scholarly journals Novel mediation analysis of human plasma proteome and metabolome reveals mediators of improved glycemia after gastric bypass surgery

2019 ◽  
Author(s):  
Jonathan M Dreyfuss ◽  
Yixing Yuchi ◽  
Hui Pan ◽  
Xuehong Dong ◽  
Donald C. Simonson ◽  
...  
Keyword(s):  
Gastric Bypass ◽  
High Throughput ◽  
Mediation Analysis ◽  
Growth Hormone Receptor ◽  
Molecular Mechanisms ◽  
Gastric Bypass Surgery ◽  
Plasma Proteome ◽  
Beta Alanine ◽  
Nonsurgical Management

AbstractMolecular mechanisms by which Roux-en-Y gastric bypass (RYGB) improves glycemic control and metabolism in type 2 diabetes (T2D) remain incompletely understood. In the SLIMM-T2D trial, participants with T2D were randomized to RYGB or nonsurgical management and their fasting plasma proteome and metabolome were analyzed for up to 3 years. To identify analytes that mediate improvement in outcomes, we developed a high-throughput mediation analysis method (Hitman), which is significantly more powerful than existing methods. Top-ranking analyte mediators of glycemia improvement were growth hormone receptor and prolylhydroxyproline, which were more significant than any clinical mediator, including BMI. Beta-alanine and Histidine Metabolism (both including CNDP1) were top differentially regulated pathways, and Valine, Leucine and Isoleucine Degradation was also a top differentially-regulated pathway and a top mediator of improvement in insulin resistance. The identified analytes may serve as novel targets for T2D therapy. More broadly, Hitman can identify analyte mediators of outcomes in randomized trials for which high-throughput data are available.

scholarly journals High-throughput mediation analysis of human proteome and metabolome identifies mediators of post-bariatric surgical diabetes control

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jonathan M. Dreyfuss ◽  
Yixing Yuchi ◽  
Xuehong Dong ◽  
Vissarion Efthymiou ◽  
Hui Pan ◽  
...  
Keyword(s):  
High Throughput ◽  
Mediation Analysis ◽  
Growth Hormone Receptor ◽  
Glucose Production ◽  
Linear Modeling ◽  
Empirical Bayesian ◽  
Induce Resistance ◽  
Surgical Diabetes ◽  
Plasma Gh

AbstractTo improve the power of mediation in high-throughput studies, here we introduce High-throughput mediation analysis (Hitman), which accounts for direction of mediation and applies empirical Bayesian linear modeling. We apply Hitman in a retrospective, exploratory analysis of the SLIMM-T2D clinical trial in which participants with type 2 diabetes were randomized to Roux-en-Y gastric bypass (RYGB) or nonsurgical diabetes/weight management, and fasting plasma proteome and metabolome were assayed up to 3 years. RYGB caused greater improvement in HbA1c, which was mediated by growth hormone receptor (GHR). GHR’s mediation is more significant than clinical mediators, including BMI. GHR decreases at 3 months postoperatively alongside increased insulin-like growth factor binding proteins IGFBP1/BP2; plasma GH increased at 1 year. Experimental validation indicates (1) hepatic GHR expression decreases in post-bariatric rats; (2) GHR knockdown in primary hepatocytes decreases gluconeogenic gene expression and glucose production. Thus, RYGB may induce resistance to diabetogenic effects of GH signaling.Trial Registration: Clinicaltrials.gov NCT01073020.

The Pros and Cons of Gastric Bypass Surgery in Obese Individuals with Type 2 Diabetes—Nationwide, Matched, Observational Cohort Study

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 131-OR
Author(s):  
VASILEIOS LIAKOPOULOS ◽  
ANN-MARIE SVENSSON ◽  
INGMAR NASLUND ◽  
BJORN ELIASSON
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Bypass ◽  
Cohort Study ◽  
Bypass Surgery ◽  
Gastric Bypass Surgery ◽  
Observational Cohort Study ◽  
Observational Cohort ◽  
Pros And Cons

scholarly journals Mechanisms behind the immediate effects of Roux-en-Y gastric bypass surgery on type 2 diabetes

2013 ◽  
Vol 10 (1) ◽  
Author(s):  
Roland E Allen ◽  
Tyler D Hughes ◽  
Jia Lerd Ng ◽  
Roberto D Ortiz ◽  
Michel Abou Ghantous ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Bypass ◽  
Bypass Surgery ◽  
Gastric Bypass Surgery

Long-Term Effects of Sleeve Gastrectomy and Roux-en-Y Gastric Bypass Surgery on Type 2 Diabetes Mellitus in Morbidly Obese Subjects

2012 ◽  
Vol 256 (6) ◽  
pp. 1023-1029 ◽  
Author(s):  
Amanda Jiménez ◽  
Roser Casamitjana ◽  
Lílliam Flores ◽  
Judith Viaplana ◽  
Ricard Corcelles ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Gastric Bypass ◽  
Bypass Surgery ◽  
Gastric Bypass Surgery ◽  
Morbidly Obese ◽  
Long Term Effects ◽  
Obese Subjects

scholarly journals Pancreatic hyperplasia after gastric bypass surgery in a GK rat model of non-obese type 2 diabetes

2015 ◽  
Vol 228 (1) ◽  
pp. 13-23 ◽  
Author(s):  
Xinrong Zhou ◽  
Bangguo Qian ◽  
Ning Ji ◽  
Conghui Lui ◽  
Zhiyuan Liu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Bypass ◽  
Rat Model ◽  
Bypass Surgery ◽  
Gastric Bypass Surgery ◽  
Cell Mass ◽  
Cell Area ◽  
Obese Patients ◽  
Β Cell

Gastric bypass surgery produces clear antidiabetic effects in a substantial proportion of morbidly obese patients. In view of the recent trend away from ‘bariatric’ surgery and toward ‘metabolic’ surgery, it is important to elucidate the enhancing effect of bypass surgery on pancreatic β-cell mass, which is related to diabetes remission in non-obese patients. We investigated the effects of gastric bypass surgery on glycemic control and other pancreatic changes in a spontaneous non-obese type 2 diabetes Goto-Kakizaki rat model. Significant improvements in postprandial hyperglycemia and plasma c-peptide level were observed when glucose was administered orally post-surgery. Other important events observed after surgery were enhanced first phase insulin secretion in a in site pancreatic perfusion experiment, pancreatic hyperplasia, improved islet structure (revealed by immunohistochemical analysis), striking increase in β-cell mass, slight increase in ratio of β-cell area to total pancreas area, and increased number of small islets closely related to exocrine ducts. No notable changes were observed in ratio of β-cell to non-β endocrine cell area, β-cell apoptosis, or β-cell proliferation. These findings demonstrate that gastric bypass surgery in this rat model increases endocrine cells and pancreatic hyperplasia, and reflect the important role of the gastrointestinal system in regulation of metabolism.

scholarly journals Metabolic Outcomes 1 Year after Gastric Bypass Surgery in Obese People with Type 2 Diabetes

2012 ◽  
Vol 21 (2) ◽  
pp. 125-128 ◽  
Author(s):  
Yared N. Demssie ◽  
Jhalini Jawaheer ◽  
Seleena Farook ◽  
John P. New ◽  
Akheel A. Syed
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Bypass ◽  
Bypass Surgery ◽  
Gastric Bypass Surgery ◽  
Obese People ◽  
Metabolic Outcomes

scholarly journals Role of Gut-Related Peptides and Other Hormones in the Amelioration of Type 2 Diabetes after Roux-en-Y Gastric Bypass Surgery

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Mirella P. Hage ◽  
Bassem Safadi ◽  
Ibrahim Salti ◽  
Mona Nasrallah
Keyword(s):  
Type 2 Diabetes ◽  
Weight Loss ◽  
Gastric Bypass ◽  
Bypass Surgery ◽  
Cell Function ◽  
Gastric Bypass Surgery ◽  
Gastrointestinal Hormones ◽  
Gut Peptides

Bariatric surgery is currently the most effective and durable therapy for obesity. Roux-en-Y gastric bypass surgery, the most commonly performed procedure worldwide, causes substantial weight loss and improvement in several comorbidities associated with obesity, especially type 2 diabetes. Several mechanisms are proposed to explain the improvement in glucose metabolism after RYGB surgery: the caloric restriction and weight loss per se, the improvement in insulin resistance and beta cell function, and finally the alterations in the various gastrointestinal hormones and adipokines that have been shown to play an important role in glucose homeostasis. However, the timing, exact changes of these hormones, and the relative importance of these changes in the metabolic improvement postbariatric surgery remain to be further clarified. This paper reviews the various changes post-RYGB in adipokines and gut peptides in subjects with T2D.

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