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 () and SOALS () can be found on their respective websites.

中文翻译：

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网络衍生代谢物簇与波多黎各血统成年人中流行的 2 型糖尿病的关联


简介 我们调查了网络分析是否揭示了与波多黎各成年人中流行的 2 型糖尿病 (T2D) 相关的协同调节代谢物簇。研究设计和方法 我们使用液相色谱-质谱法测量波士顿波多黎各健康研究（BPRHS；发现）和圣胡安超重成人纵向研究（SOALS；复制）中 40-75 岁参与者的空腹血浆代谢物 (>600) ），分别有（n=357；n=77）和没有（n=322；n=934）T2D。在 BPRHS 参与者中，我们使用基于无监督偏相关网络的方法来识别和计算代谢物簇分数。 Logistic 回归用于评估 BPRHS 基线抽血时代谢物簇与流行 T2D 之间的横断面关联，并且在 SOALS 中复制了显着关联。使用逆方差加权随机效应荟萃分析来结合特定队列的估计。结果 6 个代谢物簇与 BPRHS 中流行的 T2D 显着相关，并在 SOALS 中得到复制（错误发现率 (FDR) <0.05）。在这两个队列的荟萃分析中，对于主要以葡萄糖转运为特征的簇，流行的 T2D 的 OR 和 95% CI（簇评分每增加 1 个 SD）如下（0.21（0.16 至 0.30）；FDR <0。 0001）、鞘脂（0.40（0.29 至 0.53）；FDR <0.0001）、酰胆碱（0.35（0.22 至 0.56）；FDR <0.0001）、糖代谢（2.28（1.68 至 3.09）；FDR <0.0001）。 0001）、支链和芳香氨基酸（2.22（1.60 至 3.08）；FDR <0.0001）和脂肪酸生物合成（1.54（1.29 至 1.85）；FDR <0.0001）。 以氨基酸代谢、细胞膜成分和芳香族氨基酸代谢为特征的另外三个簇显示出与 BPRHS 中流行的 T2D 显着相关，但这些关联在 SOALS 中并未重复。结论 在波多黎各成年人中，我们发现了几种与流行的 T2D 相关的已知和新颖的代谢物簇。数据可根据合理要求提供。有关从 BPRHS () 和 SOALS () 请求数据的信息可以在各自的网站上找到。