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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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Colás A, Varela M, Mraz M, Novak D, Cuesta-Frau D, Vigil L, Benes M, Pelikanova T, Haluzik M, Burda V, Vargas B. Influence of glucometric 'dynamical' variables on duodenal-jejunal bypass liner (DJBL) anthropometric and metabolic outcomes. Diabetes Metab Res Rev 2020; 36:e3287. [PMID: 31916665 DOI: 10.1002/dmrr.3287] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2018] [Revised: 11/19/2019] [Accepted: 12/30/2019] [Indexed: 12/23/2022]
Abstract
BACKGROUND The endoscopically implanted duodenal-jejunal bypass liner (DJBL) is an attractive alternative to bariatric surgery for obese diabetic patients. This article aims to study dynamical aspects of the glycaemic profile that may influence DJBL effects. METHODS Thirty patients underwent DJBL implantation and were followed for 10 months. Continuous glucose monitoring (CGM) was performed before implantation and at month 10. Dynamical variables from CGM were measured: coefficient of variation of glycaemia, mean amplitude of glycaemic excursions (MAGE), detrended fluctuation analysis (DFA), % of time with glycaemia under 6.1 mmol/L (TU6.1), area over 7.8 mmol/L (AO7.8) and time in range. We analysed the correlation between changes in both anthropometric (body mass index, BMI and waist circumference) and metabolic (fasting blood glucose, FBG and HbA1c) variables and dynamical CGM-derived metrics and searched for variables in the basal CGM that could predict successful outcomes. RESULTS There was a poor correlation between anthropometric and metabolic outcomes. There was a strong correlation between anthropometric changes and changes in glycaemic tonic control (∆BMI-∆TU6.1: rho = - 0.67, P < .01) and between metabolic outcomes and glycaemic phasic control (∆FBG-∆AO7.8: r = .60, P < .01). Basal AO7.8 was a powerful predictor of successful metabolic outcome (0.85 in patients with AO7.8 above the median vs 0.31 in patients with AO7.8 below the median: Chi-squared = 5.67, P = .02). CONCLUSIONS In our population, anthropometric outcomes of DJBL correlate with improvement in tonic control of glycaemia, while metabolic outcomes correlate preferentially with improvement in phasic control. Assessment of basal phasic control may help in candidate profiling for DJBL implantation.
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Affiliation(s)
- Ana Colás
- Department of Internal Medicine, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Manuel Varela
- Department of Internal Medicine, Hospital Universitario de Móstoles, Madrid, Spain
| | - Milos Mraz
- Department of Diabetes, Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- Department of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic
| | - Daniel Novak
- Department of Cybernetics, Czech Technical University in Prague, Prague, Czech Republic
| | - David Cuesta-Frau
- Technological Institute of Informatics, Universitat Politècnica de València, Alcoi, Spain
| | - Luis Vigil
- Department of Internal Medicine, Hospital Universitario de Móstoles, Madrid, Spain
| | - Marek Benes
- Hepatogastroenterology Department, Transplantation Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Terezie Pelikanova
- Department of Diabetes, Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Martin Haluzik
- Department of Diabetes, Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
- Department of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic
- Laboratory of Experimental Diabetology, Experimental Medicine Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Vaclav Burda
- Department of Cybernetics, Czech Technical University in Prague, Prague, Czech Republic
| | - Borja Vargas
- Department of Internal Medicine, Hospital Universitario de Móstoles, Madrid, Spain
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Li N, Yan QT, Jing Q, Pan RY, Wang HJ, Jiang B, Li XJ, Wang Y, Dong JH, Wang XJ, Zhang MJ, Meng QG, Li XZ, Liu ZJ, Gao ZQ, Qu MH. Duodenal-Jejunal Bypass Ameliorates Type 2 Diabetes Mellitus by Activating Insulin Signaling and Improving Glucose Utilization in the Brain. Obes Surg 2019; 30:279-289. [DOI: 10.1007/s11695-019-04153-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
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Ohira M, Yamaguchi T, Saiki A, Nakamura S, Tanaka S, Oka R, Watanabe Y, Sato Y, Oshiro T, Murano T, Tatsuno I. Laparoscopic Sleeve Gastrectomy Significantly Increases Serum Lipoprotein Lipase Level in Obese Patients. Obes Facts 2019; 12:357-368. [PMID: 31167211 PMCID: PMC6696888 DOI: 10.1159/000500360] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Accepted: 04/15/2019] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVES Obesity is one of the causes of metabolic disorders. Laparoscopic sleeve gastrectomy (LSG) confers beneficial effects not only on body weight (BW) but also on metabolic disorders. The lipoprotein lipase (LPL) level in preheparin serum is associated with visceral adipose tissue and reflects insulin resistance. However, the change in serum preheparin LPL levels after LSG remains unclear. This study aimed to examine the effect of LSG on preheparin LPL level in obese patients compared with nonsurgical treatment. METHODS We retrospectively reviewed a total of 100 obese patients who were treated for obesity and had preheparin LPL levels measured before and 12 months after LSG or after 12 months of nonsurgical treatment. Fifty-six patients received LSG (LSG group), and 44 patients had no surgical treatment (nonsurgical group). We compared clinical parameters such as body mass index (BMI), hemoglobin A1c (HbA1c), and preheparin LPL level before and 12 months after treatment. RESULTS BMI and HbA1c decreased significantly in both groups, but decreases in both parameters were greater in the LSG group than in the nonsurgical group. Estimated glomerular filtration was significantly improved only in the LSG group. Preheparin LPL level increased significantly only in the LSG group (from 45.8 ± 21.6 to 75.0 ± 34.9 ng/mL, p < 0.001). Multiple regression identified LSG and decreased BMI as independent predictors of preheparin LPL level increase. CONCLUSIONS These results suggest that LSG independently increases pre-heparin LPL level beyond BW reduction in obese patients.
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Affiliation(s)
- Masahiro Ohira
- Center for Diabetes, Endocrinology, and Metabolism, Toho University Sakura Medical Center, Chiba, Japan,
| | - Takashi Yamaguchi
- Center for Diabetes, Endocrinology, and Metabolism, Toho University Sakura Medical Center, Chiba, Japan
| | - Atsuhito Saiki
- Center for Diabetes, Endocrinology, and Metabolism, Toho University Sakura Medical Center, Chiba, Japan
| | - Shoko Nakamura
- Center for Diabetes, Endocrinology, and Metabolism, Toho University Sakura Medical Center, Chiba, Japan
| | - Shou Tanaka
- Center for Diabetes, Endocrinology, and Metabolism, Toho University Sakura Medical Center, Chiba, Japan
| | - Rena Oka
- Center for Diabetes, Endocrinology, and Metabolism, Toho University Sakura Medical Center, Chiba, Japan
| | - Yasuhiro Watanabe
- Center for Diabetes, Endocrinology, and Metabolism, Toho University Sakura Medical Center, Chiba, Japan
| | - Yuta Sato
- Center for Diabetes, Endocrinology, and Metabolism, Toho University Sakura Medical Center, Chiba, Japan
| | - Takashi Oshiro
- Department of Surgery, Toho University Sakura Medical Center, Chiba, Japan
| | - Takeyoshi Murano
- Department of Clinical Laboratory Medicine, Toho University Sakura Medical Center, Chiba, Japan
| | - Ichiro Tatsuno
- Center for Diabetes, Endocrinology, and Metabolism, Toho University Sakura Medical Center, Chiba, Japan
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Abstract
The growing prevalence of obesity explains the rising interest in bariatric surgery. Compared with non-surgical treatment options, bariatric surgery results in greater and sustained improvements in weight loss, obesity associated complications, all-cause mortality and quality of life. These encouraging metabolic and weight effects come with a downside, namely the risk of nutritional deficiencies. Particularly striking is the risk to develop iron deficiency. Postoperatively, the prevalence of iron deficiency varies between 18 and 53 % after Roux-en-Y gastric bypass and between 1 and 54 % after sleeve gastrectomy. Therefore, preventive strategies and effective treatment options for iron deficiency are crucial to successfully manage the iron status of patients after bariatric surgery. With this review, we discuss the risks and the contributing factors of developing iron deficiency after bariatric surgery. Furthermore, we highlight the discrepancy in the diagnosis of iron deficiency, iron deficiency anaemia and anaemia and highlight the evidence supporting the current nutritional recommendations in the field of bariatric research. In conclusion, we advocate for more nutrition-related research in patient populations in order to provide strong evidence-based guidelines after bariatric surgery.
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Haluzík M, Kratochvílová H, Haluzíková D, Mráz M. Gut as an emerging organ for the treatment of diabetes: focus on mechanism of action of bariatric and endoscopic interventions. J Endocrinol 2018; 237:R1-R17. [PMID: 29378901 DOI: 10.1530/joe-17-0438] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 01/29/2018] [Indexed: 01/19/2023]
Abstract
Increasing worldwide prevalence of type 2 diabetes mellitus and its accompanying pathologies such as obesity, arterial hypertension and dyslipidemia represents one of the most important challenges of current medicine. Despite intensive efforts, high percentage of patients with type 2 diabetes does not achieve treatment goals and struggle with increasing body weight and poor glucose control. While novel classes of antidiabetic medications such as incretin-based therapies and gliflozins have some favorable characteristics compared to older antidiabetics, the only therapeutic option shown to substantially modify the progression of diabetes or to achieve its remission is bariatric surgery. Its efficacy in the treatment of diabetes is well established, but the exact underlying modes of action are still only partially described. They include restriction of food amount, enhanced passage of chymus into distal part of small intestine with subsequent modification of gastrointestinal hormones and bile acids secretion, neural mechanisms, changes in gut microbiota and many other possible mechanisms underscoring the importance of the gut in the regulation of glucose metabolism. In addition to bariatric surgery, less-invasive endoscopic methods based on the principles of bariatric surgery were introduced and showed promising results. This review highlights the role of the intestine in the regulation of glucose homeostasis focusing on the mechanisms of action of bariatric and especially endoscopic methods of the treatment of diabetes. A better understanding of these mechanisms may lead to less invasive endoscopic treatments of diabetes and obesity that may complement and widen current therapeutic options.
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Affiliation(s)
- Martin Haluzík
- Centre for Experimental MedicineInstitute for Clinical and Experimental Medicine, Prague, Czech Republic
- Diabetes CentreInstitute for Clinical and Experimental Medicine, Prague, Czech Republic
- Department of Medical Biochemistry and Laboratory DiagnosticsGeneral University Hospital, Charles University in Prague, 1st Faculty of Medicine, Prague, Czech Republic
| | - Helena Kratochvílová
- Centre for Experimental MedicineInstitute for Clinical and Experimental Medicine, Prague, Czech Republic
- Department of Medical Biochemistry and Laboratory DiagnosticsGeneral University Hospital, Charles University in Prague, 1st Faculty of Medicine, Prague, Czech Republic
| | - Denisa Haluzíková
- Department of Sports MedicineGeneral University Hospital, Charles University in Prague, 1st Faculty of Medicine, Prague, Czech Republic
| | - Miloš Mráz
- Diabetes CentreInstitute for Clinical and Experimental Medicine, Prague, Czech Republic
- Department of Medical Biochemistry and Laboratory DiagnosticsGeneral University Hospital, Charles University in Prague, 1st Faculty of Medicine, Prague, Czech Republic
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Abstract
There is mounting evidence, derived from mechanistic studies, RCTs, and other high-quality studies that there are weight loss independent antidiabetic effects of gastrointestinal surgery. Additionally, there appears to be no relation between the positive metabolic outcomes to baseline BMI. The outdated US National Health Institutes guidelines from 1991 were centered on BMI only criterion and often misleading. The Second Diabetes Surgery Summit held in collaboration with leading diabetes organizations and endorsed by a large group of international Professional Societies developed guidelines that defined eligibility based on the severity and degree of T2D medical control while referring to obesity as a qualifier and not the sole criterion. That is the first time that guidelines are provided to put metabolic surgery into the T2D treatment algorithms.
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Hao Z, Townsend RL, Mumphrey MB, Morrison CD, Münzberg H, Berthoud HR. RYGB Produces more Sustained Body Weight Loss and Improvement of Glycemic Control Compared with VSG in the Diet-Induced Obese Mouse Model. Obes Surg 2017; 27:2424-2433. [PMID: 28386755 PMCID: PMC5808920 DOI: 10.1007/s11695-017-2660-3] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND Weight regain and type-2 diabetes relapse has been reported in a significant proportion of vertical sleeve gastrectomy (VSG) patients in some studies, but definitive conclusions regarding the long-term comparative effectiveness of VSG and Roux-en-Y gastric bypass (RYGB) surgery are lacking both in humans and rodent models. This study's objective was to compare the effects of murine models of VSG and RYGB surgery on body weight, body composition, food intake, energy expenditure, and glycemic control. METHODS VSG, RYGB, and sham surgery was performed in high-fat diet-induced obese mice, and the effects on body weight and glycemic control were observed for a period of 12 weeks. RESULTS After the initial weight loss, VSG mice regained significant amounts of body weight and fat mass that were only marginally lower than in sham-operated mice. In contrast, RYGB produced sustained loss of body weight and fat mass up to 12 weeks and drastically improved fasting insulin and HOMA-IR compared with sham-operated mice. Using weight-matched control groups, we also found that the adaptive hypometabolic response to weight loss was blunted by both VSG and RYGB, and that despite large weight/fat regain, fasting insulin and HOMA-IR were markedly improved, but not reversed, in VSG mice. CONCLUSIONS VSG is less effective to lastingly suppress body weight and improve glycemic control compared with RYGB in mice. Given similar observations in many human studies, the run towards replacing RYGB with VSG is premature and should await carefully controlled randomized long-term trials with VSG and RYGB.
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Affiliation(s)
- Zheng Hao
- Neurobiology of Nutrition and Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA, 70808, USA
| | - R Leigh Townsend
- Neurobiology of Nutrition and Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA, 70808, USA
| | - Michael B Mumphrey
- Neurobiology of Nutrition and Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA, 70808, USA
| | - Christopher D Morrison
- Neurobiology of Nutrition and Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA, 70808, USA
| | - Heike Münzberg
- Neurobiology of Nutrition and Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA, 70808, USA
| | - Hans-Rudolf Berthoud
- Neurobiology of Nutrition and Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA, 70808, USA.
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Kamvissi-Lorenz V, Raffaelli M, Bornstein S, Mingrone G. Role of the Gut on Glucose Homeostasis: Lesson Learned from Metabolic Surgery. Curr Atheroscler Rep 2017; 19:9. [PMID: 28185153 PMCID: PMC5306308 DOI: 10.1007/s11883-017-0642-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Purpose of Review Bariatric surgery was initially intended to reduce weight, and only subsequently was the remission of type two diabetes (T2D) observed as a collateral event. At the moment, the term “metabolic surgery” is used to underline the fact that this type of surgery is performed specifically to treat diabetes and its metabolic complications, such as hyperlipidemia. Recent Findings Randomized, controlled studies have recently supported the use of bariatric surgery, and in particular of Roux-en-Y gastric bypass (RYGB) and biliopancreatic diversion (BPD) as an effective treatment for decompensated T2D. The lesson learned from these randomized and many other non-randomized clinical studies is that the stomach and the small intestine play a central role in glucose homeostasis. Bypassing the duodenum and parts of the jejunum exerts a substantial effect on insulin sensitivity and secretion. In fact, with BPD, nutrient transit bypasses duodenum, the entire jejunum and a small portion of the ileum, resulting in reversal of insulin sensitivity back to normal and reduction of insulin secretion, whereas RYGB has little effect on insulin resistance but increases insulin secretion. Hypotheses concerning the mechanism of action of metabolic surgery for diabetes remission vary from theories focusing on jejunal nutrient sensing, to incretin action, to the blunted secretion of putative insulin resistance hormone(s), to changes in the microbiota. Summary Whatever the mechanism, metabolic surgery has the undoubted merit of exposing the central role of the small intestine in insulin sensitivity and glucose homeostasis.
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Affiliation(s)
- V Kamvissi-Lorenz
- Department of Medicine 3, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Germany. .,Diabetes and Nutritional Sciences, King's College London, Henr. Rahp. R. 3.6, Guy's Campus, 19 Newcomen Street, London, SE1 1UL, UK.
| | - M Raffaelli
- Department of Surgery, Catholic University, Rome, Italy
| | - S Bornstein
- Department of Medicine 3, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Germany.,Diabetes and Nutritional Sciences, King's College London, Henr. Rahp. R. 3.6, Guy's Campus, 19 Newcomen Street, London, SE1 1UL, UK
| | - G Mingrone
- Diabetes and Nutritional Sciences, King's College London, Henr. Rahp. R. 3.6, Guy's Campus, 19 Newcomen Street, London, SE1 1UL, UK.,Department of Internal Medicine, Catholic University, Rome, Italy
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10
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Cohen R, Caravatto PP, Petry TZ. Innovative metabolic operations. Surg Obes Relat Dis 2016; 12:1247-55. [DOI: 10.1016/j.soard.2016.02.034] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2016] [Accepted: 02/23/2016] [Indexed: 02/07/2023]
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Petry TBZ, Caravatto PP, Pechy FQ, Correia JLL, Guerbali CCL, da Silva RM, Salles JE, Cohen R. How Durable Are the Effects After Metabolic Surgery? Curr Atheroscler Rep 2015; 17:54. [PMID: 26233634 DOI: 10.1007/s11883-015-0533-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Bariatric surgery was initially developed as a tool for weight reduction only, but it is gaining popularity because of its remarkable effect on glucose metabolism in morbidly obese and less obese patients. Recent publications have shown the superiority of metabolic surgery over medical treatment for diabetes, creating a new field of clinical research that is currently overflowing in the medical community with outstanding high-quality data. Metabolic surgery is effective in treating diabetes, even in non-morbidly obese patients.
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Affiliation(s)
- Tarissa Beatrice Zanata Petry
- The Center of Obesity and Diabetes, Hospital Oswaldo Cruz, Rua Cincinato Braga, 35. 5o andar, São Paulo, 01333-010, Brazil,
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Abstract
The obesity epidemic, combined with the lack of available and effective treatments for morbid obesity, is a scientific and public health priority. Worldwide, bariatric and metabolic surgeries are increasingly being performed to effectively aid weight loss in patients with severe obesity, as well as because of the favourable metabolic effects of the procedures. The positive effects of bariatric surgery, especially with respect to improvements in type 2 diabetes mellitus, have expanded the eligibility criteria for metabolic surgery to patients with diabetes mellitus and a BMI of 30-35 kg/m(2). However, the limitations of BMI, both in the diagnosis and follow-up of patients, need to be considered, particularly for determining the actual adiposity and fat distribution of the patients following weight loss. Understanding the characteristics shared by bariatric and metabolic surgeries, as well as their differential aspects and outcomes, is required to enhance patient benefits and operative achievements. For a holistic approach that focuses on the multifactorial effects of bariatric and metabolic surgery to be possible, a paradigm shift that goes beyond the pure semantics is needed. Such a shift could lead to profound clinical implications for eligibility criteria and the definition of success of the surgical approach.
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Affiliation(s)
- Gema Frühbeck
- Department of Endocrinology &Nutrition, CIBEROBN, Clínica Universidad de Navarra, University of Navarra, IdiSNA, Avda. Pío XII 36, 31008 Pamplona, Spain
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13
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Raghow R. Ménage-à-trois of bariatric surgery, bile acids and the gut microbiome. World J Diabetes 2015; 6:367-370. [PMID: 25897347 PMCID: PMC4398893 DOI: 10.4239/wjd.v6.i3.367] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2014] [Revised: 12/26/2014] [Accepted: 01/12/2015] [Indexed: 02/05/2023] Open
Abstract
Bariatric surgeries have emerged as highly effective treatments for obesity associated type-2 diabetes mellitus. Evidently, the desired therapeutic endpoints such as rates of weight loss, lower levels of glycated hemoglobin and remission of diabetes are achieved more rapidly and last longer following bariatric surgery, as opposed to drug therapies alone. In light of these findings, it has been suspected that in addition to causing weight loss dependent glucose intolerance, bariatric surgery induces other physiological changes that contribute to the alleviation of diabetes. However, the putative post-surgical neuro-hormonal pathways that underpin the therapeutic benefits of bariatric surgery remain undefined. In a recent report, Ryan and colleagues shed new light on the potential mechanisms that determine the salutary effects of bariatric surgery in mice. The authors demonstrated that the improved glucose tolerance and weight loss in mice after vertical sleeve gastrectomy (VSG) surgery were likely to be caused by post-surgical changes in circulating bile acids and farnesoid-X receptor (FXR) signaling, both of which were also mechanistically linked to changes in the microbial ecology of the gut. The authors arrived at this conclusion from a comparison of genome-wide, metabolic consequences of VSG surgery in obese wild type (WT) and FXR knockout mice. Gene expression in the distal small intestines of WT and FXR knockout mice revealed that the pathways regulating bile acid composition, nutrient metabolism and anti-oxidant defense were differentially altered by VSG surgery in WT and FXR-/- mice. Based on these data Ryan et al, hypothesized that bile acid homeostasis and FXR signaling were mechanistically linked to the gut microbiota that played a role in modulating post-surgical changes in total body mass and glucose tolerance. The authors’ data provide a plausible explanation for putative weight loss-independent benefits of bariatric surgery and its relationship with metabolism of bile acids.
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14
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Guan X. The CNS glucagon-like peptide-2 receptor in the control of energy balance and glucose homeostasis. Am J Physiol Regul Integr Comp Physiol 2014; 307:R585-96. [PMID: 24990862 DOI: 10.1152/ajpregu.00096.2014] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The gut-brain axis plays a key role in the control of energy balance and glucose homeostasis. In response to luminal stimulation of macronutrients and microbiota-derived metabolites (secondary bile acids and short chain fatty acids), glucagon-like peptides (GLP-1 and -2) are cosecreted from endocrine L cells in the gut and coreleased from preproglucagonergic neurons in the brain stem. Glucagon-like peptides are proposed as key mediators for bariatric surgery-improved glycemic control and energy balance. Little is known about the GLP-2 receptor (Glp2r)-mediated physiological roles in the control of food intake and glucose homeostasis, yet Glp1r has been studied extensively. This review will highlight the physiological relevance of the central nervous system (CNS) Glp2r in the control of energy balance and glucose homeostasis and focuses on cellular mechanisms underlying the CNS Glp2r-mediated neural circuitry and intracellular PI3K signaling pathway. New evidence (obtained from Glp2r tissue-specific KO mice) indicates that the Glp2r in POMC neurons is essential for suppressing feeding behavior, gastrointestinal motility, and hepatic glucose production. Mice with Glp2r deletion selectively in POMC neurons exhibit hyperphagic behavior, accelerated gastric emptying, glucose intolerance, and hepatic insulin resistance. GLP-2 differentially modulates postsynaptic membrane excitability of hypothalamic POMC neurons in Glp2r- and PI3K-dependent manners. GLP-2 activates the PI3K-Akt-FoxO1 signaling pathway in POMC neurons by Glp2r-p85α interaction. Intracerebroventricular GLP-2 augments glucose tolerance, suppresses glucose production, and enhances insulin sensitivity, which require PI3K (p110α) activation in POMC neurons. Thus, the CNS Glp2r plays a physiological role in the control of food intake and glucose homeostasis. This review will also discuss key questions for future studies.
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Affiliation(s)
- Xinfu Guan
- U.S. Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics; and Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, Texas
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15
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Rubino F. From bariatric to metabolic surgery: definition of a new discipline and implications for clinical practice. Curr Atheroscler Rep 2014; 15:369. [PMID: 24194467 DOI: 10.1007/s11883-013-0369-x] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Bariatric surgery indicates a variety of gastrointestinal (GI) surgical procedures originally designed to induce weight reduction in morbidly obese patients. Benefits of bariatric surgery, however, extend well beyond weight loss and include dramatic improvement of type 2 diabetes, hypertension, dyslipidemia, and reduction of overall mortality. Furthermore, studies in rodents and humans show that the anti-diabetes effect of certain bariatric procedures results from a variety of neuroendocrine and metabolic mechanisms secondary to changes in GI anatomy. The recognition that benefits and mechanisms of GI operations are not limited to weight reduction provided a rationale for the emergence of metabolic surgery intended as a surgical approach primarily aimed to the treatment of diabetes and metabolic disease. Consistent with the goals of improving glycemic and metabolic control, in contrast to mere weight loss, metabolic surgery implies the development of a new model of care distinct from traditional bariatric surgery. This paper discusses the definition of metabolic surgery and its clinical practice.
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Abstract
OBJECTIVE This study investigated the practical clinical consequences of offering surgery for metabolic disease and diabetes as opposed to weight loss. BACKGROUND The terms "metabolic" and "diabetes surgery" indicate a surgical approach whose primary intent is the control of metabolic alterations/hyperglycemia in contrast to "bariatric surgery," conceived as a mere weight-reduction therapy. METHODS A "metabolic surgery" program distinct from the "bariatric surgery" program was recently established at a tertiary US academic medical center. The 2 programs differ in their stated goals but offer the same procedures and use identical eligibility criteria for patients with morbid obesity. Demographics, clinical characteristics, and 30-day postoperative morbidity and mortality were assessed from a prospective database of 200 consecutive patients who underwent surgery at these units. RESULTS Metabolic surgery patients were older (45.8±13.4 v 41.8±11.7, P<0.05), had a lower body mass index (42.4±7.1 vs 48.6±9.5 kg/m; P<0.01), and a higher prevalence of being of the male sex (42% vs 26%, P<0.05), having diabetes (62% vs 35%; P<0.01), hypertension (68% vs 52%; P<0.05), dyslipidemia (48% vs 31%; P<0.05), and cardiovascular disease (14% vs 5%; P<0.05). Diabetes was more severe among metabolic surgery patients (higher glycated hemoglobin levels; greater percentage of insulin use). There was no mortality, and there were no differences in perioperative complications. CONCLUSIONS Offering surgery to treat metabolic disease or diabetes rather than as a mere weight-reduction therapy changes demographical and clinical characteristics of surgical candidates. This has important and practical ramifications for clinical care and support consideration of metabolic/diabetes surgery as a novel practice distinct from traditional bariatric surgery.
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Raghow R. Bariatric surgery-mediated weight loss and its metabolic consequences for type-2 diabetes. World J Diabetes 2013; 4:47-50. [PMID: 23772272 PMCID: PMC3680623 DOI: 10.4239/wjd.v4.i3.47] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2013] [Accepted: 04/11/2013] [Indexed: 02/05/2023] Open
Abstract
The worldwide epidemic of obesity and its medical complications are being dealt with a combination of life style changes (e.g., healthier diet and exercise), medications and a variety of surgical interventions. The Roux-en Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) are two of the most common weight loss surgeries for morbid obesity-associated metabolic syndrome and insulin resistance. A vast majority of patients that undergo RYGB and LAGB are known to experience marked weight loss and attenuation of diabetes. A number of recent studies have indicated that the rates of remission in glycemic control and insulin sensitivity are significantly greater in patients that have undergone RYGB. A plausible hypothesis to explain this observation is that the gastric bypass surgery as opposed to the gastric banding procedure impinges on glucose homeostasis by a weight loss-independent mechanism. In a recent paper, Bradley et al have experimentally explored this hypothesis. The authors compared several clinical and laboratory parameters of insulin sensitivity and β-cell function in cohorts of RYGB and LAGB patients before and after they lost approximately 20% of their body mass. After weight loss, both groups of patients underwent similar changes in their intra-abdominal and total adipose tissue volume, hepatic triglyceride and circulating leptin levels. The RYGB patients who lost 20% body mass, manifested higher postprandial output of glucose, insulin and glucagon-like peptide-1; these laboratory parameters remained unchanged in LABG patients. Irrespective of the observed differences in transient responses of RYGB and LAGB patients to mixed meal, the overall glycemic control as judged by glucose tolerance, multi-organ insulin sensitivity and β-cell function were nearly identical in the two groups. Both RYGB and LAGB patient cohorts also experienced similar changes in the expression of a number of pro- and anti-inflammatory markers. Based on these analyses, Bradley et al concluded that similar restoration of insulin sensitivity and b-cell function in non-diabetic obese patients that have undergone RYGB and LAGB were directly due to marked weight loss. These data have important implications for the risk/benefit analysis of weight loss therapy by bariatric procedures.
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Cohen R, Caravatto PP, Petry T. Surgery for Diabetes. CURRENT SURGERY REPORTS 2013. [DOI: 10.1007/s40137-013-0023-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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