Urinary Metabolomic Changes Accompanying Albuminuria Remission following Gastric Bypass Surgery for Type 2 Diabetic Kidney Disease

William Martin; Daniel Malmodin; Anders Pedersen; Martina Wallace; Lars Fändriks; Cristina Aboud; Tarissa Petry; Lívia Cunha da Silveira; Ana da Costa Silva; Ricardo Cohen; Carel Roux; Neil Docherty

doi:10.3390/metabo12020139

Urinary Metabolomic Changes Accompanying Albuminuria Remission following Gastric Bypass Surgery for Type 2 Diabetic Kidney Disease

William Martin
, Daniel Malmodin
, Anders Pedersen
, Martina Wallace
, Lars Fändriks
, Cristina Aboud
, Tarissa Petry
, Lívia Cunha da Silveira
, Ana da Costa Silva
, Ricardo Cohen
, Carel Roux
, Neil Docherty

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

111 Downloads (Pure)

Abstract

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.

Original language	English
Article number	139
Pages (from-to)	1-31
Number of pages	31
Journal	Metabolites
Volume	12
Issue number	2
Early online date	2 Feb 2022
DOIs	https://doi.org/10.3390/metabo12020139
Publication status	Published (in print/issue) - 2 Feb 2022

Bibliographical note

Funding Information:
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.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Funding

Funding Information: 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. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

BCAA
NMR spectroscopy
Type 2 diabetes
Metabolomics
Obesity
Bariatric surgery
Gastric bypass
Chronic kidney disease
Albuminuria
Diabetic kidney disease

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metabolites-12-00139-v2.pdfFinal published version, 2.73 MBLicence: CC BY

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Martin, W., Malmodin, D., Pedersen, A., Wallace, M., Fändriks, L., Aboud, C., Petry, T., Cunha da Silveira, L., da Costa Silva, A., Cohen, R., Roux, C., & Docherty, N. (2022). Urinary Metabolomic Changes Accompanying Albuminuria Remission following Gastric Bypass Surgery for Type 2 Diabetic Kidney Disease. Metabolites, 12(2), 1-31. Article 139. https://doi.org/10.3390/metabo12020139

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abstract = "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.",

keywords = "BCAA, NMR spectroscopy, Type 2 diabetes, Metabolomics, Obesity, Bariatric surgery, Gastric bypass, Chronic kidney disease, Albuminuria, Diabetic kidney disease",

author = "William Martin and Daniel Malmodin and Anders Pedersen and Martina Wallace and Lars F{\"a}ndriks and Cristina Aboud and Tarissa Petry and \{Cunha da Silveira\}, L{\'i}via and \{da Costa Silva\}, Ana and Ricardo Cohen and Carel Roux and Neil Docherty",

note = "Funding Information: 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. Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

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Martin, W, Malmodin, D, Pedersen, A, Wallace, M, Fändriks, L, Aboud, C, Petry, T, Cunha da Silveira, L, da Costa Silva, A, Cohen, R, Roux, C & Docherty, N 2022, 'Urinary Metabolomic Changes Accompanying Albuminuria Remission following Gastric Bypass Surgery for Type 2 Diabetic Kidney Disease', Metabolites, vol. 12, no. 2, 139, pp. 1-31. https://doi.org/10.3390/metabo12020139

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T1 - Urinary Metabolomic Changes Accompanying Albuminuria Remission following Gastric Bypass Surgery for Type 2 Diabetic Kidney Disease

AU - Martin, William

AU - Malmodin, Daniel

AU - Pedersen, Anders

AU - Wallace, Martina

AU - Fändriks, Lars

AU - Aboud, Cristina

AU - Petry, Tarissa

AU - Cunha da Silveira, Lívia

AU - da Costa Silva, Ana

AU - Cohen, Ricardo

AU - Roux, Carel

AU - Docherty, Neil

N1 - Funding Information: 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. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/2/2

Y1 - 2022/2/2

N2 - 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.

AB - 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.

KW - BCAA

KW - NMR spectroscopy

KW - Type 2 diabetes

KW - Metabolomics

KW - Obesity

KW - Bariatric surgery

KW - Gastric bypass

KW - Chronic kidney disease

KW - Albuminuria

KW - Diabetic kidney disease

UR - https://www.scopus.com/pages/publications/85124271840

U2 - 10.3390/metabo12020139

DO - 10.3390/metabo12020139

M3 - Article

C2 - 35186675

SN - 2218-1989

VL - 12

SP - 1

EP - 31

JO - Metabolites

JF - Metabolites

IS - 2

M1 - 139

ER -

Urinary Metabolomic Changes Accompanying Albuminuria Remission following Gastric Bypass Surgery for Type 2 Diabetic Kidney Disease

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

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