The metabolomic signature of weight loss and remission in the Diabetes Remission Clinical Trial (DiRECT)
© 2023. The Author(s)..
AIMS/HYPOTHESIS: High-throughput metabolomics technologies in a variety of study designs have demonstrated a consistent metabolomic signature of overweight and type 2 diabetes. However, the extent to which these metabolomic patterns can be reversed with weight loss and diabetes remission has been weakly investigated. We aimed to characterise the metabolomic consequences of a weight-loss intervention in individuals with type 2 diabetes.
METHODS: We analysed 574 fasted serum samples collected within an existing RCT (the Diabetes Remission Clinical Trial [DiRECT]) (N=298). In the trial, participating primary care practices were randomly assigned (1:1) to provide either a weight management programme (intervention) or best-practice care by guidelines (control) treatment to individuals with type 2 diabetes. Here, metabolomics analysis was performed on samples collected at baseline and 12 months using both untargeted MS and targeted 1H-NMR spectroscopy. Multivariable regression models were fitted to evaluate the effect of the intervention on metabolite levels.
RESULTS: Decreases in branched-chain amino acids, sugars and LDL triglycerides, and increases in sphingolipids, plasmalogens and metabolites related to fatty acid metabolism were associated with the intervention (Holm-corrected p<0.05). In individuals who lost more than 9 kg between baseline and 12 months, those who achieved diabetes remission saw greater reductions in glucose, fructose and mannose, compared with those who did not achieve remission.
CONCLUSIONS/INTERPRETATION: We have characterised the metabolomic effects of an integrated weight management programme previously shown to deliver weight loss and diabetes remission. A large proportion of the metabolome appears to be modifiable. Patterns of change were largely and strikingly opposite to perturbances previously documented with the development of type 2 diabetes.
DATA AVAILABILITY: The data used for analysis are available on a research data repository ( https://researchdata.gla.ac.uk/ ) with access given to researchers subject to appropriate data sharing agreements. Metabolite data preparation, data pre-processing, statistical analyses and figure generation were performed in R Studio v.1.0.143 using R v.4.0.2. The R code for this study has been made publicly available on GitHub at: https://github.com/lauracorbin/metabolomics_of_direct.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:67 |
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| Enthalten in: |
Diabetologia - 67(2024), 1 vom: 17. Jan., Seite 74-87 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Corbin, Laura J [VerfasserIn] |
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| Links: |
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| Themen: |
DiRECT |
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| Anmerkungen: |
Date Completed 08.01.2024 Date Revised 10.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00125-023-06019-x |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Corbin, Laura J |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The metabolomic signature of weight loss and remission in the Diabetes Remission Clinical Trial (DiRECT) |
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| 500 | |a Date Revised 10.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a AIMS/HYPOTHESIS: High-throughput metabolomics technologies in a variety of study designs have demonstrated a consistent metabolomic signature of overweight and type 2 diabetes. However, the extent to which these metabolomic patterns can be reversed with weight loss and diabetes remission has been weakly investigated. We aimed to characterise the metabolomic consequences of a weight-loss intervention in individuals with type 2 diabetes | ||
| 520 | |a METHODS: We analysed 574 fasted serum samples collected within an existing RCT (the Diabetes Remission Clinical Trial [DiRECT]) (N=298). In the trial, participating primary care practices were randomly assigned (1:1) to provide either a weight management programme (intervention) or best-practice care by guidelines (control) treatment to individuals with type 2 diabetes. Here, metabolomics analysis was performed on samples collected at baseline and 12 months using both untargeted MS and targeted 1H-NMR spectroscopy. Multivariable regression models were fitted to evaluate the effect of the intervention on metabolite levels | ||
| 520 | |a RESULTS: Decreases in branched-chain amino acids, sugars and LDL triglycerides, and increases in sphingolipids, plasmalogens and metabolites related to fatty acid metabolism were associated with the intervention (Holm-corrected p<0.05). In individuals who lost more than 9 kg between baseline and 12 months, those who achieved diabetes remission saw greater reductions in glucose, fructose and mannose, compared with those who did not achieve remission | ||
| 520 | |a CONCLUSIONS/INTERPRETATION: We have characterised the metabolomic effects of an integrated weight management programme previously shown to deliver weight loss and diabetes remission. A large proportion of the metabolome appears to be modifiable. Patterns of change were largely and strikingly opposite to perturbances previously documented with the development of type 2 diabetes | ||
| 520 | |a DATA AVAILABILITY: The data used for analysis are available on a research data repository ( https://researchdata.gla.ac.uk/ ) with access given to researchers subject to appropriate data sharing agreements. Metabolite data preparation, data pre-processing, statistical analyses and figure generation were performed in R Studio v.1.0.143 using R v.4.0.2. The R code for this study has been made publicly available on GitHub at: https://github.com/lauracorbin/metabolomics_of_direct | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a DiRECT | |
| 650 | 4 | |a Diabetes remission | |
| 650 | 4 | |a Metabolomics | |
| 650 | 4 | |a Randomised controlled trial | |
| 650 | 4 | |a Type 2 diabetes | |
| 650 | 4 | |a Weight loss | |
| 650 | 7 | |a Glucose |2 NLM | |
| 650 | 7 | |a IY9XDZ35W2 |2 NLM | |
| 700 | 1 | |a Hughes, David A |e verfasserin |4 aut | |
| 700 | 1 | |a Bull, Caroline J |e verfasserin |4 aut | |
| 700 | 1 | |a Vincent, Emma E |e verfasserin |4 aut | |
| 700 | 1 | |a Smith, Madeleine L |e verfasserin |4 aut | |
| 700 | 1 | |a McConnachie, Alex |e verfasserin |4 aut | |
| 700 | 1 | |a Messow, Claudia-Martina |e verfasserin |4 aut | |
| 700 | 1 | |a Welsh, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Taylor, Roy |e verfasserin |4 aut | |
| 700 | 1 | |a Lean, Michael E J |e verfasserin |4 aut | |
| 700 | 1 | |a Sattar, Naveed |e verfasserin |4 aut | |
| 700 | 1 | |a Timpson, Nicholas J |e verfasserin |4 aut | |
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