Schauer, P. R. et al. Bariatric surgery versus intensive medical therapy for diabetes — 5-year outcomes. N. Engl. J. Med. 376, 641–651 (2017). This 5-year follow-up to the STAMPEDE clinical trial randomized patients with T2DM to RYGB, VSG or medical management, and showed that RYGB and VSG were superior to medical therapy in terms of weight loss, glycaemic control and reduction in medication use.

PubMed  PubMed Central  Google Scholar 

Kirwan, J. P. et al. Diabetes remission in the alliance of randomized trials of medicine versus metabolic surgery in type 2 diabetes (ARMMS-T2D). Diabetes Care 45, 1574–1583 (2022).

PubMed  Google Scholar 

Mingrone, G. et al. Metabolic surgery versus conventional medical therapy in patients with type 2 diabetes: 10-year follow-up of an open-label, single-centre, randomised controlled trial. Lancet 397, 293–304 (2021).

PubMed  Google Scholar 

Pories, W. J. et al. Is type II diabetes mellitus (NIDDM) a surgical disease? Ann. Surg. 215, 633–642 (1992).

CAS  PubMed  PubMed Central  Google Scholar 

Riddle, M. C. et al. Consensus report: definition and interpretation of remission in type 2 diabetes. J. Clin. Endocrinol. Metab. 44, 2438–2444 (2021).

CAS  Google Scholar 

Carlsson, L. M. et al. Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. N. Engl. J. Med. 367, 695–704 (2012).

CAS  PubMed  Google Scholar 

Yoshino, M. et al. Effects of diet versus gastric bypass on metabolic function in diabetes. N. Engl. J. Med. 383, 721–753 (2020). This study examined key metabolic phenotypes related to glucose metabolism and insulin sensitivity in participants undergoing matched weight loss via surgery or dietary restriction, showing similar metabolic and physiological responses.

CAS  PubMed  PubMed Central  Google Scholar 

Dang, J. T. et al. Predictive factors for diabetes remission after bariatric surgery. Can. J. Surg. 62, 315–319 (2019).

PubMed  PubMed Central  Google Scholar 

Sjöholm, K., Sjöström, E., Carlsson, L. M. S. & Peltonen, M. Weight change-adjusted effects of gastric bypass surgery on glucose metabolism: two- and 10-year results from the Swedish obese subjects (SOS) study. Diabetes Care 39, 625–631 (2016).

PubMed  Google Scholar 

Mcglone, E. et al. Bariatric surgery for patients with type 2 diabetes mellitus requiring insulin: clinical outcome and cost-effectiveness analyses. PLoS Med. 17, 5 (2020).

Google Scholar 

Nosso, G. et al. Comparative effects of Roux-en-Y gastric bypass and sleeve gastrectomy on glucose homeostasis and incretin hormones in obese type 2 diabetic patients: a one-year prospective study. Horm. Metab. Res. 48, 312–317 (2016).

CAS  PubMed  Google Scholar 

Nannipieri, M. et al. Roux-en-Y gastric bypass and sleeve gastrectomy: mechanisms of diabetes remission and role of gut hormones. J. Clin. Endocrinol. Metab. 98, 4391–4399 (2013).

CAS  PubMed  Google Scholar 

Keidar, A. et al. Roux-en-Y gastric bypass vs sleeve gastrectomy for obese patients with type 2 diabetes: a randomised trial. Diabetologia 56, 1914–1918 (2013).

PubMed  Google Scholar 

Lee, W.-J. et al. Gastric bypass vs sleeve gastrectomy for type 2 diabetes mellitus: a randomized controlled trial. Arch. Surg. 146, 143–148 (2011).

PubMed  Google Scholar 

Blackstone, R., Bunt, J., Celaya Cortes, M. & Sugerman, H. Type 2 diabetes after gastric bypass: remission in five models using HbA1c, fasting blood glucose, and medication status. Surg. Obes. Relat. Dis. 8, 548–555 (2012).

PubMed  Google Scholar 

Zechner, J. F. et al. Weight-independent effects of Roux-en-Y gastric bypass on glucose homeostasis via melanocortin-4 receptors in mice and humans. Gastroenterology 144, 580–590.e7 (2013).

CAS  PubMed  Google Scholar 

Pontiroli, A. E., Gniuli, D. & Mingrone, G. Early effects of gastric banding (LGB) and of biliopancreatic diversion (BPD) on insulin sensitivity and on glucose and insulin response after OGTT. Obes. Surg. 20, 474–479 (2010).

PubMed  Google Scholar 

Petrov, M. S. & Taylor, R. Intra-pancreatic fat deposition: bringing hidden fat to the fore. Nat. Rev. Gastroenterol. Hepatol. 19, 153–168 (2022).

PubMed  Google Scholar 

Steven, S. et al. Very low-calorie diet and 6 months of weight stability in type 2 diabetes: pathophysiological changes in responders and nonresponders. Diabetes Care 39, 808–815 (2016).

CAS  PubMed  Google Scholar 

Chambers, A. P. et al. Regulation of gastric emptying rate and its role in nutrient-induced GLP-1 secretion in rats after vertical sleeve gastrectomy. AJP Endocrinol. Metab. 306, E424–E432 (2014).

CAS  Google Scholar 

Cavin, J. B. et al. Differences in alimentary glucose absorption and intestinal disposal of blood glucose after Roux-en-Y gastric bypass vs sleeve gastrectomy. Gastroenterology 150, 454–464.e9 (2016).

CAS  PubMed  Google Scholar 

Saeidi, N. et al. Reprogramming of intestinal glucose metabolism and glycemic control in rats after gastric bypass. Science 341, 406–410 (2013).

CAS  PubMed  PubMed Central  Google Scholar 

Ku, C. R. et al. Intestinal glycolysis visualized by FDG PET/CT correlates with glucose decrement after gastrectomy. Diabetes 66, 385–391 (2017).

CAS  PubMed  Google Scholar 

Franquet, E. et al. PET-CT reveals increased intestinal glucose uptake after gastric surgery. Surg. Obes. Relat. Dis. 15, 643–649 (2019).

PubMed  PubMed Central  Google Scholar 

Ben-Zvi, D. et al. Time-dependent molecular responses differ between gastric bypass and dieting but are conserved across species. Cell Metab. 28, 310–323.e6 (2018). This study examined the molecular changes in multiple tissues after RYGB in mice and humans, identifying key molecular responses.

CAS  PubMed  PubMed Central  Google Scholar 

Kim, K.-S. et al. Vertical sleeve gastrectomy induces enteroendocrine cell differentiation of intestinal stem cells through bile acid signaling. JCI Insight 1, e154302 (2022). This paper finds bile acid-driven increases in enteroendocrine cell differentiation in a mouse model of VSG.

Google Scholar 

Chambers, A. P. et al. Weight-independent changes in blood glucose homeostasis after gastric bypass or vertical sleeve gastrectomy in rats. Gastroenterology 141, 950–958 (2011).

CAS  PubMed  Google Scholar 

Yan, Y. et al. Roux-en-Y gastric bypass surgery suppresses hepatic gluconeogenesis and increases intestinal gluconeogenesis in a T2DM rat model. Obes. Surg. 26, 2683–2690 (2016).

PubMed  Google Scholar 

Stefater, M. A. et al. Portal venous metabolite profiling after RYGB in male rats highlights changes in gut-liver axis. J. Endocrinol. 4, bvaa003 (2020). This paper compared the metabolomic profile of metabolites in the portal vein after RYGB in rats to sham surgery control rats.

Google Scholar 

Bozadjieva-Kramer, N. et al. Intestinal-derived FGF15 protects against deleterious effects of vertical sleeve gastrectomy in mice. Nat. Commun. 12, 4768 (2021).

CAS  PubMed  PubMed Central  Google Scholar 

Rabl, C. & Campos, G. M. The impact of bariatric surgery on nonalcoholic steatohepatitis. Semin. Liver Dis. 32, 80–91 (2012).

CAS  PubMed  Google Scholar 

Whang, E. et al. Vertical sleeve gastrectomy attenuates the progression of non-alcoholic steatohepatitis in mice on a high-fat high-cholesterol diet. Obes. Surg. 29, 2420–2429 (2019).

PubMed  PubMed Central  Google Scholar 

Verbeek, J. et al. Roux-en-y gastric bypass attenuates hepatic mitochondrial dysfunction in mice with non-alcoholic steatohepatitis. Gut 64, 673–683 (2015).

CAS  PubMed  Google Scholar 

Romero-Gómez, M., Zelber-Sagi, S. & Trenell, M. Treatment of NAFLD with diet, physical activity and exercise. J. Hepatol. 67, 829–846 (2017).

PubMed  Google Scholar 

Myronovych, A. et al. The role of small heterodimer partner in nonalcoholic fatty liver disease improvement after sleeve gastrectomy in mice. Obesity 22, 2301–2311 (2014).

CAS  PubMed  Google Scholar 

Ben-Haroush Schyr, R. et al. Sleeve gastrectomy suppresses hepatic glucose production and increases hepatic insulin clearance independent of weight loss. Diabetes 70, 2289–2298 (2021).

PubMed  PubMed Central  Google Scholar 

Mazzini, G. S. et al. Gastric bypass increases circulating bile acids and activates hepatic farnesoid X receptor (FXR) but requires intact peroxisome proliferator activator receptor alpha (PPARα) signaling to significantly reduce liver fat content. J. Gastrointest. Surg. 25, 871–879 (2021).

PubMed  Google Scholar 

Grayson, B. E. et al. Bariatric surgery emphasizes biological sex differences in rodent hepatic lipid handling. Biol. Sex Differ. 8, 4 (2017).

PubMed  PubMed Central  Google Scholar 

Klein, S. et al. Gastric bypass surgery improves metabolic and hepatic abnormalities associated with nonalcoholic fatty liver disease. Gastroenterology 130, 1564–1572 (2006).

CAS  PubMed  Google Scholar 

Hankir, M. K. et al. Gastric bypass surgery recruits a gut PPAR-α-striatal D1R pathway to reduce fat appetite in obese rats. Cell Metab. 25, 335–344 (2017).

CAS  PubMed  Google Scholar 

Hutch, C. R. et al. Oea signaling pathways and the metabolic benefits of vertical sleeve gastrectomy. Ann. Surg. 271, 509–518 (2020).

PubMed  Google Scholar 

Karthickeyan, C. K., Mehrabian, M. & Lusis, A. J. Sex differences in metabolism and cardiometabolic disorders. Curr. Opin. Lipidol. 29, 404–410 (2018).

Google Scholar 

Hutch, C. R. et al. Diet-dependent sex differences in the response to vertical sleeve gastrectomy. Am. J. Physiol. Endocrinol. Metab. 321, E11–E23 (2021).

CAS  PubMed  PubMed Central  Google Scholar 

Bhatia, H., Pattnaik, B. R. & Datta, M. Inhibition of mitochondrial β-oxidation by miR-107 promotes hepatic lipid accumulation and impairs glucose tolerance in vivo. Int. J. Obes. 40, 861–869 (2016).

CAS  Google Scholar 

Bhatia, H., Verma, G. & Datta, M. MiR-107 orchestrates ER stress induction and lipid accumulation by post-transcriptional regulation of fatty acid synthase in hepatocytes. Biochim. Biophys. Acta Gene Regul. Mech. 1839, 334–343 (2014).

CAS  Google Scholar 

Kornfeld, J. W. et al. Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b. Nature 494, 111–115 (2013).

CAS  PubMed  Google Scholar 

Trajkovski, M. et al. MicroRNAs 103 and 107 regulate insulin sensitivity. Nature 474, 649–653 (2011).

CAS  PubMed  Google Scholar