Corbin, Laura J.
Hughes, David A.
Bull, Caroline J.
Vincent, Emma E.
Smith, Madeleine L.
McConnachie, Alex
Messow, Claudia-Martina
Welsh, Paul
Taylor, Roy
Lean, Michael E. J.
Sattar, Naveed
Timpson, Nicholas J.
Funding for this research was provided by:
Wellcome Trust (202802/Z/16/Z)
Diabetes UK (13/0004691)
Medical Research Council (MC_UU_00011)
Article History
Received: 13 February 2023
Accepted: 4 August 2023
First Online: 25 October 2023
Acknowledgements
: We thank the NHS Primary Care Research Network and North East Commissioning Support for their support and valuable input to recruitment. We thank E. Butler, J. Cooney, S.-J. Duffus and P. Stewart from the University of Glasgow for providing technical assistance, H. Pilkington from the Newcastle upon Tyne Hospitals NHS Foundation Trust for providing research nurse support, and S. Weeden and S. Cadzow from the Robertson Centre for Biostatistics. We thank W. Leslie and research dietitians L. McCombie, G. Thom, N. Brosnahan and A. Barnes for their contributions to the collection and transport of samples. We are enormously grateful to the GP practices, healthcare professionals and volunteers for their participation.We thank D. Pournaras (Department of Bariatric and Metabolic Surgery, North Bristol NHS Trust) for his contribution to manuscript preparation.
: The data used for analysis are available on a research data repository (ExternalRef removed) with access given to researchers subject to appropriate data sharing agreements. Requests to access data should be made to the Principal Investigators of DiRECT via ExternalRef removed quoting project title ‘What lies behind the causal impact of body mass index (BMI) level and change on human health? Added value from complementary study design and deep metabolic phenotyping’. Metabolite data preparation, data pre-processing, statistical analyses and figure generation were performed in R Studio v.1.0.143 [CitationRef removed] using R v.4.0.2 [CitationRef removed]. The R code for this study has been made publicly available on GitHub at: ExternalRef removed.
: The DiRECT study was funded as a Strategic Research Initiative by Diabetes UK (award no. 13/0004691). The formula diet was donated by Cambridge Weight Plan. Neither organisation had any input into the study design, data analysis or interpretation. Metabolomics analysis was funded by Wellcome Trust (award number 202802/Z/16/Z). NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the principal investigator of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011/1), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A29019). DAH and LJC are supported by NJT’s Wellcome Investigator Award (202802/Z/16/Z). EEV is supported by a Diabetes UK RD Lawrence Fellowship (17/0005587), by Cancer Research UK (C18281/A29019) and by the World Cancer Research Fund (WCRF UK), as part of the World Cancer Research Fund International grant programme (IIG_2019_2009). CJB is supported by EEV’s World Cancer Research Fund grant (IIG_2019_2009). MLS is supported by the Wellcome Trust through a PhD studentship (218495/Z/19/Z). RT is the chief investigator of the study ‘Reversal of Type 2 diabetes Upon Normalisation of Energy intake in non-obese people’ (ReTUNE) funded by Diabetes UK (17/0005645). NS acknowledges funding support from the British Heart Foundation Research Excellence Award (RE/18/6/34217). This research was funded in whole, or in part, by the Wellcome Trust (202802/Z/16/Z).The study sponsors/funders were not involved in the design of the study; the collection, analysis, and interpretation of data; and writing the report; and did not impose any restrictions regarding the publication of the report.
: RT has received lecture honoraria from Eli Lilly, Nestle Health and Janssen. NS has received consulting and/or speaker honoraria from Abbott Laboratories, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi, and grant funding support paid to his University from AstraZeneca, Boehringer Ingelheim, Novartis and Roche Diagnostics outside the submitted work. LC is an Associate Editor at <i>Diabetologia</i>. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.
: NJT, LJC and NS made substantial contributions to the conception or design of the work. NJT, LJC, RT, MEJL, AM, PW and C-MM contributed through acquisition of data and LJC, NJT, NS, MLS, CJB, EEV and DAH through analysis and interpretation of data. LJC, NJT, NS, RT, MEJL, MLS, PW, CJB, AM, C-MM and EEV contributed to the drafting the article and reviewing it critically for important intellectual content. All authors gave final approval of the version to be published. LJC is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.