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Carlson TL, Colbert K, Vieira M, Guerina FV, Bryant CLN, Habegger K, Pasricha PJ, Petersen J, Polomoscanik S, Jozefiak TH, Nimgaonkar A. Development of a targeted oral pharmacologic duodenal exclusion therapy for the treatment of metabolic diseases. SCIENCE ADVANCES 2025; 11:eadu1326. [PMID: 40446040 PMCID: PMC12124365 DOI: 10.1126/sciadv.adu1326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 04/24/2025] [Indexed: 06/02/2025]
Abstract
Type 2 diabetes (T2D) and obesity are chronic metabolic diseases with global morbidity and mortality. Decades of evidence from surgical and endoscopic procedures bypassing the duodenum underscore the duodenum's critical role in regulating glycemia and body weight. Although metabolic surgeries and endoscopic procedures are effective, their invasiveness, cost, and scalability limit patient access. We developed an orally administered mucin complexing polymeric (MCP) drug, designed to replicate duodenal exclusion physiology. MCPs, intended to have electrostatic and covalent cross-linkages with mucin glycoproteins, form extended network structures with resulting alteration of mucus barrier properties. Selective targeting of the duodenum is achieved via pH-based activation chemistry. Following screening for physiochemical properties, pharmacokinetics, and efficacy, GLY-200 emerged as the lead drug candidate replicating duodenal exclusion physiology with improved glycemia, reduced body weight, and modulation of gut hormones in rodent models. This targeted oral therapy holds promise for treatment of T2D and obesity by mimicking duodenal exclusion without the invasiveness of surgery or endoscopic procedures.
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Affiliation(s)
| | - Kevin Colbert
- Glyscend Therapeutics Inc., Baltimore, MD, 21205, USA
| | - Marcela Vieira
- Gastroenterology Imaging, Clario (eResearch Technology) , Philadelphia, PA 19103, USA
| | - Florence V. Guerina
- Department of Molecular Cell Biology and Biochemistry, Boston University, Boston, MA 02215, USA
| | | | - Kirk Habegger
- Division of Endocrinology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Pankaj Jay Pasricha
- Division of Gastroenterology, Department of Medicine, Mayo Clinic, Phoenix, AZ 85054, USA
| | - John Petersen
- Glyscend Therapeutics Inc., Baltimore, MD, 21205, USA
| | | | | | - Ashish Nimgaonkar
- Glyscend Therapeutics Inc., Baltimore, MD, 21205, USA
- Center for Bioengineering Innovation and Design, Department of Biomedical Engineering, The Johns Hopkins Hospital, Baltimore, MD 21287, USA
- Division of Gastroenterology, Department of Medicine, The Johns Hopkins Hospital, Baltimore, MD 21287, USA
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Zhen TT, Li SZ, Pan ST, Yin TY, Wang M, Guo XJ, Zhang H, Qin RY. Nonalcoholic fatty liver disease following laparoscopic duodenum-preserving pancreatic total head resection vs laparoscopic pancreaticoduodenectomy: A retrospective cohort study. World J Gastroenterol 2025; 31:104046. [PMID: 40248065 PMCID: PMC12001169 DOI: 10.3748/wjg.v31.i13.104046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 02/21/2025] [Accepted: 03/10/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of fat in the liver in individuals who do not consume alcohol. Several risk factors influencing the onset of NAFLD after laparoscopic pancreaticoduodenectomy (LPD) have been identified. This study investigated the risk factors associated with the development of fatty liver after laparoscopic duodenum-preserving pancreatic total head resection (LDPPHRt) and LPD. AIM To compare the effects of LDPPHRt and LPD on the development of postoperative NAFLD. METHODS This retrospective cohort study included 59 patients who were histologically diagnosed with benign or low-grade malignant pancreatic tumors and who underwent laparoscopic pancreatic surgery (LDPPHRt or LPD) between May 2020 and April 2023. Patient data on perioperative and postoperative variables were analyzed and compared. Multivariate logistic regression was used to identify pre-, peri-, and postoperative risk factors for NAFLD, with statistical significance set at P < 0.05. RESULTS Of the 59 patients included in the study, 17 (28.8%) developed NAFLD within 6-12 months post-surgery. The incidence of NAFLD was significantly higher in the LPD group compared to the LDPPHRt group (40.0% vs 12.5%, P = 0.022). Multivariable analysis identified the LDPPHRt surgical approach (compared to LPD) as an independent protective factor against the development of postoperative NAFLD, with an odds ratio of 0.208 (95% confidence interval: 0.046-0.931; P = 0.040). CONCLUSION Our findings indicate that LDPPHRt is more effective than LPD in reducing the incidence of postoperative NAFLD, which may inform surgical decision-making and optimize patient outcomes after laparoscopic pancreatic surgery.
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Affiliation(s)
- Ting-Ting Zhen
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Shi-Zhen Li
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Shu-Tao Pan
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Tao-Yuan Yin
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Min Wang
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Xing-Jun Guo
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Hang Zhang
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Ren-Yi Qin
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
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Yoshida MC, Luong D, Tan S, Pan J, Luu J, Pyke O, Kella V, Brathwaite CEM, Levine J. Enhanced Total Weight Loss 2 Years Post-Roux-en-Y Gastric Bypass with Longer Biliopancreatic Limb. Obes Surg 2025; 35:1493-1503. [PMID: 40100614 DOI: 10.1007/s11695-025-07797-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 02/06/2025] [Accepted: 03/10/2025] [Indexed: 03/20/2025]
Abstract
BACKGROUND Despite widespread use of Roux-en-Y gastric bypass (RYGB), there are no standardized limb lengths in the United States. METHODS A multi-center retrospective cohort study was conducted from 2020 to 2023. Eligible patients who had undergone RYGB were divided into subgroups based on BP limb lengths: short (50-75 cm), intermediate (80-125 cm), and long (150-175 cm). Primary outcomes were total weight loss (TWL) and % TWL at 1 and 2 years. Secondary outcomes were post-operative BMI and % BMI change at 1 and 2 years, micronutrient deficiencies, hypothyroidism, acute kidney injury (AKI) requiring treatment, and remission in associated medical problems. Subgroups were compared using multivariate analysis. RESULTS Two hundred twenty-eight patients received a long BP limb, 194 patients received an intermediate BP limb, while 152 patients received a short BP limb. Primary outcomes TWL and % TWL were significantly different between the groups at 1 year: TWL and % TWL were greater in patients with long BP limbs. The difference between the long and short BP limb groups increased at the 2-year mark. Patients who had long BP limbs had higher rates of DM remission (12.3% vs 11.9% 6.6%), HTN (8.8% vs 5.7% vs 7.9%), GERD symptoms (14.5% vs 9.8% vs 5.3%), and OSA (8.8% vs 7.7% vs 5.3%). Vitamin A deficiency rates were higher in the long BP limb group. CONCLUSIONS The results suggest that longer BP limb lengths are conducive to TWL and overall treatment of obesity-related problems without severe rates of complications. Additional longer longitudinal studies are needed to assess the impact of long BP limbs on nutrition and weight loss in the long term.
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Affiliation(s)
| | - Diana Luong
- NYU Langone Hospital - Long Island, Mineola, NY, USA
| | - Sally Tan
- NYU Langone Hospital - Long Island, Mineola, NY, USA
| | - Jennifer Pan
- NYU Langone Hospital - Long Island, Mineola, NY, USA
| | | | - Owen Pyke
- NYU Langone Hospital - Long Island, Mineola, NY, USA
| | - Venkata Kella
- NYU Langone Hospital - Long Island, Mineola, NY, USA
| | | | - Jun Levine
- NYU Langone Hospital - Long Island, Mineola, NY, USA
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4
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Brial F, Le Lay A, Rouch C, Henrion E, Bourgey M, Bourque G, Lathrop M, Magnan C, Gauguier D. Transcriptome atlases of rat brain regions and their adaptation to diabetes resolution following gastrectomy in the Goto-Kakizaki rat. Mol Brain 2025; 18:9. [PMID: 39920851 PMCID: PMC11806591 DOI: 10.1186/s13041-025-01176-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 01/13/2025] [Indexed: 02/09/2025] Open
Abstract
Brain regions drive multiple physiological functions through specific gene expression patterns that adapt to environmental influences, drug treatments and disease conditions. To generate a detailed atlas of the brain transcriptome in the context of diabetes, we carried out RNA sequencing in hypothalamus, hippocampus, brainstem and striatum of the Goto-Kakizaki (GK) rat model of spontaneous type 2 diabetes, which was applied to identify gene transcription adaptation to improved glycemic control following vertical sleeve gastrectomy (VSG) in the GK. Over 19,000 distinct transcripts were detected in the rat brain, including 2794 which were consistently expressed in the four brain regions. Region-specific gene expression was identified in hypothalamus (n = 477), hippocampus (n = 468), brainstem (n = 1173) and striatum (n = 791), resulting in differential regulation of biological processes between regions. Differentially expressed genes between VSG and sham operated rats were only found in the hypothalamus and were predominantly involved in the regulation of endothelium and extracellular matrix. These results provide a detailed atlas of regional gene expression in the diabetic rat brain and suggest that the long term effects of gastrectomy-promoted diabetes remission involve functional changes in the hypothalamus endothelium.
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Affiliation(s)
- François Brial
- Université Paris Cité, INSERM U1132 Biologie de l'os et du Cartilage (BIOSCAR), 75010, Paris, France
| | - Aurélie Le Lay
- Université Paris Cité, Functional and Adaptive Biology, UMR 8251, CNRS, 4 Rue Marie Andrée Lagroua Weill-Halle, 75013, Paris, France
| | - Claude Rouch
- Université Paris Cité, Functional and Adaptive Biology, UMR 8251, CNRS, 4 Rue Marie Andrée Lagroua Weill-Halle, 75013, Paris, France
| | - Edouard Henrion
- Victor Phillip Dahdaleh Institute of Genomic Medicine at McGill University, 740 Doctor Penfield Avenue, Montreal, QC, H3A 0G1, Canada
| | - Mathieu Bourgey
- Victor Phillip Dahdaleh Institute of Genomic Medicine at McGill University, 740 Doctor Penfield Avenue, Montreal, QC, H3A 0G1, Canada
| | - Guillaume Bourque
- Victor Phillip Dahdaleh Institute of Genomic Medicine at McGill University, 740 Doctor Penfield Avenue, Montreal, QC, H3A 0G1, Canada
| | - Mark Lathrop
- Victor Phillip Dahdaleh Institute of Genomic Medicine at McGill University, 740 Doctor Penfield Avenue, Montreal, QC, H3A 0G1, Canada
| | - Christophe Magnan
- Université Paris Cité, Functional and Adaptive Biology, UMR 8251, CNRS, 4 Rue Marie Andrée Lagroua Weill-Halle, 75013, Paris, France
| | - Dominique Gauguier
- Université Paris Cité, Functional and Adaptive Biology, UMR 8251, CNRS, 4 Rue Marie Andrée Lagroua Weill-Halle, 75013, Paris, France.
- Victor Phillip Dahdaleh Institute of Genomic Medicine at McGill University, 740 Doctor Penfield Avenue, Montreal, QC, H3A 0G1, Canada.
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan.
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Aukan MI, Rehfeld JF, Holst JJ, Martins C. Plasma concentration of gastrointestinal hormones and subjective appetite ratings after diet or bariatric surgery: 1-year results from the DISGAP study. Int J Obes (Lond) 2025; 49:306-314. [PMID: 39572763 DOI: 10.1038/s41366-024-01658-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 10/10/2024] [Accepted: 10/14/2024] [Indexed: 01/04/2025]
Abstract
OBJECTIVE Long-term weight loss outcomes are contrasting between bariatric surgery and dietary restriction alone. This is the first study to investigate changes in gastrointestinal (GI) hormones involved in appetite regulation, and subjective appetite feelings, at 1-year follow-up, after initial weight loss induced by a very-low energy (VLED) alone (controls), or with bariatric surgery. METHODS Patients scheduled for Sleeve Gastrectomy (SG) (n = 19) or Roux-en-Y gastric Bypass (RYGB) (n = 19), and controls (n = 16) were recruited. All groups underwent 10 weeks of a VLED (initial phase), followed by a 9-month maintenance phase. Body weight/composition, plasma concentrations of ghrelin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY), cholecystokinin (CCK), and appetite ratings were measured before and after a meal, at baseline, week 11(W11), and 1Y follow-up. RESULTS Participants who completed all three follow ups were included in the analysis. Initial changes in body weight/composition were comparable across groups. SG (n = 11) and RYGB (n = 12) continued to lose weight from W11 to 1Y, whereas controls (n = 12) had regained weight. Postprandial GLP-1 increased over time post bariatric surgery and remained unchanged and lower in controls. Postprandial PYY increased in all groups, but greatest post-RYGB. Basal ghrelin decreased over time post-SG, while a small or marked increase was seen after RYGB and diet, respectively, with the control group exhibiting the greatest basal and postprandial concentrations at 1Y. A reduction in basal and postprandial CCK was seen in controls at 1Y, while no changes were observed post-bariatric surgery. Overall, small changes in subjective appetite ratings were seen over time. CONCLUSION Weight change at 1Y follow up after SG and RYGB is followed by a GI hormone profile favoring a lower drive to eat and increased satiety. The opposite is seen 1Y after WL induced by dietary restriction alone. CLINICAL TRIAL REGISTRATION clinicaltrials.gov NCT04051190.
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Affiliation(s)
- Marthe Isaksen Aukan
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
- Centre of Obesity and Innovation (ObeCe), Clinic of Surgery, St. Olav University Hospital, Trondheim, Norway.
| | - Jens Frederik Rehfeld
- Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Jens Juul Holst
- The Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, University of Copenhagen, The Panum Institute, Copenhagen, Denmark
| | - Catia Martins
- Department of Nutrition Sciences, University of Alabama at Birmingham (UAB), Birmingham, AL, USA
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6
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Li H, He J, Hou J, He C, Dai X, Song Z, Liu Q, Wang Z, Huang H, Ding Y, Qi T, Zhang H, Wu L. Intestinal rearrangement of biliopancreatic limbs, alimentary limbs, and common limbs in obese type 2 diabetic mice after duodenal jejunal bypass surgery. Front Endocrinol (Lausanne) 2025; 15:1456885. [PMID: 39845886 PMCID: PMC11750664 DOI: 10.3389/fendo.2024.1456885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Accepted: 12/17/2024] [Indexed: 01/24/2025] Open
Abstract
Bariatric surgery is an effective treatment for type 2 Diabetes Mellitus (T2DM), yet the precise mechanisms underlying its effectiveness remain incompletely understood. While previous research has emphasized the role of rearrangement of the gastrointestinal anatomy, gaps persist regarding the specific impact on the gut microbiota and barriers within the biliopancreatic, alimentary, and common limbs. This study aimed to investigate the effects of duodenal-jejunal bypass (DJB) surgery on obese T2DM mice. We performed DJB and SHAM surgery in obese T2DM mice to investigate changes in the gut microbiota and barrier across different intestinal limbs. The effects on serum metabolism and potential associations with T2DM improvement were also investigated. Following DJB surgery, there was an increased abundance of commensals across various limbs. Additionally, the surgery improved intestinal permeability and inflammation in the alimentary and common limbs, while reducing inflammation in the biliopancreatic limbs. Furthermore, DJB surgery also improved T2DM by increasing L-glutamine, short-chain fatty acids, and bile acids and decreasing branched-chain amino acids. This study underscores the role of intestinal rearrangement in reshaping gut microbiota composition and enhancing gut barrier function, thereby contributing to the amelioration of T2DM following bariatric surgery, and providing new insights for further research on bariatric surgery.
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Affiliation(s)
- Heng Li
- Department of Metabolic Surgery, Jinshazhou Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Department of Endocrinology and Metabolism, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Jipei He
- Department of Basic Medical Research, General Hospital of Southern Theater Command of People's Liberation Army (PLA), Guangzhou, China
| | - Jie Hou
- Department of Metabolic Surgery, Jinshazhou Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Chengjun He
- Department of Metabolic Surgery, Jinshazhou Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiaojiang Dai
- Department of Metabolic Surgery, Jinshazhou Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zhigao Song
- Department of Cardiovascular Surgery, Zhujiang Hospital of Southern Medical University, Guangzhou, China
| | - Qing Liu
- Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Guangzhou, China
| | - Zixin Wang
- Department of Metabolic Surgery, Jinshazhou Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Hongyan Huang
- Department of Metabolic Surgery, Jinshazhou Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yunfa Ding
- Department of Metabolic Surgery, Jinshazhou Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Tengfei Qi
- Department of Metabolic Surgery, Jinshazhou Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Hongbin Zhang
- Department of Basic Medical Research, General Hospital of Southern Theater Command of People's Liberation Army (PLA), Guangzhou, China
- School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
| | - Liangping Wu
- Department of Metabolic Surgery, Jinshazhou Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- Guangzhou Hualiang Qingying Biotechnology Co. Ltd, Guangzhou, China
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7
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Park KB, Jun KH. Bariatric surgery for treatment of morbid obesity in adults. Korean J Intern Med 2025; 40:24-39. [PMID: 39778524 PMCID: PMC11725483 DOI: 10.3904/kjim.2024.219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 09/02/2024] [Accepted: 10/20/2024] [Indexed: 01/11/2025] Open
Abstract
Morbid obesity requires active intervention, with treatment options including lifestyle modification, pharmacotherapy, and surgery. As the prevalence of obesity continues to rise in Korea, it is crucial for specialists and general practitioners to have a comprehensive understanding of obesity and its management. Bariatric surgery is the most effective treatment modality for obesity, leading to significant weight loss and metabolic benefits. It involves surgical alterations of normal anatomical structures to improve overall health. Therefore, selecting the appropriate procedure based on the individual characteristics of patients is crucial. This review highlights the two most commonly performed bariatric procedures worldwide, including in Korea: sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). Furthermore, it provides a comprehensive overview of the surgical techniques involved in SG and RYGB, addresses potential complications, and presents findings from key studies on the weight loss and metabolic outcomes of these surgeries. Additionally, to support clinical application, the review provides outcome data for these procedures based on studies conducted in Korean populations. In addition to SG and RYGB, this review briefly introduces other surgical and endoscopic options, as well as pharmacological treatments that are currently available or may become viable options in the near future.
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Affiliation(s)
- Ki Bum Park
- Department of Surgery, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Clinic of Metabolic and Bariatric Surgery, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Kyong-Hwa Jun
- Department of Surgery, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
- Clinic of Metabolic and Bariatric Surgery, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
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8
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Foschi D, Sarro G, Serbelloni M, Rizzi A, Chiappa A. Type 2 diabetes mellitus remission following laparoscopic sleeve gastrectomy and hindgut-based procedure: a retrospective multicenter study. Updates Surg 2024:10.1007/s13304-024-02035-7. [PMID: 39602074 DOI: 10.1007/s13304-024-02035-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 11/17/2024] [Indexed: 11/29/2024]
Abstract
Sleeve gastrectomy (SG) is considered the standard bariatric surgery due to its excellent outcomes. However, in patients with obesity and type 2 diabetes mellitus (T2DM), SG alone carries a high risk of metabolic failure. To achieve better metabolic results, SG can be combined with either foregut- or hindgut-based procedures, although a direct comparison between these approaches is lacking. In this retrospective study, we compared the bariatric and metabolic effects of SG (n = 20 patients) with SG associated with duodenal diversion and ileal interposition (SG-DD-II) (n = 20), SG associated with duodenal-ileal anastomosis (SADI-S) (n = 20), and SG associated with single gastro-ileal anastomosis (SASI-S) (n = 20). Patient data, including anthropometric measurements and T2DM characteristics, were extracted from our database. The evaluation criteria included weight loss (% excess weight loss), fasting glycemia (FGL), glycated hemoglobin (HbA1C) percentage, and T2DM remission rates. Our statistical analysis (p < 0.05) revealed that shortly after surgery, all procedures demonstrated acceptable outcomes in terms of weight loss and T2DM remission. However, after 3 and 5 years post-surgery, the T2DM relapse rate was significantly higher following SG alone compared to hindgut-based operations. In patients with obesity and T2DM, we recommend combining SG with a hindgut-based procedure to reduce the long-term relapse rate.
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Affiliation(s)
- Diego Foschi
- Institute San Gaudenzio, Via Enrico Bottini 3, 28100, Novara, Italy.
| | - Giuliano Sarro
- Institute San Gaudenzio, Via Enrico Bottini 3, 28100, Novara, Italy
| | | | - Andrea Rizzi
- Ospedale Generale Tradate, ATS Sette Laghi, Varese, Italy
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9
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Poljo A, Kraljević M, Peterli R, Müller BP, Billeter AT. Role of sleeve gastrectomy in improving metabolic syndrome: an overview. Updates Surg 2024:10.1007/s13304-024-02038-4. [PMID: 39586962 DOI: 10.1007/s13304-024-02038-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Accepted: 11/17/2024] [Indexed: 11/27/2024]
Abstract
Metabolic syndrome (MetS) presents a global health challenge characterized by cardiometabolic risk factors like central obesity, elevated blood pressure, dyslipidemia, and high fasting glucose levels. Despite lifestyle interventions and medications, the increasing prevalence of MetS calls for effective treatments. Sleeve gastrectomy (SG) has emerged as a promising intervention. This review examines the role of SG in improving MetS outcomes, drawing from a PubMed/Medline literature search. It highlights SG's multifaceted metabolic effects, including hormonal changes and improved insulin sensitivity, contributing to improved metabolic outcomes. Additionally, SG leads to significant weight loss and effectively addresses comorbidities like hypertension, dyslipidemia, and type 2 diabetes mellitus (T2DM), with low rates of early morbidity and mortality. However, long-term studies indicate that Roux-en-Y gastric bypass (RYGB) provides more sustained weight loss and superior resolution of metabolic comorbidities, whereas SG is associated with fewer early complications and a lower risk of nutritional deficiencies. In conclusion, SG offers a valuable option for managing MetS, providing significant weight loss and comorbidity improvement. Nevertheless, potential long-term complications, such as gastroesophageal reflux disease (GERD) and suboptimal weight response, emphasize careful patient selection and monitoring.
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Affiliation(s)
- Adisa Poljo
- Division of Metabolic Bariatric Surgery, Department of Visceral Surgery, Clarunis, University Digestive Health Care Center Basel, St. Clara Hospital and University Hospital Basel, Basel, Switzerland
| | - Marko Kraljević
- Division of Metabolic Bariatric Surgery, Department of Visceral Surgery, Clarunis, University Digestive Health Care Center Basel, St. Clara Hospital and University Hospital Basel, Basel, Switzerland
| | - Ralph Peterli
- Division of Metabolic Bariatric Surgery, Department of Visceral Surgery, Clarunis, University Digestive Health Care Center Basel, St. Clara Hospital and University Hospital Basel, Basel, Switzerland
| | - Beat P Müller
- Division of Metabolic Bariatric Surgery, Department of Visceral Surgery, Clarunis, University Digestive Health Care Center Basel, St. Clara Hospital and University Hospital Basel, Basel, Switzerland
| | - Adrian T Billeter
- Division of Metabolic Bariatric Surgery, Department of Visceral Surgery, Clarunis, University Digestive Health Care Center Basel, St. Clara Hospital and University Hospital Basel, Basel, Switzerland.
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10
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Ghusn W, Calderon G, Abu Dayyeh BK, Acosta A. Mechanism of action and selection of endoscopic bariatric therapies for treatment of obesity. Clin Endosc 2024; 57:701-710. [PMID: 39206501 PMCID: PMC11637673 DOI: 10.5946/ce.2024.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 01/26/2024] [Accepted: 02/03/2024] [Indexed: 09/04/2024] Open
Abstract
Endoscopic bariatric therapies (EBTs) are minimally invasive and safe procedures with favorable weight loss outcomes in obesity treatment. We aimed to present the weight loss mechanism of action of EBTs and an individualized selection method for patients with obesity. We searched PubMed, Medline, Scopus, Embase, and Google Scholar databases for studies on the topic from databases inception to July 1, 2023, written in English. We focused on EBTs potential mechanism of action to induce weight loss. We also present an expert opinion on a novel selection of EBTs based on their mechanism of action. EBTs can result in weight loss through variable mechanisms of action. They can induce earlier satiation, delay gastric emptying, restrict the accommodative response of the stomach, decrease caloric absorption, and alter the secretion of gastrointestinal hormones. Selecting EBTs may be guided through their mechanism of action by which patients with abnormal satiation may benefit more from tissue apposition devices and aspiration therapy while patients with fast gastric emptying may be better candidates for intragastric devices, endoscopic anastomosis devices, and duodenal mucosal resurfacing. Consequently, the selection of EBTs should be guided by the mechanism of action which is specific to each type of therapy.
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Affiliation(s)
- Wissam Ghusn
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Gerardo Calderon
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | | | - Andres Acosta
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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11
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Busch CBE, Meiring S, van Baar ACG, Holleman F, Nieuwdorp M, Bergman JJGHM. Recellularization via electroporation therapy of the duodenum combined with glucagon-like peptide-1 receptor agonist to replace insulin therapy in patients with type 2 diabetes: 12-month results of a first-in-human study. Gastrointest Endosc 2024; 100:896-904. [PMID: 38692517 DOI: 10.1016/j.gie.2024.04.2904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 03/29/2024] [Accepted: 04/22/2024] [Indexed: 05/03/2024]
Abstract
BACKGROUND AND AIMS Studies have shown that hydrothermal duodenal mucosal ablation results in improved glycemic control. Recellularization via electroporation therapy (ReCET) is a novel endoscopic procedure that uses electroporation to induce cellular apoptosis and subsequent reepithelization. In this study, we aimed to eliminate exogenous insulin treatment in type 2 diabetes (T2D) patients through a single ReCET procedure combined with a glucagon-like peptide-1 receptor agonist. Feasibility, safety, and (dose) efficacy of ReCET were assessed. METHODS This first-in-human study included patients with T2D on basal insulin (age, 28-75 years; body mass index, 24-40 kg/m2; glycosylated hemoglobin, ≤64 mmol/mol; C-peptide, ≥0.2 nmol/L). The electroporation dose was optimized during the study, starting with single 600 V and ending with double 750 V treatments. All patients underwent ReCET, after which insulin was discontinued and semaglutide (glucagon-like peptide-1 receptor agonist) was initiated. The primary endpoints were feasibility (procedure time [from catheter in to catheter out], technical success rate), safety, and efficacy (patients off insulin at 6 months; HbA1c, ≤58 mmol/mol). RESULTS Fourteen patients underwent endoscopic ReCET. The median procedure time was 58 (interquartile range, 49-73) minutes. ReCET demonstrated a technical success rate of 100%. No device-related severe adverse events or severe hypoglycemic events were observed. At the 12-month follow-up, 12 (86%) patients remained off exogenous insulin therapy, with significant improvements in glycemic control and metabolic parameters. The 2 patients in whom insulin therapy was reintroduced both received ReCET at the lowest voltage (single 600 V). CONCLUSION These results suggest that ReCET is feasible and safe. In combination with semaglutide, ReCET may be a promising therapeutic option to replace insulin therapy in selected T2D patients while improving glycemic control and metabolic health.
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Affiliation(s)
- Celine B E Busch
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Suzanne Meiring
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Annieke C G van Baar
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
| | - Frits Holleman
- Department of Internal Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Max Nieuwdorp
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, Amsterdam Gastroenterology Endocrinology Metabolism, University of Amsterdam, Amsterdam, The Netherlands
| | - Jacques J G H M Bergman
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
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Boškoski I, Gualtieri L, Matteo MV. Small Bowel Therapies for Metabolic Disease and Obesity. Gastrointest Endosc Clin N Am 2024; 34:715-732. [PMID: 39277300 DOI: 10.1016/j.giec.2024.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/17/2024]
Abstract
The small bowel has a crucial role in metabolic homeostasis. Small bowel endoscopic bariatric metabolic treatments (EBMTs) include several devices aimed at providing minimally invasive approaches for the management of metabolic disorders. The aim of this review is to provide an updated and exhaustive overview of the EBMTs targeting the small bowel developed to date, including the duodenal mucosa resurfacing, the duodenal-jejunal bypass liners, gastro-jejunal bypass sleeve, and the incisioneless magnetic anastomosis system, as well as to mention the future perspectives in the field.
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Affiliation(s)
- Ivo Boškoski
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168, Roma, Italy; Università Cattolica del Sacro Cuore, Roma 00168, Italy
| | - Loredana Gualtieri
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168, Roma, Italy; Università Cattolica del Sacro Cuore, Roma 00168, Italy
| | - Maria Valeria Matteo
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168, Roma, Italy; Università Cattolica del Sacro Cuore, Roma 00168, Italy.
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13
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Liu ZT, Yang GW, Zhao X, Dong SH, Jiao Y, Ge Z, Yu A, Zhang XQ, Xu XZ, Cheng ZQ, Zhang X, Wang KX. Growth hormone improves insulin resistance in visceral adipose tissue after duodenal-jejunal bypass by regulating adiponectin secretion. World J Diabetes 2024; 15:1340-1352. [PMID: 38983805 PMCID: PMC11229968 DOI: 10.4239/wjd.v15.i6.1340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 03/12/2024] [Accepted: 04/15/2024] [Indexed: 06/11/2024] Open
Abstract
BACKGROUND The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass (DJB) surgery is not clear. AIM To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model. METHODS DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model. All adipose tissue was weighed and observed under microscope. Use inguinal fat to represent subcutaneous adipose tissue (SAT) and mesangial fat to represent visceral adipose tissue. RNA-sequencing was utilized to evaluate gene expression alterations adipocytes. The hematoxylin and eosin staining, reverse transcription-quantitative polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay were used to study the changes. Insulin resistance was evaluated by immunofluorescence. RESULTS After DJB, whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved. Fat cell volume in both visceral adipose tissue (VAT) and SAT increased. Compared to SAT, VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone (GH) pathway and downstream adiponectin secretion were involved in metabolic regulation. The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased. Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity. CONCLUSION GH improves insulin resistance in VAT in male diabetic rats after receiving DJB, possibly by increasing adiponectin secretion.
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Affiliation(s)
- Zi-Tian Liu
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Guang-Wei Yang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Xiang Zhao
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Shuo-Hui Dong
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Yang Jiao
- Department of General Surgery, Shandong University of Qilu Hospital (Qingdao), Qingdao 266000, Shandong Province, China
| | - Zheng Ge
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Ao Yu
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Xi-Qiang Zhang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Xin-Zhen Xu
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Zhi-Qiang Cheng
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Xiang Zhang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Ke-Xin Wang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
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Gala K, Ghusn W, Abu Dayyeh BK. Gut motility and hormone changes after bariatric procedures. Curr Opin Endocrinol Diabetes Obes 2024; 31:131-137. [PMID: 38533785 DOI: 10.1097/med.0000000000000860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/28/2024]
Abstract
PURPOSE OF REVIEW Metabolic and bariatric surgery (MBS) and endoscopic bariatric therapies (EBT) are being increasingly utilized for the management of obesity. They work through multiple mechanisms, including restriction, malabsorption, and changes in the gastrointestinal hormonal and motility. RECENT FINDINGS Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) cause decrease in leptin, increase in GLP-1 and PYY, and variable changes in ghrelin (generally thought to decrease). RYGB and LSG lead to rapid gastric emptying, increase in small bowel motility, and possible decrease in colonic motility. Endoscopic sleeve gastroplasty (ESG) causes decrease in leptin and increase in GLP-1, ghrelin, and PYY; and delayed gastric motility. SUMMARY Understanding mechanisms of action for MBS and EBT is critical for optimal care of patients and will help in further refinement of these interventions.
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Affiliation(s)
- Khushboo Gala
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Wissam Ghusn
- Department of Internal Medicine, Boston University Medical Center, Boston, Massachusetts, USA
| | - Barham K Abu Dayyeh
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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15
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Busch CBE, Bergman JJGHM, Nieuwdorp M, van Baar ACG. Role of the Intestine and Its Gut Microbiota in Metabolic Syndrome and Obesity. Am J Gastroenterol 2024; 119:1038-1046. [PMID: 38372280 DOI: 10.14309/ajg.0000000000002730] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 02/14/2024] [Indexed: 02/20/2024]
Abstract
The metabolic syndrome (MetSyn) is currently one of the biggest global health challenges because of its impact on public health. MetSyn includes the cluster of metabolic disorders including obesity, high blood pressure, hyperglycemia, high triglyceride levels, and hepatic steatosis. Together, these abnormalities increase the cardiovascular risk of individuals and pose a threat to healthcare systems worldwide. To better understand and address this complex issue, recent research has been increasingly focusing on unraveling the delicate interplay between metabolic disorders and the intestines and more specifically our gut microbiome. The gut microbiome entails all microorganisms inhabiting the gastrointestinal tract and plays a pivotal role in metabolic processes and overall health of its host. Emerging evidence proves an association between the gut microbiome composition and aspects of MetSyn, such as obesity. Understanding these relationships is crucial because they offer valuable insights into the mechanisms underlying development and progression of metabolic disorders and possible treatment options. Yet, how should we interpret this relationship? This review focuses on the interplay between the gut and MetSyn. In addition, we have reviewed the existing evidence of the gut microbiome and its association with and impact on metabolic disorders, in an attempt to understand the complex interactions and nature of this association. We also explored potential therapeutic options targeting the gut to modify metabolic disorders and obesity.
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Affiliation(s)
- Celine B E Busch
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Research Institute, Amsterdam, the Netherlands
| | - Jacques J G H M Bergman
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Research Institute, Amsterdam, the Netherlands
| | - Max Nieuwdorp
- Amsterdam Gastroenterology Endocrinology Metabolism, Research Institute, Amsterdam, the Netherlands
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands
| | - Annieke C G van Baar
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Research Institute, Amsterdam, the Netherlands
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Nedelcut S, Axer S, Olbers T. The risk and benefit of revisional vs. primary metabolic- bariatric surgery and drug therapy - A narrative review. Metabolism 2024; 154:155799. [PMID: 38281557 DOI: 10.1016/j.metabol.2024.155799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 01/17/2024] [Accepted: 01/19/2024] [Indexed: 01/30/2024]
Abstract
Metabolic and bariatric surgery (MBS) leads to long-term weight loss, reduced risk of cardiovascular events and cancer, and reduced mortality. Sleeve gastrectomy and Roux-en-Y gastric bypass are currently the most common surgical techniques. Weight loss after MBS was previously believed to work through restriction and malabsorption, however, mechanistic studies show that MBS techniques with long term efficacy instead alter physiological signaling between the gut and the brain. In revisional MBS, the initial surgical technique is corrected, modified, or converted to a new one. The indication for revisional MBS can be to achieve further weight loss or improvement in obesity comorbidity, but it may be necessary due to complications (e.g., gastroesophageal reflux or obstruction). Revisional MBS is associated with an increased risk of surgical complications and often less weight loss compared to the results following primary surgery. This narrative review summarizes data from revisional MBS where information is often presented with inconsistent definitions for indications and outcomes, making comparison between strategies difficult. In summary, we suggest careful weighing of potential benefits and risks with revisional MBS, bearing in mind the option of add-on therapy with new anti-obesity drugs.
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Affiliation(s)
| | - Stephan Axer
- Faculty of Health and Medicine, Örebro University, Campus USÖ, 701 82 Örebro, Sweden; Department of General Surgery, Torsby Hospital, Box 502, 685 29 Torsby, Sweden
| | - Torsten Olbers
- Department of Biomedical and Clinical Sciences, Department of Surgery, Linköping University, Norrköping, Sweden
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17
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Hu Z, Chen K, Dai H, Lv Z, Li J, Yu P, Feng J, Abdulkarem AM, Wu H, He R, Li G. ROUX-en-Y gastric bypass surgery improves metabolic syndrome-related erectile dysfunction in mice via the IRS-1/PI3K/AKT/eNOS pathway. Sex Med 2024; 12:qfae029. [PMID: 38817951 PMCID: PMC11134102 DOI: 10.1093/sexmed/qfae029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Revised: 04/10/2024] [Accepted: 05/05/2024] [Indexed: 06/01/2024] Open
Abstract
Objective Although many clinical studies have shown that ROUX-en-Y gastric bypass (RYGB) surgery significantly improves metabolic syndrome-related erectile dysfunction (MED), the role and mechanism are unclear. Aim In this study we used a mouse model to explore how RYGB improves MED induced by a high-fat diet (HFD). Methods We established a mouse model of metabolic syndrome by feeding an HFD for 16 weeks. The mice were randomly assigned to the standard chow diet (SCD), HFD, or RYGB groups. Body weight, fasting blood glucose, plasma insulin, and total plasma cholesterol were analyzed. Erectile responses were evaluated by determining the mean systolic blood pressure and the intracavernosal pressure (ICP). Penile histologic examination (Masson's trichrome and immunohistochemical stain) and Western blot were performed. Result Compared with the SCD group, the ICP in the sham group was significantly lower, and the ICP of the RYGB was significantly increased. Masson's trichrome and immunohistochemical staining showed that the content of endothelium and smooth muscle in the corpus cavernosum of mice with MED was significantly reduced. Western blot analysis showed a significant decrease in α-smooth muscle actin and a significant increase in osteopontin in penile tissue in the sham group, which was improved by RYGB surgery. Furthermore, RYGB significantly increased IRS-1/PI3K/Akt/eNOS phosphorylation. Clinical Translation In this study we explored the mechanism of bariatric surgery to improve erectile dysfunction associated with metabolic syndrome and provided a theoretical basis for clinical research. Strengths and Limitations First, we did not investigate the mechanism by which RYGB affects the IRS-1/PI3K/Akt/eNOS signaling pathway. Second, the effect of the IRS-1/PI3K/Akt/eNOS signaling pathway on the function of corpus cavernosum endothelial cells and smooth muscle cells remains to be investigated in cellular studies. Conclusion This study demonstrated that RYGB may not only improve metabolic parameters but also restore erectile function in MED patients. The mechanism of the therapeutic effect of RYGB may be reactivation of the IRS-1/PI3K/Akt/eNOS pathway.
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Affiliation(s)
- Zhenxing Hu
- Department of Urology, General Hospital of Ningxia Medical University, Ningxia Medical University, Xingqing District, Yinchuan 750000, People’s Republic of China
- Department of Urology, The First Affiliated Hospital of Yangtze University, Jingzhuo 434000, People’s Republic of China
| | - Keming Chen
- Department of Urology, General Hospital of Ningxia Medical University, Ningxia Medical University, Xingqing District, Yinchuan 750000, People’s Republic of China
| | - Haitao Dai
- Department of Urology, The First Affiliated Hospital of Yangtze University, Jingzhuo 434000, People’s Republic of China
| | - Zhiyong Lv
- Department of Urology, General Hospital of Ningxia Medical University, Ningxia Medical University, Xingqing District, Yinchuan 750000, People’s Republic of China
| | - Jian Li
- Department of Urology, General Hospital of Ningxia Medical University, Ningxia Medical University, Xingqing District, Yinchuan 750000, People’s Republic of China
| | - Puguang Yu
- Department of Urology, General Hospital of Ningxia Medical University, Ningxia Medical University, Xingqing District, Yinchuan 750000, People’s Republic of China
| | - Jiajing Feng
- Department of Urology, General Hospital of Ningxia Medical University, Ningxia Medical University, Xingqing District, Yinchuan 750000, People’s Republic of China
| | - Alqaisi Mohammed Abdulkarem
- Department of Urology, General Hospital of Ningxia Medical University, Ningxia Medical University, Xingqing District, Yinchuan 750000, People’s Republic of China
| | - Haifeng Wu
- Department of Urology, General Hospital of Ningxia Medical University, Ningxia Medical University, Xingqing District, Yinchuan 750000, People’s Republic of China
| | - Rui He
- Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750000, People’s Republic of China
| | - Guangyong Li
- Department of Urology, General Hospital of Ningxia Medical University, Ningxia Medical University, Xingqing District, Yinchuan 750000, People’s Republic of China
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Kashihara H, Okikawa S, Morine Y, Yoshikawa K, Tokunaga T, Nishi M, Takasu C, Nishiyama M, Zushi M, Shimada M. Impact of Daikenchuto (TU-100) on the early postoperative period in duodenal-jejunal bypass. THE JOURNAL OF MEDICAL INVESTIGATION 2024; 71:210-218. [PMID: 39462554 DOI: 10.2152/jmi.71.210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/29/2024]
Abstract
INTRODUCTION We investigated the effect of Daikenchuto (TU-100) on the early postoperative period in duodenal-jejunal bypass (DJB). METHODS Study 1:The effect of TU-100 on diabetic rats was investigated. Rats were sacrificed after receiving TU-100 for one week. Study 2:The effect of TU-100 on DJB was investigated. Rats in the DJB and TU-100 treated DJB groups were sacrificed 24 hours postoperation to evaluate blood glucose, cytokine expression, and gut microbiome. RESULTS Study 1:TU-100 did not affect glucose or body weight. TU-100 suppressed intestinal inflammation and modified the gut microbiome. Specifically, Bifidobacterium and Blautia were increased, and Turicibacter were decreased in this group. Study 2:Both DJB and TU-100 treated DJB rats showed lower blood glucose at 24 hours postoperation than at preoperation. Cytokine expression in the liver and small intestine of the TU-100 treated DJB group was significantly lower than that of the DJB group. The gut microbiome composition in TU-100 treated DJB rats was altered. In particular, Bifidobacterium and Blautia were increased in this group. CONCLUSION DJB suppressed blood glucose during the early postoperative period. TU-100 may enhance the anti-diabetic effect of metabolic surgery by changing the gut microbiome and suppressing inflammation in the early postoperative period. J. Med. Invest. 71 : 210-218, August, 2024.
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Affiliation(s)
| | - Shohei Okikawa
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Yuji Morine
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Kozo Yoshikawa
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Takuya Tokunaga
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Masaaki Nishi
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Chie Takasu
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Mitsue Nishiyama
- Tsumura Kampo Research Laboratories, Tsumura & Co., Ami, Ibaraki, Japan
| | - Makoto Zushi
- Tsumura Kampo Research Laboratories, Tsumura & Co., Ami, Ibaraki, Japan
| | - Mitsuo Shimada
- Department of Surgery, Tokushima University, Tokushima, Japan
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Gala K, Ghusn W, Brunaldi V, Vargas EJ, Storm AC, Acosta A, Dayyeh BKA. Applicability of individualized metabolic surgery score for prediction of diabetes remission after endoscopic sleeve gastroplasty. Ther Adv Gastrointest Endosc 2024; 17:26317745241247175. [PMID: 38682042 PMCID: PMC11047249 DOI: 10.1177/26317745241247175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 03/27/2024] [Indexed: 05/01/2024] Open
Abstract
Background Endoscopic sleeve gastroplasty (ESG) is a safe and effective obesity treatment. The individualized metabolic score (IMS) is a validated score that uses preoperative variables predicting T2D remission (DR) in bariatric surgery. Objectives We evaluated the applicability of using the IMS score to predict DR in patients after ESG. Design/Methods We performed a retrospective review of patients with obesity and T2D who underwent ESG. We calculated DR, IMS score, and severity, and divided patients based on IMS category. Results The cohort comprised 20 patients: 25% (5) mild, 55% (11) moderate, and 20% (4) severe IMS stages. DR was achieved in 60%, 45.5%, and 0% of patients with mild, moderate, and severe IMS scores (p = 0.08), respectively. IMS score was significantly associated with DR (p = 0.03), with the area under the curve of the receiver operating characteristic for predicting DR 0.85. Conclusion These pilot data demonstrate that the IMS score appears to be useful in predicting DR after ESG.
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Affiliation(s)
- Khushboo Gala
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Wissam Ghusn
- Department of Internal Medicine, Boston University Medical Center, Boston, MA, USA
| | - Vitor Brunaldi
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Eric J. Vargas
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Andrew C. Storm
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Andres Acosta
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Barham K. Abu Dayyeh
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
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García-Honores L, Caballero-Alvarado J, Bustamante-Cabrejos A, Lozano-Peralta K, Zavaleta-Corvera C. LAPAROSCOPIC SLEEVE GASTRECTOMY VERSUS LAPAROSCOPIC ROUX-EN-Y GASTRIC BYPASS FOR WEIGHT LOSS IN OBESE PATIENTS: WHICH IS MORE EFFECTIVE? A SYSTEMATIC REVIEW AND META-ANALYSIS. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2023; 36:e1782. [PMID: 38088727 PMCID: PMC10712920 DOI: 10.1590/0102-672020230064e1782] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 08/18/2023] [Indexed: 12/17/2023]
Abstract
BACKGROUND Bariatric surgery is the most effective option to reduce weight in morbid obesity patients. The techniques most employed are the restrictive surgery laparoscopic sleeve gastrectomy (LSG), surgical procedures of intestinal malabsorption, and both types (restrictive and intestinal malabsorption) such as the Roux-en-Y laparoscopic gastric bypass (RYLGB). AIMS To determine if LSG is more effective than RYLGB for weight loss. METHODS A systematic review and meta-analysis was carried out, including five clinical trials and sixteen cohorts comparing LSG versus RYLGB in weight loss and secondary outcomes: resolution of comorbidities, postoperative complications, operative time, hospital stay, and improvement in quality of life. RESULTS Excess weight loss was 10.2% (mean difference [MD] 10.2; 95%CI -10.14; -9.90) higher in patients undergoing LSG than in patients submitted to RYLGB. Diabetes mellitus type 2 was resolved in 17% (relative risk [RR] 0.83; 95%CI 0.77-0.90) of cases, more significantly after LSG, arterial hypertension in 23% (RR 0.77; 95%CI 0.69-0.84), and dyslipidemia in 17% (RR 0.83; 95%CI 0.77-0.90). Postoperative complications were 73% higher in patients undergoing RYLGB (MD 0.73; 95%CI 0.63-0.83). The operative time was 35.76 minutes shorter in the LSG (MD -35.76; 95%CI -37.28; -34.24). Finally, the quality of life improved more in patients operated by LSG (MD 0.37; 95%CI -0.48; -0.26). CONCLUSIONS The study demonstrated that LSG could be more effective than RYLGB in reducing the percentage of excess weight, comorbidities, postoperative complications, operative time, hospital stay, and in improving quality of life.
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Affiliation(s)
- Laura García-Honores
- Antenor Orrego Private University, School of Medicine - Trujillo, La Libertad, Peru
| | - Jose Caballero-Alvarado
- Antenor Orrego Private University, School of Medicine - Trujillo, La Libertad, Peru
- Regional Hospital of Trujillo, Department of surgery - Trujillo, La Libertad, Peru
| | - Alexander Bustamante-Cabrejos
- Antenor Orrego Private University, School of Medicine - Trujillo, La Libertad, Peru
- Alta Complejidad Virgen de la Puerta Hospital, Department of surgery - Trujillo, La Libertad, Peru
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Yang SM, Myeong S, Yun SK, Kwak MH, Cho YK, Choi MG, Park JM. Duodenal mucosal resurfacing with photodynamic therapy using methylene blue in a mouse model. Photodiagnosis Photodyn Ther 2023; 44:103733. [PMID: 37536555 DOI: 10.1016/j.pdpdt.2023.103733] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 07/28/2023] [Accepted: 07/31/2023] [Indexed: 08/05/2023]
Abstract
BACKGROUND The duodenum has emerged as a key player in metabolic diseases. The objective was to evaluate the safety and efficacy of intra-duodenal PDT using methylene blue in managing glycemic control and weight reduction. METHODS Optimal concentration of methylene blue and conditions for intra-duodenal PDT were determined through in vitro experiments. After injecting methylene blue into the duodenum, we performed intra-duodenal PDT. High-fat diet rats were used to assess the efficacy of intra-duodenal PDT through measures of oral glucose tolerance, insulin sensitivity, and weight change. Immunohistochemical staining was also conducted to examine GLP-1 and GIP-producing cells in the ileum and duodenum, respectively. RESULTS Introduodenal PDT reduced villous height of duodenum at 48 h, which was fully recovered at 30 days without complications. Rats treated with PDT showed significantly lower blood glucose levels with glucose loading and improved insulin sensitivity than rats in the sham-treatment group. The PDT group also had a significant reduction in body weight compared to the sham-treatment group at 30 days after intervention, although food intake was not significantly different between the two groups. Numbers of GLP-1 and GIP producing cells in the ileum and irradiated area were significantly higher in the PDT group than in the sham-treatment group. CONCLUSIONS Intra-duodenal PDT using methylene blue showed a feasible therapeutic modality in improving metabolic parameters. However, large animal experiments and mechanism studies are needed to determine the clinical relevance. The possibility of repeating this treatment every 30 days and its accompanying complications should be further studied.
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Affiliation(s)
- Seung Mok Yang
- Catholic Photomedicine Research Institute, The Catholic University of Korea, Seoul 06591, the Republic of Korea South Korea
| | - Seokho Myeong
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-GU, Seoul 06591, the Republic of Korea South Korea
| | - Seul Ki Yun
- Catholic Photomedicine Research Institute, The Catholic University of Korea, Seoul 06591, the Republic of Korea South Korea; Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-GU, Seoul 06591, the Republic of Korea South Korea
| | - Moon Hwa Kwak
- Catholic Photomedicine Research Institute, The Catholic University of Korea, Seoul 06591, the Republic of Korea South Korea; Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul, the Republic of Korea South Korea
| | - Yu Kyung Cho
- Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-GU, Seoul 06591, the Republic of Korea South Korea
| | - Myung-Gyu Choi
- Catholic Photomedicine Research Institute, The Catholic University of Korea, Seoul 06591, the Republic of Korea South Korea; Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-GU, Seoul 06591, the Republic of Korea South Korea
| | - Jae Myung Park
- Catholic Photomedicine Research Institute, The Catholic University of Korea, Seoul 06591, the Republic of Korea South Korea; Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-GU, Seoul 06591, the Republic of Korea South Korea; Department of Medical Life Sciences, College of Medicine, The Catholic University of Korea, Seoul, the Republic of Korea South Korea.
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Kehagias D, Lampropoulos C, Georgopoulos N, Habeos I, Kalavrizioti D, Vamvakas SS, Davoulou P, Kehagias I. Diabetes Remission After LRYGBP With and Without Fundus Resection: a Randomized Clinical Trial. Obes Surg 2023; 33:3373-3382. [PMID: 37783932 PMCID: PMC10602944 DOI: 10.1007/s11695-023-06857-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Revised: 09/13/2023] [Accepted: 09/24/2023] [Indexed: 10/04/2023]
Abstract
BACKGROUND Glycemic control, after metabolic surgery, is achieved in two stages, initially with neuroendocrine alterations and in the long-term with sustainable weight loss. The resection of the gastric fundus, as the major site of ghrelin production, is probably related with optimized glucose regulation. The aim of the present study is to investigate whether the modification of laparoscopic Roux-en-Y gastric bypass (LRYGBP) with fundus resection offers superior glycemic control, compared to typical LRYGBP. MATERIALS AND METHODS Participants were 24 patients with body mass index (BMI) ≥40kg/m2 and type II diabetes mellitus (T2DM), who were randomly assigned to undergo LRYGBP and LRYGBP with fundus resection (LRYGBP+FR). Gastrointestinal (GI) hormones [ghrelin, glucagon-like-peptide-1 (GLP-1), peptide-YY (PYY)] and glycemic parameters (glucose, insulin, HbA1c, C-peptide, insulinogenic index, HOMA-IR) were measured preoperatively, at 6 and 12 months during an oral glucose tolerance test (OGTT). RESULTS Ninety-five percent of patients showed complete remission of T2DM after 12 months. LRYGBP+FR was not related with improved glycemic control, compared to LRYGBP. Ghrelin levels were not significantly reduced at 6 and 12 months after LRYGBP+FR. GLP-1 and PYY levels were remarkably increased postprandially in both groups at 6 and 12 months postoperatively (p<0.01). Patients who underwent LRYGBP+FR achieved a significantly lower BMI at 12 months in comparison to LRYGBP (p<0.05). CONCLUSION Fundus resection is not associated with improved glycemic regulation, compared to typical LRYGBP and the significant decrease in BMI after LRYGBP+FR has to be further confirmed with longer follow-up.
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Affiliation(s)
| | | | - Neoklis Georgopoulos
- Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, University of Patras Medical School, 26504, Rio, Greece
| | - Ioannis Habeos
- Department of Internal Medicine, Division of Endocrinology and Diabetes, University Hospital of Patras, 26504, Rio, Greece
| | - Dimitra Kalavrizioti
- Department of Nephrology and Renal Transplantation, University Hospital of Patras, 26504, Rio, Greece
| | | | - Panagiota Davoulou
- Department of Nephrology and Renal Transplantation, University Hospital of Patras, 26504, Rio, Greece
| | - Ioannis Kehagias
- Department of Surgery, Division of Bariatric and Metabolic Surgery, University Hospital of Patras, 26504, Rio, Greece
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23
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Palumbo P, Banchelli F, Miloro C, Toschi PF, Mecheri F, Gabriele S, Pantaleoni M, D'Amico R, Menozzi R. Weight loss trend after bariatric surgery in a population of obese patients. Clin Nutr ESPEN 2023; 57:58-64. [PMID: 37739709 DOI: 10.1016/j.clnesp.2023.06.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 04/29/2023] [Accepted: 06/17/2023] [Indexed: 09/24/2023]
Abstract
BACKGROUND AND AIMS Bariatric Surgery (BS) is a therapeutic option in patients with severe obesity whose non-surgical techniques have failed. No work has previously explored trajectories of weight loss and how long this was maintained. Aim of study is to describe effect of BS and nutritional intervention on body weight trend in patients with obesity. METHODS 792 patients who underwent BS from 1996 to 2021 were included. The Protocol provides Laparoscopic Sleeve Gastrectomy (LSG), Vertical Gastroplasty (VBG) and Roux-en-Y Gastric Bypass (GB). %Total Weight Loss (%TWL) and %Excess Weight Loss (%EWL) were evaluated in three cohort of patients. Cumulative incidence of clinical goal after surgery was calculated at two and five years after BS. RESULTS At two years of follow-up, average %TWL and %EWL were 31.2% (95% CI = 29.0-33.4%) and 71% (95% CI = 65.4-76.5%) for VBG, 34.7% (95% CI = 33.8-35.6%) and 78.0% (95% CI = 75.9-89.1%) for GB and 33.8% (95% CI = 32.5-35.1%) and 68.8% (95% CI = 66.1-71.6%) for LSG. At two years from surgery the cumulative incidence of clinical goal was 70.7% (95% CI = 59.1-79.1%) for VBG, 86.4% (95% CI = 82.4-89.6%) for GB and 83.4% (95% CI = 76.0-87.1%) for LSG. At five years from surgery, average % TWL and % EWL were 22.5% (95% CI = 10.2-34.8%) and 58.2% (95% CI = 28.4-88.1%) for VBG, 31.8% (95% CI = 30.2-33.3%) and 70.8% (95% CI = 67.5-74.1%) for GB and 29.5% (95% CI = 26.2-32.8%) and 62.0% (95% CI = 53.4-70.6%) for LSG respectively. At five years after having reached clinical goal the share of people who were able to maintain their weight was 49.5% (95% CI = 30.8-79.6%) for VBG, 69.5% (95% CI = 58.3-82.8%) for GB and 55.9% (95% CI = 42.1-74.3%) for LSG. The median time of clinical goal maintaining was 4.8 years for VBG (95% CI lower limit = 4.1), 6.6 years for GB (95% CI lower limit = 6.2) and 5.3 years for LSG (95% CI lower limit = 4.8). CONCLUSIONS Our work confirm effectiveness of BS in patients with obesity and show that who do not reach clinical goal within 2 years, hardly will reach it later and suggest necessity for a medium and long-term follow-up to prevent weight regain.
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Affiliation(s)
- Patrizia Palumbo
- Division of Metabolic Diseases and Clinical Nutrition, University Hospital of Modena, Modena, Italy
| | - Federico Banchelli
- Unit of Statistical and Methodological Support to Clinical Research, University Hospital of Modena, Modena, Italy; Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Clelia Miloro
- Division of Metabolic Diseases and Clinical Nutrition, University Hospital of Modena, Modena, Italy
| | - Patrizia Federica Toschi
- Division of Metabolic Diseases and Clinical Nutrition, University Hospital of Modena, Modena, Italy
| | - Fouzia Mecheri
- Bariatric Surgery Unit, Department of General Surgery, Emergency and New Technologies, Baggiovara, AOU of Modena, Modena, Italy
| | - Silvia Gabriele
- Division of Metabolic Diseases and Clinical Nutrition, University Hospital of Modena, Modena, Italy
| | - Monica Pantaleoni
- Division of Metabolic Diseases and Clinical Nutrition, University Hospital of Modena, Modena, Italy
| | - Roberto D'Amico
- Unit of Statistical and Methodological Support to Clinical Research, University Hospital of Modena, Modena, Italy; Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Renata Menozzi
- Division of Metabolic Diseases and Clinical Nutrition, University Hospital of Modena, Modena, Italy.
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Norton BC, Telese A, Papaefthymiou A, Aslam N, Makaronidis J, Murray C, Haidry R. Metabolic and Bariatric Endoscopy: A Mini-Review. Life (Basel) 2023; 13:1905. [PMID: 37763308 PMCID: PMC10532500 DOI: 10.3390/life13091905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 09/07/2023] [Accepted: 09/08/2023] [Indexed: 09/29/2023] Open
Abstract
We are currently in a worldwide obesity pandemic, which is one of the most significant health problems of the 21st century. As the prevalence of obesity continues to rise, new and innovate treatments are becoming available. Metabolic and bariatric endoscopic procedures are exciting new areas of gastroenterology that have been developed as a direct response to the obesity crisis. These novel interventions offer a potentially reversible, less invasive, safer, and more cost-effective method of tackling obesity compared to traditional bariatric surgery. Minimally invasive endoscopic treatments are not entirely novel, but as technology has rapidly improved, many of the procedures have been proven to be extremely effective for weight loss and metabolic health, based on high-quality clinical trial data. This mini-review examines the existing evidence for the most prominent metabolic and bariatric procedures, followed by a discussion on the future trajectory of this emerging subspecialty.
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Affiliation(s)
- Benjamin Charles Norton
- Digestive Diseases and Surgery Institute, Cleveland Clinic London, 33 Grosvenor Pl, London SW1X 7HY, UK
- Department of Gastroenterology, University College London Hospital Euston Road, London NW1 2BU, UK
- Centre for Obesity Research, Rayne Institute, Department of Medicine, University College London, London WC1E 6BT, UK
| | - Andrea Telese
- Digestive Diseases and Surgery Institute, Cleveland Clinic London, 33 Grosvenor Pl, London SW1X 7HY, UK
- Centre for Obesity Research, Rayne Institute, Department of Medicine, University College London, London WC1E 6BT, UK
| | - Apostolis Papaefthymiou
- Department of Gastroenterology, University College London Hospital Euston Road, London NW1 2BU, UK
| | - Nasar Aslam
- Department of Gastroenterology, University College London Hospital Euston Road, London NW1 2BU, UK
| | - Janine Makaronidis
- Centre for Obesity Research, Rayne Institute, Department of Medicine, University College London, London WC1E 6BT, UK
- Bariatric Centre for Weight Management and Metabolic Surgery, University College London Hospital, London WC1E 6BT, UK
- Department of Endocrinology and Diabetes, University College London Hospital, London WC1E 6BT, UK
- National Institute of Health Research, UCLH Biomedical Research Centre, London W1T 7DN, UK
| | - Charles Murray
- Digestive Diseases and Surgery Institute, Cleveland Clinic London, 33 Grosvenor Pl, London SW1X 7HY, UK
| | - Rehan Haidry
- Digestive Diseases and Surgery Institute, Cleveland Clinic London, 33 Grosvenor Pl, London SW1X 7HY, UK
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25
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Çeler Ö, Er HC, Sancak S, Çırak E, Özdemir A, Sertbaş Y, Karip AB, Esen Bulut N, Aydın MT, Altun H, Memişoğlu K. The Effects of Laparoscopic Sleeve Gastrectomy (LSG) on Obesity-Related Type 2 Diabetes Mellitus: a Prospective Observational Study from a Single Center. Obes Surg 2023; 33:2695-2701. [PMID: 37490195 DOI: 10.1007/s11695-023-06707-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 06/19/2023] [Accepted: 06/26/2023] [Indexed: 07/26/2023]
Abstract
PURPOSE The objective of the study is to evaluate the effects of laparoscopic sleeve gastrectomy (LSG) on mid- to long-term regulation of blood glucose in patients with obesity and type 2 diabetes mellitus (T2DM) MATERIALS AND METHODS : In this prospective and observational single-center study, a total of 234 patients with obesity and a diagnosis of T2DM who underwent LSG between 2015 and 2020 were evaluated. The demographics and laboratory data, consisting of body mass index (BMI), glycosylated hemoglobin (HbA1c%), and fasting plasma glucose (FPG) and total weight loss (TWL%), were compared preoperative and postoperative at 12th and 18th months and annual follow-up for seven consecutive years. RESULTS The mean age of 234 patients (female(n)/male(n):191/43) included in the study was 44.69±9.72 years, while the preoperative mean BMI, FPG, and HbA1c values were 47.9±6.82, 132.09±42.84 mg/dl, and 7.02±1.35% respectively. The mean rate of weight loss (TWL%), which was 34.7 in the 18 months, decreased to 23.15 in the 7th year. While the HbA1c % value was 7.02±1.35 in the preoperative, it was found 5.71 ± 0.75 (p<0.001) and 6.30 ± 1.77 (p<0.05) at the 18th month and 7th year after the operation, respectively. While the DM remission rate was 71.1% at the postoperative 18th month, it was 45.4% at the 7th year, despite the patients regaining weight in the follow-ups. CONCLUSIONS Our study revealed that LSG resulted in high remission rates that continued for 7 years after the surgery, although sustained improvement or remission of diabetes despite some weight regain after the first 18 months.
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Affiliation(s)
- Özgen Çeler
- Department of Internal Medicine, Endocrinology and Metabolism Disorders, University of Health Sciences, Fatih Sultan Mehmet Education and Research Hospital, Atasehir, 34752, Istanbul, Turkey.
| | - Hatice Cansu Er
- Department of Internal Medicine, University of Health Sciences, Fatih Sultan Mehmet Education and Research Hospital, Atasehir, 34752, Istanbul, Turkey
| | - Seda Sancak
- Department of Internal Medicine, Endocrinology and Metabolism Disorders, University of Health Sciences, Fatih Sultan Mehmet Education and Research Hospital, Atasehir, 34752, Istanbul, Turkey
| | - Elif Çırak
- Department of Internal Medicine, University of Health Sciences, Fatih Sultan Mehmet Education and Research Hospital, Atasehir, 34752, Istanbul, Turkey
| | - Ali Özdemir
- Department of Internal Medicine, University of Health Sciences, Fatih Sultan Mehmet Education and Research Hospital, Atasehir, 34752, Istanbul, Turkey
| | - Yaşar Sertbaş
- Department of Internal Medicine, University of Health Sciences, Fatih Sultan Mehmet Education and Research Hospital, Atasehir, 34752, Istanbul, Turkey
| | - Aziz Bora Karip
- General Surgery Clinic, Fatih Sultan Mehmet Education and Research Hospital, University of Health Sciences, Atasehir, 34752, Istanbul, Turkey
| | - Nuriye Esen Bulut
- General Surgery Clinic, Fatih Sultan Mehmet Education and Research Hospital, University of Health Sciences, Atasehir, 34752, Istanbul, Turkey
| | - Mehmet Timuçin Aydın
- General Surgery Clinic, Fatih Sultan Mehmet Education and Research Hospital, University of Health Sciences, Atasehir, 34752, Istanbul, Turkey
| | - Hasan Altun
- General Surgery Clinic, Fatih Sultan Mehmet Education and Research Hospital, University of Health Sciences, Atasehir, 34752, Istanbul, Turkey
- Interbariatrics Clinic, Şişli, 34365, Istanbul, Turkey
| | - Kemal Memişoğlu
- General Surgery Clinic, Fatih Sultan Mehmet Education and Research Hospital, University of Health Sciences, Atasehir, 34752, Istanbul, Turkey
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26
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Ren M, Ji F. Small intestine-targeted endoscopic bariatrics: Current status and future perspectives. Dig Endosc 2023; 35:684-697. [PMID: 37086381 DOI: 10.1111/den.14575] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Accepted: 04/21/2023] [Indexed: 04/23/2023]
Abstract
The global obesity epidemic shows no signs of slowing down. Endoscopic bariatric and metabolic therapies (EBMTs) are being increasingly adopted as treatment options for obesity and obesity-related comorbidities, due to their minimally invasive nature and ease of delivery. According to the site of action along the gastrointestinal tract, EBMTs can be divided into two categories: gastric EBMTs, and small intestine-targeted EBMTs. Unlike gastric EBMTs, which work through a volume-restricting mechanism leading to early satiety and reduced caloric intake, small intestine-targeted EBMTs can be metabolically beneficial through foregut and/or hindgut pathways independent of weight loss, and therefore have great potential for the treatment of obesity-related metabolic comorbidities such as type 2 diabetes. Although none of the small intestine-targeted EBMTs have been approved by the US Food and Drug Administration to date, their clinical efficacy and safety have been extensively explored in investigational trials. This review aims to summarize and provide a comprehensive understanding of small intestine-targeted EBMTs in clinical and preclinical settings, and to further discuss their potential mechanisms of action.
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Affiliation(s)
- Mengting Ren
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Feng Ji
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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27
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Fineman MS, Bryant CLN, Colbert K, Jozefiak TH, Petersen JS, Horowitz M, Vora J, Rayner CK, Wabnitz P, Nimgaonkar A. First-in-human study of a pharmacological duodenal exclusion therapy shows reduced postprandial glucose and insulin and increased bile acid and gut hormone concentrations. Diabetes Obes Metab 2023; 25:2447-2456. [PMID: 37380614 DOI: 10.1111/dom.15066] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 03/14/2023] [Accepted: 03/22/2023] [Indexed: 06/30/2023]
Abstract
AIMS To address the need for noninvasive alternatives to metabolic surgery or duodenal exclusion devices for the management of type 2 diabetes (T2D) and obesity by developing an orally administered therapeutic polymer, GLY-200, designed to bind to and enhance the barrier function of mucus in the gastrointestinal tract to establish duodenal exclusion noninvasively. MATERIALS AND METHODS A Phase 1, randomized, double-blind, placebo-controlled, single- (SAD) and multiple-ascending-dose (MAD) healthy volunteer study was conducted. In the SAD arm, four cohorts received a single dose of 0.5 g up to 6.0 g GLY-200 or placebo, while in the MAD arm, four cohorts received 5 days of twice-daily or three-times-daily dosing (total daily dose 2.0 g up to 6.0 g GLY-200 or placebo). Assessments included safety and tolerability (primary) and exploratory pharmacodynamics, including serum glucose, insulin, bile acids and gut hormones. RESULTS No safety signals were observed; tolerability signals were limited to mild to moderate dose-dependent gastrointestinal events. In the MAD arm (Day 5), reductions in glucose and insulin and increases in bile acids, glucagon-like peptide-1, peptide YY and glicentin, were observed following a nonstandardized meal in subjects receiving twice-daily dosing of 2.0 g GLY-200 (N = 9) versus those receiving placebo (N = 8). CONCLUSIONS GLY-200 is safe and generally well tolerated at doses of ≤2.0 g twice daily. Pharmacodynamic results mimic the biomarker signature observed after Roux-en-Y gastric bypass and duodenal exclusion devices, indicating a pharmacological effect in the proximal small intestine. This study represents the first clinical demonstration that duodenal exclusion can be achieved with an oral drug and supports further development of GLY-200 for the treatment of obesity and/or T2D.
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Affiliation(s)
| | | | - Kevin Colbert
- Glyscend Therapeutics, Inc., Lowell, Massachusetts, USA
| | | | | | - Michael Horowitz
- Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Jiten Vora
- Liverpool University Hospitals Foundation Trust, Liverpool, UK
| | - Christopher K Rayner
- Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Paul Wabnitz
- CALHN Integrated Care, Royal Adelaide Hospital, Adelaide, South Australia, Australia
- Transform Clinical Pty Ltd, CO-HAB Tonsley, St Marys, South Australia, Australia
| | - Ashish Nimgaonkar
- Glyscend Therapeutics, Inc., Lowell, Massachusetts, USA
- Division of Gastroenterology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
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28
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Yin M, Wang Y, Han M, Liang R, Li S, Wang G, Gang X. Mechanisms of bariatric surgery for weight loss and diabetes remission. J Diabetes 2023; 15:736-752. [PMID: 37442561 PMCID: PMC10509523 DOI: 10.1111/1753-0407.13443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 06/12/2023] [Accepted: 06/26/2023] [Indexed: 07/15/2023] Open
Abstract
Obesity and type 2 diabetes(T2D) lead to defects in intestinal hormones secretion, abnormalities in the composition of bile acids (BAs), increased systemic and adipose tissue inflammation, defects of branched-chain amino acids (BCAAs) catabolism, and dysbiosis of gut microbiota. Bariatric surgery (BS) has been shown to be highly effective in the treatment of obesity and T2D, which allows us to view BS not simply as weight-loss surgery but as a means of alleviating obesity and its comorbidities, especially T2D. In recent years, accumulating studies have focused on the mechanisms of BS to find out which metabolic parameters are affected by BS through which pathways, such as which hormones and inflammatory processes are altered. The literatures are saturated with the role of intestinal hormones and the gut-brain axis formed by their interaction with neural networks in the remission of obesity and T2D following BS. In addition, BAs, gut microbiota and other factors are also involved in these benefits after BS. The interaction of these factors makes the mechanisms of metabolic improvement induced by BS more complicated. To date, we do not fully understand the exact mechanisms of the metabolic alterations induced by BS and its impact on the disease process of T2D itself. This review summarizes the changes of intestinal hormones, BAs, BCAAs, gut microbiota, signaling proteins, growth differentiation factor 15, exosomes, adipose tissue, brain function, and food preferences after BS, so as to fully understand the actual working mechanisms of BS and provide nonsurgical therapeutic strategies for obesity and T2D.
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Affiliation(s)
- Mengsha Yin
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Yao Wang
- Department of OrthopedicsThe Second Hospital Jilin UniversityChangchunChina
| | - Mingyue Han
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Ruishuang Liang
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Shanshan Li
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Guixia Wang
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Xiaokun Gang
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
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29
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Sridhar A, Khan D, Elliott JA, Naughton V, Flatt PR, Irwin N, Moffett CR. RYGB surgery has modest effects on intestinal morphology and gut hormone populations in the bypassed biliopancreatic limb but causes reciprocal changes in GLP-2 and PYY in the alimentary limb. PLoS One 2023; 18:e0286062. [PMID: 37228045 DOI: 10.1371/journal.pone.0286062] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 05/09/2023] [Indexed: 05/27/2023] Open
Abstract
Roux-en-Y gastric-bypass (RYGB) induced alterations in intestinal morphology and gut-cell hormone expression profile in the bypassed biliopancreatic-limb (BPL) versus the alimentary-limbs (AL) are poorly characterised. This pilot study has therefore explored effects following RYGB in high-fat-diet (HFD) and normal-diet (ND) rats. Female Wistar rats (4-week-old) were fed HFD or ND for 23-weeks prior to RYGB or sham surgeries. Immunohistochemical analysis of excised tissue was conducted three-weeks post-surgery. After RYGB, intestinal morphology of the BPL in both HFD and ND groups was unchanged with exception of a small decrease in villi width in the ND-RYGB and crypt depth in the HFD-RYGB group. However, in the AL, villi width was decreased in ND-RYGB rats but increased in the HFD-RYGB group. In addition, crypt depth decreased after RYGB in the AL of HFD rats. GIP positive cells in either limb of both groups of rats were unchanged by RYGB. Similarly, there was little change in GLP-1 positive cells, apart from a small decrease of numbers in the villi of the BPL in HFD rats. RYGB increased GLP-2 cell numbers in the AL of ND-RYGB rats, including in both crypts and villi. This was associated with decreased numbers of cells expressing PYY in the AL of ND-RYGB rats. The BPL appears to maintain normal morphology and unchanged enteroendocrine cell populations despite being bypassed in RYGB-surgery. In contrast, in the AL, villi area is generally enhanced post-RYGB in ND rats with increased numbers of GLP-2 positive cells and decreased expression of PYY.
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Affiliation(s)
- Ananyaa Sridhar
- Biomedical Sciences Research Institute, School of Biomedical Sciences, Ulster University, Coleraine, N. Ireland, United Kingdom
| | - Dawood Khan
- Biomedical Sciences Research Institute, School of Biomedical Sciences, Ulster University, Coleraine, N. Ireland, United Kingdom
| | - Jessie A Elliott
- Department of Surgery, Trinity Centre for Health Sciences and St. James's Hospital, Dublin, Ireland
| | - Violetta Naughton
- Biomedical Sciences Research Institute, School of Biomedical Sciences, Ulster University, Coleraine, N. Ireland, United Kingdom
| | - Peter R Flatt
- Biomedical Sciences Research Institute, School of Biomedical Sciences, Ulster University, Coleraine, N. Ireland, United Kingdom
| | - Nigel Irwin
- Biomedical Sciences Research Institute, School of Biomedical Sciences, Ulster University, Coleraine, N. Ireland, United Kingdom
| | - Charlotte R Moffett
- Biomedical Sciences Research Institute, School of Biomedical Sciences, Ulster University, Coleraine, N. Ireland, United Kingdom
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Xu TQ, Kindel TL. The role of weight control in the management of type 2 diabetes mellitus: Bariatric surgery. Diabetes Res Clin Pract 2023; 199:110667. [PMID: 37037264 PMCID: PMC10192054 DOI: 10.1016/j.diabres.2023.110667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Accepted: 04/06/2023] [Indexed: 04/12/2023]
Abstract
Diabetes mellitus is one of the major epidemics in the United States. It is heavily associated with obesity and multiple metabolic derangements that lead to long term morbidity, mortality as well as financial burden. Although medical therapy has been the mainstay in the management of diabetes mellitus, there remains a large portion of this patient population which struggles to obtain adequate glycemic control and long-term weight control with medical management alone. Bariatric surgery is a powerful tool in combating diabetes mellitus and affects glucose homeostasis through a variety of pathways. While it does provide a durable pathway for weight loss, improvement in glucose homeostasis is not only affected by the weight loss seen after bariatric surgery. Changes in gut hormone secretion, insulin regulation, and gut microbial composition also affect how these operations improve glucose homeostasis. Through improvement in the management of diabetes mellitus, comorbidities including cardiovascular disease, in turn demonstrate improvement. In this article, we will discuss the role of bariatric (metabolic) surgery as it relates to long term weight loss and the impact that weight loss has on improvement in diabetes mellitus.
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Affiliation(s)
- Thomas Q Xu
- Division of Minimally Invasive and Gastrointestinal Surgery, The Medical College of Wisconsin, United States
| | - Tammy Lyn Kindel
- Division of Minimally Invasive and Gastrointestinal Surgery, The Medical College of Wisconsin, United States.
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Hassan LS, Fahmy MH, Elmonim AMA, Elshal M. Effect of post-gastric sleeve pyloric length on control of type II diabetes mellitus. THE EGYPTIAN JOURNAL OF SURGERY 2023; 42:464-472. [DOI: 10.4103/ejs.ejs_89_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
Abstract
Background
Although the effectiveness and safety of laparoscopic sleeve gastrectomy (LSG) have been demonstrated, there is still debate about the best surgical method, with the resection distance from pylorus (DP) being among the most contentious topics. In patients who had LSG for morbid obesity, the effect of the resection distance from the pylorus on the management of type II diabetes mellitus during the postoperative phase was examined.
Patients and methods
After receiving each patient’s agreement, a total of 46 obese individuals were enrolled. Patients were prospectively randomized into two groups, group A (‘AP group’) and group B (‘AR group’), based on the distance between the initial reload firing and the pylorus (4 cm for group A and 2 cm for group B, respectively). Blood sugar levels were measured three, six months, and one year following LSG. After a year of follow-up, the percentage of excess weight loss (%EWL) was calculated.
Results
Postoperative weight was statistically significant lower and EWL% was statistically significant higher in group B: LSG ‘2 cm’ compared to group A: LSG ‘4 cm’. As regard outcomes of type 2 diabetes mellitus after LSG, in spite of nonsignificant statistical value, we reported that there was higher frequency of complete remission after 3, 6 and 12 months in group B: LSG ‘2 cm’ compared to group A: LSG ‘4 cm’ and cases with complete remission were associated with significant higher EWL%.
Conclusion
Patients undergoing laparoscopic sleeve gastrectomy are recommended to have shorter resection distance from pylorus (DP) done. It has been linked to superior surgical results, weight reduction, and diabetes mellitus management with no problems recorded.
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Affiliation(s)
| | - Mohamed H. Fahmy
- Department of General Surgery, Faculty of Medicine, Cairo University, Cairo, Egypt
| | | | - Mohamed Elshal
- Department of General Surgery, Faculty of Medicine, Cairo University, Cairo, Egypt
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Albaugh VL, Axelrod C, Belmont KP, Kirwan JP. Physiology Reconfigured: How Does Bariatric Surgery Lead to Diabetes Remission? Endocrinol Metab Clin North Am 2023; 52:49-64. [PMID: 36754497 DOI: 10.1016/j.ecl.2022.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Bariatric surgery improves glucose homeostasis and glycemic control in patients with type 2 diabetes. Over the past 20 years, a breadth of studies has been conducted in humans and rodents aimed to identify the regulatory nodes responsible for surgical remission of type 2 diabetes. The review herein discusses central mechanisms of type 2 diabetes remission associated with weight loss and surgical modification of the gastrointestinal tract.
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Affiliation(s)
- Vance L Albaugh
- Metamor Institute, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA; Integrative Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, LA 70808, USA
| | - Christopher Axelrod
- Integrative Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, LA 70808, USA
| | - Kathryn P Belmont
- Integrative Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, LA 70808, USA
| | - John P Kirwan
- Integrative Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, LA 70808, USA.
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Liu T, Zou X, Ruze R, Xu Q. Bariatric Surgery: Targeting pancreatic β cells to treat type II diabetes. Front Endocrinol (Lausanne) 2023; 14:1031610. [PMID: 36875493 PMCID: PMC9975540 DOI: 10.3389/fendo.2023.1031610] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 01/19/2023] [Indexed: 02/17/2023] Open
Abstract
Pancreatic β-cell function impairment and insulin resistance are central to the development of obesity-related type 2 diabetes mellitus (T2DM). Bariatric surgery (BS) is a practical treatment approach to treat morbid obesity and achieve lasting T2DM remission. Traditionally, sustained postoperative glycemic control was considered a direct result of decreased nutrient intake and weight loss. However, mounting evidence in recent years implicated a weight-independent mechanism that involves pancreatic islet reconstruction and improved β-cell function. In this article, we summarize the role of β-cell in the pathogenesis of T2DM, review recent research progress focusing on the impact of Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) on pancreatic β-cell pathophysiology, and finally discuss therapeutics that have the potential to assist in the treatment effect of surgery and prevent T2D relapse.
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Affiliation(s)
- Tiantong Liu
- Department of General Surgery, Peking Union Medical College Hospital, Beijing, China
- School of Medicine, Tsinghua University, Beijing, China
| | - Xi Zou
- Department of General Surgery, Peking Union Medical College Hospital, Beijing, China
- Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Rexiati Ruze
- Department of General Surgery, Peking Union Medical College Hospital, Beijing, China
- Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qiang Xu
- Department of General Surgery, Peking Union Medical College Hospital, Beijing, China
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Taleb NN, West J. Working with Convex Responses: Antifragility from Finance to Oncology. ENTROPY (BASEL, SWITZERLAND) 2023; 25:343. [PMID: 36832709 PMCID: PMC9955868 DOI: 10.3390/e25020343] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 01/23/2023] [Accepted: 01/25/2023] [Indexed: 06/07/2023]
Abstract
We extend techniques and learnings about the stochastic properties of nonlinear responses from finance to medicine, particularly oncology, where it can inform dosing and intervention. We define antifragility. We propose uses of risk analysis for medical problems, through the properties of nonlinear responses (convex or concave). We (1) link the convexity/concavity of the dose-response function to the statistical properties of the results; (2) define "antifragility" as a mathematical property for local beneficial convex responses and the generalization of "fragility" as its opposite, locally concave in the tails of the statistical distribution; (3) propose mathematically tractable relations between dosage, severity of conditions, and iatrogenics. In short, we propose a framework to integrate the necessary consequences of nonlinearities in evidence-based oncology and more general clinical risk management.
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Affiliation(s)
| | - Jeffrey West
- Integrated Mathematical Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA
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Okikawa S, Kashihara H, Shimada M, Yoshikawa K, Tokunaga T, Nishi M, Takasu C, Wada Y, Yoshimoto T. Effect of duodenal-jejunal bypass on diabetes in the early postoperative period. Sci Rep 2023; 13:1856. [PMID: 36726038 PMCID: PMC9892584 DOI: 10.1038/s41598-023-28923-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2022] [Accepted: 01/27/2023] [Indexed: 02/03/2023] Open
Abstract
Metabolic surgery is an effective treatment for patients with type 2 diabetes mellitus (T2DM). The aim of this study was to investigate the effect of duodenal-jejunal bypass (DJB) in a rat model of T2DM during the early postoperative period. A rat model of non-obese T2DM was allocated to two groups: a sham group and a DJB group. On postoperative day 1 (1POD), oral glucose tolerance testing (OGTT) was performed and the changes of glucose transporter expressions in the small intestine was evaluated. [18F]-fluorodeoxyglucose ([18]-FDG) uptake was measured in sham- and DJB-operated rats using positron emission tomography-computed tomography (PET-CT). DJB improved the glucose tolerance of the rats on 1POD. The expression of sodium-glucose cotransporter 1 (SGLT1) and glucose transporter 1 (GLUT1) was high, and that of GLUT2 was low in the alimentary limb (AL) of rats in the DJB group. PET-CT showed that [18F]-FDG uptake was high in the proximal jejunum of DJB-operated rats. These results may show that DJB improve glucose tolerance in very early postoperative period as the result of glucose accumulation in the AL because of changes in glucose transporter expression.
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Affiliation(s)
- Shohei Okikawa
- Department of Surgery, Tokushima University, 3-18-15 Kuramoto-Cho, Tokushima, Tokushima, 770-8503, Japan
| | - Hideya Kashihara
- Department of Surgery, Tokushima University, 3-18-15 Kuramoto-Cho, Tokushima, Tokushima, 770-8503, Japan.
| | - Mitsuo Shimada
- Department of Surgery, Tokushima University, 3-18-15 Kuramoto-Cho, Tokushima, Tokushima, 770-8503, Japan
| | - Kozo Yoshikawa
- Department of Surgery, Tokushima University, 3-18-15 Kuramoto-Cho, Tokushima, Tokushima, 770-8503, Japan
| | - Takuya Tokunaga
- Department of Surgery, Tokushima University, 3-18-15 Kuramoto-Cho, Tokushima, Tokushima, 770-8503, Japan
| | - Masaaki Nishi
- Department of Surgery, Tokushima University, 3-18-15 Kuramoto-Cho, Tokushima, Tokushima, 770-8503, Japan
| | - Chie Takasu
- Department of Surgery, Tokushima University, 3-18-15 Kuramoto-Cho, Tokushima, Tokushima, 770-8503, Japan
| | - Yuma Wada
- Department of Surgery, Tokushima University, 3-18-15 Kuramoto-Cho, Tokushima, Tokushima, 770-8503, Japan
| | - Toshiaki Yoshimoto
- Department of Surgery, Tokushima University, 3-18-15 Kuramoto-Cho, Tokushima, Tokushima, 770-8503, Japan
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Valadez LZM, Frigolet ME, Dominguez RM, Pescarus R, Zerrweck C, Boudreau V, Doumouras A, Cookson T, Anvari M. Metabolic and Bariatric Surgery in Diabetes Management. THE DIABETES TEXTBOOK 2023:673-690. [DOI: 10.1007/978-3-031-25519-9_42] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Kwon Y, Lee S, Kim D, ALRomi A, Park SH, Lee CM, Kim JH, Park S. Biliopancreatic Limb Length as a Potential Key Factor in Superior Glycemic Outcomes After Roux-en-Y Gastric Bypass in Patients With Type 2 Diabetes: A Meta-Analysis. Diabetes Care 2022; 45:3091-3100. [PMID: 36455123 DOI: 10.2337/dc22-0835] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 08/29/2022] [Indexed: 12/03/2022]
Abstract
BACKGROUND Optimal length of biliopancreatic (BP) and Roux limb in Roux-en-Y gastric bypass (RYGB) for improved glycemic control are not known. PURPOSE To investigate how the lengths of the BP and Roux limbs in RYGB differentially affect postoperative glycemic outcomes in patients with type 2 diabetes. DATA SOURCES We conducted a systematic literature search using the PubMed, Embase, and the Cochrane Library databases. STUDY SELECTION We included studies that reported glycemic outcomes after RYGB and lengths of the BP and Roux limbs. DATA EXTRACTION A total of 28 articles were included for data extraction. Glycemic outcomes after RYGB were assessed on the basis of two definitions: remission and improvement. DATA SYNTHESIS We categorized the included studies into four groups according to the BP and Roux limb lengths. The type 2 diabetes remission/improvement rates were as follows: long BP-long Roux group 0.80 (95% CI 0.70-0.90)/0.81 (0.73-0.89), long BP-short Roux group 0.76 (0.66-0.87)/0.82 (0.75-0.89), short BP-long Roux group 0.57 (0.36-0.78)/0.64 (0.53-0.75), and short BP-short Roux group 0.62 (0.43-0.80)/0.53 (0.45-0.61). Meta-regression analysis also showed that a longer BP limb resulted in higher postoperative type 2 diabetes remission and improvement rates, whereas a longer Roux limb did not. There was no significant difference or heterogeneity in baseline characteristics, including diabetes-related variables, among the four groups. LIMITATIONS Not all included studies were randomized controlled trials. CONCLUSIONS Longer BP limb length led to higher rates of type 2 diabetes remission and improvement by 1 year after RYGB in comparisons with the longer Roux limb length.
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Affiliation(s)
- Yeongkeun Kwon
- Division of Foregut Surgery, Korea University College of Medicine, Seoul, South Korea
- Center for Obesity and Metabolic Diseases, Korea University Anam Hospital, Seoul, South Korea
- Gut & Metabolism Laboratory, Korea University College of Medicine, Seoul, South Korea
| | - Sungho Lee
- Department of Medicine, Korea University College of Medicine, Seoul, South Korea
| | - Dohyang Kim
- Department of Statistics, Daegu University, Gyeongbuk, South Korea
| | - Ahmad ALRomi
- Division of Foregut Surgery, Korea University College of Medicine, Seoul, South Korea
| | - Shin-Hoo Park
- Division of Foregut Surgery, Korea University College of Medicine, Seoul, South Korea
- Center for Obesity and Metabolic Diseases, Korea University Anam Hospital, Seoul, South Korea
- Gut & Metabolism Laboratory, Korea University College of Medicine, Seoul, South Korea
| | - Chang Min Lee
- Division of Foregut Surgery, Korea University College of Medicine, Seoul, South Korea
- Gut & Metabolism Laboratory, Korea University College of Medicine, Seoul, South Korea
| | - Jong-Han Kim
- Division of Foregut Surgery, Korea University College of Medicine, Seoul, South Korea
- Gut & Metabolism Laboratory, Korea University College of Medicine, Seoul, South Korea
| | - Sungsoo Park
- Division of Foregut Surgery, Korea University College of Medicine, Seoul, South Korea
- Center for Obesity and Metabolic Diseases, Korea University Anam Hospital, Seoul, South Korea
- Gut & Metabolism Laboratory, Korea University College of Medicine, Seoul, South Korea
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Zhang Y, Niu J, Zhang S, Si X, Bian TT, Wu H, Li D, Sun Y, Jia J, Xin E, Yan X, Li Y. Comparative study on the gastrointestinal- and immune- regulation functions of Hedysari Radix Paeparata Cum Melle and Astragali Radix Praeparata cum Melle in rats with spleen-qi deficiency, based on fuzzy matter-element analysis. PHARMACEUTICAL BIOLOGY 2022; 60:1237-1254. [PMID: 35763552 PMCID: PMC9246251 DOI: 10.1080/13880209.2022.2086990] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 05/31/2022] [Accepted: 06/02/2022] [Indexed: 05/27/2023]
Abstract
CONTEXT Hedysari Radix Praeparata Cum Melle (HRPCM) and Astragali Radix Praeparata Cum Melle (ARPCM) are used interchangeably in clinics to treat spleen-qi deficiency (SQD) symptom mainly including gastrointestinal dysfunction and decreased immunity, which has unknown differences in efficacy. OBJECTIVE To investigate the differences between HRPCM and ARPCM on intervening gastrointestinal- and immune-function with SQD syndrome. MATERIALS AND METHODS After the SQD model was established, the Sprague-Dawley (SD) rats were randomly divided into nine groups (n = 10): normal; model; Bu-Zhong-Yi-Qi Pills; 18.9, 12.6 and 6.3 g/kg dose groups of HRPCM and ARPCM. Gastrointestinal function including d-xylose, gastrin, amylase vasoactive intestinal peptide, motilin, pepsin, H+/K+-ATPase, Na+/K+-ATPase, sodium-glucose cotransporter 1 (SGLT1), glucose transporter 2 (GLUT2) and immune function including spleen and thymus index, blood routine, interleukin (IL)-2, IL-6, interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), immunoglobulin (Ig) M, IgA, IgG and delayed-type hypersensitivity (DTH) were detected. Finally, the efficacy differences were analysed comprehensively by the fuzzy matter-element method. RESULTS In regulating immune, the doses differences in efficacy between HRPCM and ARPCM showed in the high-dose (18.9 g/kg), but there were no differences in the middle- and low- dose (12.6 and 6.37 g/kg); the efficacy differences were primarily reflected in levels of IL-6, IFN-γ, TNF-α and IgM in serum, and the mRNA expression of IL-6 and IFN-γ in the spleen. In regulating gastrointestinal, the efficacy differences were primarily reflected in the levels of D-xylose, MTL, and GAS in serum, and the mRNA and protein expression of SGLT1 and GLUT2 in jejunum and ileum. DISCUSSION AND CONCLUSIONS HRPCM is more effective than ARPCM on regulating gastrointestinal function and immune function with SQD syndrome. Therefore, we propose that HRPCM should be mainly used to treat SQD syndrome in the future.
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Affiliation(s)
- Yugui Zhang
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, PR China
- Key Laboratory of Standard and Quality of Chinese Medicine Research of Gansu, Engineering Research Center of Chinese Medicine Pharmaceutical Process of Gansu, Gansu University of Chinese Medicine, Lanzhou, PR China
| | - Jiangtao Niu
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, PR China
- Key Laboratory of Standard and Quality of Chinese Medicine Research of Gansu, Engineering Research Center of Chinese Medicine Pharmaceutical Process of Gansu, Gansu University of Chinese Medicine, Lanzhou, PR China
| | - Shujuan Zhang
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, PR China
- Key Laboratory of Standard and Quality of Chinese Medicine Research of Gansu, Engineering Research Center of Chinese Medicine Pharmaceutical Process of Gansu, Gansu University of Chinese Medicine, Lanzhou, PR China
| | - Xinlei Si
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, PR China
- Key Laboratory of Standard and Quality of Chinese Medicine Research of Gansu, Engineering Research Center of Chinese Medicine Pharmaceutical Process of Gansu, Gansu University of Chinese Medicine, Lanzhou, PR China
| | - Tian-Tian Bian
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, PR China
- Key Laboratory of Standard and Quality of Chinese Medicine Research of Gansu, Engineering Research Center of Chinese Medicine Pharmaceutical Process of Gansu, Gansu University of Chinese Medicine, Lanzhou, PR China
| | - Hongwei Wu
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, PR China
- Key Laboratory of Standard and Quality of Chinese Medicine Research of Gansu, Engineering Research Center of Chinese Medicine Pharmaceutical Process of Gansu, Gansu University of Chinese Medicine, Lanzhou, PR China
| | - Donghui Li
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, PR China
- Key Laboratory of Standard and Quality of Chinese Medicine Research of Gansu, Engineering Research Center of Chinese Medicine Pharmaceutical Process of Gansu, Gansu University of Chinese Medicine, Lanzhou, PR China
| | - Yujing Sun
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, PR China
- Key Laboratory of Standard and Quality of Chinese Medicine Research of Gansu, Engineering Research Center of Chinese Medicine Pharmaceutical Process of Gansu, Gansu University of Chinese Medicine, Lanzhou, PR China
| | - Jing Jia
- College of Acupuncture-Moxibustion and Tuina, Laboratory of Molecular Biology, Gansu University of Chinese Medicine, Lanzhou, PR China
| | - Erdan Xin
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, PR China
- Key Laboratory of Standard and Quality of Chinese Medicine Research of Gansu, Engineering Research Center of Chinese Medicine Pharmaceutical Process of Gansu, Gansu University of Chinese Medicine, Lanzhou, PR China
| | - Xingke Yan
- College of Acupuncture-Moxibustion and Tuina, Laboratory of Molecular Biology, Gansu University of Chinese Medicine, Lanzhou, PR China
| | - Yuefeng Li
- College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, PR China
- Key Laboratory of Standard and Quality of Chinese Medicine Research of Gansu, Engineering Research Center of Chinese Medicine Pharmaceutical Process of Gansu, Gansu University of Chinese Medicine, Lanzhou, PR China
- Scientific Research and Experimental Center, Gansu University of Chinese Medicine, Lanzhou, PR China
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Abstract
Modern changes in diet and lifestyle have led to an explosion of insulin resistance and metabolic diseases around the globe which, if left unchecked, will become a principal driver of morbidity and mortality in the 21st century. The nature of the metabolic homeostatic shift within the body has therefore become a topic of considerable interest. While the gut has long been recognized as an acute nutrient sensor with signaling mechanisms to the other metabolic organs of the body, its role in regulating the body's metabolic status over longer periods of time has been underappreciated. Recent insights from bariatric surgery and intestinal nutrient stimulation experiments provide a window into the adaptive role of the intestinal mucosa in a foregut/hindgut metabolic balance model that helps to define metabolic parameters within the body-informing the metabolic regulation of insulin resistance versus sensitivity, hunger versus satiety, energy utilization versus energy storage, and protection from hypoglycemia versus protection from hyperglycemia. This intestinal metabolic balance model provides an intellectual framework with which to understand the distinct roles of proximal and distal intestinal segments in metabolic regulation. The model may also aid in the development of novel disease-modifying therapies that can correct the dysregulated metabolic signals from the intestine and stem the tide of metabolic diseases in society.
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Affiliation(s)
- Harith Rajagopalan
- Fractyl Health, Inc., Lexington,
MA, USA
- Harith Rajagopalan, M.D. PhD.,
Fractyl Health, Inc., 17 Hartwell Avenue, Lexington, MA 02421, USA.
| | | | - David C. Klonoff
- Diabetes Research Institute,
Mills-Peninsula Medical Center, San Mateo, California
| | - Alan D. Cherrington
- Department of Molecular
Physiology and Biophysics, Vanderbilt University School of Medicine,
Nashville, TN, USA
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40
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Ren M, Zhou X, Lv L, Ji F. Endoscopic Bariatric and Metabolic Therapies for Liver Disease: Mechanisms, Benefits, and Associated Risks. J Clin Transl Hepatol 2022; 10:986-994. [PMID: 36304503 PMCID: PMC9547260 DOI: 10.14218/jcth.2021.00448] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 01/02/2022] [Accepted: 01/11/2022] [Indexed: 12/04/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD), including advanced-stage nonalcoholic steatohepatitis (NASH), is currently the most common chronic liver disease worldwide and is projected to become the leading indication for liver transplantation (LT). However, there are no effective pharmacological therapies for NAFLD. Endoscopic bariatric and metabolic therapies (EBMTs) are less invasive procedures for the treatment of obesity and its metabolic comorbidities. Several recent studies have demonstrated the beneficial effects of EBMTs on NAFLD/NASH. In this review, we summarize the major EBMTs and their mechanisms of action. We further discuss the current evidence on the efficacy and safety of EBMTs in people with NAFLD/NASH and obese cirrhotic LT candidates. The potential utility of EBMTs in reducing liver volume and perioperative complications in bariatric surgery candidates is also discussed. Moreover, we review the development of liver abscesses as a common serious adverse event in duodenal-jejunal bypass liner implantation.
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Affiliation(s)
| | | | | | - Feng Ji
- Correspondence to: Feng Ji, Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, Zhejiang 310003, China. ORCID: https://orcid.org/0000-0002-1426-0802. Tel: +86-571-87236863, Fax: 86-571-87236611, E-mail:
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Gimenes GM, Santana GO, Scervino MVM, Curi R, Pereira JNB. A short review on the features of the non-obese diabetic Goto-Kakizaki rat intestine. Braz J Med Biol Res 2022; 55:e11910. [PMID: 36000611 PMCID: PMC9394691 DOI: 10.1590/1414-431x2022e11910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Accepted: 06/30/2022] [Indexed: 11/23/2022] Open
Abstract
The Goto-Kakizaki (GK) rat is a non-obese experimental model of type 2 diabetes
mellitus (T2DM) that allows researchers to monitor diabetes-induced changes
without jeopardizing the effects of obesity. This rat strain exhibits notable
gastrointestinal features associated with T2DM, such as marked alterations in
intestinal morphology, reduced intestinal motility, slow transit, and modified
microbiota compared to Wistar rats. The primary treatments for diabetic patients
include administration of hypoglycemic agents and insulin, and lifestyle
changes. Emerging procedures, including alternative therapies, metabolic
surgeries, and modulation of the intestinal microbiota composition, have been
shown to improve the diabetic state of GK rats. This review describes the
morpho-physiological diabetic-associated features of the gastrointestinal tract
(GIT) of GK rats. We also describe promising strategies, e.g., metabolic surgery
and modulation of gut microbiota composition, used to target the GIT of this
animal model to improve the diabetic state.
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Affiliation(s)
- G M Gimenes
- Programa de Pós-Graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, SP, Brasil
| | - G O Santana
- Programa de Pós-Graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, SP, Brasil
| | - M V M Scervino
- Programa de Pós-Graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, SP, Brasil
| | - R Curi
- Programa de Pós-Graduação Interdisciplinar em Ciências da Saúde, Universidade Cruzeiro do Sul, São Paulo, SP, Brasil.,Centro Bioindustrial, Instituto Butantan, São Paulo, SP, Brasil
| | - J N B Pereira
- Laboratório Estratégico de Diagnóstico Molecular, Instituto Butantan, São Paulo, SP, Brasil
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Cheng ZQ, Liu TM, Ren PF, Chen C, Wang YL, Dai Y, Zhang X. Duodenal-jejunal bypass reduces serum ceramides via inhibiting intestinal bile acid-farnesoid X receptor pathway. World J Gastroenterol 2022; 28:4328-4337. [PMID: 36159007 PMCID: PMC9453759 DOI: 10.3748/wjg.v28.i31.4328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 05/12/2022] [Accepted: 07/25/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Bile acids play an important role in the amelioration of type 2 diabetes following duodenal-jejunal bypass (DJB). Serum bile acids are elevated postoperatively. However, the clinical relevance is not known. Bile acids in the peripheral circulation reflect the amount of bile acids in the gut. Therefore, a further investigation of luminal bile acids following DJB is of great significance.
AIM To investigate changes of luminal bile acids following DJB.
METHODS Salicylhydroxamic acid (SHAM), DJB, and DJB with oral chenodeoxycholic acid (CDCA) supplementation were performed in a high-fat-diet/streptozotocin-induced diabetic rat model. Body weight, energy intake, oral glucose tolerance test, luminal bile acids, serum ceramides and intestinal ceramide synthesis were analyzed at week 12 postoperatively.
RESULTS Compared to SHAM, DJB achieved rapid and durable improvement in glucose tolerance and led to increased total luminal bile acid concentrations with preferentially increased proportion of farnesoid X receptor (FXR) - inhibitory bile acids within the common limb. Intestinal ceramide synthesis was repressed with decreased serum ceramides, and this phenomenon could be partially antagonized by luminal supplementation of FXR activating bile acid CDCA.
CONCLUSION DJB significantly changes luminal bile acid composition with increased proportion FXR-inhibitory bile acids and reduces serum ceramide levels. There observations suggest a novel mechanism of bile acids in metabolic regulation after DJB.
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Affiliation(s)
- Zhi-Qiang Cheng
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Tong-Ming Liu
- Department of Colorectal and Anal Surgery, Feicheng Hospital Affiliated to Shandong First Medical University, Feicheng 271600, Shandong Province, China
| | - Peng-Fei Ren
- Department of General Surgery, Lincheng People’s Hospital, Dezhou 253500, Shandong Province, China
| | - Chang Chen
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Yan-Lei Wang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Yong Dai
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Xiang Zhang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
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Schneider R, Kraljević M, Peterli R, Rohm TV, Bosch AJ, Low AJ, Keller L, AlAsfoor S, Häfliger S, Yilmaz B, Peterson CJ, Lazaridis II, Vonaesch P, Delko T, Cavelti-Weder C. Roux-en-Y gastric bypass with a long compared to a short biliopancreatic limb improves weight loss and glycemic control in obese mice. Surg Obes Relat Dis 2022; 18:1286-1297. [DOI: 10.1016/j.soard.2022.06.286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 05/02/2022] [Accepted: 06/18/2022] [Indexed: 11/30/2022]
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The Obesogenic and Glycemic Effect of Bariatric Surgery in a Family with a Melanocortin 4 Receptor Loss-of-Function Mutation. Metabolites 2022; 12:metabo12050430. [PMID: 35629934 PMCID: PMC9143288 DOI: 10.3390/metabo12050430] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 05/04/2022] [Accepted: 05/09/2022] [Indexed: 01/25/2023] Open
Abstract
We report the long-term response to bariatric surgery in a singular family of four adolescents with severe obesity (41–82 kg/m2), homozygous for the C271R loss-of-function mutation in the melanocortin 4 receptor (MC4R), and three adults heterozygous for the same mutation. All patients had similar sociodemographic backgrounds and were followed for an average of 7 years. Three of the four homozygous patients regained their full weight (42–77 kg/m2), while the fourth lost weight but remained obese with a body mass index of 60 kg/m2. Weight regain was associated with relapse of most comorbidities, yet hyperglycemia did not relapse or was delayed. A1c levels were reduced in homozygous and heterozygous patients. The long-term follow-up data on this very unique genetic setting show that weight loss and amelioration of obesity following bariatric surgery require active MC4R signaling, while the improvement in glycemia is in part independent of weight loss. The study validates animal models and demonstrates the importance of biological signaling in the regulation of weight, even after bariatric surgery.
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Oh TJ, Lee H, Cho YM. East Asian perspectives in metabolic and bariatric surgery. J Diabetes Investig 2022; 13:756-761. [PMID: 35029061 PMCID: PMC9077716 DOI: 10.1111/jdi.13748] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 01/07/2022] [Accepted: 01/11/2022] [Indexed: 11/28/2022] Open
Abstract
The prevalence of diabetes and obesity continues to rise in East Asia. As the risk of diabetes increases at a lower body mass index (BMI) in East Asians than in Europeans, the threshold of BMI values for metabolic and bariatric surgery (MBS) is lower in East Asians. MBS is considered upon reaching a BMI of 27.5 kg/m2 and is recommended at a BMI of ≥ 32.5 kg/m2 , depending on the status of glucose homeostasis. The most commonly performed MBS in East Asia is sleeve gastrectomy, followed by Roux-en-Y gastric bypass (RYGB). Because the incidence of gastric cancer is higher in East Asia than in other regions, concerns regarding surveillance for gastric cancer might be related to a preference for sleeve gastrectomy over RYGB in this region. Even though there is a paucity of data on direct comparisons of the efficacy of MBS among different ethnic groups, the degree of weight reduction in East Asians is not inferior to other ethnic groups. Moreover, studies suggest that the diabetes remission rate in East Asians seemed to be higher than in other ethnic groups. Future studies involving multiethnic groups are necessary to identify possible ethnic differences in diabetes remission and to determine the appropriate BMI threshold for MBS according to ethnicity.
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Affiliation(s)
- Tae Jung Oh
- Department of Internal MedicineSeoul National University College of Medicine and Seoul National University Bundang HospitalSeongnamKorea
| | - Hyuk‐Joon Lee
- Department of SurgerySeoul National University HospitalSeoulKorea
| | - Young Min Cho
- Department of Internal MedicineSeoul National University College of Medicine and Seoul National University HospitalSeoulKorea
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Losurdo G, Gravina AG, Maroni L, Gabrieletto EM, Ianiro G, Ferrarese A. Future challenges in gastroenterology and hepatology, between innovations and unmet needs: A SIGE Young Editorial Board's perspective. Dig Liver Dis 2022; 54:583-597. [PMID: 34509394 DOI: 10.1016/j.dld.2021.08.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 08/09/2021] [Accepted: 08/12/2021] [Indexed: 02/08/2023]
Abstract
Gastroenterology, Digestive Endoscopy and Hepatology have faced significant improvements in terms of diagnosis and therapy in the last decades. However, many fields still remain poorly explored, and many questions unanswered. Moreover, basic-science, as well as translational and clinical discoveries, together with technology advancement will determine further steps toward a better, refined care for many gastroenterological disorders in the future. Therefore, the Young Investigators of the Italian Society of Gastroenterology (SIGE) joined together, offering a perspective on major future innovations in some hot clinical topics in Gastroenterology, Endoscopy, and Hepatology, as well as the current pitfalls and the grey zones.
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Affiliation(s)
- Giuseppe Losurdo
- Gastroenterology Unit, Department of Emergency and Organ Transplantation, University 'Aldo Moro' of Bari; PhD Course in Organs and Tissues Transplantation and Cellular Therapies, Department of Emergency and Organ Transplantation, University 'Aldo Moro' of Bari.
| | - Antonietta Gerarda Gravina
- Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Luca Maroni
- Department of Gastroenterology, Marche Polytechnic University, Ancona, Italy
| | | | - Gianluca Ianiro
- Digestive Disease Center, Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Alberto Ferrarese
- Gastroenterology and Hepatology, Azienda Ospedaliera Universitaria Integrata, Ospedale Borgo Trento, Verona, Italy
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Zhu H, Cai H, Wang X, Chen T, Zhen C, Zhang Z, Ruan X, Li G. Sodium-glucose co-transporter 1 (SGLT1) differentially regulates gluconeogenesis and GLP-1 receptor (GLP-1R) expression in different diabetic rats: a preliminary validation of the hypothesis of "SGLT1 bridge" as an indication for "surgical diabetes". ANNALS OF TRANSLATIONAL MEDICINE 2022; 10:481. [PMID: 35571394 PMCID: PMC9096370 DOI: 10.21037/atm-22-1769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 04/20/2022] [Indexed: 11/24/2022]
Abstract
BACKGROUND Sodium-glucose co-transporter 1 (SGLT1) may play a synergistic role in gluconeogenesis (GNG) and glucagon-like peptide-1 (GLP-1) expression. We proposed the hypothesis of a "SGLT1 bridge" as an indication for "surgical diabetes" that was preliminary validated in the present study. METHODS We selected nonobese diabetic Goto-Kakizaki (GK) rats and Zuker diabetic fat (ZDF) rats to represent advanced and early diabetes, respectively. Based on glucose gavage with or without SGLT1 inhibitor phlorizin, the rats were divided into 4 groups: Gk-Glu, GK-P, ZDF-Glu, and ZDF-P. The expressions of SGLT1, GLP-1 receptor (GLP-1R), glucose-6 phosphatase (G6Pase), and phosphoenolpyruvate carboxykinase-1 (Pck1) were determined by immunohistochemistry (IHC) or quantitative reverse transcription polymerase chain reaction (RT-qPCR), and the effects of phlorizin were analyzed. RESULTS Glucose tolerance was worse in GK rats and the homeostasis model assessment-insulin resistance (HOMA-IR) was higher in ZDF rats, indicating different pathophysiological conditions between the different diabetic rats. GK rats showed higher activity of duodenal SGLT1 (P=0.022) and jejunal SGLT1 mRNA expression (P=0.000) and lower SGLT1 mRNA expression in the liver (P=0.000) and pancreas (P=0.000). Phlorizin effectively inhibited the activity of duodenal SGLT1 in both GK rats (P=0.000) and ZDF rats (P=0.000). In ZDF rats, the expression of GLP-1R mRNA was downregulated in the jejunum (P=0.001) and upregulated in the pancreas (P=0.021) by phlorizin, but there were no regulatory effects on GLP-1R mRNA in the jejunum and pancreas of GK rats. As for the regulatory effects on GNG, phlorizin upregulated Pck1 mRNA in the duodenum (P=0.000) and the jejunum (P=0.038), whereas it downregulated hepatic G6Pase mRNA in ZDF rats (P=0.005) and Pck1 mRNA expression in GK rats (P=0.001), suggesting that SGLT1 inhibitor may have upregulated intestinal GNG in ZDF rats and downregulated hepatic GNG in both ZDF and GK rats. CONCLUSIONS SGLT1 showed synergistic regulatory effects on the entero-insular axis (EIA) and the gut-brain-liver axis (GBLA), preliminarily validating the hypothesis of a "SGLT1 bridge". The distinct expression of SGLT1 and its differentially regulatory effects on diabetic rats with different pathophysiological conditions may provide probable potential indications involved in the "Surgical Diabetes" that is supposed as the inclusion for diabetic surgery.
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Affiliation(s)
- Hengliang Zhu
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, China
- Department of General Surgery, Shenzhen University General Hospital & Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, China
| | - Huajie Cai
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xiaokun Wang
- Department of Gastrointestinal & Hernia Surgery, Ganzhou People’s Hospital, Ganzhou, China
| | - Tao Chen
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Chaohui Zhen
- Department of General Surgery, Shenzhen University General Hospital & Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, China
| | - Zhenzhan Zhang
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xiaojiao Ruan
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Guoxin Li
- Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Atila Uslu G, Uslu H. Evaluating the effects of Juglans regia L. extract on hyperglycaemia and insulin sensitivity in experimental type 2 diabetes in rat. Arch Physiol Biochem 2022; 128:121-125. [PMID: 31545080 DOI: 10.1080/13813455.2019.1668018] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
OBJECTIVE The present study aimed to investigate the effects of Juglans regia (JR) extract on hyperglycaemia and insulin sensitivity. METHODS Forty rats were divided into 4 groups: Control (C), Diabetes Control (DC), Diabetes + Juglans regia (D + JR) and Diabetes + Metformin (D + M). RESULTS In the D + JR group, Fasting blood glucose (FBG) levels decreased from day 14 onwards. There was a significant decrease in plasma levels of Fibronectin Type III Domain Containing 5 (FNDC5) and adiponectin (ADP) in the DC group compared to the C group (p < .01, p < .001 respectively). In the D + JR group, there was a significant increase in plasma FNDC5 and ADP (p < .05), while the plasma Tumour necrosis factor-alpha (TNF-α) levels were decreased compared to the DC group (p < .001). CONCLUSIONS In conclusion, the present study found that JR and its bioactive components alleviated insulin resistance by increasing ADP and FNDC5 and decreasing FBG in a rat model of streptozotocin (STZ) + nicotinamide (NAD)-induced type 2 diabetes (T2D).HighlightsJuglans regia extract increased insulin sensitivity.Juglans regia extract significantly reduced the level of fasting blood glucose.Juglans regia extract reduced TNF-α levels in rats with type 2 diabetes.Juglans regia extract prevent weight loss in type 2 diabetes.
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Affiliation(s)
- Gözde Atila Uslu
- Department of Physiology, Faculty of Veterinary Medicine, University of Kafkas, Kars, Turkey
| | - Hamit Uslu
- Department of Health Care Services, Atatürk Vocational School of Health Services, University of Kafkas, Kars, Turkey
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Genetic reprogramming of remnant duodenum may contribute to type 2 diabetes improvement after Roux en-Y gastric bypass. Nutrition 2022; 99-100:111631. [DOI: 10.1016/j.nut.2022.111631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 12/31/2021] [Accepted: 02/07/2022] [Indexed: 11/22/2022]
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Comparison of the Outcomes of Single Anastomosis Duodeno-Ileostomy with Sleeve Gastrectomy (SADI-S), Single Anastomosis Sleeve Ileal (SASI) Bypass with Sleeve Gastrectomy, and Sleeve Gastrectomy Using a Rodent Model with Diabetes. Obes Surg 2022; 32:1209-1215. [PMID: 35050482 DOI: 10.1007/s11695-022-05920-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Revised: 01/12/2022] [Accepted: 01/14/2022] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Single anastomosis duodeno-ileostomy with sleeve gastrectomy (SADI-S) is a powerful form of bariatric surgery; however, it has a high risk of malnutrition. Single anastomosis sleeve ileal (SASI) bypass with sleeve gastrectomy may be used as an alternative procedure to avoid malnutrition associated with SADI-S; however, no comparison between the two procedures has been performed. METHODS Sprague-Dawley rats with diabetes (n = 32) were divided into four groups: SADI-S (n = 8), SASI (n = 8), SG (n = 8), and SHAM (n = 8). Body weight, food intake, and fasting blood glucose were measured, and the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed before and after surgery. Blood samples were collected before and after the surgery to assess the levels of glucagon-like peptide-1 (GLP-1), hemoglobin, albumin, vitamin B12, calcium, and iron. RESULTS The SADI-S and SASI groups showed significantly greater weight loss and better glucose control than the SG group postoperatively. The SADI-S and SASI groups showed similar improvements in glucose control throughout the study. The SADI-S and SASI groups had significantly higher GLP-1 levels than the SG group at 6 months. The SADI-S and SASI groups presented with various degrees of deficiencies, with the SADI-S group showing a higher risk for hypoalbuminemia and iron deficiency than the SASI group. CONCLUSIONS The SASI procedure may be a better alternative as it has excellent bariatric and metabolic results with lower risk for hypoalbuminemia and can be easily converted into either SADI-S or SG procedures. Nevertheless, further clinical results are needed.
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