期刊
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
卷 107, 期 2, 页码 E767-E782出版社
ENDOCRINE SOC
DOI: 10.1210/clinem/dgab608
关键词
GLP-1; oxyntomodulin; PYY; bariatric surgery; caloric restriction; metabolomics
资金
- UK Medical Research Council (MRC)
- Biotechnology and Biomedical Sciences Research Council (BBSRC)
- National Institute for Health Research (NIHR)
- MRC [MR/K02115X/1, MR/R010676/1, MR/P002536/1]
- NIHR [MC_PC_12025]
- Academy of Medical Sciences
- Society for Endocrinology
- British Society for Neuroendocrinology
- European Foundation for the Study of Diabetes
- EPSRC
- European Research Council [715662]
- NIHR Imperial Biomedical Research Centre (BRC)
- J.P. Moulton Charitable Trust
- MRC [MR/R010676/1] Funding Source: UKRI
- European Research Council (ERC) [715662] Funding Source: European Research Council (ERC)
The metabolic effects of a combined infusion of glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM), and peptideYY (PYY) (tripeptide GOP) were compared to a placebo infusion, Roux-en-Y gastric bypass (RYGB) surgery, and a very low-calorie diet (VLCD). The results showed that, compared to VLCD and RYGB, the tripeptide GOP had minimal effects on metabolites.
Context: The gut-derived peptide hormones glucagon-like peptide-1 (GLP-1), oxyntomodulin (OXM), and peptideYY (PYY) are regulators of energy intake and glucose homeostasis and are thought to contribute to the glucose-lowering effects of bariatric surgery. Objective: To establish the metabolomic effects of a combined infusion of GLP-1, OXM, and PYY (tripeptide GOP) in comparison to a placebo infusion, Roux-en-Y gastric bypass (RYGB) surgery, and a very low-calorie diet (VLCD). Design and Setting: Subanalysis of a single-blind, randomized, placebo-controlled study of GOP infusion (ClinicalTrials.gov NCT01945840), including VLCD and RYGB comparator groups. Patients and Interventions: Twenty-five obese patients with type 2 diabetes or prediabetes were randomly allocated to receive a 4-week subcutaneous infusion of GOP (n = 14) or 0.9% saline control (n = 11). An additional 22 patients followed a VLCD, and 21 underwent RYGB surgery. Main Outcome Measures: Plasma and urine samples collected at baseline and 4 weeks into each intervention were subjected to cross-platform metabolomic analysis, followed by unsupervised and supervised modeling approaches to identify similarities and differences between the effects of each intervention. Results: Aside from glucose, very few metabolites were affected by GOP, contrasting with major metabolomic changes seen with VLCD and RYGB. Conclusions: Treatment with GOP provides a powerful glucose-lowering effect but does not replicate the broader metabolomic changes seen with VLCD and RYGB. The contribution of these metabolomic changes to the clinical benefits of RYGB remains to be elucidated.
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