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Published in final edited form as: Diabetes Res Clin Pract. 2023 Apr 8;199:110667. doi: 10.1016/j.diabres.2023.110667

The Role of Weight Control in the Management of Type 2 Diabetes Mellitus: Bariatric Surgery

Thomas Q Xu 1, Tammy Lyn Kindel 1,*
PMCID: PMC10192054  NIHMSID: NIHMS1891820  PMID: 37037264

Summary

Diabetes mellitus is one of the major epidemics in the United States. It is heavily associated with obesity and multiple metabolic derangements that lead to long term morbidity, mortality as well as financial burden. Although medical therapy has been the mainstay in the management of diabetes mellitus, there remains a large portion of this patient population which struggles to obtain adequate glycemic control and long-term weight control with medical management alone.

Bariatric surgery is a powerful tool in combating diabetes mellitus and affects glucose homeostasis through a variety of pathways. While it does provide a durable pathway for weight loss, improvement in glucose homeostasis is not only affected by the weight loss seen after bariatric surgery. Changes in gut hormone secretion, insulin regulation, and gut microbial composition also affect how these operations improve glucose homeostasis. Through improvement in the management of diabetes mellitus, comorbidities including cardiovascular disease, in turn demonstrate improvement.

In this article, we will discuss the role of bariatric (metabolic) surgery as it relates to long term weight loss and the impact that weight loss has on improvement in diabetes mellitus.

Types of Metabolic Surgery

The history of modern metabolic surgery extends back to the work of Dr Edward Mason who performed a side-to-side anastomosis between the very upper third of a divided stomach and a loop of jejunum to treat duodenal ulcer disease with the side effect of weight loss [1]. Metabolic surgery has undergone many different iterations and variations through the resultant decades, but in the modern medical world there are three major operations that bariatric surgeons perform: minimally invasive sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB) and duodenal switch.

The SG was first utilized in a staged approach for patients with very high body weights where the perioperative risk was unacceptably high to proceed with a duodenal switch. Patients would first undergo SG with the goal of major weight loss prior to undergoing the second stage, duodenal switch [2]. However, given the major weight loss seen with a primary SG, it became a stand-alone bariatric operation [3]. In the SG, the majority of the fundus and body of the stomach are resected creating a tubularized stomach. Due to its lower risk profile as well as being less technically challenging than other bariatric operations, it has become the most commonly performed bariatric procedure in the United States.

The RYGB has the most extensive history as a bariatric procedure [4]. A RYGB involves creation of a small gastric pouch and two separate, enteric anastomosis (a gastrojejunostomy and a jejunojejunostomy). The biliopancreatic diversion with duodenal switch is the operation with the highest amount of potential weight loss, but also with the highest risk profile. After completion of a SG, two enteric separate anastomoses are created: a duodeno-ileostomy and an ileo-ileostomy [5]. Due to the high degree of technical expertise required as well as the risk of associated malnutrition, this procedure is performed only at select centers in specific patient populations prepared to manage the long-term micronutrient deficiencies and side effects.

Weight loss outcomes with metabolic surgery

Metabolic surgery is able to induce long term weight loss through a variety of different pathways and mechanisms. Historically, we grouped the effects of metabolic surgery into two major distinct processes: 1) caloric restriction and 2) malabsorption. We now know that these two groupings do not apply to the physiology of food intake and metabolic regulation and consider both SG and RYGB to be metabolic surgeries which act via neuro-hormonal mechanisms. These factors include anatomic remodeling of the gastrointestinal tract which may alter meal-induced thermogenesis, modulation of the hypothalamic neural circuits involved in appetite regulation as well as energy balance, altered perception of taste, changes in post-operative food preferences and eating patterns, as well as changes in gut-brain signaling pathways [6]. Many of these mechanisms may also be important for changes in glucose homeostasis after metabolic surgery and will be discussed in greater length below.

Weight loss has been studied in both short-term and longer- term outcomes after metabolic surgery. Typically, patients undergoing SG can be expected to lose roughly 50 to 75% of their excess body weight at one year postoperatively, which is defined as the difference between their ideal body weight and their actual body weight [7]. Patients undergoing RYGB can be expected to lose 60 to 80% of their excess body weight at one year postoperatively [8]. Duodenal switch patients may lose 85-90% of their excess body weight.

In the Swedish Obese Subjects study, body weight remained reduced by 16% at ten years after bariatric surgery while in a matched, control group, it increased by 1.6% [9]. In a prospective Utah-based study in over 1000 obese patients that underwent RYGB, weight loss reached 28% up to 6 years postoperatively and 94% of patients who underwent RYGB maintained at least 20% of their initial weight loss at 2 years postoperatively and 76% maintained at least 20% at six years [10].

These findings of durable, long-term weight loss after bariatric surgery have led some authors to hypothesize that these operations change the body’s “set point” for weight in the subcortical areas of the brain [11]. Postoperatively, the body’s “set point” is lowered for patients which allows for the initial weight loss to be maintained. However, we would add that metabolic surgery allows for the acceptance of a new body weight set point that may be gastrointestinal anatomy-dependent. If the surgical anatomy is removed, the new set point is often not defended to the extent seen with intact surgical anatomy. This is clearly seen in cases of RYGB reversal on patients of normal body weight, where patients are at risk to regain substantial weight, often to the elevated body weight of pre-surgical levels, with return of obesity-associated medical conditions [12].

Mechanisms for improvement in type 2 diabetes mellitus after metabolic surgery

Weight Loss.

Weight loss is a strong mechanism for the effect of metabolic surgery on type 2 diabetes mellitus, independent of surgical type. In the first few weeks after surgery, patients may only be consuming 400-600 Kcal/day. Caloric restriction has been shown to have beneficial effects on glycemic control. Studies of patients with diabetes mellitus have demonstrated that caloric restriction that is similar to the caloric restriction of post-operative RYGB patients during the first 10 to 20 days postoperatively yields similar effects on insulin sensitivity and blood glucose [13]. Acute caloric restriction rapidly improves hepatic insulin sensitivity due to reduced hepatic glycogen content and glucose production [14]. This suggests increased insulin sensitivity is at least in part modulated by the profound weight loss after metabolic surgery.

Foregut Exclusion Hypothesis.

The existence of an entero-hormonal mechanism to explain diabetes improvement after metabolic surgery has been hypothesized for many years. The foregut hypothesis was first postulated after a series of experiments demonstrated improved glucose homeostasis after duodenojejunal bypass, a stomach sparing operation that diverts nutrients from the pyloric region to the jejunum, with bypass of the duodenum and proximal jejunum. [15]. In a study of rodent duodenojejunal bypass, no changes in weight loss or food intake were observed, but glucose homeostasis improved [16]. When the duodenum was restored in continuity with the alimentary tract, glycemic control subsequently worsened [17].

More recent studies have taken this a step further with the development of endoscopic therapies designed to ablate duodenal mucosa [18]. Studies have shown improvement in glycemic control with reduction of hemoglobin A1c at six months; this improvement has been sustained through two years [19].

Hindgut Hypothesis.

This hypothesis postulates that the hindgut plays a major role in the beneficial effects of metabolic surgery. The re-routing of food through a surgically altered digestive tract results in increased nutrient exposure to the hind gut which causes overstimulation of specialized enteroendocrine cells, such as L-cells [20]. L-cells release gut hormones such as GLP-1 and PYY, both of which enhance satiety and are implicated in weight loss effects after metabolic surgery [21]. These hormones also play a major role in glycemic control and insulin regulation. GLP-1 stimulates insulin release in response to food intake and enhances insulin biosynthesis. It also exhibits appetite and body weight regulatory properties. It also exerts glucoregulatory actions by slowing gastric emptying, inducing glucose-dependent inhibition of glucagon secretion and stimulating pancreatic beta cell proliferation, and differentiation of islet progenitors and islet neogenesis. The role of GLP-1 in glucose homeostasis have been well documented in patients after RYGB who develop postprandial hyperinsulinemic hypoglycemia. These individuals have a greater meal-induced insulin and GLP-1 response. Studies have demonstrated that administration of a GLP-1 antagonist corrects this hypoglycemia by suppressing insulin secretion, supporting the critical role of GLP-1 in glucose homeostasis [22, 23].

PYY is a peptide hormone synthesized by the L cells of the distal gastrointestinal tract and released in response to food ingestion. PYY is a peptide hormone synthesized by the L cells of the distal gastrointestinal tract and released in response to food ingestion. Up-regulation of these molecules after metabolic surgery may provide an explanation for the weight loss as well as improved glycemic control post-operatively [24]. This hypothesis has been supported by experimental surgeries like ileal transposition [25]. In this operation there is interposition of a segment of ileum with intact neural and vascular supply to the proximal intestine. The total length of the alimentary tract does not change but the exposure of the transposed ileum to undigested nutrients is greatly enhanced. In animal models, rodents have exaggerated levels of PYY, GLP-1 and enteroglucagon responses [26, 27]. These rodents exhibit reduced food intake, weight loss, as well as improved insulin sensitivity and glycemic control. Several studies have reported increased levels of PYY, both fasting and meal-stimulated, in patients after RYGB [28, 29]. After SG, studies have demonstrated increases in PYY, though to a lesser so greater than after RYGB [30]. While the hindgut hypothesis may apply to RYGB and duodenal switch operations, similar increases of GLP-1 and PYY are seen after SG which also rapidly alters glucose homeostasis, suggesting rapid nutrient delivery to the distal small bowel may not be the critical factor driving enhanced GLP-1 and PYY secretion after metabolic surgery.

Orexigenic hormones.

Ghrelin is a gut hormone that is secreted mainly by the oxyntic glands of the fundus of the stomach and in smaller amounts in the rest of the small bowel. It is involved in the release of growth hormone and stimulates pre-meal hunger. Individuals with obesity present with a decreased suppression of ghrelin after a meal. Ghrelin inhibits insulin secretion as well and can suppress the insulin-sensitizing hormone adiponectin, negatively affecting glucose homeostasis. Because of these negative effects on glucose homeostasis, the reduction of ghrelin after bariatric surgery could be beneficial for overall glycemic control [31].

In randomized trials, ghrelin levels have been found to be lower in patients that underwent SG versus RYGB, likely due to the complete removal of the gastric fundus [32]. This decrease in ghrelin has been seen as early as one week after SG and could play a role in glucose homeostasis changes [33]. Levels of ghrelin are reduced even at one year after SG [34]. Sustained reduction in ghrelin levels after SG have also been correlated with improvements in glucose homeostasis and dyslipidemia [35].

Gut Microbiome.

Alterations in the composition and diversity of the gut microbiome are associated with obesity and diabetes mellitus [36]. This causal relationship is supported by data from studies demonstrating that fecal transplantation of the gut microbiota from metabolically abnormal individuals can transmit the abnormal phenotype to gnotobiotic mice and transplantation of fecal microbiota from healthy lean donors to those with metabolic syndrome improves their insulin sensitivity [37].

RYGB is associated with an increase in post-operative microbial diversity/richness. The ratio of Bacteroidetes to Firmicutes species increases after bariatric surgery as well as the gene richness and overall bacterial diversity which is thought to facilitate the clinical benefits of bariatric surgery which include decreased body weight, fat mass, improved HgA1c and inflammatory markers [38]. After SG, the ratio of Bacteroidetes and Fusobacteria also increased at one year postoperatively [39]. Further, transfer of the fecal microbiota from patients who had RYGB to germ-free mice resulted in reduced accumulation of body fat in recipient mice [40]. Fecal microbiota transfer from post-RYGB patients to obese individuals has also been shown to improve insulin sensitivity, suggesting improved glucose homeostasis is related to changes in gut microbiota [41].

Diabetes-specific Outcomes with Metabolic Surgery

There has been considerable evidence to support that metabolic surgery helps with the treatment of diabetes mellitus. Metabolic surgery improves glucose homeostasis. Patients after metabolic surgery have decreased hemoglobin A1c as well as concomitant increases in circulating incretin concentrations, improved insulin sensitivity and beta cell function. Many patients who have undergone metabolic surgery have complete remission of their diabetes, as defined as having a normal hemoglobin A1c without needing anti-hyperglycemic medication at one year.

In patients who underwent bariatric surgery versus those who did not, the patients who underwent bariatric surgery had a dramatically higher rate of diabetes remission, even at two years. Patients with just medical management of diabetes mellitus had essentially a zero percent chance of remission at two years, whereas patients who underwent bariatric surgery had a 75-95% chance of remission at two years [42].

There have been multiple randomized controlled trials evaluating the impact metabolic surgery has on diabetes mellitus. In the STAMPEDE trial, patients with type 2 diabetes mellitus and a BMI between 27 and 43 were randomized to receive either intensive medical therapy or intensive medical therapy in combination with bariatric surgery (SG or RYGB). This trial demonstrated that bariatric surgery was superior to intensive medical therapy in terms of glycemic control and weight reduction [43]. Patients who underwent SG or RYGB were significantly more likely to achieve and maintain a hemoglobin A1c below 6.0%; most of the surgical patients achieved this without the use of diabetic medications. Surgical patients at five years required fewer diabetes medications, including insulin.

Randomized controlled trials have also investigated if there is a difference between SG and RYGB as it relates to the management of type 2 diabetes mellitus. SM-BOSS compared the difference in weight loss between SG and RYGB in patients with severe obesity [44]. A subset of both of these groups had patients with type 2 diabetes mellitus (26% in SG cohort and 27% in RYGB cohort). Remission was achieved in 62% of the SG cohort and in 68% of the RYGB cohort with no significant difference between the two groups. No significant difference between groups was found related to fasting glucose or hemoglobin A1c. However, the STAMPEDE trial demonstrated that RYGB was superior to SG with regards to the number of antidiabetic medications taken [43]. In SLEEVEPASS, patients were also randomized to undergo SG or RYGB [45]. Ten-year follow up did not demonstrate non-equivalence between SG and RYGB in the rate of type 2 diabetes remission. In addition, there was no difference in fasting glucose or hemoglobin A1c between the two groups at ten-year follow-up.

Given the heterogeneity in the severity of type 2 diabetes mellitus, predictive models have been created to evaluate the likelihood of type 2 diabetes mellitus remission. Common predictive models include: DiaRem score [46], ABCD score [47], Ad-DiaRem [48], DiaBetter [49] and the IMS score [50]. The DiaRem score is comprised of age, hemoglobin A1c, and insulin usage. Table 1 highlights the components that are taken into account for various different diabetes mellitus remission predictive models.

Table 1:

Components of Different Diabetes Remission Predictive Models

Predictive Model Components
DiaRem Age, hemoglobin A1c, insulin usage
Ad-DiaRem Age, hemoglobin A1c, insulin usage, number of anti-diabetes medications
ABCD Age, BMI, C-peptide, duration of type 2 diabetes mellitus
DiaBetter Hemoglobin A1c, duration of diabetes (years), number of antidiabetes medications
IMS Number of diabetes medications, insulin use, duration of diabetes (years), glycemic control
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A meta-analysis comparing these different predictive models demonstrated that Ad-DiaRem had the highest sensitivity at 91% while IMS had the highest specificity at 86% [51]. Pre-operatively glycemic control appears to be a consistent predictor of type 2 diabetes remission after metabolic surgery across models.

Metabolic Surgery and Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus

Metabolic surgery has many benefits for diabetic patients; specifically, it improves morbidity and mortality from cardiovascular disease [52]. High-quality randomized controlled trials have been performed for metabolic surgery in the management of poorly controlled diabetic patients but few randomized trials have looked at cardiovascular disease endpoints as its primary outcome. Observational studies have demonstrated improved cardiovascular outcomes following bariatric and metabolic surgery. The Swedish Obese Subjects (SOS) study was a prospective, matched cohort study that demonstrated that metabolic surgery as compared to non-surgical treatment of obesity improved surrogate markers of cardiovascular disease including: new-onset diabetes, hypertriglyceridemia, low high-density lipoprotein levels and hypertension. Macrovascular complication of cardiovascular disease including myocardial infarction, cerebrovascular accident and lower extremity amputation were reduced in the surgical arm and mortality was decreased [53]. Other large retrospective studies have shown similar findings after bariatric and metabolic surgery, namely a reduction in major adverse cardiovascular events [54, 55].

Studies have demonstrated a significant reduction in any adverse cardiovascular event among patients with type 2 diabetes mellitus undergoing metabolic surgery compared to non-surgical controls [56]. In addition, all-cause mortality risk in individuals with type 2 diabetes mellitus was reduced by almost half in surgical patients as compared to the non-surgical controls [57]. Even with adjustments to take other confounding factors into consideration, all-cause mortality risk was reduced by forty percent in surgical patients as compared to the controls.

Coronary Artery Disease.

Observational studies suggest an improvement in coronary artery disease after metabolic and bariatric surgery. Atherogenic lipoprotein levels, which are linked closely to atherosclerotic heart disease, are improved after metabolic and bariatric surgery [58]. After metabolic surgery, patients also require fewer cardiac revascularization procedures, suggesting an improvement in coronary artery disease [59]. A meta-analysis that compared almost 30,000 patients undergoing metabolic surgery with greater than 160,000 control patients from 14 studies demonstrated a risk reduction in myocardial infarction by almost half within the surgical arm as compared to the non-surgical controls [60].

Heart Failure.

Observational studies have demonstrated a reduction in the incidence of heart failure following metabolic and bariatric surgery consistent with previous studies that have shown that weight loss is associated with improvements in cardiac function [61]. Systolic function can potentially improve after metabolic surgery, particularly in patients with non-ischemic cardiomyopathy. A retrospective, controlled study involving 22 patients with systolic congestive heart failure demonstrated improvements in left ventricular ejection fraction, NYHA class, and readmission rates in the surgical arm as compared to the control group [62]. Studies have suggested that this improvement is related to beneficial, structural remodeling within the myocardium [63].

Metabolic Surgery and Non-alcoholic Steatohepatitis in Patients with Type 2 Diabetes Mellitus

Type 2 diabetes is intrinsically connected to the pathogenesis associated with non-alcoholic steatohepatitis through hyperinsulinemia and insulin resistance [64]. Diabetic patients with known fatty liver disease have been shown to have improved glycemic control as compared to diabetic patients without fatty liver disease [65]. Studies have demonstrated that as compared to matched cohorts of patients who did not undergo bariatric surgery, patients that underwent bariatric surgery demonstrated improved five-year hemoglobin A1c levels as well as non-worsening of liver fibrosis [64].

Conclusion

Metabolic surgery has been shown to impact the management of diabetes mellitus through a variety of mechanisms, both weight-dependent as well as weight-independent. While the exact mechanisms are not known, we are closer to understanding how metabolic surgery contributes to better glucose homeostasis and in turn improvements in diabetes mellitus management. The beneficial impacts of improved diabetes control from metabolic surgery extend to improvements in cardiovascular health, one of the major sources of morbidity and mortality in the United States.

Figure 1: Sleeve Gastrectomy.

Figure 1:

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Reprinted with permission from Phillips BT, Shikora SA. The history of metabolic and bariatric surgery: Development of standards for patient safety and efficacy. Metabolism. 2018 Feb;79:97-107. doi: 10.1016/j.metabol.2017.12.010. Epub 2018 Jan 5. PMID: 29307519.

Figure 2: Roux-en-Y Gastric Bypass.

Figure 2:

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Reprinted with permission from Phillips BT, Shikora SA. The history of metabolic and bariatric surgery: Development of standards for patient safety and efficacy. Metabolism. 2018 Feb;79:97-107. doi: 10.1016/j.metabol.2017.12.010. Epub 2018 Jan 5. PMID: 29307519.

Footnotes

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Conflict of interest

The authors declare no conflict of interest.

References

  • 1.Mason EE, Ito C. Gastric bypass in obesity. Surg Clin North Am. 1967; 47:1345. [DOI] [PubMed] [Google Scholar]
  • 2.Hess DS, Hess DW. Biliopancreatic diversion with a duodenal switch. Obes Surg. 1998; 8:267–82. [DOI] [PubMed] [Google Scholar]
  • 3.Rosenthal RJ. International sleeve gastrectomy expert panel consensus statement: best practice guidelines based on >12,000 cases. Surg Obes Relat Dis. 2012; 8:8–19. [DOI] [PubMed] [Google Scholar]
  • 4.Wittgrove AC, Clark GW, Tremblay LJ. Laparoscopic gastric bypass, Roux en Y: preliminary report of five vases. Obes Surg. 1994; 4(4): 353–7. [DOI] [PubMed] [Google Scholar]
  • 5.Scopinaro N, Gianetta E, Civalleri D, Bonalumi U, Bachi V. Biliopancreatic bypass to obesity: II. Initial experience in man. Br J Surg. 1979; 55:518. [DOI] [PubMed] [Google Scholar]
  • 6.Sumithran P, Prendergast LA, Delbridge E, Purcell K<, Shulkes A, Kriketos A, Proietto J. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011; 365(17):1597–604. [DOI] [PubMed] [Google Scholar]
  • 7.Grönroos S, Helmiö M, Juuti A, Tiusanen R, Hurme S, Löyttyniemi E, Ovaska J, Leivonen M, Peromaa-Haavisto P, Mäklin S, Sintonen H, Sammalkorpi H, Nuutila P, Salminen P. Effect of Laparoscopic Sleeve Gastrectomy vs Roux-en-Y Gastric Bypass on Weight Loss and Quality of Life at 7 Years in Patients With Morbid Obesity: The SLEEVEPASS Randomized Clinical Trial. JAMA Surg. 2021. Feb 1;156(2):137–146. doi: 10.1001/jamasurg.2020.5666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Sjöström CD, Lissner L, Wedel H, Sjöström L. Reduction in incidence of diabetes, hypertension and lipid disturbances after intentional weight loss induced by bariatric surgery: the SOS Intervention Study. Obes Res. 1999;7:477–484. [DOI] [PubMed] [Google Scholar]
  • 9.Sjöström L, Gummesson A, Sjöström CD, Narbro K, Peltonen M, Wedel H, Jacobson P. Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish Obese Subjects Study): a prospective, controlled intervention trial. Lanc Oncol. 2009;10:653–662. [DOI] [PubMed] [Google Scholar]
  • 10.Adams TD, Gress RE, Smith SC, Halverson RC, Simper SC, Rosamond WD, Lamonte MJ, Stroup AM, Hunt SC. Long-term mortality after gastric bypass surgery. N Engl J Med. 2007. Aug 23;357(8):753–61. doi: 10.1056/NEJMoa066603. [DOI] [PubMed] [Google Scholar]
  • 11.Hao Z, Mumphrey MB, Morrison CD, Münzberg H, Ye J, Berthoud HR. Does gastric bypass surgery change body weight set point? Int J Obes Suppl. 2016. Dec;6(Suppl 1):S37–S43. doi: 10.1038/ijosup.2016.9. Epub 2016 Nov 16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Moon RC, Frommelt A, Teixeira AF, Jawad MA. Indications and outcomes of reversal of Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2015. Jul-Aug;11(4):821–6. doi: 10.1016/j.soard.2014.11.026. Epub 2014 Dec 3. [DOI] [PubMed] [Google Scholar]
  • 13.Abbasi J Unveiling the “magic” of diabetes remission after weight-loss surgery. JAMA. 2017;317:571–574. doi: 10.1001/jama.2017.0020. [DOI] [PubMed] [Google Scholar]
  • 14.Kirk E, Reeds DN, Finck BN, Mayurranjan SM, Patterson BW, Klein S. Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction. Gastroenterology. 2009;136:1552–60. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Hickey MS, Pories WJ, MacDonald KG Jr, Cory KA, Dohm GL, Swanson MS, Israel RG, Barakat HA, Considine RV, Caro JF, Houmard JA. A new paradigm for type 2 diabetes mellitus: could it be a disease of the foregut? Ann Surg. 1998. May;227(5):637–43; discussion 643-4. doi: 10.1097/00000658-199805000-00004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Rubino F, Marescaux J. Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease. Ann Surg. 2004. Jan;239(1):1–11. doi: 10.1097/01.sla.0000102989.54824.fc. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Rubino F, Forgione A, Cummings DE, Vix M, Gnuli D, Mingrone G, Castagneto M, Marescaux J. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg. 2006. Nov;244(5):741–9. doi: 10.1097/01.sla.0000224726.61448.1b. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.van Baar ACG, Beuers U, Wong K, Haidry R, Costamagna G, Hafedi A, Deviere J, Ghosh SS, Lopez-Talavera JC, Rodriguez L, Galvao Neto MP, Sanyal A, Bergman JJGHM. Endoscopic duodenal mucosal resurfacing improves glycaemic and hepatic indices in type 2 diabetes: 6-month multicentre results. JHEP Rep. 2019. Nov 5;1(6):429–437. doi: 10.1016/j.jhepr.2019.10.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.van Baar ACG, Devière J, Hopkins D, Crenier L, Holleman F, Galvão Neto MP, Becerra P, Vignolo P, Rodriguez Grunert L, Mingrone G, Costamagna G, Nieuwdorp M, Guidone C, Haidry RJ, Hayee B, Magee C, Carlos Lopez-Talavera J, White K, Bhambhani V, Cozzi E, Rajagopalan H, J G H M Bergman J. Durable metabolic improvements 2 years after duodenal mucosal resurfacing (DMR) in patients with type 2 diabetes (REVITA-1 Study). Diabetes Res Clin Pract. 2022. Feb;184:109194. doi: 10.1016/j.diabres.2022.109194. Epub 2022 Jan 13. [DOI] [PubMed] [Google Scholar]
  • 20.Batterham RL, Cummings DE. Mechanisms of Diabetes Improvement Following Bariatric/Metabolic Surgery. Diabetes Care. 2016. Jun;39(6):893–901. doi: 10.2337/dc16-0145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Holst JJ, Madsbad S, Bojsen-Møller KN, Svane MS, Jørgensen NB, Dirksen C, Martinussen C. Mechanisms in bariatric surgery: Gut hormones, diabetes resolution, and weight loss. Surg Obes Relat Dis. 2018. May;14(5):708–714. doi: 10.1016/j.soard.2018.03.003. Epub 2018 Mar 8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Smith EP, Polanco G, Yaqub A, Salehi M. Altered glucose metabolism after bariatric surgery: What's GLP-1 got to do with it? Metabolism. 2018. Jun;83:159–166. doi: 10.1016/j.metabol.2017.10.014. Epub 2017 Nov 4. [DOI] [PubMed] [Google Scholar]
  • 23.Salehi M, D'Alessio DA. Mechanisms of surgical control of type 2 diabetes: GLP-1 is the key factor-Maybe. Surg Obes Relat Dis. 2016. Jul;12(6):1230–5. doi: 10.1016/j.soard.2016.05.008. Epub 2016 May 11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Svane MS, Bojsen-Møller KN, Madsbad S, Holst JJ. Updates in weight loss surgery and gastrointestinal peptides. Curr Opin Endocrinol Diabetes Obes. 2015. Feb;22(1):21–8. doi: 10.1097/MED.0000000000000131. [DOI] [PubMed] [Google Scholar]
  • 25.Strader AD. Ileal transposition provides insight into the effectiveness of gastric bypass surgery. Physiol Behav. 2006. Jun 30;88(3):277–82. doi: 10.1016/j.physbeh.2006.05.034. Epub 2006 Jun 19. [DOI] [PubMed] [Google Scholar]
  • 26.Duan J, Zhou J, Ren F, Tan C, Wang S, Yuan L. Mid to distal small bowel resection with the preservation of the terminal ileum improves glucose homeostasis in diabetic rats by activating the hindgut-dependent mechanism. J Gastrointest Surg. 2014. Jun;18(6):1186–93. doi: 10.1007/s11605-014-2507-3. Epub 2014 Apr 1. [DOI] [PubMed] [Google Scholar]
  • 27.Imoto H, Shibata C, Ikezawa F, Kikuchi D, Someya S, Miura K, Naitoh T, Unno M. Effects of duodeno-jejunal bypass on glucose metabolism in obese rats with type 2 diabetes. Surg Today. 2014. Feb;44(2):340–8. doi: 10.1007/s00595-013-0638-x. Epub 2013 Jun 20. [DOI] [PubMed] [Google Scholar]
  • 28.Chan JL, Mun EC, Stoyneva V, Mantzoros CS, Goldfine AB. Peptide YY levels are elevated after gastric bypass surgery. Obesity (Silver Spring). 2006. Feb;14(2):194–8. doi: 10.1038/oby.2006.25. [DOI] [PubMed] [Google Scholar]
  • 29.Kowalka AM, Alexiadou K, Cuenco J, Clarke RE, Minnion J, Williams EL, Bech P, Purkayastha S, Ahmed AR, Takats Z, Whitwell HJ, Romero MG, Bloom SR, Camuzeaux S, Lewis MR, Khoo B, Tan TM. The postprandial secretion of peptide YY1-36 and 3-36 in obesity is differentially increased after gastric bypass versus sleeve gastrectomy. Clin Endocrinol (Oxf). 2022. Nov 7. doi: 10.1111/cen.14846. Epub ahead of print. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Yang J, Gao Z, Williams DB, Wang C, Lee S, Zhou X, Qiu P. Effect of laparoscopic Roux-en-Y gastric bypass versus laparoscopic sleeve gastrectomy on fasting gastrointestinal and pancreatic peptide hormones: A prospective nonrandomized trial. Surg Obes Relat Dis. 2018. Oct;14(10):1521–1529. doi: 10.1016/j.soard.2018.06.003. Epub 2018 Jun 14. [DOI] [PubMed] [Google Scholar]
  • 31.Makris MC, Alexandrou A, Papatsoutsos EG, Malietzis G, Tsilimigras DI, Guerron AD, Moris D. Ghrelin and Obesity: Identifying Gaps and Dispelling Myths. A Reappraisal. In Vivo. 2017. Nov-Dec;31(6):1047–1050. doi: 10.21873/invivo.11168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Kalinowski P, Paluszkiewicz R, Wroblewski T, Remiszewski P, Grodzicki M, Bartoszewicz Z, Krawczyk M. Ghrelin, leptin, and glycemic control after sleeve gastrectomy versus Roux-en-Y gastric bypass-results of a randomized clinical trial. Surg Obes Relat Dis. 2017. Feb;13(2):181–188. doi: 10.1016/j.soard.2016.08.025. Epub 2016 Aug 18. [DOI] [PubMed] [Google Scholar]
  • 33.Wang L, Shi C, Yan H, Xia M, Zhu X, Sun X, Yang X, Jiao H, Wu H, Lou W, Chang X, Gao X, Bian H. Acute Effects of Sleeve Gastrectomy on Glucose Variability, Glucose Metabolism, and Ghrelin Response. Obes Surg. 2021. Sep;31(9):4005–4014. doi: 10.1007/s11695-021-05534-3. Epub 2021 Jul 8. [DOI] [PubMed] [Google Scholar]
  • 34.Anderson B, Switzer NJ, Almamar A, Shi X, Birch DW, Karmali S. The impact of laparoscopic sleeve gastrectomy on plasma ghrelin levels: a systematic review. Obes Surg. 2013. Sep;23(9):1476–80. doi: 10.1007/s11695-013-0999-7. [DOI] [PubMed] [Google Scholar]
  • 35.Salman MA, El-Ghobary M, Soliman A, El Sherbiny M, Abouelregal TE, Albitar A, Abdallah A, Mikhail HMS, Nafea MA, Sultan AAEA, Elshafey HE, Shaaban HE, Azzam A, GabAllah GMK, Salman AA. Long-Term Changes in Leptin, Chemerin, and Ghrelin Levels Following Roux-en-Y Gastric Bypass and Laparoscopic Sleeve Gastrectomy. Obes Surg. 2020. Mar;30(3):1052–1060. doi: 10.1007/s11695-019-04254-z. [DOI] [PubMed] [Google Scholar]
  • 36.Ridaura VK, Faith JJ, Rey FE, et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013;341:1241214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Debédat J, Le Roy T, Voland L, Belda E, Alili R, Adriouch S, Bel Lassen P, Kasahara K, Hutchison E, Genser L, Torres L, Gamblin C, Rouault C, Zucker JD, Kapel N, Poitou C, Marcelin G, Rey FE, Aron-Wisnewsky J, Clément K. The human gut microbiota contributes to type-2 diabetes non-resolution 5-years after Roux-en-Y gastric bypass. Gut Microbes. 2022. Jan-Dec;14(1):2050635. doi: 10.1080/19490976.2022.2050635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Debédat J, Clément K, Aron-Wisnewsky J. Gut Microbiota Dysbiosis in Human Obesity: Impact of Bariatric Surgery. Curr Obes Rep. 2019. Sep;8(3):229–242. doi: 10.1007/s13679-019-00351-3. [DOI] [PubMed] [Google Scholar]
  • 39.Fukuda N, Ojima T, Hayata K, Katsuda M, Kitadani J, Takeuchi A, Goda T, Ueda Y, Iwakura H, Nishi M, Yamaue H. Laparoscopic sleeve gastrectomy for morbid obesity improves gut microbiota balance, increases colonic mucosal-associated invariant T cells and decreases circulating regulatory T cells. Surg Endosc. 2022. Oct;36(10):7312–7324. doi: 10.1007/s00464-022-09122-z. Epub 2022 Feb 19. [DOI] [PubMed] [Google Scholar]
  • 40.Ilhan ZE, DiBaise JK, Dautel SE, Isern NG, Kim YM, Hoyt DW, Schepmoes AA, Brewer HM, Weitz KK, Metz TO, Crowell MD, Kang DW, Rittmann BE , Krajmalnik-Brown R. Temporospatial shifts in the human gut microbiome and metabolome after gastric bypass surgery. NPJ Biofilms Microbiomes. 2020. Mar 13;6(1):12. doi: 10.1038/s41522-020-0122-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.de Groot P, Scheithauer T, Bakker GJ, Prodan A, Levin E, Khan MT, Herrema H, Ackermans M, Serlie MJM, de Brauw M, Levels JHM, Sales A, Gerdes VE, Ståhlman M, Schimmel AWM, Dallinga-Thie G, Bergman JJ, Holleman F, Hoekstra JBL, Groen A, Bäckhed F, Nieuwdorp M. Donor metabolic characteristics drive effects of faecal microbiota transplantation on recipient insulin sensitivity, energy expenditure and intestinal transit time. Gut. 2020. Mar;69(3):502–512. doi: 10.1136/gutjnl-2019-318320. Epub 2019 May 30. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Koliaki C, Liatis S, le Roux CW, Kokkinos A. The role of bariatric surgery to treat diabetes: current challenges and perspectives. BMC Endocr Disord. 2017. Aug 10;17(1):50. doi: 10.1186/s12902-017-0202-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Aminian A, Brethauer SA, Navaneethan SD, Singh RP, Pothier CE, Nissen SE, Kashyap SR; STAMPEDE Investigators. Bariatric Surgery versus Intensive Medical Therapy for Diabetes - 5-Year Outcomes. N Engl J Med. 2017. Feb 16;376(7):641–651. doi: 10.1056/NEJMoa1600869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Peterli R, Wölnerhanssen BK, Peters T, Vetter D, Kröll D, Borbély Y, Schultes B, Beglinger C, Drewe J, Schiesser M, Nett P, Bueter M. Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss in Patients With Morbid Obesity: The SM-BOSS Randomized Clinical Trial. JAMA. 2018. Jan 16;319(3):255–265. doi: 10.1001/jama.2017.20897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Salminen P, Grönroos S, Helmiö M, Hurme S, Juuti A, Juusela R, Peromaa-Haavisto P, Leivonen M, Nuutila P, Ovaska J. Effect of Laparoscopic Sleeve Gastrectomy vs Roux-en-Y Gastric Bypass on Weight Loss, Comorbidities, and Reflux at 10 Years in Adult Patients With Obesity: The SLEEVEPASS Randomized Clinical Trial. JAMA Surg. 2022. Aug 1;157(8):656–666. doi: 10.1001/jamasurg.2022.2229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Still CD, Wood GC, Benotti P, et al. Preoperative prediction of type 2 diabetes remission after Roux-en-Y gastric bypass surgery: a retrospective cohort study. Lancet Diabetes Endocrinol. 2014;2(1):38–45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Lee WJ, Hur KY, Lakadawala M, et al. Predicting success of metabolic surgery: age, body mass index, C-peptide, and duration score. Surgery for Obesity and Related Diseases. 2013;9(3):379–84. [DOI] [PubMed] [Google Scholar]
  • 48.Aron-Wisnewsky J, Sokolovska N, Liu Y, et al. The advanced-DiaRem score improves prediction of diabetes remission 1 year post-Roux-en-Y gastric bypass. Diabetologia. 2017;60(10):1892–902. [DOI] [PubMed] [Google Scholar]
  • 49.Pucci A, Tymoszuk U, Cheung WH, et al. Type 2 diabetes remission 2 years post Roux-en-Y gastric bypass and sleeve gastrectomy: the role of the weight loss and comparison of DiaRem and DiaBetter scores. Diabet Med. 2018;35(3):360–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Aminian A, Brethauer SA, Andalib A, Nowacki AS, Jimenez A, Corcelles R, Hanipah ZN, Punchai S, Bhatt DL, Kashyap SR, Burguera B, Lacy AM, Vidal J, Schauer PR. Individualized Metabolic Surgery Score: Procedure Selection Based on Diabetes Severity. Ann Surg. 2017. Oct;266(4):650–657. doi: 10.1097/SLA.0000000000002407. [DOI] [PubMed] [Google Scholar]
  • 51.de Abreu Sesconetto L, da Silva RBR, Galletti RP, Agareno GA, Colonno BB, de Sousa JHB, Tustumi F. Scores for Predicting Diabetes Remission in Bariatric Surgery: a Systematic Review and Meta-analysis. Obes Surg. 2023. Feb;33(2):600–610. doi: 10.1007/s11695-022-06382-5. Epub 2022 Dec 1. [DOI] [PubMed] [Google Scholar]
  • 52.Eliasson B, Liakopoulos V, Franzén S, Näslund I, Svensson AM, Ottosson J, Gudbjörnsdottir S. Cardiovascular disease and mortality in patients with type 2 diabetes after bariatric surgery in Sweden: a nationwide, matched, observational cohort study. Lancet Diabetes Endocrinol. 2015. Nov;3(11):847–54. doi: 10.1016/S2213-8587(15)00334-4. Epub 2015 Sep 28. [DOI] [PubMed] [Google Scholar]
  • 53.Sjostrom L Review of the key results from the Swedish Obese Subjects (SOS) trial—a prospective controlled intervention study of bariatric surgery. J Intern Med 2013;273:219–34. [DOI] [PubMed] [Google Scholar]
  • 54.Flum DR, Dellinger EP. Impact of gastric bypass operation on survival: a population-based analysis. J Am Coll Surg 2004;199:543–51. [DOI] [PubMed] [Google Scholar]
  • 55.Christou NV, Sampalis JS, Liberman M, Look D, Auger S, McLean AP, et al. Surgery decreases long-term mortality, morbidity, and health care use in morbidly obese patients. Ann Surg 2004;240:416–23; discussion 23-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Fisher DP, Johnson E, Haneuse S, Arterburn D, Coleman KJ, O'Connor PJ, O'Brien R, Bogart A, Theis MK, Anau J, Schroeder EB, Sidney S. Association Between Bariatric Surgery and Macrovascular Disease Outcomes in Patients With Type 2 Diabetes and Severe Obesity. JAMA. 2018. Oct 16;320(15):1570–1582. doi: 10.1001/jama.2018.14619. Erratum in: JAMA. 2018 Dec 11;320(22):2381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57.Aminian A, Zajichek A, Arterburn DE, Wolski KE, Brethauer SA, Schauer PR, Kattan MW, Nissen SE. Association of Metabolic Surgery With Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes and Obesity. JAMA. 2019. Oct 1;322(13):1271–1282. doi: 10.1001/jama.2019.14231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Bhatt DL, Aminian A, Kashyap SR, Kirwan JP, Wolski K, Brethauer SA, Hazen SL, Nissen SE, Schauer PR. Cardiovascular Biomarkers After Metabolic Surgery Versus Medical Therapy for Diabetes. J Am Coll Cardiol. 2019. Jul 16;74(2):261–263. doi: 10.1016/j.jacc.2019.04.058. [DOI] [PubMed] [Google Scholar]
  • 59.Michaels AD, Mehaffey JH, Hawkins RB, Kern JA, Schirmer BD, Hallowell PT. Bariatric surgery reduces long-term rates of cardiac events and need for coronary revascularization: a propensity-matched analysis. Surg Endosc. 2020. Jun;34(6):2638–2643. doi: 10.1007/s00464-019-07036-x. Epub 2019 Aug 2. [DOI] [PubMed] [Google Scholar]
  • 60.Kwok CS, Pradhan A, Khan MA, Anderson SG, Keavney BD, Myint PK, Mamas MA, Loke YK. Bariatric surgery and its impact on cardiovascular disease and mortality: a systematic review and meta-analysis. Int J Cardiol. 2014. Apr 15;173(1):20–8. doi: 10.1016/j.ijcard.2014.02.026. Epub 2014 Feb 24. [DOI] [PubMed] [Google Scholar]
  • 61.Aminian A, Zajichek A, Arterburn DE, Wolski KE, Brethauer SA, Schauer PR, Kattan MW, Nissen SE. Association of Metabolic Surgery With Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes and Obesity. JAMA. 2019. Oct 1;322(13):1271–1282. doi: 10.1001/jama.2019.14231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62.Mikhalkova D, Holman SR, Jiang H, Saghir M, Novak E, Coggan AR, O'Connor R, Bashir A, Jamal A, Ory DS, Schaffer JE, Eagon JC, Peterson LR. Bariatric Surgery-Induced Cardiac and Lipidomic Changes in Obesity-Related Heart Failure with Preserved Ejection Fraction. Obesity (Silver Spring). 2018. Feb;26(2):284–290. doi: 10.1002/oby.22038. Epub 2017 Dec 15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63.Leichman JG, Wilson EB, Scarborough T, Aguilar D, Miller CC 3rd, Yu S, Algahim MF, Reyes M, Moody FG, Taegtmeyer H. Dramatic reversal of derangements in muscle metabolism and left ventricular function after bariatric surgery. Am J Med. 2008. Nov;121(11):966–73. doi: 10.1016/j.amjmed.2008.06.033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 64.Alkharaiji M, Anyanwagu U, Crabtree T, Idris I. The metabolic and liver-related outcomes of bariatric surgery in adult patients with insulin-treated type 2 diabetes and nonalcoholic fatty liver disease at high risk of liver fibrosis. Surg Obes Relat Dis. 2021. Apr;17(4):792–798. doi: 10.1016/j.soard.2020.11.015. Epub 2020 Nov 20. [DOI] [PubMed] [Google Scholar]
  • 65.Vangoitsenhoven R, Wilson RL, Cherla DV, Tu C, Kashyap SR, Cummings DE, Schauer PR, Aminian A. Presence of Liver Steatosis Is Associated With Greater Diabetes Remission After Gastric Bypass Surgery. Diabetes Care. 2021. Feb;44(2):321–325. doi: 10.2337/dc20-0150. Epub 2020 Dec 15. [DOI] [PMC free article] [PubMed] [Google Scholar]

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