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Qanaq D, O'Keeffe M, Cremona S, Bernardo WM, McIntyre RD, Papada E, Benkalkar S, Rubino F. The Role of Dietary Intake in the Weight Loss Outcomes of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy: A Systematic Review and Meta-analysis. Obes Surg 2024; 34:3021-3037. [PMID: 38907132 PMCID: PMC11289176 DOI: 10.1007/s11695-024-07183-8] [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: 05/13/2023] [Revised: 03/15/2024] [Accepted: 03/15/2024] [Indexed: 06/23/2024]
Abstract
The relationship between postoperative dietary intake and weight loss after bariatric surgery remains unclear. We performed a systematic review and meta-analysis of studies published between January 2000 and May 2023, reporting weight loss outcomes, and dietary intake before and after Roux-en-Y gastric bypass and sleeve gastrectomy. A total of 42 studies were included. There was no detectable difference in dietary intake between the two procedures. Roux-en-Y gastric bypass induced an average decrease in energy intake of 886 kcal/day at 12-month post-surgery; however, there was no correlation between daily energy intake and weight loss. These findings show a substantial reduction of energy intake in the first year after bariatric surgery but do not support a link between lower energy intake and greater weight loss.
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Affiliation(s)
- Dalal Qanaq
- School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, James Black Centre, Denmark Hill Campus, 125 Coldharbour Road, London, SE5 9RJ, UK
- College of Applied Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences, 11481, Riyadh, Kingdom of Saudi Arabia
- King Abdullah International Medical Research Centre, 11481, Riyadh, Kingdom of Saudi Arabia
- Department of Nutritional Sciences, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK
| | - Majella O'Keeffe
- Department of Nutritional Sciences, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK
- School of Food and Nutritional Sciences, University College Cork, College Road, Cork, Ireland
| | - Simone Cremona
- School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, James Black Centre, Denmark Hill Campus, 125 Coldharbour Road, London, SE5 9RJ, UK
- General and Digestive Surgery Department of Hospital Del Mar de, 08003, Barcelona, Spain
| | | | - Robert D McIntyre
- School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, James Black Centre, Denmark Hill Campus, 125 Coldharbour Road, London, SE5 9RJ, UK
- School of Sport, Exercise and Applied Science, St Mary's University, Twickenham, London, TW1 4SX, UK
| | - Efstathia Papada
- School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, James Black Centre, Denmark Hill Campus, 125 Coldharbour Road, London, SE5 9RJ, UK
- Division of Medicine, University College London, London, WC1E 6JF, UK
| | - Saumit Benkalkar
- School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, James Black Centre, Denmark Hill Campus, 125 Coldharbour Road, London, SE5 9RJ, UK
| | - Francesco Rubino
- School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, James Black Centre, Denmark Hill Campus, 125 Coldharbour Road, London, SE5 9RJ, UK.
- Bariatric and Metabolic Surgery, King's College Hospital, London, SE5 9RS, UK.
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Monpellier VM, Geurten RJ, Janssen IMC, Ruwaard D, Struijs JN, van Dijk PR, Bilo HJG, Elissen AMJ. Evaluation of Healthcare Utilisation and Expenditures in Persons with Type 2 Diabetes Undergoing Bariatric-Metabolic Surgery. Obes Surg 2024; 34:723-732. [PMID: 38198097 PMCID: PMC10899363 DOI: 10.1007/s11695-023-06849-z] [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: 05/10/2023] [Revised: 09/15/2023] [Accepted: 09/24/2023] [Indexed: 01/11/2024]
Abstract
PURPOSE Changes in healthcare utilisation and expenditures after bariatric-metabolic surgery (BMS) for people with type 2 diabetes mellitus (T2DM) are unclear. We used the Dutch national all-payer claims database (APCD) to evaluate utilisation and expenditures in people with T2DM who underwent BMS. METHODS In this cohort study, patients with T2DM who had BMS in 2016 were identified in the APCD. This group was matched 1:2 to a control group with T2DM who did not undergo BMS based on age, gender and healthcare expenditures. Data on healthcare expenditures and utilisation were collected for 2013-2019. RESULTS In total, 1751 patients were included in the surgery group and 3502 in the control group. After BMS, total median expenditures in the surgery group stabilised (€ 3156 to € 3120) and increased in the control group (€ 3174 to € 3434). Total pharmaceutical expenditures decreased 28% in the surgery group (€957 to €494) and increased 55% in the control group (€605 to €936). In the surgery group, 67.1% did not use medication for T2DM in 2019 compared to 13.3% in the control group. Healthcare use for microvascular complications increased in the control group, but not in the surgery group. CONCLUSION BMS in people with T2DM stabilises healthcare expenditures and decreases medication use and care use for microvascular complications. In contrast, healthcare use and expenditures in T2DM patients who do not undergo surgery gradually increase over time. Due to the progressive nature of T2DM, it is expected that these differences will become larger in the long-term.
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Affiliation(s)
- Valerie M Monpellier
- Nederlandse Obesitas Kliniek (Dutch Obesity Clinic), Huis ter Heide, The Netherlands
| | - Rose J Geurten
- Department of Health Services Research, CAPHRI Care and Public Health Research Institute, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands.
| | - Ignace M C Janssen
- Nederlandse Obesitas Kliniek (Dutch Obesity Clinic), Huis ter Heide, The Netherlands
| | - Dirk Ruwaard
- Department of Health Services Research, CAPHRI Care and Public Health Research Institute, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
| | - Jeroen N Struijs
- Department of Quality of Care and Health Economics, Centre for Nutrition, Prevention and Health Services, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands
- Department Public Health and Primary Care, Leiden University Medical Centre, Campus The Hague, The Hague, The Netherlands
| | - Peter R van Dijk
- Department of Endocrinology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
| | - Henk J G Bilo
- Department of Internal Medicine, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
| | - Arianne M J Elissen
- Department of Health Services Research, CAPHRI Care and Public Health Research Institute, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands
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Kokkorakis M, Katsarou A, Katsiki N, Mantzoros CS. Milestones in the journey towards addressing obesity; Past trials and triumphs, recent breakthroughs, and an exciting future in the era of emerging effective medical therapies and integration of effective medical therapies with metabolic surgery. Metabolism 2023; 148:155689. [PMID: 37689110 DOI: 10.1016/j.metabol.2023.155689] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 08/28/2023] [Accepted: 08/28/2023] [Indexed: 09/11/2023]
Abstract
The 21st century is characterized by an increasing incidence and prevalence of obesity and the burden of its associated comorbidities, especially cardiometabolic diseases, which are reaching pandemic proportions. In the late '90s, the "black box" of adipose tissue and energy homeostasis was opened with the discovery of leptin, transforming the adipose tissue from an "inert fat-storage organ" to the largest human endocrine organ and creating the basis on which more intensified research efforts to elucidate the pathogenesis of obesity and develop novel treatments were based upon. Even though leptin was eventually not proven to be the "standalone magic bullet" for the treatment of common/polygenic obesity, it has been successful in the treatment of monogenic obesity syndromes. Additionally, it shifted the paradigm of treating obesity from a condition due to "lack of willpower" to a disease due to distinct underlying biological mechanisms for which specific pharmacotherapies would be needed in addition to lifestyle modification. Subsequently, the melanocortin pathway proved to be an equally valuable pathway for the pharmacotherapy of obesity. Melanocortin receptor agonists have recently been approved for treating certain types of syndromic obesity. Other molecules- such as incretins, implicated in energy and glucose homeostasis- are secreted by the gastrointestinal tract. Glucagon-like peptide 1 (GLP-1) is the most prominent one, with GLP-1 analogs approved for common/polygenic obesity. Unimolecular combinations with other incretins, e.g., GLP-1 with gastric inhibitory polypeptide and/or glucagon, are expected to be approved soon as more effective pharmacotherapies for obesity and its comorbidities. Unimolecular combinations with other compounds and small molecules activating the receptors of these molecules are currently under investigation as promising future pharmacotherapies. Moreover, metabolic and bariatric surgery has also demonstrated impressive results, especially in the case of morbid obesity. Consequently, this broadening therapeutic armamentarium calls for a well-thought-after and well-coordinated multidisciplinary approach, for instance, through cardiometabolic expertise centers, that would ideally address effectively and cost-effectively obesity and its comorbidities, providing tangible benefits to large segments of the population.
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Affiliation(s)
- Michail Kokkorakis
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Angeliki Katsarou
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Niki Katsiki
- Department of Nutritional Sciences and Dietetics, International Hellenic University, 57400 Thessaloniki, Greece
| | - Christos S Mantzoros
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Section of Endocrinology, VA Boston Healthcare System, Harvard Medical School, Boston, MA 02115, USA.
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Özdemir A, Yozgat A, Işgın-Atıcı K, Avcı E, Yıldız BD, Gündoğdu A, Nalbantoğlu U, Turhan T, Doğruman-Al F, Büyüktuncer Z. Potential associations between alterations in gut microbiome and obesity-related traits after the bariatric surgery. J Hum Nutr Diet 2022; 36:981-996. [PMID: 36082501 DOI: 10.1111/jhn.13087] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 09/01/2022] [Indexed: 11/29/2022]
Abstract
AIM This study aimed to examine the effects of both obesity and bariatric surgery on gut microbiome, dietary intake, as well as metabolic and inflammatory parameters. METHODS All participants (15 with morbid obesity who had bariatric surgery, 8 with morbid obesity and 11 non-obese) were followed-up for a 6-month period with the interviews at baseline (M0), at the end of 3 (M3) and 6 months (M6). Dietary assessment was done, and blood and faecal samples were collected. RESULTS Dietary energy and nutrient intakes as well as serum levels glucose, total cholesterol, LDL-cholesterol, and hs-CRP levels decreased by surgery (p<0.05, for each). Participants with morbid obesity had higher levels of Firmicutes and lower levels of Bacteroidetes at M0 compared to non-obese participants. The abundances of Bacteroidetes increased (p=0.02) while Firmicutes decreased (p>0.05) by the surgery, leading a significant decrease in Firmicutes/Bacteroidetes ratio (p=0.01). At sub-phylum level, the abundances of Lactobacillus and Bifidobacterium decreased while Akkermansia increased by the surgery (p<0.01, for each). Although participants who are morbidly obese had a distinct profile according to ß-diversity indices at M0, it became similar with the profile of non-obese participants (p>0.05) at M3 and M6. Similarly, α-diversity indices were lower in subjects with morbid obesity at M0, but became similar to levels in non-obese controls at M6. CONCLUSION This study confirmed that bariatric surgery has substantial impacts on gut microbiome composition and diversity, as well as anthropometrical measurements and biochemical parameters, which were associated with the alterations in dietary intake patterns. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Aslıhan Özdemir
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Hacettepe University, Ankara, Turkey
| | - Ahmet Yozgat
- Department of Gastroenterology, Ankara Numune Research and Education Hospital, Ankara, Turkey
| | - Kübra Işgın-Atıcı
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Hacettepe University, Ankara, Turkey
| | - Enver Avcı
- Department of Gastroenterology, Ankara Numune Research and Education Hospital, Ankara, Turkey
| | - Barış D Yıldız
- Department of General Surgery, Ankara Numune Research and Education Hospital, Ankara, Turkey
| | - Aycan Gündoğdu
- Department of Microbiology and Clinical Microbiology, School of Medicine, Erciyes University, Kayseri, Turkey.,Genome and Stem Cell, Center, Erciyes University, Kayseri, Turkey.,ENBIOSIS Biotechnology, Istanbul, Turkey
| | - Ufuk Nalbantoğlu
- Genome and Stem Cell, Center, Erciyes University, Kayseri, Turkey.,ENBIOSIS Biotechnology, Istanbul, Turkey.,Department of Computer Engineering, School of Engineering, Erciyes University, Kayseri, Turkey
| | - Turan Turhan
- Department of Biochemistry, Ankara Numune Research and Education Hospital, Ankara, Turkey
| | - Funda Doğruman-Al
- Department of Medical Microbiology, School of Medicine, Gazi University, Ankara, Turkey
| | - Zehra Büyüktuncer
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Hacettepe University, Ankara, Turkey
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Scarano Pereira JP, Owen E, Martinino A, Akmal K, Abouelazayem M, Graham Y, Weiner S, Sakran N, Dekker LR, Parmar C, Pouwels S. Epicardial adipose tissue, obesity and the occurrence of atrial fibrillation: an overview of pathophysiology and treatment methods. Expert Rev Cardiovasc Ther 2022; 20:307-322. [PMID: 35443854 DOI: 10.1080/14779072.2022.2067144] [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] [Indexed: 10/18/2022]
Abstract
INTRODUCTION Obesity is a chronic disease, which has significant health consequences and is a staggering burden to health care systems. Obesity can have harmful effects on the cardiovascular system, including heart failure, hypertension, coronary heart disease, and atrial fibrillation (AF). One of the possible substrates might be epicardial adipose tissue (EAT), which can be the link between AF and obesity. EAT is a fat deposit located between the myocardium and the visceral pericardium. Numerous studies have demonstrated that EAT plays a pivotal role in this relationship regarding atrial fibrillation. AREAS COVERED This review will focus on the role of obesity and the occurrence of atrial fibrillation (AF) and examine the connection between these and epicardial adipose tissue (EAT). The first part of this review will explain the pathophysiology of EAT and its association with the occurrence of AF. Secondly, we will review bariatric and metabolic surgery and its effects on EAT and AF. EXPERT COMMENTARY In this review, the epidemiology, pathophysiology, and treatments methods of AF are explained. Secondly the effects on EAT were elucidated. Due to the complex pathophysiological link between EAT, AF, and obesity, it is still uncertain which treatment strategy is superior.
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Affiliation(s)
| | - Eloise Owen
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
| | | | - Kiran Akmal
- Faculty of Medicine, Brighton and Sussex Medical School, Brighton, United Kingdom
| | - Mohamed Abouelazayem
- Department of Surgery, Royal Free London Hospitals NHS Foundation, London, United Kingdom
| | - Yitka Graham
- Faculty of Health Sciences and Wellbeing, University of Sunderland, Sunderland, United Kingdom.,Facultad de Psucologia, Universidad Anahuac Mexico, Mexico City, Mexico
| | - Sylvia Weiner
- Department of Bariatric and Metabolic Surgery, Krankenhaus Nordwest, Frankfurt am Main, Germany
| | - Nasser Sakran
- Department of Surgery, Holy Family Hospital, Nazareth, Israel.,Azrieli, Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Lukas R Dekker
- Department of Cardiology, Catharina Hospital, Eindhoven, The Netherlands
| | - Chetan Parmar
- Department of Surgery, Whittington Health NHS Trust, London, United Kingdom
| | - Sjaak Pouwels
- Department of Intensive Care Medicine, Elisabeth-Tweesteden Hospital, Tilburg, The Netherlands
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Mou D, Tavakkoli A. Surgical Management of Obesity. NUTRITION, WEIGHT, AND DIGESTIVE HEALTH 2022:257-267. [DOI: 10.1007/978-3-030-94953-2_16] [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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7
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Lo T, Lee Y, Tseng CY, Hu Y, Connelly MA, Mantzoros CS, Karp JM, Tavakkoli A. Daily transient coating of the intestine leads to weight loss and improved glucose tolerance. Metabolism 2022; 126:154917. [PMID: 34687727 PMCID: PMC8666968 DOI: 10.1016/j.metabol.2021.154917] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 10/13/2021] [Accepted: 10/19/2021] [Indexed: 01/03/2023]
Abstract
INTRODUCTION Roux-en-Y gastric bypass surgery (RYGB) has been shown to be the gold standard treatment for obesity associated type-2-diabetes (T2D), however many T2D patients do not qualify or are reluctant to proceed with surgery due to its potential risks and permanent changes to GI anatomy. We have previously described a novel oral formulation, LuCI, that provides a transient coating of the proximal bowel and mimics the effects of RYGB. Herein, we aim to investigate the outcome of chronic LuCI administration on weight and glucose homeostasis. METHODS Sprague-Dawley rats on a high fat diet achieving diet-induced obesity (DIO) received 5 weeks of daily LuCI or normal saline as control (n = 8/group). Daily weights and glucose tolerance were monitored throughout the experiment. At 5 weeks, systemic blood was sampled through a surgically placed jugular vein catheter, before and during an intestinal glucose bolus, to investigate changes in key hormones involved in glucose metabolism. To elucidate the effects of LuCI on nutrient absorption, fecal output and food intake were measured simultaneously with the analysis of homogenized stool samples performed using bomb calorimetry. RESULTS At 5 weeks, LuCI animals weighted 8.3% less and had lower fasting glucose levels than Controls (77.6 ± 3.8 mg/dl vs. 99.1 ± 2.7 mg/dl, P < 0.001). LuCI-treated animals had lower baseline insulin and HOMA-IR. Post-prandially, LuCI group had increased GLP-1 and GIP secretion following a glucose challenge. Serum lipid analysis revealed lowered LDL levels highlighting the potential to not only improve glucose control but also modify cardiovascular risk. We then investigated whether LuCI's effect on proximal bowel exclusion may play a role in energy balance. Bomb calorimetry analysis suggested that LuCI reduced calorie absorption with no difference in caloric consumption. CONCLUSION We demonstrated that LuCI recapitulates the physical and hormonal changes seen after RYGB and can ameliorate weight gain and improve insulin sensitivity in a DIO rat model. Since LuCI's effect is transient and without systemic absorption, LuCI has the potential to be a novel therapy for overweight or obese T2D patients.
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Affiliation(s)
- Tammy Lo
- Laboratory for Surgical and Metabolic Research, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Yuhan Lee
- Department of Anesthesiology, Perioperative, and Pain Medicine, Center for Nanomedicine, Center for Regenerative Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Harvard Stem Cell Institute, Harvard-MIT, Division of Health Sciences and Technology, Boston, MA, USA
| | - Chung-Yi Tseng
- Department of Anesthesiology, Perioperative, and Pain Medicine, Center for Nanomedicine, Center for Regenerative Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Harvard Stem Cell Institute, Harvard-MIT, Division of Health Sciences and Technology, Boston, MA, USA
| | - Yangshuo Hu
- Department of Anesthesiology, Perioperative, and Pain Medicine, Center for Nanomedicine, Center for Regenerative Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Harvard Stem Cell Institute, Harvard-MIT, Division of Health Sciences and Technology, Boston, MA, USA
| | - Margery A Connelly
- Laboratory Corporation of America Holdings (Labcorp), Morrisville, NC, USA
| | - Christos S Mantzoros
- Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA, USA
| | - Jeffrey M Karp
- Department of Anesthesiology, Perioperative, and Pain Medicine, Center for Nanomedicine, Center for Regenerative Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Harvard Stem Cell Institute, Harvard-MIT, Division of Health Sciences and Technology, Boston, MA, USA.
| | - Ali Tavakkoli
- Laboratory for Surgical and Metabolic Research, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Division of General and GI Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
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Reduction of Major Adverse Cardiovascular Events (MACE) after Bariatric Surgery in Patients with Obesity and Cardiovascular Diseases: A Systematic Review and Meta-Analysis. Nutrients 2021; 13:nu13103568. [PMID: 34684569 PMCID: PMC8537443 DOI: 10.3390/nu13103568] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 10/06/2021] [Accepted: 10/10/2021] [Indexed: 12/25/2022] Open
Abstract
Cardiovascular diseases (CVDs) are the leading cause of death worldwide and obesity is a major risk factor that increases the morbidity and mortality of CVDs. Lifestyle modifications (e.g., diet control, physical exercise and behavioral changes) have been the first-line managements of obesity for decades. Nonetheless, when such interventions fail, pharmacotherapies and bariatric surgery are considered. Interestingly, a sudden weight loss (e.g., due to bariatric surgery) could also increase mortality. Thus, it remains unclear whether the bariatric surgery-associated weight reduction in patients with obesity and CVDs is beneficial for the reduction of Major Adverse Cardiovascular Events (MACE). Here, we performed a systematic literature search and meta-analysis of published studies comparing MACE in patients with obesity and CVDs who underwent bariatric surgery with control patients (no surgery). Eleven studies, with a total of 1,772,305 patients, which consisted of 74,042 patients who underwent any form of bariatric surgery and 1,698,263 patients with no surgery, were included in the systematic review. Next, the studies' data, including odds ratio (OR) and adjusted hazard ratio (aHR), were pooled and analyzed in a meta-analysis using a random effect model. The meta-analysis of ten studies showed that the bariatric surgery group had significantly lower odds of MACE as compared to no surgery (OR = 0.49; 95% CI 0.40-0.60; p < 0.00001; I2 = 93%) and the adjustment to confounding variables in nine studies revealed consistent results (aHR = 0.57; 95% CI 0.49-0.66; p < 0.00001; I2 = 73%), suggesting the benefit of bariatric surgery in reducing the occurrence of MACE in patients with obesity and CVDs (PROSPERO ID: CRD42021274343).
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9
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Yang C, Brecht J, Weiß C, Reissfelder C, Otto M, Buchwald JN, Vassilev G. Serum Glucagon, Bile Acids, and FGF-19: Metabolic Behavior Patterns After Roux-en-Y Gastric Bypass and Vertical Sleeve Gastrectomy. Obes Surg 2021; 31:4939-4946. [PMID: 34471996 DOI: 10.1007/s11695-021-05677-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 08/14/2021] [Accepted: 08/19/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Metabolic/bariatric surgery is a highly effective treatment for obesity and metabolic diseases. Serum glucagon, bile acids, and FGF-19 are key effectors of various metabolic processes and may play central roles in bariatric surgical outcomes. It is unclear whether these factors behave similarly after Roux-en-Y gastric bypass (RYGB) vs vertical sleeve gastrectomy (VSG). METHODS Serum glucagon, bile acids (cholic acid [CA], chenodeoxycholic acid [CDCA], deoxycholic acid [DCA]), and FGF-19 were analyzed in samples of fasting blood collected before bariatric surgery, on postoperative days 2 and 10, and at 3- and 6-month follow-up. RESULTS From September 2016 to July 2017, patients with obesity underwent RYGB or VSG; 42 patients (RYGB n = 21; VSG n = 21) were included in the analysis. In the RYGB group, glucagon, CA, and CDCA increased continuously after surgery (p = 0.0003, p = 0.0009, p = 0.0001, respectively); after an initial decrease (p = 0.04), DCA increased significantly (p = 0.0386). Serum FGF-19 was unchanged. In the VSG group, glucagon increased on day 2 (p = 0.0080), but decreased over the 6-month study course (p = 0.0025). Primary BAs (CA and CDCA) decreased immediately after surgery (p = 0.0016, p = 0.0091) and then rose (p = 0.0350, p = 0.0350); DCA followed the curve of the primary BAs until it fell off at 6 months (p = 0.0005). VSG group serum FGF-19 trended upward. CONCLUSION RYGB and VSG involve different surgical techniques and final anatomical configurations. Between postoperative day 2 and 6-month follow-up, RYGB and VSG resulted in divergent patterns of change in serum glucagon, bile acids, and FGF-19.
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Affiliation(s)
- Cui Yang
- Department of Surgery, University Medicine Mannheim, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Julia Brecht
- Department of Surgery, University Medicine Mannheim, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Christel Weiß
- Department of Medical Statistics and Biomathematics, Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany
| | - Christoph Reissfelder
- Department of Surgery, University Medicine Mannheim, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Mirko Otto
- Department of Surgery, University Medicine Mannheim, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Jane N Buchwald
- Division of Scientific Research Writing, Medwrite Medical Communications, Maiden Rock, WI, 54750, USA
| | - Georgi Vassilev
- Department of Surgery, University Medicine Mannheim, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
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10
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Dascalu AM, Stoian AP, Cherecheanu AP, Serban D, Costea DO, Tudosie MS, Stana D, Tanasescu D, Sabau AD, Gangura GA, Costea AC, Nicolae VA, Smarandache CG. Outcomes of Diabetic Retinopathy Post-Bariatric Surgery in Patients with Type 2 Diabetes Mellitus. J Clin Med 2021; 10:jcm10163736. [PMID: 34442032 PMCID: PMC8396947 DOI: 10.3390/jcm10163736] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 08/13/2021] [Accepted: 08/19/2021] [Indexed: 12/23/2022] Open
Abstract
Bariatric surgery is an emerging therapeutic approach for obese type 2 diabetes mellitus (T2DM) patients, with proven benefits for achieving target glucose control and even remission of diabetes. However, the effect of bariatric surgery upon diabetic retinopathy is still a subject of debate as some studies show a positive effect while others raise concerns about potential early worsening effects. We performed a systematic review, on PubMed, Science Direct, and Web of Science databases regarding the onset and progression of diabetic retinopathy in obese T2DM patients who underwent weight-loss surgical procedures. A total of 6375 T2DM patients were analyzed. Most cases remained stable after bariatric surgery (89.6%). New onset of diabetic retinopathy (DR) was documented in 290 out of 5972 patients (4.8%). In cases with DR at baseline, progression was documented in 50 out of 403 (12.4%) and regression in 90 (22.3%). Preoperative careful preparation of hemoglobin A1c (HbA1c), blood pressure, and lipidemia should be provided to minimize the expectation of DR worsening. Ophthalmologic follow-up should be continued regularly in the postoperative period even in the case of diabetic remission. Further randomized trials are needed to better understand the organ-specific risk factors for progression and provide personalized counseling for T2DM patients planned for bariatric surgery.
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Affiliation(s)
- Ana Maria Dascalu
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy Bucharest, 020021 Bucharest, Romania; (A.M.D.); (A.P.C.); (M.S.T.); (G.A.G.); (V.A.N.); (C.G.S.)
- Department of Ophthalmology, Emergency University Hospital Bucharest, 050098 Bucharest, Romania;
| | - Anca Pantea Stoian
- Department of Diabetes, Nutrition and Metabolic Diseases, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania;
| | - Alina Popa Cherecheanu
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy Bucharest, 020021 Bucharest, Romania; (A.M.D.); (A.P.C.); (M.S.T.); (G.A.G.); (V.A.N.); (C.G.S.)
- Department of Ophthalmology, Emergency University Hospital Bucharest, 050098 Bucharest, Romania;
| | - Dragos Serban
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy Bucharest, 020021 Bucharest, Romania; (A.M.D.); (A.P.C.); (M.S.T.); (G.A.G.); (V.A.N.); (C.G.S.)
- Fourth Department of General Surgery, Emergency University Hospital Bucharest, 050098 Bucharest, Romania
- Correspondence:
| | - Daniel Ovidiu Costea
- Faculty of Medicine, Ovidius University, 900470 Constanta, Romania;
- First Surgery Department, Emergency County Hospital, 900591 Constanta, Romania
| | - Mihail Silviu Tudosie
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy Bucharest, 020021 Bucharest, Romania; (A.M.D.); (A.P.C.); (M.S.T.); (G.A.G.); (V.A.N.); (C.G.S.)
- ICU II Toxicology, Clinical Emergency Hospital, 014461 Bucharest, Romania
| | - Daniela Stana
- Department of Ophthalmology, Emergency University Hospital Bucharest, 050098 Bucharest, Romania;
| | - Denisa Tanasescu
- Fourth Department of Dental Medicine and Nursing, Faculty of Medicine, “Lucian Blaga” University, 550169 Sibiu, Romania;
| | - Alexandru Dan Sabau
- 3rd Clinical Department, Faculty of Medicine, “Lucian Blaga” University Sibiu, 550024 Sibiu, Romania;
| | - Gabriel Andrei Gangura
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy Bucharest, 020021 Bucharest, Romania; (A.M.D.); (A.P.C.); (M.S.T.); (G.A.G.); (V.A.N.); (C.G.S.)
- Second Department of General Surgery, Emergency University Hospital Bucharest, 050098 Bucharest, Romania
| | | | - Vanessa Andrada Nicolae
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy Bucharest, 020021 Bucharest, Romania; (A.M.D.); (A.P.C.); (M.S.T.); (G.A.G.); (V.A.N.); (C.G.S.)
- Department of Ophthalmology, Emergency University Hospital Bucharest, 050098 Bucharest, Romania;
| | - Catalin Gabriel Smarandache
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy Bucharest, 020021 Bucharest, Romania; (A.M.D.); (A.P.C.); (M.S.T.); (G.A.G.); (V.A.N.); (C.G.S.)
- Fourth Department of General Surgery, Emergency University Hospital Bucharest, 050098 Bucharest, Romania
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11
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Salman AA, Salman MA, Marie MA, Rabiee A, Helmy MY, Tourky MS, Qassem MG, Shaaban HED, Sarhan MD. Factors associated with resolution of type-2 diabetes mellitus after sleeve gastrectomy in obese adults. Sci Rep 2021; 11:6002. [PMID: 33727637 PMCID: PMC7966796 DOI: 10.1038/s41598-021-85450-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 03/01/2021] [Indexed: 02/06/2023] Open
Abstract
Many bariatric procedures are more effective for improving type-2 diabetes mellitus (T2DM) than conventional pharmacotherapy. The current research evaluated factors linked to complete and partial remission or improvement of T2DM after laparoscopic sleeve gastrectomy (LSG). The current prospective study included all diabetic patients who were submitted LSG between January 2015 and June 2018 and completed a 2-year follow-up period. Patients were assessed at baseline and 2 years after LSG. This work comprised of 226 diabetic cases. Two years after LSG, 86 patients (38.1%) achieved complete remission of DM, and 24 (10.6%) reached partial remission. Only 14 patients (6.2%) showed no change in their diabetic status. On univariate analysis, age ≤ 45 years, duration of diabetes ≤ 5 years, use of a single oral antidiabetic, HbA1c ≤ 6.5%, HOMA-IR ≤ 4.6, C-peptide > 2.72 ng/mL, and BMI ≤ 40 kg/m2 predicted complete remission. The independent predictors of complete remission were age ≤ 45 years, duration of diabetes ≤ 5 years, use of a single oral antidiabetic, HOMA-IR ≤ 4.6, and C-peptide > 2.72 ng/mL. A combined marker of young age, short duration of DM, and low HOMA-IR predicted complete remission with sensitivity 93% and specificity 82%. Independent predictors of complete remission of T2DM after LSG were younger age, shorter duration, single oral antidiabetic, lower HOMA-IR, and higher C-peptide.
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Affiliation(s)
| | | | - Mohamed A Marie
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Rabiee
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mona Youssry Helmy
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Sabry Tourky
- Department of Surgery, Great Western Hospitals NHS Foundation Trust, Swindon, UK
| | - Mohamed Gamal Qassem
- Department of General Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Hossam El-Din Shaaban
- Gastroenterology Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Mohamed D Sarhan
- General Surgery Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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12
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Ahlin S, Cefalo C, Bondia-Pons I, Trošt K, Capristo E, Marini L, Romero M, Zorzano A, Gastaldelli A, Mingrone G, Nolan JJ. Metabolite Changes After Metabolic Surgery - Associations to Parameters Reflecting Glucose Homeostasis and Lipid Levels. Front Endocrinol (Lausanne) 2021; 12:786952. [PMID: 34975758 PMCID: PMC8716486 DOI: 10.3389/fendo.2021.786952] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 11/16/2021] [Indexed: 12/25/2022] Open
Abstract
AIMS To test the hypothesis that adipose tissue gene expression patterns would be affected by metabolic surgery and we aimed to identify genes and metabolic pathways as well as metabolites correlating with metabolic changes following metabolic surgery. MATERIALS AND METHODS This observational study was conducted at the Obesity Unit at the Catholic University Hospital of the Sacred Heart in Rome, Italy. Fifteen patients, of which six patients underwent Roux-en-Y gastric bypass and nine patients underwent biliopancreatic diversion, were included. The participants underwent an oral glucose tolerance test and a hyperinsulinemic euglycemic clamp. Small polar metabolites were analyzed with a two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC-TOFMS). Gene expression analysis of genes related to metabolism of amino acids and fatty acids were analyzed in subcutaneous adipose tissue. All procedures were performed at study start and at follow-up (after 185.3 ± 72.9 days). RESULTS Twelve metabolites were significantly changed after metabolic surgery. Six metabolites were identified as 3-indoleacetic acid, 2-hydroxybutyric acid, valine, glutamic acid, 4-hydroxybenzeneacetic acid and alpha-tocopherol. The branched chain amino acids displayed a significant decrease together with a decrease in BCAT1 adipose tissue mRNA levels. Changes in the identified metabolites were associated to changes in lipid, insulin and glucose levels. CONCLUSIONS Our study has identified metabolites and metabolic pathways that are altered by metabolic surgery and may be used as biomarkers for metabolic improvement.
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Affiliation(s)
- Sofie Ahlin
- Department of Molecular and Clinical Medicine, Institute of Medicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden
- Department of Medical and Surgery Sciences, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
- *Correspondence: Sofie Ahlin,
| | - Consuelo Cefalo
- Department of Medical and Surgery Sciences, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
| | | | - Kajetan Trošt
- Research Department, Steno Diabetes Center, Gentofte, Denmark
| | - Esmeralda Capristo
- Department of Medical and Surgery Sciences, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
| | - Luca Marini
- Department of Medical and Surgery Sciences, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
| | - Montserrat Romero
- Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain
- Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
- CIBERDEM, Centro de Investigación Biomédica en Red (CIBER) de Diabetes y Enfermedades Metabólicas Asociadas, Barcelona, Instituto de Salud Carlos III, Barcelona, Spain
| | - Antonio Zorzano
- Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain
- Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain
- CIBERDEM, Centro de Investigación Biomédica en Red (CIBER) de Diabetes y Enfermedades Metabólicas Asociadas, Barcelona, Instituto de Salud Carlos III, Barcelona, Spain
| | - Amalia Gastaldelli
- Cardiometabolic Risk Laboratory, Institute of Clinical Physiology, Consiglio Nazionale delle Ricerche (CNR), Pisa, Italy
| | - Geltrude Mingrone
- Department of Medical and Surgery Sciences, Fondazione Policlinico Universitario A. Gemelli Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy
- Department of Diabetes & Nutritional Sciences, Faculty of Life Sciences & Medicine, King’s College, London, United Kingdom
| | - John J. Nolan
- Research Department, Steno Diabetes Center, Gentofte, Denmark
- Department of Clinical Medicine, Trinity College, Dublin, Ireland
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13
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Potential associations between alterations in gut microbiome and obesity-related traits after the bariatric surgery. Proc Nutr Soc 2021. [DOI: 10.1017/s0029665121000744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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14
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Shenoy SS, Gilliam A, Mehanna A, Kanakala V, Bussa G, Gill T, Sanderson K, Viswanath YKS, Shanmugam V. Laparoscopic Sleeve Gastrectomy Versus Laparoscopic Roux-en-Y Gastric Bypass in Elderly Bariatric Patients: Safety and Efficacy-a Systematic Review and Meta-analysis. Obes Surg 2020; 30:4467-4473. [PMID: 32594469 DOI: 10.1007/s11695-020-04819-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
INTRODUCTION Obesity is a chronic disease due to excess fat storage, a genetic predisposition, and environmental contribution where surgery offers a viable treatment option. The surgical treatment of obesity in the elderly population (> 55 years) remains controversial. PURPOSE To evaluate the safety and efficacy of laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) in elderly bariatric patients. MATERIALS AND METHODS Data was sourced from MEDLINE, EMBASE, CINAHL, PubMed, and Cochrane databases for peer-reviewed, randomized controlled trials, and observational studies in the English language were searched from the year 1991 until 2019. From the extracted data, early and late procedural complications and mortality were used as safety outcomes. Weight loss was the primary outcome for effectiveness while the resolution of obesity-related comorbidities was included as secondary outcomes. The Review Manager (Rev Man 5.3)™ software was used for statistical analysis. RESULTS Of the forty-one screened studies, nine studies were included in the final analysis. There was no difference between LSG and LRYGB regarding early complications and mortality 3.6% versus 5.8% (p = 0.15) and 0.1% versus 0.8% (p = 0.27). Patients who underwent LRYGB had more late complications compared with those who underwent LSG (0.07% and 0.03%, p = 0.001). There was no difference in terms of weight loss at the end of 1 year. Patients who underwent LRYGB had a better resolution of obesity-related comorbidities, not statistically significant. CONCLUSION LRYGB has better efficacy when compared with LSG. However, high-risk elderly patients should be considered for LSG given the lesser morbidity and comparable efficacy with LRYGB.
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Affiliation(s)
- Sachin S Shenoy
- Department of Surgery, County Durham and Darlington NHS Foundation Trust, Darlington, UK
| | - Andrew Gilliam
- County Durham and Darlington NHS Foundation Trust, Darlington, UK
| | - Ahmed Mehanna
- Department of Surgery, James Cook University Hospital, Middlesbrough, UK
| | - Venkatesh Kanakala
- James Cook University Hospital, South Tees Hospital NHS Foundation Trust, Middlesbrough, UK
| | - Gopinath Bussa
- North Tees and Hartlepool NHS Foundation Trust, Stockton on Tees, UK
| | - Talvinder Gill
- North Tees and Hartlepool NHS Foundation Trust, Stockton on Tees, UK
| | - Katherine Sanderson
- SHSC Women and Children's Health/Public Health, Teesside University, Middlesbrough, UK
| | - Y K S Viswanath
- James Cook University Hospital, South Tees Hospital NHS Foundation Trust, Middlesbrough, UK.
- Endoscopy Suites, James Cook University Hospital, Middlesbrough, Cleveland, TS43BW, UK.
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15
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Chong CYL, Orr D, Plank LD, Vatanen T, O’Sullivan JM, Murphy R. Randomised Double-Blind Placebo-Controlled Trial of Inulin with Metronidazole in Non-Alcoholic Fatty Liver Disease (NAFLD). Nutrients 2020; 12:nu12040937. [PMID: 32230987 PMCID: PMC7230525 DOI: 10.3390/nu12040937] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 03/19/2020] [Accepted: 03/24/2020] [Indexed: 12/17/2022] Open
Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) can be ameliorated by weight loss although difficult to maintain. Emerging evidence indicates that prebiotics and antibiotics improve NAFLD. Aim: To determine whether inulin supplementation after brief metronidazole therapy is effective in reducing alanine aminotransferase (ALT) and maintaining weight loss achieved through a very-low-calorie diet (VLCD) among people with NAFLD. Methods: Sixty-two people with NAFLD commenced 4-week VLCD using Optifast meal replacements (600 kcal/day). Sixty were then randomised into a 12-week double-blind, placebo-controlled, parallel three-arm trial: (1) 400 mg metronidazole twice daily in Week 1 then inulin 4 g twice daily OR (2) placebo twice daily in week one then inulin OR (3) placebo-placebo. Main outcomes were ALT and body weight at 12 weeks. Fecal microbiota changes were also evaluated. Results: Mean body mass index (BMI) and ALT reduced after VLCD by 2.4 kg/m2 and 11 U/L, respectively. ALT further decreased after metronidazole-inulin compared to after placebo-placebo (mean ALT change -19.6 vs. -0.2 U/L, respectively; p = 0.026); however, weight loss maintenance did not differ. VLCD treatment decreased the ratio of Firmicutes/Bacteroidetes (p = 0.002). Conclusion: Brief metronidazole followed by inulin supplementation can reduce ALT beyond that achieved after VLCD in patients with NAFLD.
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Affiliation(s)
- Clara Yieh Lin Chong
- Liggins Institute, The University of Auckland, Auckland 1142, New Zealand; (C.Y.L.C.); (T.V.); (J.M.O.)
| | - David Orr
- New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland 1023, New Zealand
- Correspondence: (D.O.); (R.M.); Tel.: +64-9-923-6313
| | - Lindsay D. Plank
- Department of Surgery, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1142, New Zealand;
| | - Tommi Vatanen
- Liggins Institute, The University of Auckland, Auckland 1142, New Zealand; (C.Y.L.C.); (T.V.); (J.M.O.)
| | - Justin M. O’Sullivan
- Liggins Institute, The University of Auckland, Auckland 1142, New Zealand; (C.Y.L.C.); (T.V.); (J.M.O.)
| | - Rinki Murphy
- Department of Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1142, New Zealand
- Correspondence: (D.O.); (R.M.); Tel.: +64-9-923-6313
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16
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Civi Karaaslan T, Leblebici G, Ucgul MS, Yilmaz M, Kalayci MG, Kuran Aslan G. Exercise Program in Patients After Bariatric Surgery: A Systematic Review. Bariatr Surg Pract Patient Care 2020. [DOI: 10.1089/bari.2019.0048] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Affiliation(s)
- Tugba Civi Karaaslan
- Division of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Gokce Leblebici
- Division of Physiotherapy and Rehabilitation, Istanbul Medeniyet University, Istanbul, Turkey
- Department of Physiotherapy and Rehabilitation, Postgraduate Education Institute, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Merve Suay Ucgul
- Department of Physiotherapy and Rehabilitation, Postgraduate Education Institute, Istanbul University-Cerrahpasa, Istanbul, Turkey
- Health Directorate of Iskenderun, Physical Activity Consulting Department, Hatay, Turkey
| | - Mustafa Yilmaz
- Department of Physiotherapy and Rehabilitation, Postgraduate Education Institute, Istanbul University-Cerrahpasa, Istanbul, Turkey
- Sisli Kolan International Hospital, Orthopedics and Traumatology, Istanbul, Turkey
| | - Melike Gizem Kalayci
- Department of Physiotherapy and Rehabilitation, Postgraduate Education Institute, Istanbul University-Cerrahpasa, Istanbul, Turkey
- Physiotherapy Program, Avrupa Vocational School, Istanbul, Turkey
| | - Goksen Kuran Aslan
- Division of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Istanbul University-Cerrahpasa, Istanbul, Turkey
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17
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Boutari C, Bouzoni E, Joshi A, Stefanakis K, Farr OM, Mantzoros CS. Metabolism updates: new directions, techniques, and exciting research that is broadening the horizons. Metabolism 2020; 102:154009. [PMID: 31715175 DOI: 10.1016/j.metabol.2019.154009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Accepted: 10/15/2019] [Indexed: 12/19/2022]
Affiliation(s)
- Chrysoula Boutari
- Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
| | - Eirini Bouzoni
- Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Aditya Joshi
- Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Konstantinos Stefanakis
- Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Olivia M Farr
- Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Christos S Mantzoros
- Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, Boston, MA 02130, USA.
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18
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Ying LD, Breuer GA, Hubbard MO, Nadzam GS, Hwa J, Martin KA. Technical Feasibility of a Murine Model of Sleeve Gastrectomy with Ileal Transposition. Obes Surg 2019; 29:593-600. [PMID: 30353248 DOI: 10.1007/s11695-018-3555-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Sleeve gastrectomy with ileal transposition has been shown to be superior to sleeve gastrectomy alone for promoting weight loss in rat and porcine models. The absence of a mouse model for this procedure has impeded efforts to understand the molecular physiology underlying its efficacy. This study demonstrates the long-term survivability of sleeve gastrectomy with ileal transposition in mice. MATERIALS AND METHODS In this study of technical feasibility, a sleeve gastrectomy with ileal transposition (SGIT), sleeve gastrectomy (SG), or sham surgery (SH) was performed on 7- to 8-week-old C57Bl/6J mice (n = 8 for each). To evaluate long-term survivability, mice were placed on an obesogenic diet and weighed weekly for 10 weeks. The intestinal identity of the transposed segment was assessed with gene expression analysis of duodenal-, jejunal-, and ileal-specific hormones using quantitative polymerase chain reaction. RESULTS Overall, SGIT better prevented weight gain than the SG or sham procedures (10-week post-operative weight: SH 45.3 ± 1.0 g, SG 41.25 ± 1.6 g, SGIT 35.4 ± 0.8 g). Gene expression pattern analysis of three markers of intestinal identity (gastrin, cholecystokinin, and peptide YY) suggests that the ileal identity of the transposed segment is maintained 10 weeks after transposition. CONCLUSIONS We demonstrate for the first time a reproducible mouse model of sleeve gastrectomy with ileal transposition. Future studies utilizing this model will expand our understanding of the molecular pathways through which the hindgut regulates satiety.
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Affiliation(s)
- Lee D Ying
- Yale University School of Medicine, New Haven, CT, 06511, USA.,Yale Cardiovascular Research Center, 300 George St, Room 759, New Haven, CT, 06511, USA
| | | | - Matthew O Hubbard
- Yale University School of Medicine, New Haven, CT, 06511, USA.,Department of Gastrointestinal Surgery, Yale New Haven Health, New Haven, CT, 06511, USA
| | - Geoffrey S Nadzam
- Yale University School of Medicine, New Haven, CT, 06511, USA.,Department of Gastrointestinal Surgery, Yale New Haven Health, New Haven, CT, 06511, USA
| | - John Hwa
- Yale University School of Medicine, New Haven, CT, 06511, USA.,Yale Cardiovascular Research Center, 300 George St, Room 759, New Haven, CT, 06511, USA
| | - Kathleen A Martin
- Yale University School of Medicine, New Haven, CT, 06511, USA. .,Yale Cardiovascular Research Center, 300 George St, Room 759, New Haven, CT, 06511, USA.
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19
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Hastuti AAMB, Costas-Rodríguez M, Anoshkina Y, Parnall T, Madura JA, Vanhaecke F. High-precision isotopic analysis of serum and whole blood Cu, Fe and Zn to assess possible homeostasis alterations due to bariatric surgery. Anal Bioanal Chem 2019; 412:727-738. [PMID: 31836925 DOI: 10.1007/s00216-019-02291-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Revised: 11/02/2019] [Accepted: 11/18/2019] [Indexed: 12/13/2022]
Abstract
Bariatric surgery is an effective procedure to achieve weight loss in obese patients. However, homeostasis of essential metals may be disrupted as the main absorption site is bypassed. In this study, we determined Cu, Fe and Zn isotopic compositions in paired serum and whole blood samples of patients who underwent Roux-en-Y gastric bypass (RYGB) surgery for evaluation of longitudinal changes and their potential relation to mineral element concentrations and relevant clinical parameters used for monitoring the patient's condition. Samples from eight patients were collected pre-surgery and at 3, 6 and 12 months post-surgery. Multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) was used for high-precision isotope ratio measurements. Alterations in metal homeostasis related to bariatric surgery were reflected in the serum and whole blood Cu, Fe and Zn isotopic compositions. The serum and whole blood Cu became isotopically lighter (lower δ65Cu values) after bariatric surgery, reaching statistical significance at 6 months post-surgery (p < 0.05). The difference between the serum and the whole blood Zn isotopic composition increased after surgery, reaching significance from 6 months post-surgery onwards (p < 0.05). Those changes in Cu, Fe and Zn isotopic compositions were not accompanied by similar changes in their respective concentrations, making isotopic analysis more sensitive to physiological changes than elemental content. Furthermore, the Zn isotopic composition correlates with blood glycaemic and lipid parameters, while the Fe isotopic composition correlates with glycaemic parameters. Graphical Abstract.
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Affiliation(s)
- Agustina A M B Hastuti
- Department of Chemistry, Atomic & Mass Spectrometry-A&MS Research Unit, Ghent University, Campus Sterre, Krijgslaan 281 - S12, 9000, Ghent, Belgium
| | - Marta Costas-Rodríguez
- Department of Chemistry, Atomic & Mass Spectrometry-A&MS Research Unit, Ghent University, Campus Sterre, Krijgslaan 281 - S12, 9000, Ghent, Belgium
| | - Yulia Anoshkina
- Department of Chemistry, Atomic & Mass Spectrometry-A&MS Research Unit, Ghent University, Campus Sterre, Krijgslaan 281 - S12, 9000, Ghent, Belgium
| | - Taylor Parnall
- Department of General Surgery, Mayo Clinic, 5779 E Mayo Blvd, Phoenix, AZ, 85054, USA
| | - James A Madura
- Department of General Surgery, Mayo Clinic, 5779 E Mayo Blvd, Phoenix, AZ, 85054, USA
| | - Frank Vanhaecke
- Department of Chemistry, Atomic & Mass Spectrometry-A&MS Research Unit, Ghent University, Campus Sterre, Krijgslaan 281 - S12, 9000, Ghent, Belgium.
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20
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Lo T, Tavakkoli A. Bariatric surgery and its role in obesity pandemic. CURRENT OPINION IN PHYSIOLOGY 2019. [DOI: 10.1016/j.cophys.2019.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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21
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More than an Anti-diabetic Bariatric Surgery, Metabolic Surgery Alleviates Systemic and Local Inflammation in Obesity. Obes Surg 2019; 28:3658-3668. [PMID: 30187424 DOI: 10.1007/s11695-018-3400-z] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Obesity, associated with increased risk of type 2 diabetes (T2D), cardiovascular disease, and hepatic steatosis et al., has become a major global health problem. Recently, obesity has been proven to be under a status of low-grade, chronic inflammation, which contributes to insulin resistance and T2D. Bariatric surgery is currently an effective treatment for the control of morbid obesity and T2D, which impels ongoing efforts to clarify physiological and molecular mechanisms mediating these benefits. The correlation between obesity, inflammation, and T2D has been revealed to a certain extent, and studies have shed light on the effect of bariatric surgery on inflammatory status of subjects with obesity. Based on recent findings, this review focuses on the relationship between inflammation, obesity, and bariatric surgery.
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22
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Maric T, Kanu C, Johnson MR, Savvidou MD. Maternal, neonatal insulin resistance and neonatal anthropometrics in pregnancies following bariatric surgery. Metabolism 2019; 97:25-31. [PMID: 30959039 DOI: 10.1016/j.metabol.2019.04.005] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Revised: 03/10/2019] [Accepted: 04/03/2019] [Indexed: 01/18/2023]
Abstract
OBJECTIVE An increasing number of women present pregnant having undergone bariatric surgery, a popular treatment for sustainable weight loss. The aim of the study was to investigate the effect, if any, of bariatric surgery on maternal and neonatal insulin resistance (IR) and neonatal body fat composition. METHODS Maternal IR, at 28 weeks of gestation during 2-hour 75 g oral glucose tolerance test (OGTT), neonatal IR, from umbilical cord venous blood, and neonatal birthweight and body fat composition (calculated by measuring skin folds) at birth were evaluated in 41 post-bariatric and 82 pregnant women with similar early pregnancy body mass index but no history of such surgery. Insulin resistance was assessed using the homeostasis model assessment of IR (HOMA-IR). RESULTS In the post-bariatric surgery group, compared to the no surgery group, maternal HOMA-IR (1.15 [1.04-2.07] vs 2.20 [1.53-3.38]; p < 0.01), neonatal birthweight (p < 0.01) and body fat (p < 0.01) were significantly lower whereas neonatal cord HOMA-IR was similar (1.29 [0.65-2.39] vs 1.19 [0.46-1.93]; p = 0.49). In the no surgery group, there was a positive correlation between maternal and neonatal HOMA-IR (p = 0.03) and between neonatal HOMA-IR and body fat (p < 0.01). However, no such significant correlations were detected in the post-bariatric surgery group. CONCLUSION Pregnancy following bariatric surgery is associated with a reduction in maternal IR and altered neonatal body composition with significantly lower birthweight and adiposity but no improvement in cord IR.
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Affiliation(s)
- Tanya Maric
- Fetal Medicine Unit, Academic Department of Obstetrics and Gynaecology, Institute of Reproductive and Developmental Biology, Chelsea and Westminster Hospital, Imperial College London, London, UK; Academic Department of Obstetrics and Gynaecology, Institute of Reproductive and Developmental Biology, Chelsea and Westminster Hospital, Imperial College London, London, UK.
| | - Chidimma Kanu
- Fetal Medicine Unit, Academic Department of Obstetrics and Gynaecology, Institute of Reproductive and Developmental Biology, Chelsea and Westminster Hospital, Imperial College London, London, UK; Academic Department of Obstetrics and Gynaecology, Institute of Reproductive and Developmental Biology, Chelsea and Westminster Hospital, Imperial College London, London, UK.
| | - Mark R Johnson
- Academic Department of Obstetrics and Gynaecology, Institute of Reproductive and Developmental Biology, Chelsea and Westminster Hospital, Imperial College London, London, UK.
| | - Makrina D Savvidou
- Fetal Medicine Unit, Academic Department of Obstetrics and Gynaecology, Institute of Reproductive and Developmental Biology, Chelsea and Westminster Hospital, Imperial College London, London, UK; Academic Department of Obstetrics and Gynaecology, Institute of Reproductive and Developmental Biology, Chelsea and Westminster Hospital, Imperial College London, London, UK.
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Athinarayanan SJ, Adams RN, Hallberg SJ, McKenzie AL, Bhanpuri NH, Campbell WW, Volek JS, Phinney SD, McCarter JP. Long-Term Effects of a Novel Continuous Remote Care Intervention Including Nutritional Ketosis for the Management of Type 2 Diabetes: A 2-Year Non-randomized Clinical Trial. Front Endocrinol (Lausanne) 2019; 10:348. [PMID: 31231311 PMCID: PMC6561315 DOI: 10.3389/fendo.2019.00348] [Citation(s) in RCA: 184] [Impact Index Per Article: 30.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Accepted: 05/14/2019] [Indexed: 02/06/2023] Open
Abstract
Purpose: Studies on long-term sustainability of low-carbohydrate approaches to treat diabetes are limited. We previously reported the effectiveness of a novel digitally-monitored continuous care intervention (CCI) including nutritional ketosis in improving weight, glycemic outcomes, lipid, and liver marker changes at 1 year. Here, we assess the effects of the CCI at 2 years. Materials and methods: An open label, non-randomized, controlled study with 262 and 87 participants with T2D were enrolled in the CCI and usual care (UC) groups, respectively. Primary outcomes were retention, glycemic control, and weight changes at 2 years. Secondary outcomes included changes in body composition, liver, cardiovascular, kidney, thyroid and inflammatory markers, diabetes medication use and disease status. Results: Reductions from baseline to 2 years in the CCI group resulting from intent-to-treat analyses included: HbA1c, fasting glucose, fasting insulin, weight, systolic blood pressure, diastolic blood pressure, triglycerides, and liver alanine transaminase, and HDL-C increased. Spine bone mineral density in the CCI group was unchanged. Use of any glycemic control medication (excluding metformin) among CCI participants declined (from 55.7 to 26.8%) including insulin (-62%) and sulfonylureas (-100%). The UC group had no changes in these parameters (except uric acid and anion gap) or diabetes medication use. There was also resolution of diabetes (reversal, 53.5%; remission, 17.6%) in the CCI group but not in UC. All the reported improvements had p < 0.00012. Conclusion: The CCI group sustained long-term beneficial effects on multiple clinical markers of diabetes and cardiometabolic health at 2 years while utilizing less medication. The intervention was also effective in the resolution of diabetes and visceral obesity with no adverse effect on bone health. Clinical Trial Registration: Clinicaltrials.gov NCT02519309.
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Affiliation(s)
| | | | - Sarah J. Hallberg
- Virta Health Corp, San Francisco, CA, United States
- Indiana University Health Arnett, Lafayette, IN, United States
| | | | | | - Wayne W. Campbell
- Department of Nutrition Science, Purdue University, West Lafayette, IN, United States
| | - Jeff S. Volek
- Virta Health Corp, San Francisco, CA, United States
- Department of Human Sciences, The Ohio State University, Columbus, OH, United States
| | | | - James P. McCarter
- Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States
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Halpern B, Mancini MC. Metabolic surgery for the treatment of type 2 diabetes in patients with BMI lower than 35 kg/m 2 : Why caution is still needed. Obes Rev 2019; 20:633-647. [PMID: 30821085 DOI: 10.1111/obr.12837] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 12/17/2018] [Accepted: 12/21/2018] [Indexed: 12/13/2022]
Abstract
Bariatric surgery has shifted from being a risky procedure to an evidence-based one, with proven benefits on all-cause mortality, cardiovascular disease, cancer, and diabetes control. The procedure has an overall positive result on type 2 diabetes mellitus (T2DM), with a substantial number of patients achieving disease remission. This has resulted in several studies assessing possible weight-independent effects of bariatric surgery on glycemic improvement, in addition to recommendation of the procedure to patients with class 1 obesity and T2DM, for whom the procedure was classically not indicated, and adoption of a new term, "metabolic surgery," to highlight the overall metabolic benefit of the procedure beyond weight loss. Recently, the Diabetes Surgery Summit (DSS) has included metabolic surgery in its T2DM treatment algorithm. Although the discussion brought by this consensus is highly relevant, the recommendation of metabolic surgery for patients with uncontrolled T2DM and a body mass index of 30 to 35 kg/m2 still lacks enough evidence. This article provides an overall view of the metabolic benefits of bariatric/metabolic surgery in patients with class 1 obesity, compares the procedure against clinical treatment, and presents our rationale for defending caution on recommending the procedure to less obese individuals.
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Affiliation(s)
- Bruno Halpern
- Obesity Group, Department of Endocrinology and Metabolism, Clinics Hospital, University of São Paulo Medical School, São Paulo, Brazil
| | - Marcio Correa Mancini
- Obesity Group, Department of Endocrinology and Metabolism, Clinics Hospital, University of São Paulo Medical School, São Paulo, Brazil
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Laursen TL, Hagemann CA, Wei C, Kazankov K, Thomsen KL, Knop FK, Grønbæk H. Bariatric surgery in patients with non-alcoholic fatty liver disease - from pathophysiology to clinical effects. World J Hepatol 2019; 11:138-149. [PMID: 30820265 PMCID: PMC6393715 DOI: 10.4254/wjh.v11.i2.138] [Citation(s) in RCA: 118] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Revised: 11/01/2018] [Accepted: 12/05/2018] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a significant liver disease, and it covers the disease spectrum from simple steatosis with a risk of development of non-alcoholic steatohepatitis (NASH) to fibrosis, subsequent cirrhosis, end-stage liver failure, and liver cancer with a potential need for liver transplantation. NAFLD and NASH are closely related to obesity, metabolic syndrome, and type 2 diabetes (T2D). The role of gut hormones, especially glucagon-like peptide 1 (GLP-1), is important in NAFLD. Bariatric surgery has the potential for inducing great weight loss and may improve the symptoms of metabolic syndrome and T2D. Recent data demonstrated significant effects of bariatric surgery on GLP-1 and other gut hormones and important lipid metabolic and inflammatory abnormalities in the pathophysiology of NAFLD. Therefore, bariatric surgery may reverse the pathological liver changes in NAFLD and NASH patients. In the present review, we describe NAFLD and NASH pathophysiology and the primary effects of bariatric surgery on metabolic pathways. We performed a systematic review of the beneficial and harmful effects and focused on changes in liver disease severity in NAFLD and NASH patients. The specific focus was liver histopathology as assessed by the invasive liver biopsy. Additionally, we reviewed several non-invasive methods used for the assessment of liver disease severity following bariatric surgery.
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Affiliation(s)
- Tea L Laursen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
| | - Christoffer A Hagemann
- Gubra ApS, Hørsholm 2970, Denmark
- Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte Hospital, Hellerup 2900, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark
| | - Chunshan Wei
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
- Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen 518033, China
| | - Konstantin Kazankov
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
| | - Karen L Thomsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
| | - Filip K Knop
- Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte Hospital, Hellerup 2900, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark
| | - Henning Grønbæk
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus N DK-8200, Denmark
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Burgansky-Eliash Z, Achiron A, Hecht I, Shimonov M. Reduction of intraocular pressure after bariatric surgery. Acta Ophthalmol 2018; 96:e592-e595. [PMID: 29488346 DOI: 10.1111/aos.13722] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2017] [Accepted: 01/15/2018] [Indexed: 11/26/2022]
Abstract
PURPOSE To investigate the effects of bariatric surgery on intraocular pressure (IOP). METHODS We prospectively enroled consecutive obese patients who underwent a laparoscopic sleeve gastrectomy procedure. We measured IOP prior to and 3-6 months following surgery and recorded medical and demographical parameters. RESULTS Thirty-two patients completed all evaluations. Mean age was 40.5 ± 12 and 24 (75%) were men. Following surgery, mean body-mass index (BMI) decreased from 42 ± 6 to 31 ± 8 (p < 0.001). The mean IOP decreased from 16.9 ± 4 mmHg to 14.1 ± 3 mmHg (p < 0.001). The extent of IOP reduction was correlated with the baseline IOP (Pearson r = 0.737, p < 0.001) and central corneal thickness (Pearson r = 0.453, p = 0.010). CONCLUSION In a cohort of obese individuals undergoing sleeve gastrectomy, there was a significant decrease in IOP measured 3-6 months after the procedure. Our results suggest that significant weight loss could have beneficial effects on IOP in obese individuals with ocular hypertension which might enable avoidance of antiglaucoma medications. The high likelihood of a reduction in IOP should be taken into account when considering bariatric surgery in such patients.
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Affiliation(s)
- Zvia Burgansky-Eliash
- Department of Ophthalmology; Edith Wolfson Medical Center; Holon Israel
- Sackler School of Medicine; Tel Aviv University; Tel Aviv Israel
| | - Asaf Achiron
- Department of Ophthalmology; Edith Wolfson Medical Center; Holon Israel
- Sackler School of Medicine; Tel Aviv University; Tel Aviv Israel
| | - Idan Hecht
- Department of Ophthalmology; Edith Wolfson Medical Center; Holon Israel
- Sackler School of Medicine; Tel Aviv University; Tel Aviv Israel
| | - Mordechai Shimonov
- Sackler School of Medicine; Tel Aviv University; Tel Aviv Israel
- Department of Surgery A; Edith Wolfson Medical Center; Holon Israel
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27
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Grong E, Nord C, Arbo IB, Eriksson M, Kulseng BE, Ahlgren U, Mårvik R. The effect of hypergastrinemia following sleeve gastrectomy and pantoprazole on type 2 diabetes mellitus and beta-cell mass in Goto-Kakizaki rats. J Endocrinol Invest 2018; 41:691-701. [PMID: 29168078 DOI: 10.1007/s40618-017-0793-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2017] [Accepted: 11/12/2017] [Indexed: 01/30/2023]
Abstract
PURPOSE Metabolic surgery alters the secretion of gastrointestinal hormones that influence glycemic control. Elevated gastrin has been suggested to benefit patients with type 2 diabetes and has been reported following sleeve gastrectomy in rats. The present study compares the effect of hypergastrinemia following sleeve gastrectomy with proton-pump inhibitor therapy on glycemic control and beta-cell mass in lean, diabetic animals. METHODS Thirty-three diabetic Goto-Kakizaki rats were randomized into pantoprazole + sham operation (GK-PPI), sleeve gastrectomy (GK-SG) and vehicle + sham operation (GK-V). Body weight, glucose parameters, HbA1c, glucagon-like peptide 1, gastrin, insulin and lipids were evaluated for eighteen postoperative weeks. Total beta-cell mass was quantified by optical projection tomography. RESULTS After surgery, body weight development was equal among groups (P g = 0.75). Fasting and stimulated gastrin increased for GK-PPI and GK-SG vs. GK-V (p < 0.05 for all). Fasting blood glucose was decreased for GK-PPI and GK-SG vs. GK-V (p < 0.05 and p = 0.052). HbA1c was lower for GK-SG vs. GK-V at 6 weeks and for GK-PPI vs. GK-V at twelve- and eighteen weeks postoperative (p < 0.05 for all); a borderline difference was observed for GK-SG vs. GK-V at 18 weeks (p = 0.054). Total- and LDL cholesterol was elevated for GK-PPI compared to the other two groups (p < 0.05 for all). Beta-cell mass did not differ among groups (p = 0.35). CONCLUSIONS Hypergastrinemia following sleeve gastrectomy and pantoprazole has a similar, modest effect on glycemic control in Goto-Kakizaki rats but does not enhance beta-cell mass after 18 weeks. Hypergastrinemia in the setting of T2DM might be of clinical relevance.
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Affiliation(s)
- E Grong
- Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Post Box 8905, 7491, Trondheim, Norway.
- Department of Gastrointestinal Surgery and Norwegian National Advisory Unit on Advanced Laparoscopic Surgery (NSALK), St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
| | - C Nord
- Umeå Center for Molecular Medicine (UCMM), Umeå University, Umeå, Sweden
| | - I B Arbo
- Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Post Box 8905, 7491, Trondheim, Norway
| | - M Eriksson
- Umeå Center for Molecular Medicine (UCMM), Umeå University, Umeå, Sweden
| | - B E Kulseng
- Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Post Box 8905, 7491, Trondheim, Norway
- Centre for Obesity Research and Innovation (ObeCe), St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
- Department of Endocrinology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - U Ahlgren
- Umeå Center for Molecular Medicine (UCMM), Umeå University, Umeå, Sweden
| | - R Mårvik
- Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Post Box 8905, 7491, Trondheim, Norway
- Centre for Obesity Research and Innovation (ObeCe), St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
- Department of Gastrointestinal Surgery and Norwegian National Advisory Unit on Advanced Laparoscopic Surgery (NSALK), St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
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Biggs EK, Liang L, Naylor J, Madalli S, Collier R, Coghlan MP, Baker DJ, Hornigold DC, Ravn P, Reimann F, Gribble FM. Development and characterisation of a novel glucagon like peptide-1 receptor antibody. Diabetologia 2018; 61:711-721. [PMID: 29119245 PMCID: PMC5890879 DOI: 10.1007/s00125-017-4491-0] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Accepted: 10/05/2017] [Indexed: 02/06/2023]
Abstract
AIMS/HYPOTHESIS Glucagon like peptide-1 (GLP-1) enhances glucose-dependent insulin secretion by binding to GLP-1 receptors (GLP1Rs) on pancreatic beta cells. GLP-1 mimetics are used in the clinic for the treatment of type 2 diabetes, but despite their therapeutic success, several clinical effects of GLP-1 remain unexplained at a mechanistic level, particularly in extrapancreatic tissues. The aim of this study was to generate and characterise a monoclonal antagonistic antibody for the GLP1R for use in vivo. METHODS A naive phage display selection strategy was used to isolate single-chain variable fragments (ScFvs) that bound to GLP1R. The ScFv with the highest affinity, Glp1R0017, was converted into a human IgG1 and characterised further. In vitro antagonistic activity was assessed in a number of assays: a cAMP-based homogenous time-resolved fluorescence assay in GLP1R-overexpressing cell lines, a live cell cAMP imaging assay and an insulin secretion assay in INS-1 832/3 cells. Glp1R0017 was further tested in immunostaining of mouse pancreas, and the ability of Glp1R0017 to block GLP1R in vivo was assessed by both IPGTT and OGTT in C57/Bl6 mice. RESULTS Antibodies to GLP1R were selected from naive antibody phage display libraries. The monoclonal antibody Glp1R0017 antagonised mouse, human, rat, cynomolgus monkey and dog GLP1R. This antagonistic activity was specific to GLP1R; no antagonistic activity was found in cells overexpressing the glucose-dependent insulinotropic peptide receptor (GIPR), glucagon like peptide-2 receptor or glucagon receptor. GLP-1-stimulated cAMP and insulin secretion was attenuated in INS-1 832/3 cells by Glp1R0017 incubation. Immunostaining of mouse pancreas tissue with Glp1R0017 showed specific staining in the islets of Langerhans, which was absent in Glp1r knockout tissue. In vivo, Glp1R0017 reversed the glucose-lowering effect of liraglutide during IPGTTs, and reduced glucose tolerance by blocking endogenous GLP-1 action in OGTTs. CONCLUSIONS/INTERPRETATION Glp1R0017 is a monoclonal antagonistic antibody to the GLP1R that binds to GLP1R on pancreatic beta cells and blocks the actions of GLP-1 in vivo. This antibody holds the potential to be used in investigating the physiological importance of GLP1R signalling in extrapancreatic tissues where cellular targets and signalling pathways activated by GLP-1 are poorly understood.
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Affiliation(s)
- Emma K Biggs
- Department of Cardiovascular and Metabolic Disease, MedImmune Ltd, Granta Park, Cambridge, UK
- Department of Antibody Discovery and Protein Engineering, MedImmune Ltd, Granta Park, Cambridge, CB21 6GH, UK
- University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK
| | - Lihuan Liang
- Department of Cardiovascular and Metabolic Disease, MedImmune Ltd, Granta Park, Cambridge, UK
| | - Jacqueline Naylor
- Department of Cardiovascular and Metabolic Disease, MedImmune Ltd, Granta Park, Cambridge, UK
| | - Shimona Madalli
- Department of Cardiovascular and Metabolic Disease, MedImmune Ltd, Granta Park, Cambridge, UK
| | - Rachel Collier
- In Vivo Sciences - UK, AstraZeneca, The Babraham Institute, Cambridge, UK
| | - Matthew P Coghlan
- Department of Cardiovascular and Metabolic Disease, MedImmune Ltd, Granta Park, Cambridge, UK
| | - David J Baker
- Department of Cardiovascular and Metabolic Disease, MedImmune Ltd, Granta Park, Cambridge, UK
| | - David C Hornigold
- Department of Cardiovascular and Metabolic Disease, MedImmune Ltd, Granta Park, Cambridge, UK
| | - Peter Ravn
- Department of Antibody Discovery and Protein Engineering, MedImmune Ltd, Granta Park, Cambridge, CB21 6GH, UK.
| | - Frank Reimann
- University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK.
| | - Fiona M Gribble
- University of Cambridge Metabolic Research Laboratories, WT-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK.
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Dadheech N, Garrel D, Buteau J. Evidence of unrestrained beta-cell proliferation and neogenesis in a patient with hyperinsulinemic hypoglycemia after gastric bypass surgery. Islets 2018; 10:213-220. [PMID: 30311843 PMCID: PMC6300081 DOI: 10.1080/19382014.2018.1513748] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Hyperinsulinemic hypoglycemia syndrome (HIHG) is a rare complication of roux-en-Y gastric bypass surgery. The pathology is associated with an excessive function of pancreatic beta-cells, and requires pancreas resection in patients that are recalcitrant to nutritional and pharmacological interventions. The exact prevalence is not clearly understood and the underlying mechanisms not yet fully characterized. We herein sought to perform histological and molecular examination of pancreatic sections obtained from a patient who developed HIHG as a complication of gastric bypass compared to 3 weight-matched controls. We studied markers of cellular replication and beta-cell differentiation by immunohistochemistry and immunofluorescence. HIHG after gastric bypass was characterized by a profound increase in beta-cell mass. Cellular proliferation was increased in islets and ducts compared to controls, suggesting unrestrained proliferation in HIHG. We also detected beta-cell differentiation markers in duct cells and occasional duct cells displaying both insulin and glucagon immunoreactivity. These histological observations suggest that beta-cell differentiation from ductal progenitor cells could also underly beta-cell mass expansion in HIHG. Altogether, our results can be construed to demonstrate that HIHG after gastric bypass is characterized by abnormal beta-cell mass expansion, resulting from both unrestrained beta-cell replication and neogenesis.
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Affiliation(s)
- Nidheesh Dadheech
- Department of Agricultural Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
| | - Dominique Garrel
- Department of Nutrition, Université de Montréal, Montréal, QC, Canada
| | - Jean Buteau
- Department of Agricultural Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
- CONTACT Dr. Jean Buteau University of Alberta, 5-126 Li Ka Shing Centre, Edmonton, AB T6G 2E1, Canada
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30
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Day SE, Garcia LA, Coletta RL, Campbell LE, Benjamin TR, De Filippis EA, Madura JA, Mandarino LJ, Roust LR, Coletta DK. Alterations of sorbin and SH3 domain containing 3 (SORBS3) in human skeletal muscle following Roux-en-Y gastric bypass surgery. Clin Epigenetics 2017; 9:96. [PMID: 28883895 PMCID: PMC5581422 DOI: 10.1186/s13148-017-0396-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Accepted: 08/24/2017] [Indexed: 12/14/2022] Open
Abstract
Background Obesity is a disease that is caused by genetic and environmental factors. However, epigenetic mechanisms of obesity are less well known. DNA methylation provides a mechanism whereby environmental factors can influence gene transcription. The aim of our study was to investigate skeletal muscle DNA methylation of sorbin and SH3 domain containing 3 (SORBS3) with weight loss induced by Roux-en-Y gastric bypass (RYGB). Results Previously, we had shown increased methylation (5.0 to 24.4%) and decreased gene expression (fold change − 1.9) of SORBS3 with obesity (BMI > 30 kg/m2) compared to lean controls. In the present study, basal muscle biopsies were obtained from seven morbidly obese (BMI > 40 kg/m2) female subjects pre- and 3 months post-RYGB surgery, in combination with euglycemic-hyperinsulinemic clamps to assess insulin sensitivity. We identified 30 significantly altered promoter and untranslated region methylation sites in SORBS3 using reduced representation bisulfite sequencing (RRBS). Twenty-nine of these sites were decreased (− 5.6 to − 24.2%) post-RYGB compared to pre-RYGB. We confirmed the methylation in 2 (Chr.8:22,423,690 and Chr.8:22,423,702) of the 29 decreased SORBS3 sites using pyrosequencing. This decreased methylation was associated with an increase in SORBS3 gene expression (fold change + 1.7) post-surgery. In addition, we demonstrated that SORBS3 promoter methylation in vitro significantly alters reporter gene expression (P < 0.0001). Two of the SORBS3 methylation sites (Chr.8:22,423,111 and Chr.8:22,423,205) were strongly correlated with fasting plasma glucose levels (r = 0.9, P = 0.00009 and r = 0.8, P = 0.0010). Changes in SORBS3 gene expression post-surgery were correlated with obesity measures and fasting insulin levels (r = 0.5 to 0.8; P < 0.05). Conclusions These results demonstrate that SORBS3 methylation and gene expression are altered in obesity and restored to normal levels through weight loss induced by RYGB surgery.
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Affiliation(s)
- Samantha E Day
- School of Life Sciences, Arizona State University, Tempe, AZ USA
| | - Luis A Garcia
- Department of Medicine, The University of Arizona College of Medicine, PO Box 245035, 1501 N. Campbell Ave, Tucson, AZ 85724-5035 USA
| | - Richard L Coletta
- Department of Medicine, The University of Arizona College of Medicine, PO Box 245035, 1501 N. Campbell Ave, Tucson, AZ 85724-5035 USA
| | | | - Tonya R Benjamin
- Endocrinology Department, Mayo Clinic in Arizona, Scottsdale, AZ USA
| | | | - James A Madura
- Endocrinology Department, Mayo Clinic in Arizona, Scottsdale, AZ USA
| | - Lawrence J Mandarino
- Department of Medicine, The University of Arizona College of Medicine, PO Box 245035, 1501 N. Campbell Ave, Tucson, AZ 85724-5035 USA
| | - Lori R Roust
- Endocrinology Department, Mayo Clinic in Arizona, Scottsdale, AZ USA
| | - Dawn K Coletta
- Department of Medicine, The University of Arizona College of Medicine, PO Box 245035, 1501 N. Campbell Ave, Tucson, AZ 85724-5035 USA.,Department of Basic Medical Sciences, The University of Arizona College of Medicine - Phoenix, Phoenix, AZ USA
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Bhatt AA, Choudhari PK, Mahajan RR, Sayyad MG, Pratyush DD, Hasan I, Javherani RS, Bothale MM, Purandare VB, Unnikrishnan AG. Effect of a Low-Calorie Diet on Restoration of Normoglycemia in Obese subjects with Type 2 Diabetes. Indian J Endocrinol Metab 2017; 21:776-780. [PMID: 28989891 PMCID: PMC5628553 DOI: 10.4103/ijem.ijem_206_17] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
INTRODUCTION Type 2 diabetes mellitus (T2DM) is considered to be an inevitably progressive disease. Complex therapies add to the financial and psychological burden. Very low-calorie diets (LCDs) are emerging as an option in the management of type 2 diabetes. METHODS We performed a clinical audit of patients with T2DM who received 12 weeks of LCD. RESULTS This case series documents that 6 out of 12 participants (median baseline HbA1c 9%) achieved HbA1c level in nondiabetes range with LCD despite stopping all antidiabetes medications. There was an improvement in serum triglycerides, HDL cholesterol, total cholesterol, C-Reactive protein, urine microalbumin, liver transaminases, liver fat and the indices of insulin resistance, beta cell secretory capacity, and insulin sensitivity. CONCLUSION If long-term follow-up proves sustained benefits, such dietary restriction may be an alternative to more drastic options for reversal of type 2 diabetes. This may also help in changing the treatment perspective of a newly detected T2DM from an incurable and inevitably progressive disease to a potentially reversible disease.
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Affiliation(s)
- Anjali Amit Bhatt
- Department of Clinical Diabetology and Endocrinology, Chellaram Diabetes Institute, Pune, Maharashtra, India
| | - Priya K. Choudhari
- Department of Dietetics and Nutrition, Chellaram Diabetes Institute, Pune, Maharashtra, India
| | - Rutuja R. Mahajan
- Department of Dietetics and Nutrition, Chellaram Diabetes Institute, Pune, Maharashtra, India
| | - Mehmood G. Sayyad
- Department of Biostatistics, Chellaram Diabetes Institute, Pune, Maharashtra, India
| | - Devi D. Pratyush
- Department of Research, Chellaram Diabetes Institute, Pune, Maharashtra, India
| | - Imtiaz Hasan
- Department of Pathology, Chellaram Diabetes Institute, Pune, Maharashtra, India
| | - Rajesh S. Javherani
- Department of Clinical Diabetology and Endocrinology, Chellaram Diabetes Institute, Pune, Maharashtra, India
| | - Manish M. Bothale
- Department of Clinical Diabetology and Endocrinology, Chellaram Diabetes Institute, Pune, Maharashtra, India
| | - Vedavati B. Purandare
- Department of Clinical Diabetology and Endocrinology, Chellaram Diabetes Institute, Pune, Maharashtra, India
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Yan J, Cohen R, Aminian A. Reoperative bariatric surgery for treatment of type 2 diabetes mellitus. Surg Obes Relat Dis 2017. [DOI: 10.1016/j.soard.2017.04.019] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Albaugh VL, Banan B, Ajouz H, Abumrad NN, Flynn CR. Bile acids and bariatric surgery. Mol Aspects Med 2017; 56:75-89. [PMID: 28390813 PMCID: PMC5603298 DOI: 10.1016/j.mam.2017.04.001] [Citation(s) in RCA: 101] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Revised: 02/27/2017] [Accepted: 04/04/2017] [Indexed: 12/12/2022]
Abstract
Bariatric surgery, specifically Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), are the most effective and durable treatments for morbid obesity and potentially a viable treatment for type 2 diabetes (T2D). The resolution rate of T2D following these procedures is between 40 and 80% and far surpasses that achieved by medical management alone. The molecular basis for this improvement is not entirely understood, but has been attributed in part to the altered enterohepatic circulation of bile acids. In this review we highlight how bile acids potentially contribute to improved lipid and glucose homeostasis, insulin sensitivity and energy expenditure after these procedures. The impact of altered bile acid levels in enterohepatic circulation is also associated with changes in gut microflora, which may further contribute to some of these beneficial effects. We highlight the beneficial effects of experimental surgical procedures in rodents that alter bile secretory flow without gastric restriction or altering nutrient flow. This information suggests a role for bile acids beyond dietary fat emulsification in altering whole body glucose and lipid metabolism strongly, and also suggests emerging roles for the activation of the bile acid receptors farnesoid x receptor (FXR) and G-protein coupled bile acid receptor (TGR5) in these improvements. The limitations of rodent studies and the current state of our understanding is reviewed and the potential effects of bile acids mediating the short- and long-term metabolic improvements after bariatric surgery is critically examined.
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MESH Headings
- Animals
- Bile Acids and Salts/metabolism
- Diabetes Mellitus, Type 2/metabolism
- Diabetes Mellitus, Type 2/microbiology
- Diabetes Mellitus, Type 2/pathology
- Diabetes Mellitus, Type 2/surgery
- Enterohepatic Circulation
- Gastrectomy
- Gastric Bypass
- Gastrointestinal Microbiome/physiology
- Gene Expression Regulation
- Glucose/metabolism
- Homeostasis/physiology
- Humans
- Insulin Resistance
- Obesity, Morbid/metabolism
- Obesity, Morbid/microbiology
- Obesity, Morbid/pathology
- Obesity, Morbid/surgery
- Receptors, Cytoplasmic and Nuclear/genetics
- Receptors, Cytoplasmic and Nuclear/metabolism
- Receptors, G-Protein-Coupled/genetics
- Receptors, G-Protein-Coupled/metabolism
- Rodentia
- Signal Transduction
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Affiliation(s)
- Vance L Albaugh
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Babak Banan
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Hana Ajouz
- American University of Beirut, Beirut, Lebanon
| | - Naji N Abumrad
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Charles R Flynn
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
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Pardina E, Ferrer R, Rossell J, Ricart-Jané D, Méndez-Lara KA, Baena-Fustegueras JA, Lecube A, Julve J, Peinado-Onsurbe J. Hepatic CD36 downregulation parallels steatosis improvement in morbidly obese undergoing bariatric surgery. Int J Obes (Lond) 2017; 41:1388-1393. [PMID: 28555086 DOI: 10.1038/ijo.2017.115] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2016] [Revised: 02/28/2017] [Accepted: 04/02/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND The notion that hepatic expression of genes involved in lipid metabolism is altered in obese patients is relatively new and its relationship with hepatic steatosis and cardiometabolic alterations remains unclear. OBJECTIVE We assessed the impact of Roux-en-Y gastric bypass surgery (RYGB) on the expression profile of genes related to metabolic syndrome in liver biopsies from morbidly obese individuals using a custom-made, focused cDNA microarray, and assessed the relationship between the expression profile and hepatic steatosis regression. MATERIALS AND METHODS Plasma and liver samples were obtained from patients at baseline and 12 months after surgery. Samples were assayed for chemical and gene expression analyses, as appropriate. Gene expression profiles were assessed using custom-made, focused TaqMan low-density array cards. RESULTS RYGB-induced weight loss produced a favorable reduction in fat deposits, insulin resistance (estimated by homeostasis model assessment of insulin resistance (HOMA-IR)), and plasma and hepatic lipid levels. Compared with the baseline values, the gene expression levels of key targets of lipid metabolism were significantly altered: CD36 was significantly downregulated (-40%; P=0.001), whereas APOB (+27%; P=0.032) and SCARB1 (+37%; P=0.040) were upregulated in response to surgery-induced weight reduction. We also observed a favorable reduction in the expression of the PAI1 gene (-80%; P=0.007) and a significant increase in the expression of the PPARA (+60%; P=0.014) and PPARGC1 genes (+36%; P=0.015). Notably, the relative fold decrease in the expression of the CD36 gene was directly associated with a concomitant reduction in the cholesterol (Spearman's r=0.92; P=0.001) and phospholipid (Spearman's r=0.76; P=0.04) contents in this tissue. CONCLUSIONS For the first time, RYGB-induced weight loss was shown to promote a favorable downregulation of CD36 expression, which was proportional to a favorable reduction in the hepatic cholesterol and phospholipid contents in our morbidly obese subjects following surgery.
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Affiliation(s)
- E Pardina
- Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain
| | - R Ferrer
- Unitat d'Hormones, Servei de Bioquímica, Hospital Universitari de la Vall d'Hebron, Barcelona, Spain
| | - J Rossell
- Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain
| | - D Ricart-Jané
- Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain
| | - K A Méndez-Lara
- Institut de Recerca de l'Hospital de La Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques de l'Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain.,Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain
| | | | - A Lecube
- Departament d'Endocrinologia i Nutrició, Hospital Universitari Arnau de Vilanova, Universitat de Lleida, Lleida, Spain.,Unitat de Recerca en Diabetes i Metabolisme, Institut de Recerca Hospital Universitari Vall d'Hebron, Barcelona, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Barcelona, Spain
| | - J Julve
- Institut de Recerca de l'Hospital de La Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques de l'Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain.,Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain.,CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Barcelona, Spain
| | - J Peinado-Onsurbe
- Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain
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Abstract
Diet, exercise, cognitive behavioral therapy and pharmacotherapy are some of the means of assisting patients to lose weight, with bariatric surgery being the most effective. Over the last two decades, the increased awareness of the systemic benefits of bariatric surgery, as well as the improved safety and the wider use of the laparoscopic approach, has made bariatric surgery flourish. In the United Kingdom, the adjustable gastric band (10%), vertical sleeve gastrectomy (37%) and Roux-en-Y gastric bypass (45%) are the three most common procedures. Obesity-associated mortality and co-morbidities such as type 2 diabetes, hypertension, dyslipidemia, obstructive sleep apnea, renal dysfunction and depression improve significantly with bariatric surgery. The mechanisms of weight loss extend beyond restriction and malabsorption and include changes in hunger and satiety, food preferences, and possibly energy expenditure. Despite its safety and efficacy, bariatric surgery is underutilized as less than 1% of adults with obesity receive it. In view of the evolution of obesity into a global threat, access to bariatric surgery should be increased, whilst developing safer and less invasive weight loss treatments.
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Affiliation(s)
- E Panteliou
- a Section of Investigative Medicine, Division of Diabetes, Endocrinology & Metabolism , Imperial College London , London , UK
| | - A D Miras
- a Section of Investigative Medicine, Division of Diabetes, Endocrinology & Metabolism , Imperial College London , London , UK
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36
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Eligibility and Success Criteria for Bariatric/Metabolic Surgery. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 960:529-543. [PMID: 28585215 DOI: 10.1007/978-3-319-48382-5_23] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Obesity is a worldwide main health concern, with a high treatment failure. This chapter focuses on the definition of obesity, based on excessive fat accumulation and thus underscores the importance of body composition, and the clinical tools currently used to diagnose it, mainly body mass index that is only a proxy measure of body composition. It also highlights the importance of the personal commitment to comply to a healthy diet and physical activity recommendations since surgery is most effective when accompanied by lifestyle modifications. Additionally, it addresses the description of types of patients who could benefit most from surgical management of excessive body fat percentage and metabolic derangements, as well as on the indications for surgery that are currently valid.
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37
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Biggs EK, Gribble FM, Reimann F. Scaling it down: new in vitro tools to get the balance right. Biochem J 2017; 474:47-50. [PMID: 28008090 DOI: 10.1042/bcj20160874] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Revised: 10/28/2016] [Accepted: 10/31/2016] [Indexed: 12/24/2022]
Abstract
Treatments for diabetes and obesity based on enteroendocrine hormones are a focus of research interest, partly due to the successes of glucagon-like peptide-1 (GLP-1) mimetic peptides in the treatment of diabetes and the correlation of altered enteroendocrine profiles with the positive metabolic outcomes of gastric bypass surgery. It is thought that simultaneous stimulation of more than one receptor might mimic the superior efficacy of the latter and dual or triple-agonist peptides are under investigation. An important step in developing multiple agonists is to establish the relative pharmacological potency and efficacy of new molecules at its different target receptors, and to optimise the balance of activities to achieve the desired treatment outcome. In a recent issue of the Biochemical Journal, Naylor et al. described how they used CRISPR technology to modulate endogenous receptor density in insulinoma cells to get the balance right for a dual incretin peptide engaging both GLP-1- and glucose-dependent insulinotropic polypeptide-receptors.
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Affiliation(s)
- Emma K Biggs
- Metabolic Research Laboratories, Wellcome Trust/MRC Institute of Metabolic Science & MRC Metabolic Diseases Unit, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ, U.K
| | - Fiona M Gribble
- Metabolic Research Laboratories, Wellcome Trust/MRC Institute of Metabolic Science & MRC Metabolic Diseases Unit, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ, U.K
| | - Frank Reimann
- Metabolic Research Laboratories, Wellcome Trust/MRC Institute of Metabolic Science & MRC Metabolic Diseases Unit, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ, U.K.
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38
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Osland E, Yunus RM, Khan S, Memon B, Memon MA. Diabetes improvement and resolution following laparoscopic vertical sleeve gastrectomy (LVSG) versus laparoscopic Roux-en-Y gastric bypass (LRYGB) procedures: a systematic review of randomized controlled trials. Surg Endosc 2016; 31:1952-1963. [PMID: 27623997 DOI: 10.1007/s00464-016-5202-5] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2016] [Accepted: 08/17/2016] [Indexed: 12/16/2022]
Abstract
BACKGROUND The prevalence of type 2 diabetes is growing in both developed and developing countries and is strongly linked with the prevalence of obesity. Bariatric surgical procedures such as laparoscopic vertical sleeve gastrectomy (LVSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) are increasingly being utilized to manage related comorbid chronic conditions, including type 2 diabetes. METHODS A systematic review of randomized controlled trials (RCTs) was undertaken using the PRISMA guidelines to investigate the postoperative impact on diabetes resolution following LVSG versus LRYGB. RESULTS Seven RCTs involving a total of 732 patients (LVSG n = 365, LRYGB n = 367) met inclusion criteria. Significant diabetes resolution or improvement was reported with both procedures across all time points. Similarly, measures of glycemic control (HbA1C and fasting blood glucose levels) improved with both procedures, with earlier improvements noted in LRYGB that stabilized and did not differ from LVSG at 12 months postoperatively. Early improvements in measures of insulin resistance in both procedures were also noted in the studies that investigated this. CONCLUSIONS This systematic review of RCTs suggests that both LVSG and LRYGB are effective in resolving or improving preoperative type 2 diabetes in obese patients during the reported 3- to 5-year follow-up periods. However, further studies are required before longer-term outcomes can be elucidated. Areas identified that need to be addressed for future studies on this topic include longer follow-up periods, standardized definitions and time point for reporting, and financial analysis of outcomes obtained between surgical procedures to better inform procedure selection.
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Affiliation(s)
- Emma Osland
- Department of Nutrition and Dietetics, Royal Brisbane and Women's Hospital, Herston, QLD, 4019, Australia.,Department of Human Movements and Nutrition, University of Queensland, Brisbane, QLD, Australia
| | | | - Shahjahan Khan
- School of Agricultural, Computational and Environmental Sciences, International Centre for Applied Climate Sciences and Centre for Health Sciences Research, University of Southern Queensland, Toowoomba, QLD, Australia
| | - Breda Memon
- Sunnybank Obesity Centre and South East Queensland Surgery (SEQS), Suite 9, McCullough Centre, 259 McCullough Street, Sunnybank, QLD, 4109, Australia
| | - Muhammed Ashraf Memon
- School of Agricultural, Computational and Environmental Sciences, International Centre for Applied Climate Sciences and Centre for Health Sciences Research, University of Southern Queensland, Toowoomba, QLD, Australia. .,Sunnybank Obesity Centre and South East Queensland Surgery (SEQS), Suite 9, McCullough Centre, 259 McCullough Street, Sunnybank, QLD, 4109, Australia. .,Mayne Medical School, School of Medicine, University of Queensland, Brisbane, QLD, Australia. .,Faculty of Health Sciences and Medicine, Bond University, Gold Coast, QLD, Australia. .,Faculty of Health and Social Science, Bolton University, Bolton, Lancashire, UK.
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Corbin LJ, Timpson NJ. Body mass index: Has epidemiology started to break down causal contributions to health and disease? Obesity (Silver Spring) 2016; 24:1630-8. [PMID: 27460712 PMCID: PMC5972005 DOI: 10.1002/oby.21554] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Revised: 04/04/2016] [Accepted: 04/05/2016] [Indexed: 12/21/2022]
Abstract
OBJECTIVES To review progress in understanding the methods and results concerning the causal contribution of body mass index (BMI) to health and disease. METHODS In the context of conventional evidence focused on the relationship between BMI and health, this review considers current literature on the common, population-based, genetic contribution to BMI and how this has fed into the developing field of applied epidemiology. RESULTS Technological and analytical developments have driven considerable success in identifying genetic variants relevant to BMI. This has enabled the implementation of Mendelian randomization to address questions of causality. The product of this work has been the implication of BMI as a causal agent in a host of health outcomes. Further breakdown of causal pathways by integration with other "omics" technologies promises to deliver additional benefit. CONCLUSIONS Gaps remain in our understanding of BMI as a risk factor for health and disease, and while promising, applied genetic epidemiology should be considered alongside alternative methods for assessing the impact of BMI on health. Potential limitations, relating to inappropriate or nonspecific measures of obesity and the improper use of genetic instruments, will need to be explored and incorporated into future research aiming to dissect BMI as a risk factor.
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Affiliation(s)
| | - Nicholas J. Timpson
- corresponding author: CONTACT INFO: MRC Integrative Epidemiology Unit, Oakfield House, Oakfield Grove, Bristol, BS8 2BN. .
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40
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van Wyk H, Daniels M. The Use of Very Low Calorie Diets in the Management of Type 2 Diabetes Mellitus. SOUTH AFRICAN JOURNAL OF CLINICAL NUTRITION 2016. [DOI: 10.1080/16070658.2016.1216514] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Wolf RM, Steele KE, Peterson LA, Zeng X, Jaffe AE, Schweitzer MA, Magnuson TH, Wong GW. C1q/TNF-Related Protein-9 (CTRP9) Levels Are Associated With Obesity and Decrease Following Weight Loss Surgery. J Clin Endocrinol Metab 2016; 101:2211-7. [PMID: 26982010 PMCID: PMC4870852 DOI: 10.1210/jc.2016-1027] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
CONTEXT C1q/TNF-related protein-9 (CTRP9) is a novel adipokine that has beneficial metabolic and cardiovascular effects in various animal models. Alterations in circulating CTRP9 have also been observed in patients with cardiovascular disease and diabetes, but little is known about the impact of obesity and bariatric surgery on CTRP9 concentrations. OBJECTIVE The aim of this study was to compare CTRP9 levels in obese and lean subjects and to determine whether circulating CTRP9 levels in morbidly obese patients are altered by bariatric surgery. DESIGN, SETTING, AND PARTICIPANTS Fifty-nine obese bariatric surgical patients and 62 lean controls were recruited to participate in a cross-sectional study at an academic medical center. The obese patients were further invited to participate in a cohort study, and 21 returned for analysis at 3 and 6 months postsurgery. INTERVENTION Bariatric surgery (Roux-en-Y gastric bypass and vertical sleeve gastrectomy) was the intervention for this study. MAIN OUTCOME MEASURES Fasting serum was obtained from all subjects on entry to the study and was analyzed in the core laboratory for hemoglobin A1c, glucose, aspartate aminotransferase, alanine aminotransferase, total cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides; CTRP9, insulin, adiponectin, and leptin were measured by ELISA. Serum from the patients in the cohort study was also analyzed at 3 and 6 months. RESULTS Serum CTRP9 was significantly higher in the obese group compared to the lean group. CTRP9 was associated with obesity, even after controlling for age, gender, and ethnicity. Following bariatric surgery, there was a significant decrease in weight at 3 and 6 months postprocedure, accompanied by decreases in CTRP9, hemoglobin A1c and leptin, and an increase in serum adiponectin. CONCLUSIONS CTRP9 levels are elevated in obesity and significantly decrease following weight loss surgery. Our data suggest that CTRP9 may play a compensatory role in obesity, similar to that of insulin, and is down-regulated following weight loss surgery.
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Affiliation(s)
- Risa M Wolf
- Departments of Pediatrics (R.M.W.), Surgery (K.E.S., L.A.P., M.A.S., T.H.M.), and Physiology (X.Z., G.W.W.), and Center for Metabolism and Obesity Research (R.M.W., G.W.W.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Lieber Institute for Brain Development (A.E.J.), Johns Hopkins Medical Campus, Baltimore, Maryland; and Departments of Mental Health (A.E.J.) and Biostatistics (A.E.J.), Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Kimberley E Steele
- Departments of Pediatrics (R.M.W.), Surgery (K.E.S., L.A.P., M.A.S., T.H.M.), and Physiology (X.Z., G.W.W.), and Center for Metabolism and Obesity Research (R.M.W., G.W.W.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Lieber Institute for Brain Development (A.E.J.), Johns Hopkins Medical Campus, Baltimore, Maryland; and Departments of Mental Health (A.E.J.) and Biostatistics (A.E.J.), Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Leigh A Peterson
- Departments of Pediatrics (R.M.W.), Surgery (K.E.S., L.A.P., M.A.S., T.H.M.), and Physiology (X.Z., G.W.W.), and Center for Metabolism and Obesity Research (R.M.W., G.W.W.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Lieber Institute for Brain Development (A.E.J.), Johns Hopkins Medical Campus, Baltimore, Maryland; and Departments of Mental Health (A.E.J.) and Biostatistics (A.E.J.), Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Xiange Zeng
- Departments of Pediatrics (R.M.W.), Surgery (K.E.S., L.A.P., M.A.S., T.H.M.), and Physiology (X.Z., G.W.W.), and Center for Metabolism and Obesity Research (R.M.W., G.W.W.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Lieber Institute for Brain Development (A.E.J.), Johns Hopkins Medical Campus, Baltimore, Maryland; and Departments of Mental Health (A.E.J.) and Biostatistics (A.E.J.), Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Andrew E Jaffe
- Departments of Pediatrics (R.M.W.), Surgery (K.E.S., L.A.P., M.A.S., T.H.M.), and Physiology (X.Z., G.W.W.), and Center for Metabolism and Obesity Research (R.M.W., G.W.W.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Lieber Institute for Brain Development (A.E.J.), Johns Hopkins Medical Campus, Baltimore, Maryland; and Departments of Mental Health (A.E.J.) and Biostatistics (A.E.J.), Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Michael A Schweitzer
- Departments of Pediatrics (R.M.W.), Surgery (K.E.S., L.A.P., M.A.S., T.H.M.), and Physiology (X.Z., G.W.W.), and Center for Metabolism and Obesity Research (R.M.W., G.W.W.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Lieber Institute for Brain Development (A.E.J.), Johns Hopkins Medical Campus, Baltimore, Maryland; and Departments of Mental Health (A.E.J.) and Biostatistics (A.E.J.), Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Thomas H Magnuson
- Departments of Pediatrics (R.M.W.), Surgery (K.E.S., L.A.P., M.A.S., T.H.M.), and Physiology (X.Z., G.W.W.), and Center for Metabolism and Obesity Research (R.M.W., G.W.W.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Lieber Institute for Brain Development (A.E.J.), Johns Hopkins Medical Campus, Baltimore, Maryland; and Departments of Mental Health (A.E.J.) and Biostatistics (A.E.J.), Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - G William Wong
- Departments of Pediatrics (R.M.W.), Surgery (K.E.S., L.A.P., M.A.S., T.H.M.), and Physiology (X.Z., G.W.W.), and Center for Metabolism and Obesity Research (R.M.W., G.W.W.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Lieber Institute for Brain Development (A.E.J.), Johns Hopkins Medical Campus, Baltimore, Maryland; and Departments of Mental Health (A.E.J.) and Biostatistics (A.E.J.), Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
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Clough A, Hamill D, Jackson S, Remilton M, Eyre R, Callahan R. Outcome of three common bariatric procedures in the public sector. ANZ J Surg 2016; 87:930-934. [DOI: 10.1111/ans.13585] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2015] [Revised: 02/24/2016] [Accepted: 02/26/2016] [Indexed: 12/12/2022]
Affiliation(s)
| | - Daniel Hamill
- Eastern Health Network; Melbourne Victoria Australia
| | - Shane Jackson
- Eastern Health Network; Melbourne Victoria Australia
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Ejaz A, Mitterberger MC, Lu Z, Mattesich M, Zwierzina ME, Hörl S, Kaiser A, Viertler HP, Rostek U, Meryk A, Khalid S, Pierer G, Bast RC, Zwerschke W. Weight Loss Upregulates the Small GTPase DIRAS3 in Human White Adipose Progenitor Cells, Which Negatively Regulates Adipogenesis and Activates Autophagy via Akt-mTOR Inhibition. EBioMedicine 2016; 6:149-161. [PMID: 27211557 PMCID: PMC4856797 DOI: 10.1016/j.ebiom.2016.03.030] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Revised: 02/26/2016] [Accepted: 03/03/2016] [Indexed: 01/14/2023] Open
Abstract
Long-term weight-loss (WL) interventions reduce insulin serum levels, protect from obesity, and postpone age-associated diseases. The impact of long-term WL on adipose-derived stromal/progenitor cells (ASCs) is unknown. We identified DIRAS3 and IGF-1 as long-term WL target genes up-regulated in ASCs in subcutaneous white adipose tissue of formerly obese donors (WLDs). We show that DIRAS3 negatively regulates Akt, mTOR and ERK1/2 signaling in ASCs undergoing adipogenesis and acts as a negative regulator of this pathway and an activator of autophagy. Studying the IGF-1–DIRAS3 interaction in ASCs of WLDs, we demonstrate that IGF-1, although strongly up-regulated in these cells, hardly activates Akt, while ERK1/2 and S6K1 phosphorylation is activated by IGF-1. Overexpression of DIRAS3 in WLD ASCs completely inhibits Akt phosphorylation also in the presence of IGF-1. Phosphorylation of ERK1/2 and S6K1 is lesser reduced under these conditions. In conclusion, our key findings are that DIRAS3 down-regulates Akt–mTOR signaling in ASCs of WLDs. Moreover, DIRAS3 inhibits adipogenesis and activates autophagy in these cells.
Long-term weight loss (WL) induces DIRAS3 and IGF-1 in ASCs of sWAT in formerly obese humans. DIRAS3 selectively down-regulates IGF-1R-Akt–mTOR signaling in ASCs and channels the IGF-1 stimulus to the ERK1/2 branch. DIRAS3 inhibits adipogenesis and activates autophagy in ASCs. Long-term weight loss (WL) interventions reduce insulin serum levels, protect from obesity and postpone age-associated diseases. The impact of WL on adipose-derived stromal/progenitor cells (ASCs), stem cell-like cells in human subcutaneous white adipose tissue (sWAT), is not understood. We found that WL induced GTP-binding RAS-like 3 (DIRAS3) and insulin-like growth factor 1 (IGF-1), regulators of the IGF-1–mTOR signal transduction pathway, in ASCs in sWAT of formerly obese humans. We demonstrate that DIRAS3 selectively down-regulates IGF-1R–Akt–mTOR signaling in ASCs upon WL even in the presence of high IGF-1 level and that DIRAS3 inhibits adipogenesis and activates autophagy in these cells.
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Affiliation(s)
- Asim Ejaz
- Division of Cell Metabolism and Differentiation Research, Institute for Biomedical Aging Research, University of Innsbruck, 6020 Innsbruck, Austria
| | - Maria C Mitterberger
- Division of Cell Metabolism and Differentiation Research, Institute for Biomedical Aging Research, University of Innsbruck, 6020 Innsbruck, Austria
| | - Zhen Lu
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Monika Mattesich
- Department of Plastic and Reconstructive Surgery, Innsbruck Medical University, 6020 Innsbruck, Austria
| | - Marit E Zwierzina
- Department of Anatomy, Histology and Embryology, Innsbruck Medical University, 6020 Innsbruck, Austria
| | - Susanne Hörl
- Division of Cell Metabolism and Differentiation Research, Institute for Biomedical Aging Research, University of Innsbruck, 6020 Innsbruck, Austria
| | - Andreas Kaiser
- Division of Cell Metabolism and Differentiation Research, Institute for Biomedical Aging Research, University of Innsbruck, 6020 Innsbruck, Austria
| | - Hans-Peter Viertler
- Division of Cell Metabolism and Differentiation Research, Institute for Biomedical Aging Research, University of Innsbruck, 6020 Innsbruck, Austria
| | - Ursula Rostek
- Division of Cell Metabolism and Differentiation Research, Institute for Biomedical Aging Research, University of Innsbruck, 6020 Innsbruck, Austria
| | - Andreas Meryk
- Division of Cell Metabolism and Differentiation Research, Institute for Biomedical Aging Research, University of Innsbruck, 6020 Innsbruck, Austria
| | - Sana Khalid
- Daniel Swarovski Research Laboratory, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, 6020 Innsbruck, Austria
| | - Gerhard Pierer
- Department of Plastic and Reconstructive Surgery, Innsbruck Medical University, 6020 Innsbruck, Austria
| | - Robert C Bast
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Werner Zwerschke
- Division of Cell Metabolism and Differentiation Research, Institute for Biomedical Aging Research, University of Innsbruck, 6020 Innsbruck, Austria.
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Vrbikova J, Kunesova M, Kyrou I, Tura A, Hill M, Grimmichova T, Dvorakova K, Sramkova P, Dolezalova K, Lischkova O, Vcelak J, Hainer V, Bendlova B, Kumar S, Fried M. Insulin Sensitivity and Secretion in Obese Type 2 Diabetic Women after Various Bariatric Operations. Obes Facts 2016; 9:410-423. [PMID: 27951535 PMCID: PMC5644812 DOI: 10.1159/000453000] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2016] [Accepted: 10/27/2016] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE To compare the effects of biliopancreatic diversion (BPD) and laparoscopic gastric banding (LAGB) on insulin sensitivity and secretion with the effects of laparoscopic gastric plication (P). METHODS A total of 52 obese women (age 30-66 years) suffering from type 2 diabetes mellitus (T2DM) were prospectively recruited into three study groups: 16 BPD; 16 LAGB, and 20 P. Euglycemic clamps and mixed meal tolerance tests were performed before, at 1 month and at 6 months after bariatric surgery. Beta cell function derived from the meal test parameters was evaluated using mathematical modeling. RESULTS Glucose disposal per kilogram of fat free mass (a marker of peripheral insulin sensitivity) increased significantly in all groups, especially after 1 month. Basal insulin secretion decreased significantly after all three types of operations, with the most marked decrease after BPD compared with P and LAGB. Total insulin secretion decreased significantly only following the BPD. Beta cell glucose sensitivity did not change significantly post-surgery in any of the study groups. CONCLUSION We documented similar improvement in insulin sensitivity in obese T2DM women after all three study operations during the 6-month postoperative follow-up. Notably, only BPD led to decreased demand on beta cells (decreased integrated insulin secretion), but without increasing the beta cell glucose sensitivity.
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Affiliation(s)
- Jana Vrbikova
- Institute of Endocrinology, Clinical Department, Prague, Czech Republic
| | - Marie Kunesova
- Institute of Endocrinology, Obesity Management Centre, Prague, Czech Republic
- 1st Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Ioannis Kyrou
- Division of Translational and Experimental Medicine, Warwick Medical School, University of Warwick, Coventry, UK
- Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham, UK
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals of Coventry and Warwickshire (UHCW) NHS Trust, Coventry, UK
| | | | - Martin Hill
- Institute of Endocrinology, Steroid Hormone and Proteofactors Department, Prague, Czech Republic
| | | | | | - Petra Sramkova
- Institute of Endocrinology, OB Klinika, Prague, Czech Republic
| | - Karin Dolezalova
- 1st Faculty of Medicine, Charles University, Prague, Czech Republic
- Institute of Endocrinology, OB Klinika, Prague, Czech Republic
| | - Olga Lischkova
- Institute of Endocrinology, Department of Molecular Endocrinology, Prague, Czech Republic
- Faculty of Science, Charles University, Prague, Czech Republic
| | - Josef Vcelak
- Institute of Endocrinology, Department of Molecular Endocrinology, Prague, Czech Republic
| | - Vojtech Hainer
- Institute of Endocrinology, Obesity Management Centre, Prague, Czech Republic
| | - Bela Bendlova
- Institute of Endocrinology, Department of Molecular Endocrinology, Prague, Czech Republic
- Faculty of Science, Charles University, Prague, Czech Republic
| | - Sudhesh Kumar
- Division of Translational and Experimental Medicine, Warwick Medical School, University of Warwick, Coventry, UK
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals of Coventry and Warwickshire (UHCW) NHS Trust, Coventry, UK
| | - Martin Fried
- 1st Faculty of Medicine, Charles University, Prague, Czech Republic
- Institute of Endocrinology, OB Klinika, Prague, Czech Republic
- *Prof. Dr. Martin Fried, OB Klinika, Pod Krejcárkem 975, 130 00 Prague 3, Czech Republic,
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Gastrin Secretion After Bariatric Surgery—Response to a Protein-Rich Mixed Meal Following Roux-En-Y Gastric Bypass and Sleeve Gastrectomy: a Pilot Study in Normoglycemic Women. Obes Surg 2015; 26:1448-56. [DOI: 10.1007/s11695-015-1985-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Irwin N, Flatt PR. New perspectives on exploitation of incretin peptides for the treatment of diabetes and related disorders. World J Diabetes 2015; 6:1285-1295. [PMID: 26557956 PMCID: PMC4635139 DOI: 10.4239/wjd.v6.i15.1285] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Revised: 09/25/2015] [Accepted: 10/27/2015] [Indexed: 02/05/2023] Open
Abstract
The applicability of stable gut hormones for the treatment of obesity-related diabetes is now undisputable. This is based predominantly on prominent and sustained glucose-lowering actions, plus evidence that these peptides can augment insulin secretion and pancreatic islet function over time. This review highlights the therapeutic potential of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), oxyntomodulin (OXM) and cholecystokinin (CCK) for obesity-related diabetes. Stable GLP-1 mimetics have already been successfully adopted into the diabetic clinic, whereas GIP, CCK and OXM molecules offer promise as potential new classes of antidiabetic drugs. Moreover, recent studies have shown improved therapeutic effects following simultaneous modulation of multiple receptor signalling pathways by combination therapy or use of dual/triple agonist peptides. However, timing and composition of injections may be important to permit interludes of beta-cell rest. The review also addresses the possible perils of incretin based drugs for treatment of prediabetes. Finally, the unanticipated utility of stable gut peptides as effective treatments for complications of diabetes, bone disorders, cognitive impairment and cardiovascular dysfunction is considered.
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47
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Effect of bariatric surgery on systemic and adipose tissue inflammation. Surg Endosc 2015; 30:3499-504. [DOI: 10.1007/s00464-015-4638-3] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2015] [Accepted: 10/17/2015] [Indexed: 01/03/2023]
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Abstract
Type 2 diabetes mellitus (T2DM) and obesity are increasingly common and major global health problems. The Edmonton obesity staging system clearly pointed towards increased mortality proportionate to the severity of obesity. Obesity itself triggers insulin resistance and thereby poses the risk of T2DM. Both obesity and T2DM have been associated with higher morbidity and mortality and this calls for institution of effective therapies to deal with the rising trend of complications arising out of this dual menace. Although lifestyle changes form the cornerstone of therapy for both the ailments, sustained results from this modalities is far from satisfactory. While Look AHEAD (action for HEAalth in diabetes) study showed significant weight loss, reduction in glycated hemoglobin and higher remission rate of T2DM at 1(st) year following intensive lifestyle measures; recurrence and relapse rate bounced back in half of subjects at 4 years, thereby indicating that weight loss and glycemic control is difficult to maintain in the long term with lifestyle interventions. Same recurrence phenomenon was also observed with pharmacotherapy with rimonabant, sibutramine and orlistat. Bariatric surgery has been seen to associate with substantial and sustained weight loss in morbidly obese patients. Interestingly, bariatric surgeries also induce higher rates of short and long-term diabetes remission. Although the exact mechanism behinds this diabetes remission are not well understood; improved insulin action, beta-cell function and complex interplay of hormones in the entero-insular axis appears to play a major role. This article reviews the effectiveness of bariatric procedures on remission or improvement in diabetes and put a perspective on its implicated mechanisms.
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Affiliation(s)
- Awadhesh Kumar Singh
- Department of Consultant Endocrinologist, G.D Hospital and Diabetes Institute, Kolkata, West Bengal, India
| | - Ritu Singh
- Consultant Gynecologist, G.D Hospital and Diabetes Institute, Kolkata, West Bengal, India
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Grams J, Garvey WT. Weight Loss and the Prevention and Treatment of Type 2 Diabetes Using Lifestyle Therapy, Pharmacotherapy, and Bariatric Surgery: Mechanisms of Action. Curr Obes Rep 2015; 4:287-302. [PMID: 26627223 DOI: 10.1007/s13679-015-0155-x] [Citation(s) in RCA: 74] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Weight loss, whether achieved by lifestyle intervention, pharmacotherapy, or bariatric surgery, is highly effective as a primary interventional strategy in both the prevention and treatment of type 2 diabetes. In high-risk patients with prediabetes and/or metabolic syndrome, weight loss effectively prevents progression to type 2 diabetes mellitus (T2DM) and improves cardiovascular risk factors. These benefits are the result of improvements in insulin resistance, which is central to the pathophysiology of cardiometabolic disease. In patients with T2DM, weight loss improves glycemia, while reducing the need for conventional glucose-lowering medicines, by affecting all three processes that produce and sustain the hyperglycemic state, namely via increments in peripheral insulin sensitivity with improvements in insulin signal transduction at the cellular level, more robust insulin secretory responses, and reduced rates of hepatic glucose production. In both nondiabetic and diabetic subjects, hypocaloric feeding (e.g., treatment with very low-calorie diet or bariatric surgery) produces a rapid improvement in insulin sensitivity due to mobilization of fat from the intramyocellular, intrahepatocellular, and intra-abdominal compartments, and via a more long-term mechanism that correlates with the loss of total body fat. In diabetes, by improving glycemia, weight loss also enhances glucose homeostasis by reversing the defects in insulin action and secretion attributable to glucose toxicity. Regardless of the therapeutic approach, weight loss of ∼ 10 % maximally prevents future diabetes in patients with prediabetes or metabolic syndrome. In T2DM, greater degrees of weight loss lead to progressive improvements in glucose homeostasis. Therefore, when accompanied by greater weight loss, the metabolic benefits following bariatric surgery are generally more pronounced than those achieved following lifestyle and medical treatment. In addition, the mechanisms by which bariatric operations improve diabetes may include both weight-dependent and weight-independent mechanisms, and the latter may involve changes in gut hormones, bile acids, or gut microflora.
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Affiliation(s)
- J Grams
- Department of Surgery, University of Alabama at Birmingham and the Birmingham VA Medical Center, KB401, 1720 2nd Ave S, Birmingham, AL, 35294-0016, USA.
| | - W Timothy Garvey
- Department of Nutrition Sciences, University of Alabama at Birmingham and the Birmingham VA Medical Center, 1675 University Boulevard, Birmingham, AL, 35294-3360, USA.
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Ardestani A, Rhoads D, Tavakkoli A. Insulin cessation and diabetes remission after bariatric surgery in adults with insulin-treated type 2 diabetes. Diabetes Care 2015; 38:659-64. [PMID: 25573879 DOI: 10.2337/dc14-1751] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE The impact of bariatric surgeries on insulin-treated type 2 diabetes (I-T2D) in the general population is largely undocumented. We assessed changes in insulin treatment after bariatric surgery in a large cohort of I-T2D patients, comparing Roux-en-Y gastric bypass surgery (RYGB) with laparoscopic adjustable gastric banding (LAGB), controlling for differences in weight loss between procedures. RESEARCH DESIGN AND METHODS Of 113,638 adult surgical patients in the Bariatric Outcomes Longitudinal Database (BOLD), 10% had I-T2D. Analysis was restricted to 5,225 patients with I-T2D and at least 1 year of postoperative follow-up. Regression models were used to identify factors that predict cessation of insulin therapy. To control for differences in weight loss patterns between RYGB and LAGB, a case-matched analysis was also performed. RESULTS Of I-T2D patients who underwent RYGB (n = 3,318), 62% were off insulin at 12 months compared with 34% (n = 1,907) after LAGB (P < 0.001). Regression analysis indicated that RYGB strongly predicted insulin cessation at both 1 and 12 months postoperatively. In the case-matched analysis at 3 months, the proportion of insulin cessation was significantly higher in the RYGB group than in the LAGB group (P = 0.03), and the diabetes remission rate was higher at all time points after this surgery. RYGB was a weight-independent predictor of insulin therapy cessation early after surgery, whereas insulin cessation after LAGB was linked to weight loss. CONCLUSIONS I-T2D patients have a greater probability of stopping insulin after RYGB than after LAGB (62% vs. 34%, respectively, at 1 year), with weight-independent effects in the early months after surgery. These findings support RYGB as the procedure of choice for reversing I-T2D.
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Affiliation(s)
- Ali Ardestani
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - David Rhoads
- Pediatric Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Ali Tavakkoli
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA Center for Weight Management and Metabolic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
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