Urinary Metabolomic Changes Accompanying Albuminuria Remission following Gastric Bypass Surgery for Type 2 Diabetic Kidney Disease
William P. Martin,
Daniel Malmodin,
Anders Pedersen,
Martina Wallace,
Lars Fändriks,
Cristina M. Aboud,
Tarissa B. Zanata Petry,
Lívia P. Cunha da Silveira,
Ana C. Calmon da Costa Silva,
Ricardo V. Cohen,
Carel W. le Roux,
Neil G. Docherty
Affiliations
William P. Martin
Diabetes Complications Research Centre, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland
Daniel Malmodin
Swedish NMR Centre, University of Gothenburg, 40530 Gothenburg, Sweden
Anders Pedersen
Swedish NMR Centre, University of Gothenburg, 40530 Gothenburg, Sweden
Martina Wallace
Institute of Food and Health, School of Agriculture and Food Science, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland
Lars Fändriks
Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden
Cristina M. Aboud
The Centre for Obesity and Diabetes, Oswaldo Cruz German Hospital, São Paulo 01333-010, Brazil
Tarissa B. Zanata Petry
The Centre for Obesity and Diabetes, Oswaldo Cruz German Hospital, São Paulo 01333-010, Brazil
Lívia P. Cunha da Silveira
The Centre for Obesity and Diabetes, Oswaldo Cruz German Hospital, São Paulo 01333-010, Brazil
Ana C. Calmon da Costa Silva
The Centre for Obesity and Diabetes, Oswaldo Cruz German Hospital, São Paulo 01333-010, Brazil
Ricardo V. Cohen
The Centre for Obesity and Diabetes, Oswaldo Cruz German Hospital, São Paulo 01333-010, Brazil
Carel W. le Roux
Diabetes Complications Research Centre, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland
Neil G. Docherty
Diabetes Complications Research Centre, School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland
In the Microvascular Outcomes after Metabolic Surgery randomised clinical trial (MOMS RCT, NCT01821508), combined metabolic surgery (gastric bypass) plus medical therapy (CSM) was superior to medical therapy alone (MTA) as a means of achieving albuminuria remission at 2-year follow-up in patients with obesity and early diabetic kidney disease (DKD). In the present study, we assessed the urinary 1H-NMR metabolome in a subgroup of patients from both arms of the MOMS RCT at baseline and 6-month follow-up. Whilst CSM and MTA both reduced the urinary excretion of sugars, CSM generated a distinctive urinary metabolomic profile characterised by increases in host–microbial co-metabolites (N-phenylacetylglycine, trimethylamine N-oxide, and 4-aminobutyrate (GABA)) and amino acids (arginine and glutamine). Furthermore, reductions in aromatic amino acids (phenylalanine and tyrosine), as well as branched-chain amino acids (BCAAs) and related catabolites (valine, leucine, 3-hydroxyisobutyrate, 3-hydroxyisovalerate, and 3-methyl-2-oxovalerate), were observed following CSM but not MTA. Improvements in BMI did not correlate with improvements in metabolic and renal indices following CSM. Conversely, urinary metabolites changed by CSM at 6 months were moderately to strongly correlated with improvements in blood pressure, glycaemia, triglycerides, and albuminuria up to 24 months following treatment initiation, highlighting the potential involvement of these shifts in the urinary metabolomic profile in the metabolic and renoprotective effects of CSM.
