Improvement in insulin resistance and estimated hepatic steatosis and fibrosis after endoscopic sleeve gastroplasty

Published:August 27, 2020DOI:

      Background and Aims

      Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the United States and is closely associated with obesity and insulin resistance (IR). Weight loss is the best treatment for NAFLD. Endoscopic sleeve gastroplasty (ESG) is a promising endoscopic procedure for treatment of obesity. Our aim is to evaluate the change in IR and estimated hepatic steatosis and fibrosis after ESG.


      One hundred eighteen patients with obesity and NAFLD underwent ESG and were followed for 2 years. Weight loss was evaluated as % total body weight loss. IR was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR). The previously validated hepatic steatosis index and NAFLD fibrosis score were used to estimate hepatic steatosis and risk of fibrosis.


      Patients' mean body mass index was 40 ± 7 kg/m2 at baseline. Eighty-four percent of patients completed 2 years of follow-up. At 2 years, the mean total body weight loss was 15.5% (95% confidence interval, 13.3%-17.8%). Patients' HOMA-IR improved significantly from 6.7 ± 11 to 3.0 ± 1.6 after only 1 week from ESG (P = .019) with continued improvement up to 2 years (P = .03). Patients' hepatic steatosis index score improved significantly, decreasing by 4 points per year (P for trend, <.001). Patients' NAFLD fibrosis score improved significantly, decreasing by 0.3 point per year (P for trend, .034). Twenty-four patients (20%) improved their risk of hepatic fibrosis from F3-F4 or indeterminate to F0-F2, whereas only 1 patient (1%) experienced an increase in the estimated risk of fibrosis (P = .02).


      Our results suggest a significant and sustained improvement in estimated hepatic steatosis and fibrosis after ESG in patients with NAFLD. Importantly, we showed an early and weight-independent improvement in insulin resistance, which lasted for 2 years after the procedure.

      Graphical abstract


      AE (adverse event), ALT (alanine aminotransferase), ASGE (American Society for Gastrointestinal Endoscopy), AST (aspartate aminotransferase), BMI (body mass index), CI (confidence interval), ESG (endoscopic sleeve gastroplasty), GLP-1 (glucagon-like peptide 1), HbA1c (hemoglobin A1c), HOMA-IR (homeostasis model assessment of insulin resistance), HSI (hepatic steatosis index), IR (insulin resistance), NAFLD (nonalcoholic fatty liver disease), NASH (nonalcoholic steatohepatitis), NFS (NAFLD fibrosis score), TBWL (total body weight loss)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Gastrointestinal Endoscopy
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Younossi Z.M.
        • Stepanova M.
        • Afendy M.
        • et al.
        Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1988 to 2008.
        Clin Gastroenterol Hepatol. 2011; 9 (quiz e60): 524-530.e1
        • Williams C.D.
        • Stengel J.
        • Asike M.I.
        • et al.
        Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study.
        Gastroenterology. 2011; 140: 124-131
        • Vernon G.
        • Baranova A.
        • Younossi Z.M.
        Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults.
        Aliment Pharmacol Ther. 2011; 34: 274-285
        • Pagano G.
        • Pacini G.
        • Musso G.
        • et al.
        Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further evidence for an etiologic association.
        Hepatology. 2002; 35: 367-372
        • Hamaguchi M.
        • Kojima T.
        • Takeda N.
        • et al.
        The metabolic syndrome as a predictor of nonalcoholic fatty liver disease.
        Ann Intern Med. 2005; 143: 722-728
        • Kral J.G.
        • Lundholm K.
        • Bjorntorp P.
        • et al.
        Hepatic lipid metabolism in severe human obesity.
        Metabolism. 1977; 26: 1025-1031
        • Sanyal A.J.
        • Campbell-Sargent C.
        • Mirshahi F.
        • et al.
        Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities.
        Gastroenterology. 2001; 120: 1183-1192
        • Gastaldelli A.
        • Harrison S.A.
        • Belfort-Aguilar R.
        • et al.
        Importance of changes in adipose tissue insulin resistance to histological response during thiazolidinedione treatment of patients with nonalcoholic steatohepatitis.
        Hepatology. 2009; 50: 1087-1093
        • Chalasani N.
        • Younossi Z.
        • Lavine J.E.
        • et al.
        The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases.
        Hepatology. 2018; 67: 328-357
        • Musso G.
        • Cassader M.
        • Rosina F.
        • et al.
        Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials.
        Diabetologia. 2012; 55: 885-904
        • Sheka A.C.
        • Adeyi O.
        • Thompson J.
        • et al.
        Nonalcoholic steatohepatitis: a review.
        JAMA. 2020; 323: 1175-1183
        • Promrat K.
        • Kleiner D.E.
        • Niemeier H.M.
        • et al.
        Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis.
        Hepatology. 2010; 51: 121-129
        • Vilar-Gomez E.
        • Martinez-Perez Y.
        • Calzadilla-Bertot L.
        • et al.
        Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis.
        Gastroenterology. 2015; 149 (quiz e14-15): 367-378.e5
        • Look AHEAD Research Group
        Eight-year weight losses with an intensive lifestyle intervention: the look AHEAD study.
        Obesity (Silver Spring). 2014; 22: 5-13
        • Yanovski S.Z.
        • Yanovski J.A.
        Long-term drug treatment for obesity: a systematic and clinical review.
        JAMA. 2014; 311: 74-86
        • Chavez-Tapia N.C.
        • Tellez-Avila F.I.
        • Barrientos-Gutierrez T.
        • et al.
        Bariatric surgery for non-alcoholic steatohepatitis in obese patients.
        Cochrane Database Syst Rev. 2010; 1: CD007340
        • Viljanen A.P.
        • Iozzo P.
        • Borra R.
        • et al.
        Effect of weight loss on liver free fatty acid uptake and hepatic insulin resistance.
        J Clin Endocrinol Metab. 2009; 94: 50-55
        • Muscelli E.
        • Mingrone G.
        • Camastra S.
        • et al.
        Differential effect of weight loss on insulin resistance in surgically treated obese patients.
        Am J Med. 2005; 118: 51-57
        • MacDonald P.E.
        • El-Kholy W.
        • Riedel M.J.
        • et al.
        The multiple actions of GLP-1 on the process of glucose-stimulated insulin secretion.
        Diabetes. 2002; 51: S434-S442
        • Greco A.V.
        • Mingrone G.
        • Giancaterini A.
        • et al.
        Insulin resistance in morbid obesity: reversal with intramyocellular fat depletion.
        Diabetes. 2002; 51: 144-151
        • De Palma G.D.
        • Forestieri P.
        Role of endoscopy in the bariatric surgery of patients.
        World J Gastroenterol. 2014; 20: 7777-7784
        • Mechanick J.I.
        • Youdim A.
        • Jones D.B.
        • et al.
        Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient--2013 update: cosponsored by American Association of Clinical Endocrinologists, the Obesity Society, and American Society for Metabolic & Bariatric Surgery.
        Surg Obes Relat Dis. 2013; 9: 159-191
        • Sharaiha R.Z.
        • Kumta N.A.
        • Saumoy M.
        • et al.
        Endoscopic sleeve gastroplasty significantly reduces body mass index and metabolic complications in obese patients.
        Clin Gastroenterol Hepatol. 2017; 15: 504-510
        • Sharaiha R.Z.
        • Kedia P.
        • Kumta N.
        • et al.
        Initial experience with endoscopic sleeve gastroplasty: technical success and reproducibility in the bariatric population.
        Endoscopy. 2015; 47: 164-166
        • Brethauer S.A.
        • Kim J.
        • el Chaar M.
        • et al.
        Standardized outcomes reporting in metabolic and bariatric surgery.
        Surg Obes Relat Dis. 2015; 11: 489-506
        • Romero-Gomez M.
        • Zelber-Sagi S.
        • Trenell M.
        Treatment of NAFLD with diet, physical activity and exercise.
        J Hepatol. 2017; 67: 829-846
        • Lee J.H.
        • Kim D.
        • Kim H.J.
        • et al.
        Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease.
        Dig Liver Dis. 2010; 42: 503-508
        • Meffert P.J.
        • Baumeister S.E.
        • Lerch M.M.
        • et al.
        Development, external validation, and comparative assessment of a new diagnostic score for hepatic steatosis.
        Am J Gastroenterol. 2014; 109: 1404-1414
        • Kwo P.Y.
        • Cohen S.M.
        • Lim J.K.
        ACG clinical guideline: evaluation of abnormal liver chemistries.
        Am J Gastroenterol. 2017; 112: 18-35
        • Angulo P.
        • Hui J.M.
        • Marchesini G.
        • et al.
        The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD.
        Hepatology. 2007; 45: 846-854
        • Matthews D.R.
        • Hosker J.P.
        • Rudenski A.S.
        • et al.
        Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.
        Diabetologia. 1985; 28: 412-419
        • Cotton P.B.
        • Eisen G.M.
        • Aabakken L.
        • et al.
        A lexicon for endoscopic adverse events: report of an ASGE workshop.
        Gastrointest Endosc. 2010; 71: 446-454
        • Lopez-Nava G.
        • Sharaiha R.Z.
        • Vargas E.J.
        • et al.
        Endoscopic sleeve gastroplasty for obesity: a multicenter study of 248 patients with 24 months follow-up.
        Obes Surg. 2017; 27: 2649-2655
        • Sartoretto A.
        • Sui Z.
        • Hill C.
        • et al.
        Endoscopic sleeve gastroplasty (ESG) is a reproducible and effective endoscopic bariatric therapy suitable for widespread clinical adoption: a large, international multicenter study.
        Obes Surg. 2018; 28: 1812-1821
        • Hedjoudje A.
        • Dayyeh B.A.
        • Cheskin L.J.
        • et al.
        Efficacy and safety of endoscopic sleeve gastroplasty: a systematic review and meta-analysis.
        Clin Gastroenterol Hepatol. 2020; 18: 1043-1053.e4
        • Hajifathalian K.
        • Ang B.
        • Dawod Q.M.
        • et al.
        Long-term follow up and outcomes after endoscopic sleeve gastroplasty for treatment of obesit (5 year data) [abstract].
        Gastrointest Endosc. 2019; 89: AB58
        • Abu Dayyeh B.K.
        • Acosta A.
        • Camilleri M.
        • et al.
        Endoscopic sleeve gastroplasty alters gastric physiology and induces loss of body weight in obese individuals.
        Clin Gastroenterol Hepatol. 2017; 15: 37-43 e1
        • Monzillo L.U.
        • Hamdy O.
        Evaluation of insulin sensitivity in clinical practice and in research settings.
        Nutr Rev. 2003; 61: 397-412
        • Schauer P.R.
        • Burguera B.
        • Ikramuddin S.
        • et al.
        Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus.
        Ann Surg. 2003; 238 (discussion 484-5): 467-484
        • Adami G.F.
        • Cordera R.
        • Camerini G.
        • et al.
        Recovery of insulin sensitivity in obese patients at short term after biliopancreatic diversion.
        J Surg Res. 2003; 113: 217-221
        • O'Brien P.E.
        • Dixon J.B.
        • Brown W.
        • et al.
        The laparoscopic adjustable gastric band (Lap-Band): a prospective study of medium-term effects on weight, health and quality of life.
        Obes Surg. 2002; 12: 652-660
        • Adams T.D.
        • Gress R.E.
        • Smith S.C.
        • et al.
        Long-term mortality after gastric bypass surgery.
        N Engl J Med. 2007; 357: 753-761
        • Rubino F.
        • Gagner M.
        • Gentileschi P.
        • et al.
        The early effect of the Roux-en-Y gastric bypass on hormones involved in body weight regulation and glucose metabolism.
        Ann Surg. 2004; 240: 236-242
        • Greenfield M.
        • Kolterman O.
        • Olefsky J.M.
        • et al.
        The effect of ten days of fasting on various aspects of carbohydrate metabolism in obese diabetic subjects with significant fasting hyperglycemia.
        Metabolism. 1978; 27: 1839-1852
        • Verrillo A.
        • de Teresa A.
        • Martino C.
        • et al.
        Somatostatin response to glucose before and after prolonged fasting in lean and obese non-diabetic subjects.
        Regul Pept. 1988; 21: 185-195
        • Lopez-Nava G.
        • Negi A.
        • Bautista-Castano I.
        • et al.
        Gut and metabolic hormones changes after endoscopic sleeve gastroplasty (ESG) vs. laparoscopic sleeve gastrectomy (LSG).
        Obes Surg. 2020; 30: 2642-2651
        • Liou J.M.
        • Lin J.T.
        • Lee W.J.
        • et al.
        The serial changes of ghrelin and leptin levels and their relations to weight loss after laparoscopic minigastric bypass surgery.
        Obes Surg. 2008; 18: 84-89
        • Kotidis E.V.
        • Koliakos G.
        • Papavramidis T.S.
        • et al.
        The effect of biliopancreatic diversion with pylorus-preserving sleeve gastrectomy and duodenal switch on fasting serum ghrelin, leptin and adiponectin levels: is there a hormonal contribution to the weight-reducing effect of this procedure?.
        Obes Surg. 2006; 16: 554-559
        • Sun K.
        • Wang J.
        • Lan Z.
        • et al.
        Sleeve gastroplasty combined with the NLRP3 inflammasome inhibitor CY-09 reduces body weight, improves insulin resistance and alleviates hepatic steatosis in mouse model.
        Obes Surg. 2020; 30: 3435-3443
        • Hickey M.S.
        • Pories W.J.
        • MacDonald Jr., K.G.
        • et al.
        A new paradigm for type 2 diabetes mellitus: could it be a disease of the foregut?.
        Ann Surg. 1998; 227 (discussion 643-4): 637-643
        • Mokadem M.
        • Zechner J.F.
        • Uchida A.
        • et al.
        Leptin is required for glucose homeostasis after Roux-en-Y gastric bypass in mice.
        PLoS One. 2015; 10e0139960
        • Mattar S.G.
        • Velcu L.M.
        • Rabinovitz M.
        • et al.
        Surgically-induced weight loss significantly improves nonalcoholic fatty liver disease and the metabolic syndrome.
        Ann Surg. 2005; 242 (discussion 618-20): 610-617
        • Barker K.B.
        • Palekar N.A.
        • Bowers S.P.
        • et al.
        Non-alcoholic steatohepatitis: effect of Roux-en-Y gastric bypass surgery.
        Am J Gastroenterol. 2006; 101: 368-373
        • de Almeida S.R.
        • Rocha P.R.
        • Sanches M.D.
        • et al.
        Roux-en-Y gastric bypass improves the nonalcoholic steatohepatitis (NASH) of morbid obesity.
        Obes Surg. 2006; 16: 270-278
        • Forlano R.
        • Ippolito A.M.
        • Iacobellis A.
        • et al.
        Effect of the BioEnterics intragastric balloon on weight, insulin resistance, and liver steatosis in obese patients.
        Gastrointest Endosc. 2010; 71: 927-933
        • Lee Y.M.
        • Low H.C.
        • Lim L.G.
        • et al.
        Intragastric balloon significantly improves nonalcoholic fatty liver disease activity score in obese patients with nonalcoholic steatohepatitis: a pilot study.
        Gastrointest Endosc. 2012; 76: 756-760

      Linked Article

      • Metabolic function and weight loss after endoscopic sleeve gastroplasty: resistance is futile
        Gastrointestinal EndoscopyVol. 93Issue 5
        • Preview
          The ongoing SARS-coronavirus2 associated disease (COVID-19) pandemic is yet another on a growing list highlighting the negative impact of obesity on comorbid conditions and patient survival. Patients with obesity are known to have more-severe COVID-19 outcomes, including higher mortality than in age- and sex-matched individuals.1 Furthermore, obesity-associated insulin resistance has been proposed as a key factor in COVID-19 severity.2
        • Full-Text
        • PDF