to assess cross-sectional associations between metabolite clusters and prevalent T2D at the baseline blood draw in the BPRHS, and significant associations were replicated in SOALS. Inverse-variance weighted random-effect meta-analysis was used to combine cohort-specific estimates.Results Six metabolite clusters were significantly associated with prevalent T2D in the BPRHS and replicated in SOALS (false discovery rate (FDR) <0.05). In a meta-analysis of the two cohorts, the OR and 95% CI (per 1 SD increase in cluster score) for prevalent T2D were as follows for clusters characterized primarily by glucose transport (0.21 (0.16 to 0.30); FDR <0.0001), sphingolipids (0.40 (0.29 to 0.53); FDR <0.0001), acyl cholines (0.35 (0.22 to 0.56); FDR <0.0001), sugar metabolism (2.28 (1.68 to 3.09); FDR <0.0001), branched-chain and aromatic amino acids (2.22 (1.60 to 3.08); FDR <0.0001), and fatty acid biosynthesis (1.54 (1.29 to 1.85); FDR <0.0001). Three additional clusters characterized by amino acid metabolism, cell membrane components, and aromatic amino acid metabolism displayed significant associations with prevalent T2D in the BPRHS, but these associations were not replicated in SOALS.Conclusions Among Puerto Rican adults, we identified several known and novel metabolite clusters that associated with prevalent T2D.Data are available upon reasonable request. Information on requesting data from the BPRHS (https://www.uml.edu/Research/UML-CPH/Research/bprhs/) and SOALS (http://soals.rcm.upr.edu/) can be found on their respective websites. ER -