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.
support from the following agencies is acknowledged; Johnson & Johnson Brasil to R.V.C. and C.W.l.R., Oswaldo Cruz German Hospital to R.V.C., Science Foundation Ireland (12/YI/B2480) to C.W.l.R., Swedish Medical Research Council (2015?02733) to L.F., C.W.l.R., and N.G.D., and European Foundation for the Study of Diabetes/Boehringer Ingelheim European Diabetes Research Programme (BI 2017_3) to C.W.l.R. and N.G.D. W.P.M.?s contribution was performed within the Irish Clinical Academic Training (ICAT) Programme, supported by the Wellcome Trust and the Health Research Board (Grant Number 203930/B/16/Z), the Health Service Executive National Doctors Training and Planning, and the Health and Social Care, Research and Development Division, Northern Ireland.
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
- NMR spectroscopy
- Type 2 diabetes
- Bariatric surgery
- Gastric bypass
- Chronic kidney disease
- Diabetic kidney disease