Metabolite signature of diabetes remission in individuals with obesity undergoing weight loss interventions
Corresponding Author
Vidhu V. Thaker
Department of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA
Correspondence
Vidhu V. Thaker, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.
Email: [email protected]
Blandine Laferrère, Division of Endocrinology, Department of Medicine, Columbia University Irving Medical Center, Russ Berrie Medical Science Pavilion, R-121-G, 1150 St. Nicholas Ave, New York, NY, USA.
Email: [email protected]
Search for more papers by this authorLydia Coulter Kwee
Duke Molecular Physiology Institute, Durham, North Carolina, USA
Search for more papers by this authorHaiying Chen
Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
Search for more papers by this authorJudy Bahnson
Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
Search for more papers by this authorOlga Ilkayeva
Duke Molecular Physiology Institute, Durham, North Carolina, USA
Sarah W. Stedman Nutrition and Metabolism Center, Durham, North Carolina, USA
Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
Search for more papers by this authorMichael J. Muehlbauer
Duke Molecular Physiology Institute, Durham, North Carolina, USA
Sarah W. Stedman Nutrition and Metabolism Center, Durham, North Carolina, USA
Search for more papers by this authorBruce Wolfe
Departments of Surgery and Medicine, Oregon Health & Science University, Portland, Oregon, USA
Search for more papers by this authorJonathan Q. Purnell
Departments of Surgery and Medicine, Oregon Health & Science University, Portland, Oregon, USA
Search for more papers by this authorXavier Pi-Sunyer
New York Obesity Research Center, Division of Endocrinology, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA
Search for more papers by this authorChristopher B. Newgard
Duke Molecular Physiology Institute, Durham, North Carolina, USA
Sarah W. Stedman Nutrition and Metabolism Center, Durham, North Carolina, USA
Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
Department of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, North Carolina, USA
Search for more papers by this authorSvati H. Shah
Duke Molecular Physiology Institute, Durham, North Carolina, USA
Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorCorresponding Author
Blandine Laferrère
New York Obesity Research Center, Division of Endocrinology, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA
Correspondence
Vidhu V. Thaker, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.
Email: [email protected]
Blandine Laferrère, Division of Endocrinology, Department of Medicine, Columbia University Irving Medical Center, Russ Berrie Medical Science Pavilion, R-121-G, 1150 St. Nicholas Ave, New York, NY, USA.
Email: [email protected]
Search for more papers by this authorThe Look AHEAD Research Group
Search for more papers by this authorCorresponding Author
Vidhu V. Thaker
Department of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA
Correspondence
Vidhu V. Thaker, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.
Email: [email protected]
Blandine Laferrère, Division of Endocrinology, Department of Medicine, Columbia University Irving Medical Center, Russ Berrie Medical Science Pavilion, R-121-G, 1150 St. Nicholas Ave, New York, NY, USA.
Email: [email protected]
Search for more papers by this authorLydia Coulter Kwee
Duke Molecular Physiology Institute, Durham, North Carolina, USA
Search for more papers by this authorHaiying Chen
Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
Search for more papers by this authorJudy Bahnson
Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
Search for more papers by this authorOlga Ilkayeva
Duke Molecular Physiology Institute, Durham, North Carolina, USA
Sarah W. Stedman Nutrition and Metabolism Center, Durham, North Carolina, USA
Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
Search for more papers by this authorMichael J. Muehlbauer
Duke Molecular Physiology Institute, Durham, North Carolina, USA
Sarah W. Stedman Nutrition and Metabolism Center, Durham, North Carolina, USA
Search for more papers by this authorBruce Wolfe
Departments of Surgery and Medicine, Oregon Health & Science University, Portland, Oregon, USA
Search for more papers by this authorJonathan Q. Purnell
Departments of Surgery and Medicine, Oregon Health & Science University, Portland, Oregon, USA
Search for more papers by this authorXavier Pi-Sunyer
New York Obesity Research Center, Division of Endocrinology, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA
Search for more papers by this authorChristopher B. Newgard
Duke Molecular Physiology Institute, Durham, North Carolina, USA
Sarah W. Stedman Nutrition and Metabolism Center, Durham, North Carolina, USA
Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
Department of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, North Carolina, USA
Search for more papers by this authorSvati H. Shah
Duke Molecular Physiology Institute, Durham, North Carolina, USA
Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA
Search for more papers by this authorCorresponding Author
Blandine Laferrère
New York Obesity Research Center, Division of Endocrinology, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA
Correspondence
Vidhu V. Thaker, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA.
Email: [email protected]
Blandine Laferrère, Division of Endocrinology, Department of Medicine, Columbia University Irving Medical Center, Russ Berrie Medical Science Pavilion, R-121-G, 1150 St. Nicholas Ave, New York, NY, USA.
Email: [email protected]
Search for more papers by this authorThe Look AHEAD Research Group
Search for more papers by this authorSvati H. Shah and Blandine Laferrère contributed equally.
Abstract
Objective
This observational study investigated metabolomic changes in individuals with type 2 diabetes (T2D) after weight loss. We hypothesized that metabolite changes associated with T2D-relevant phenotypes are signatures of improved health.
Methods
Fasting plasma samples from individuals undergoing bariatric surgery (n = 71 Roux-en-Y gastric bypass [RYGB], n = 22 gastric banding), lifestyle intervention (n = 66), or usual care (n = 14) were profiled for 139 metabolites before and 2 years after weight loss. Principal component analysis grouped correlated metabolites into factors. Association of preintervention metabolites was tested with preintervention clinical features and changes in T2D markers. Association between change in metabolites/metabolite factors and change in T2D remission markers, homeostasis model assessment of β-cell function, homeostasis model assessment of insulin resistance, and glycated hemoglobin (HbA1c) was assessed.
Results
Branched-chain amino acids (BCAAs) were associated with preintervention adiposity. Changes in BCAAs (valine, leucine/isoleucine) and branched-chain ketoacids were positively associated with change in HbA1c (false discovery rate q value ≤ 0.001) that persisted after adjustment for percentage weight change and RYGB (p ≤ 0.02). In analyses stratified by RYGB or other weight loss method, some metabolites showed association with non-RYGB weight loss.
Conclusions
This study confirmed known metabolite associations with obesity/T2D and showed an association of BCAAs with HbA1c change after weight loss, independent of the method or magnitude of weight loss.
CONFLICT OF INTEREST STATEMENT
The authors declared no conflict of interest.
Supporting Information
| Filename | Description |
|---|---|
| oby23943-sup-0001-supinfo.pdfPDF document, 144.6 KB | Data S1. Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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