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Open Access 25-10-2023 | Type 2 Diabetes | Article

The metabolomic signature of weight loss and remission in the Diabetes Remission Clinical Trial (DiRECT)

Authors: Laura J. Corbin, David A. Hughes, Caroline J. Bull, Emma E. Vincent, Madeleine L. Smith, Alex McConnachie, Claudia-Martina Messow, Paul Welsh, Roy Taylor, Michael E. J. Lean, Naveed Sattar, Nicholas J. Timpson

Published in: Diabetologia | Issue 1/2024

Abstract

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.

Graphical Abstract

Available only for authorised users

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Title: The metabolomic signature of weight loss and remission in the Diabetes Remission Clinical Trial (DiRECT)
Authors: Laura J. Corbin
David A. Hughes
Caroline J. Bull
Emma E. Vincent
Madeleine L. Smith
Alex McConnachie
Claudia-Martina Messow
Paul Welsh
Roy Taylor
Michael E. J. Lean
Naveed Sattar
Nicholas J. Timpson
Publication date: 25-10-2023
Publisher: Springer Berlin Heidelberg
Keyword: Type 2 Diabetes
Published in: Diabetologia / Issue 1/2024
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-023-06019-x

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Abstract

Aims/hypothesis

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Results

Conclusions/interpretation

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