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. 2019 Jul 4;9:9653. doi: 10.1038/s41598-019-45906-5

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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(a) Overview of the metabolites that are significantly linearly associated with HbA_1c in at least one tissue. The first column is color-coded according to a curated classification of the HMDB super-class taxonomy and the labels are explained in the legend. The following five columns represent each tissue as noted on the top of the heatmap. A black dot implies statistically significant association of the corresponding metabolite to HbA_1c (linear regression permuted p-value < 0.1; Methods – Statistical analysis). The color intensity in the cell background shows the level of the adjusted R² value from the linear regression model. (b–e) Pair-wise comparisons of levels of selected metabolites between controls (CTRL) and pre-diabetes (PD), and pre-diabetes (PD) and T2D subjects. Statistical significance is shown as follows: NS, p-value > 0.1; *0.1 ≥ p-value > 0.05; **0.05 ≥ p-value > 0.01) (Mann-Whitney U permuted test; Methods – Statistical analysis). The red dot signifies the mean value of the group. (b) Pair-wise comparisons of LPC (14:0) in skeletal muscle; (c) Pair-wise comparisons of LPC (16:0) in skeletal muscle; (d) Pair-wise comparisons of LPC (17:0) in skeletal muscle; (e) Pair-wise comparisons of deoxycholic acid glycine conjugate (G-DCA) in liver.