Wenrui Ji, Xiaomin Xie, Guirong Bai, Yanting He, Ling Li, Li Zhang and Dan Qiang
{"title":"用代谢组学方法剖析糖尿病前期向 T2DM 进展过程中的代谢失调问题","authors":"Wenrui Ji, Xiaomin Xie, Guirong Bai, Yanting He, Ling Li, Li Zhang and Dan Qiang","doi":"10.1039/D3MO00130J","DOIUrl":null,"url":null,"abstract":"<p >Many individuals with pre-diabetes eventually develop diabetes. Therefore, profiling of prediabetic metabolic disorders may be an effective targeted preventive measure. We aimed to elucidate the metabolic mechanism of progression of pre-diabetes to type 2 diabetes mellitus (T2DM) from a metabolic perspective. Four sets of plasma samples (20 subjects per group) collected according to fasting blood glucose (FBG) concentration were subjected to metabolomic analysis. An integrative approach of metabolome and WGCNA was employed to explore candidate metabolites. Compared with the healthy group (FBG < 5.6 mmol L<small><sup>−1</sup></small>), 113 metabolites were differentially expressed in the early stage of pre-diabetes (5.6 mmol L<small><sup>−1</sup></small> ⩽ FBG < 6.1 mmol L<small><sup>−1</sup></small>), 237 in the late stage of pre-diabetes (6.1 mmol L<small><sup>−1</sup></small> ⩽ FBG < 7.0 mmol L<small><sup>−1</sup></small>), and 245 in the T2DM group (FBG <img> 7.0 mmol L<small><sup>−1</sup></small>). A total of 27 differentially expressed metabolites (DEMs) were shared in all comparisons. Among them, <small>L</small>-norleucine was downregulated, whereas ethionamide, oxidized glutathione, 5-methylcytosine, and alpha-<small>D</small>-glucopyranoside beta-<small>D</small>-fructofuranosyl were increased with the rising levels of FBG. Surprisingly, 15 (11 lyso-phosphatidylcholines, <small>L</small>-norleucine, oxidized glutathione, arachidonic acid, and 5-oxoproline) of the 27 DEMs were ferroptosis-associated metabolites. WGCNA clustered all metabolites into 8 modules and the pathway enrichment analysis of DEMs showed a significant annotation to the insulin resistance-related pathway. Integrated analysis of DEMs, ROC and WGCNA modules determined 12 potential biomarkers for pre-diabetes and T2DM, including <small>L</small>-norleucine, 8 of which were <small>L</small>-arginine or its metabolites. <small>L</small>-Norleucine and <small>L</small>-arginine could serve as biomarkers for pre-diabetes. The inventory of metabolites provided by our plasma metabolome offers insights into T2DM physiology metabolism.</p>","PeriodicalId":19065,"journal":{"name":"Molecular omics","volume":" 5","pages":" 333-347"},"PeriodicalIF":3.0000,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/mo/d3mo00130j?page=search","citationCount":"0","resultStr":"{\"title\":\"Metabolomic approaches to dissect dysregulated metabolism in the progression of pre-diabetes to T2DM†\",\"authors\":\"Wenrui Ji, Xiaomin Xie, Guirong Bai, Yanting He, Ling Li, Li Zhang and Dan Qiang\",\"doi\":\"10.1039/D3MO00130J\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Many individuals with pre-diabetes eventually develop diabetes. Therefore, profiling of prediabetic metabolic disorders may be an effective targeted preventive measure. We aimed to elucidate the metabolic mechanism of progression of pre-diabetes to type 2 diabetes mellitus (T2DM) from a metabolic perspective. Four sets of plasma samples (20 subjects per group) collected according to fasting blood glucose (FBG) concentration were subjected to metabolomic analysis. An integrative approach of metabolome and WGCNA was employed to explore candidate metabolites. Compared with the healthy group (FBG < 5.6 mmol L<small><sup>−1</sup></small>), 113 metabolites were differentially expressed in the early stage of pre-diabetes (5.6 mmol L<small><sup>−1</sup></small> ⩽ FBG < 6.1 mmol L<small><sup>−1</sup></small>), 237 in the late stage of pre-diabetes (6.1 mmol L<small><sup>−1</sup></small> ⩽ FBG < 7.0 mmol L<small><sup>−1</sup></small>), and 245 in the T2DM group (FBG <img> 7.0 mmol L<small><sup>−1</sup></small>). A total of 27 differentially expressed metabolites (DEMs) were shared in all comparisons. Among them, <small>L</small>-norleucine was downregulated, whereas ethionamide, oxidized glutathione, 5-methylcytosine, and alpha-<small>D</small>-glucopyranoside beta-<small>D</small>-fructofuranosyl were increased with the rising levels of FBG. Surprisingly, 15 (11 lyso-phosphatidylcholines, <small>L</small>-norleucine, oxidized glutathione, arachidonic acid, and 5-oxoproline) of the 27 DEMs were ferroptosis-associated metabolites. WGCNA clustered all metabolites into 8 modules and the pathway enrichment analysis of DEMs showed a significant annotation to the insulin resistance-related pathway. Integrated analysis of DEMs, ROC and WGCNA modules determined 12 potential biomarkers for pre-diabetes and T2DM, including <small>L</small>-norleucine, 8 of which were <small>L</small>-arginine or its metabolites. <small>L</small>-Norleucine and <small>L</small>-arginine could serve as biomarkers for pre-diabetes. 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Metabolomic approaches to dissect dysregulated metabolism in the progression of pre-diabetes to T2DM†
Many individuals with pre-diabetes eventually develop diabetes. Therefore, profiling of prediabetic metabolic disorders may be an effective targeted preventive measure. We aimed to elucidate the metabolic mechanism of progression of pre-diabetes to type 2 diabetes mellitus (T2DM) from a metabolic perspective. Four sets of plasma samples (20 subjects per group) collected according to fasting blood glucose (FBG) concentration were subjected to metabolomic analysis. An integrative approach of metabolome and WGCNA was employed to explore candidate metabolites. Compared with the healthy group (FBG < 5.6 mmol L−1), 113 metabolites were differentially expressed in the early stage of pre-diabetes (5.6 mmol L−1 ⩽ FBG < 6.1 mmol L−1), 237 in the late stage of pre-diabetes (6.1 mmol L−1 ⩽ FBG < 7.0 mmol L−1), and 245 in the T2DM group (FBG 7.0 mmol L−1). A total of 27 differentially expressed metabolites (DEMs) were shared in all comparisons. Among them, L-norleucine was downregulated, whereas ethionamide, oxidized glutathione, 5-methylcytosine, and alpha-D-glucopyranoside beta-D-fructofuranosyl were increased with the rising levels of FBG. Surprisingly, 15 (11 lyso-phosphatidylcholines, L-norleucine, oxidized glutathione, arachidonic acid, and 5-oxoproline) of the 27 DEMs were ferroptosis-associated metabolites. WGCNA clustered all metabolites into 8 modules and the pathway enrichment analysis of DEMs showed a significant annotation to the insulin resistance-related pathway. Integrated analysis of DEMs, ROC and WGCNA modules determined 12 potential biomarkers for pre-diabetes and T2DM, including L-norleucine, 8 of which were L-arginine or its metabolites. L-Norleucine and L-arginine could serve as biomarkers for pre-diabetes. The inventory of metabolites provided by our plasma metabolome offers insights into T2DM physiology metabolism.
Molecular omicsBiochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
5.40
自引率
3.40%
发文量
91
期刊介绍:
Molecular Omics publishes high-quality research from across the -omics sciences.
Topics include, but are not limited to:
-omics studies to gain mechanistic insight into biological processes – for example, determining the mode of action of a drug or the basis of a particular phenotype, such as drought tolerance
-omics studies for clinical applications with validation, such as finding biomarkers for diagnostics or potential new drug targets
-omics studies looking at the sub-cellular make-up of cells – for example, the subcellular localisation of certain proteins or post-translational modifications or new imaging techniques
-studies presenting new methods and tools to support omics studies, including new spectroscopic/chromatographic techniques, chip-based/array technologies and new classification/data analysis techniques. New methods should be proven and demonstrate an advance in the field.
Molecular Omics only accepts articles of high importance and interest that provide significant new insight into important chemical or biological problems. This could be fundamental research that significantly increases understanding or research that demonstrates clear functional benefits.
Papers reporting new results that could be routinely predicted, do not show a significant improvement over known research, or are of interest only to the specialist in the area are not suitable for publication in Molecular Omics.