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Abstract

Background and Aims:

The prevalence of diabetes is increasing worldwide, and most of the cases are type 2 diabetes mellitus. The relationship between type 2 diabetes mellitus and obesity is well established, and surgical treatment is widely used for obese patients with type 2 diabetes mellitus. The aim was to present current knowledge about the possible mechanisms responsible for glucose control after surgical procedures and to review the surgical treatment results.

Material and Methods:

Medical literature was searched for the articles presenting the impact of surgical treatment on glycemic control, long-term results, and possible mechanisms of action among obese individuals with type 2 diabetes mellitus.

Results:

Remission of type 2 diabetes mellitus after bariatric surgery depends on the definition of the remission used. Complete remission rate after surgery with the new criteria is lower than was considered before. Randomized controlled studies demonstrate that surgery is superior to best medical treatment for the patients with type 2 diabetes mellitus. The recurrence of type 2 diabetes mellitus after bariatric surgery is observed in up to 40% of cases with ≥5 years of follow-up. Despite the recurrence of type 2 diabetes mellitus in this group, better glycemic control and lower risk of macrovascular complications are present. Incretin effects on glycemic control after bariatric surgery are well described, but the role of other possible mechanisms (bile acids, microbiota, intestinal gluconeogenesis) in humans is unclear.

Conclusion:

Surgery is an effective treatment of type 2 diabetes mellitus in obese patients. The most optimal surgical procedure for the treatment of obese patients with type 2 diabetes mellitus is still to be established. More research is needed to explore the mechanisms of glycemic control after bariatric surgery.

Keywords

Bariatric surgery gastric bypass sleeve gastrectomy type 2 diabetes mellitus

Introduction

There are two main forms of diabetes (1). Type 1 diabetes results in insulin deficiency due to autoimmune-mediated destruction of pancreatic β-cell islets, and exogenous insulin is essential for survival and prevention of ketoacidosis. In type 2 diabetes mellitus (T2DM), either insulin resistance or abnormal insulin secretion may predominate, and if diet alone or oral hypoglycemic agents is not enough for control of blood glucose levels, exogenous insulin may be used. The T2DM accounts for over 90% of all cases.

The prevalence of diabetes increases worldwide both in developed and in developing nations, and most of the cases are of T2DM, which is strongly associated with decreased physical activity and obesity (2). The relationship between T2DM and obesity was established by two population-based studies showing that the age-adjusted relative risk of developing T2DM for individuals with a body mass index (BMI) ≥35 kg/m² is 93 (95% confidence interval (CI) = 81–107) for women and 42 (95% CI = 22–81) for men as compared with those who had a BMI <22 and <23 kg/m², respectively (3, 4).

The mortality rate among people with T2DM is increased because of the higher incidence of macrovascular disease. The population-based study, which compared T2DM individuals with the non-diabetics, has shown that T2DM, independent of other known cardiovascular risk factors, is associated with twofold to threefold increased risk of myocardial infarction or stroke and twofold increased risk of death (5).

Chronic hyperglycemia is associated with both macrovascular and microvascular (nephropathy, retinopathy, and neuropathy) complications. The main goal of the treatment of T2DM is prevention of these complications. However, the benefit of lowering or intending to lower blood glucose per se on patient-relevant outcomes such as mortality and cardiovascular disease is unclear (6). Moreover, the optimal choice of glycemic target is also a matter of debate. Currently, American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) recommend a glycosylated hemoglobin A1c (HbA1c) level of less than 7.0% as the standard glycemic treatment goal (7). Despite this, some studies used target HbA1c level of 6.0%–6.5% for intensive glycemic control and 7.0%–8.0% for conventional glycemic control (8 –10). Recent meta-analysis of randomized controlled trials (RCTs) compared targeting intensive glycemic control with conventional glycemic control and did not find significant differences for all-cause and cardiovascular mortality. Targeting intensive glycemic control reduced the risk of microvascular complications while increasing the risk of hypoglycemia and serious adverse events (6). What long-term clinical implications symptomatic severe hypoglycemia can have are unknown. However, some data suggest a link between symptomatic severe hypoglycemia and increased risk of death (11) or the risk of dementia among older patients with T2DM (12).

Surgical Treatment of T2DM in Overweight and Obese Patients

Most T2DM patients are overweight or obese (BMI >30 kg/m²) and have increased visceral adiposity (13, 14). Moreover, it is suggested that accumulation of lipids in organs such as the liver, skeletal muscle, and b-cells of the pancreas, outside the classical adipose tissue depots, may induce insulin resistance, metabolic syndrome, and increase cardiovascular risk through a process known as “lipotoxicity” (15, 16). Weight loss can restore insulin sensitivity, and patients can even achieve remission of T2DM. In Swedish Obese Subjects (SOS) study, weight loss by conventional medical therapy was associated with 21.0% remission rate of T2DM at 2 years and 12.0% at 10 years (17). However, weight maintenance after conventional medical therapy is a problem, and most of the patients experience weight regain (18, 19). Inability to maintain weight loss has impact on the recurrence of T2DM and increasing incidence of new cases of T2DM among the patients treated with conventional medical therapy (20).

Surgery versus Conventional Treatment

Bariatric surgery may offer a more durable solution. Recent meta-analyses of 16 studies with 6131 patients and mean 17.3-month follow-up have found bariatric surgery to be superior to conventional medical therapy in achieving significantly more weight loss, HbA1c and fasting plasma glucose (FPG) reduction, and diabetes remission (21). The overall T2DM remission rate in this meta-analysis was 63.5% in the surgery group versus 15.6% in the conventional group (p < 0.001). The remission rate in individual studies was assessed as it was provided in each study. However, the definition of T2DM remission varies among the studies. In order to standardize the definition of complete remission of T2DM after bariatric surgery, ADA suggested definition based on return to “normal” measures of glucose metabolism (HbA1c in the normal range, FPG <5.7 mmol/L) of at least 1-year duration without medication or ongoing procedures (22). Pournaras et al. (23) compared T2DM remission rate after gastric bypass with a median of 2 years of follow-up based on new ADA and previous definitions and found that it was significantly lower with new definition (40.6% vs 57.5%; p = 0.003). This percentage is much lower than presented in the meta-analysis by Buchwald et al. (24), where T2DM remission rate after gastric bypass with less than 2 years of follow-up was 81.6%. These differences one more time emphasize the importance of precise reporting of the measures of glucose metabolism after bariatric surgery and questions relevance of data based on previous definitions such as “no usage of anti-diabetic medications.”

Four RCTs compared conventional treatment with various types of surgical procedures in the treatment of T2DM. Dixon et al. (25) randomized 60 obese patients (BMI: 30–40 kg/m²) with recently diagnosed (<2 years) T2DM into laparoscopic adjustable gastric banding (AGB) and lifestyle modification with reduced energy intake and increased physical activity groups. Preoperatively, 90% of patients had pharmacological treatment and only one had insulin; baseline average HbA1c in surgery and conventional treatment groups was 7.8% and 7.6%, respectively. Patients in both groups had best available medical treatment for T2DM. Remission of T2DM (FPG <7.0 mmol/L and HbA1c <6.2%, without glycemic therapy) at 2 years was 73% in the surgery group and 13% in the conventional treatment group (p < .001). In the surgery group, no major complications occurred, and 10% of patients needed revisional surgery within 1 year (25). As expected, the degree of postoperative weight loss correlated well with diabetes remission in this study.

Ikramuddin et al. (26) in a multicenter RCT compared Roux-en-Y gastric bypass (RYGB) with lifestyle and intensive medical management for the patients with T2DM for at least 6-month duration and BMI between 30 and 40 kg/m². A total of 60 patients were included in each group. Average duration of T2DM and percentage of patients on insulin treatment in lifestyle-medical treatment and RYGB groups were 9.1 and 8.6 years, and 43% and 62%, respectively. Average HbA1c at baseline in both groups was 9.6%. After 1 year, 49% of patients in RYGB and 19% in lifestyle-medical management group achieved primary end point (HbA_1c <7.0%, low-density lipoprotein (LDL) cholesterol level <2.59 mmol/L, and systolic blood pressure <130 mmHg). HbA_1c <6.0% was observed in 44% of the RYGB and 9% of the lifestyle-medical management group patients. In the conventional treatment group, 15 serious adverse events were observed as compared to 22 in the RYGB group.

Mingrone et al. (27) randomized 60 patients with T2DM with at least 5-year duration and BMI ≥35 kg/m² either to conventional medical treatment or to surgery (gastric bypass or biliopancreatic diversion (BPD)). A total of 20 patients were included in each group. Average duration of T2DM was 6 years, and average preoperative HbA1c was in a range from 8.5% to 8.9%. Remission of T2DM at 2 years (FPG <5.6 mmol/L, HbA1c <6.5%, without anti-diabetic medications) was achieved in 75% of gastric bypass and 95% of BPD patients. No patient in conventional therapy group achieved target glycemic control (p < 0.001). One patient in each surgical group required additional operation within 1 year after primary surgery.

Schauer et al. (28, 29) in a single-center RCT included 150 patients with T2DM and BMI 27–43 kg/m² into intensive medical therapy alone or intensive medical therapy plus either RYGB or sleeve gastrectomy (SG) group. The number of patients was equally distributed between the treatment arms. The average duration of T2DM was between 8.2 and 8.9 years, with 44% patients in every group using insulin for glycemic control. The average baseline HbA1c was in a range from 8.9% to 9.5%. Serious adverse events requiring hospitalization in medical therapy, RYGB, and SG groups were 9%, 22%, and 8%, respectively. The primary end point was HbA1c <6.0%, with or without diabetes medications. At 1-year follow-up, 12% in the medical-therapy group, 42% in the RYGB group (p = 0.002), and 37% in the SG group (p = 0.008) achieved primary end point. After 3 years, the primary end point criteria were met by 5% of the patients in the medical-therapy group as compared with 38% of those in the RYGB group (p < 0.001) and 24% of those in the SG group (p = 0.01).

One study (25) included patients with mild T2DM; in other studies (26 –28), patients had on average 6- to 9-year duration of T2DM with inadequate glycemic control (HbA1c from 8.5% to 9.6%). Surgery in all studies resulted in significantly better glycemic control, and more patients achieved primary end points.

Three studies (25, 26, 28) included patients with T2DM and lower BMI than is currently recommended for surgical treatment (30). In all studies, surgery was superior to lifestyle and best medical treatment in achieving glycemic control. These data would suggest that patients with BMI 30–35 kg/m² could benefit from surgical treatment; however, long-term follow-up is needed to draw definitive conclusions.

In all four studies (25 –28), more adverse events were observed after surgery as compared to lifestyle and intensive medical treatment. The difference is mainly due to immediate postoperative and late surgical complications, which are associated with surgical technique itself. However, some negative metabolic consequences may also occur after surgical procedures. Ikramuddin et al. (26) found higher rate of symptomatic hypoglycemia with neuroglycopenia in the RYGB group as compared to conservative treatment group, 8.3% versus 3.3%, respectively. This finding is supported by the data from a Swedish nationwide cohort study, where incidence of hospitalization for hypoglycemia after RYGB was found to be 0.2% as compared to only 0.04% in the reference population (31). Most cases of hypoglycemia after RYGB are successfully treated with low carbohydrate diet or with diazoxide, octreotide, acarbose or calcium-channel blockers (32). In severe cases, surgical intervention (reversal of RYGB, conversion of RYGB to SG, placement of adjustable gastric band over RYGB, or even subtotal/total pancreatectomy) has been proposed. The other issue is nutrient deficiencies. Iron deficiency was present in 11%–21.7%, one or more vitamin B deficiency in 18.3%, and hypoalbuminemia in 6.7%–11% of cases after RYGB or BPD (26, 27). Life-long surveillance and adequate supplementation of nutrients are essential for bariatric surgery patients. However, only one third of patients 5 years after RYGB take prescribed supplementation regularly (33).

Long-Term Results of Surgical Treatment of T2DM

The SOS study presents the longest available follow-up of patients after bariatric surgery. It is a prospective nonrandomized trial comparing surgery and conventional treatment for obesity. The data on the incidence and remission of T2DM are also available. After 10 years, the incidence of T2DM was significantly lower in the surgical group (7% vs 24%, p < 0.001). The patients after surgery were more likely to have remission of T2DM; however, the remission rate after 10 years was half of that observed after 2 years, 36% and 72%, respectively (20). Recurrence of T2DM after bariatric surgery over time was observed also in the other studies, with 19%–43% of the patients starting anti-diabetic medications again 5 or more years after surgery (34 –36). Higher recurrence rate of T2DM was observed among the patients with weight regain and among those who were treated with insulin preoperatively (36). However, despite the fact that about half of the patients need anti-diabetic medications, they could still experience better control of the disease than before surgery (34) and lower risk of macrovascular complications. In SOS trial, significant 44% reduction in myocardial infarction incidence at 13 years was found in the subgroup of patients with T2DM (37).

Sg versus Gastric Bypass

Three published RCTs, so far, have compared SG with gastric bypass in the treatment of T2DM. Lee et al. (38) from Taiwan in a RCT compared SG to mini gastric bypass (MGB) with 120 cm biliopancreatic limb. A total of 60 patients with BMI 25–35 kg/m², T2DM, and mean HbA1c level of 10.0% were equally distributed between the groups. There was no mortality or major complications in either group. Remission of T2DM (FPG <7.0 mmol/L, HbA1c <6.5% without medications) was achieved in 93% in the MGB group and in 47% in the SG group (p = 0.02). However, the authors did not use calibration tube to standardize the diameter of SG and have done approximately 2-cm-wide sleeve along the less curved side. In the recent study, Abd Ellatif et al. (39) performed multivariate analysis of factors that can influence success after SG. They found that smaller bougie size and shorter distance from pylorus were associated with significant higher percentage of excess weight loss (%EWL) (39). The lack of standardization of the procedure such as SG can lead to lower %EWL and remission rate of T2DM. The other issue worth discussing in the Lee et al. (38) study was a very high remission rate of T2DM in the MGB group among the patients with low BMI. Scopinaro et al. (40) have done BPD for the patients with the same range of BMI and used the same definition of remission of T2DM. Remission rate was 67%, much lower than that reported by Lee et al. This difference may be partially explained by the fact that Asian population has a higher amount of body and visceral fat at any given BMI as compared to Europeans (41). However, the findings of this study should be confirmed by other RCTs in different populations.

Schauer and colleagues (28, 29, 42) explored an effect of RYGB and SG on the treatment of T2DM (primary outcome was HbA1c <6.0%, with or without diabetes medications) among patients with BMI 27–43 kg/m², as part of their RCT comparing surgery versus best medical treatment. A total of 50 patients were included in each group. The rate of serious adverse events requiring hospitalization was higher after RYGB, 22% versus 8%. In all, 40% of the patients in the RYGB and 37% in the SG group achieved primary end point. The difference was not significant. However, when subgroups of RYGB and SG patients were compared 2 years after surgery, absolute reduction in truncal fat was significantly higher after RYGB. Similar results were found in the study comparing RYGB to vertical banded gastroplasty (43), suggesting that SG mimics some effects of purely restrictive procedures. In contrast, Keidar et al. (44) found better remission of T2DM after SG as compared to RYGB. They randomized 41 patients with T2DM and BMI >35 kg/m², and after 1 year, 47.4% of RYGB and 77.8% of SG patients had normal or improved FPG and normal HbA1c without anti-diabetic medications. The data about postoperative complications were not presented.

Recent meta-analysis tried to compare RYGB to SG in the treatment of T2DM (45). The conclusion was that RYGB is more effective than SG for the treatment of T2DM. Calculations of remission of T2DM were done based on the data of 60 patients from Lee et al.’s (38) study and on 14 patients from other two studies (46, 47). So far, no definitive conclusions can be drawn regarding which procedure is more effective in the treatment of T2DM. More randomized studies are needed to answer this question in the future. Even if SG will be found to be inferior in the treatment of T2DM, it has one strong argument that has to be taken into account when surgery for T2DM patients is planned. In cases of failure, it can easily be converted into gastric bypass, BPD with duodenal switch, single anastomosis duodeno-ileal bypass with SG (48), or even to newer procedures such as SG with an ileal interposition or duodenojejunal bypass with sleeve (49, 50).

Possible Mechanisms of Glycemic Control after Bariatric Surgery

Weight loss, as discussed previously, has influence on control of T2DM. Despite weight loss, short-term (7 days) 50% caloric restriction can increase insulin sensitivity and insulin secretion. Moreover, it was observed that metabolic control worsens with increasing total calorie amount even if weight loss is maintained (51). Caloric restriction may partially explain rapid improvement in blood glucose after bariatric surgery, but other proposed mechanisms may also play an important role (52, 53).

Hindgut Theory

The hindgut or incretin theory suggests that increased glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) release, because of rapid nutrient delivery to the distal small intestine, are responsible for improved glucose metabolism (54). GLP-1 increase was found after RYGB, SG, and BPD, but not after AGB, suggesting that the latter procedure may be considered as “pure” restrictive (55 –57). Incretins are released from enteroendocrine L-cells lining the distal gastrointestinal tract. Based on these observations, Mason (58) proposed ileal interposition as an operation for the treatment of T2DM. Experimental studies in rats have found that ileal interposition improves glucose and lipid metabolism and delays diabetes onset in UC Davis-T2DM rats, the rat model that is most similar to clinical T2DM in humans (59, 60). De Paula et al. (50) suggested a SG associated with an ileal interposition for morbid obese patients with T2DM and termed the technique as “neuroendocrine break.”

Foregut Theory

The foregut theory concentrates on the role of exclusion of nutrients from the duodenum and jejunum. It is supposed that nutrients in the proximal small bowel may stimulate release of unidentified anti-incretin factor, which may be responsible for decreased incretin secretion. Operations that bypass the duodenum and jejunum may restore balance between anti-incretin and incretin secretion and improve glucose control (61). The alternative therapeutic approach, such as duodenojejunal bypass sleeve (DJBS), was developed based on the foregut theory. A flexible 60-cm sleeve, which is implanted and removed endoscopically, was designed to bypass the duodenum and the first part of the jejunum (62). De Jonge et al. (63) found that DJBS increased postprandial release of GLP-1 and lowered secretion of gastric inhibitory polypeptide (GIP) within 1 week after implantation before any significant weight loss occurred. De Moura et al. (64) evaluated DJBS in the treatment of T2DM patients with an average BMI of 44.8. A total of 22 subjects were enrolled in this 52-week prospective trial, and 13 completed the study. Of the 22 subjects, 16 had an HbA1c <7% at the end of the study, compared with only 1 of 22 at baseline. However, the hypothesis of foregut was questioned during recent years as it was found that GLP-1 and weight loss increase and glucose metabolism improves after SG, the operation where nutrients are in direct contact with proximal small bowel (57).

Midgut Theory

Recently, the midgut or intestinal/hepatic regulation hypothesis was proposed. It is suggested that derivation of food into the distal small intestine after gastric bypass activates gluconeogenic enzymes and increases glucose concentrations in the portal vein, which is sensed and transmitted to the brain by vagal afferents. This results in increased suppression of hepatic glucose production by insulin and improves glucose homeostasis (65). In mice with gastroenterostomy, a model of gastric bypass without reduction of the stomach, an increase in intestinal gluconeogenesis is observed as compared to gastric band (66). Moreover, the effect of gastroenterostomy is abolished in glucose transporter 2 (GLUT-2) knockout mice, which are devoid of the capacity of portal glucose sensing, and in mice with portal vein denervation, suggesting that intestinal gluconeogenesis may be regarded as a key signal to the brain responsible for the control of glucose and energy homeostasis (65). The main question is still validity of this hypothesis in humans and how it can interact with various gastrointestinal hormonal signals.

Bile Acids

Bile acids (BA) are essential in the absorption of dietary lipid and through farnesoid X receptor (FXR) modulates BA homeostasis and hepatic lipid metabolism. A study in rodents found that BA given with food results in increased energy expenditure in fat and muscle cells and prevents obesity and insulin resistance (67). This metabolic effect is mediated through cell-membrane C-protein-coupled receptor TGR5 and is FXR-independent (67). In humans, after oral glucose tolerance test (OGTT), as compared to water ingestion, BA increase more than twofold and remain elevated during the 2-h test. Individuals with impaired glucose tolerance (IGT) exhibit a blunted excursion of BA after OGTT (68). The findings suggest direct correlation between BA levels and insulin resistance. In such a case, therapeutic manipulation of BA level may have positive metabolic effects and improve glycemic control. The studies with BA sequestrant colesevelam, a high-capacity BA-binding polymer, in humans with T2DM show significant reduction in LDL cholesterol, FPG, and HbA1c (69, 70). Patti et al. (71) have found an increase in fasting total serum BA and individual BA concentrations of taurodeoxycholic, glycocholic, glycochenodeoxycholic, and glycodeoxycholic acids levels 2–4 years after gastric bypass, as compared to non-operated individuals matched for preoperative or current BMI. It was suggested that this increase in serum BA levels might contribute to observed improvement in insulin sensitivity, incretin secretion, and postprandial glycemia after gastric bypass. Furthermore, Pournaras et al. (72) observed an early, over a 6-week period, increase in fasting total serum BA and plasma fibroblast growth factor 19 (FGF19) after RYGB, but not after AGB. An increase in plasma FGF19 is stimulated by bile acid absorption in the terminal ileum and may result from bile deviation to the ileum in RYGB. What effect bile deviation to ileum may have on glycemic control is still unknown. Steinert et al. (73) compared RYGB with SG in a RCT and have shown a similar increase in total basal plasma bile acids after both procedures with higher increase in postprandial basal acids after RYGB. There were different patterns in the increases of the BA levels and incretin secretion after surgery. Improved glycemic control and increased incretin secretion were observed already after 1 week; however, basal and postprandial BA significantly increased only 1 year after surgery (73). These data do not support the hypothesis that BA are responsible for early increase in incretin secretion after bariatric surgery. Some other possible mechanisms of direct BA action on insulin resistance were suggested. BA may inhibit gluconeogenesis, facilitate insulin-dependent control of glucose metabolism in liver, and through increase in FGF19 levels improve insulin resistance (72).

Microbiota

Recent studies show that changes in human microbiota could have an impact on weight loss and glycemic control after bariatric surgery. The large intestine has a variety of microbes responsible for different metabolic pathways (74). The bacteroidetes and the firmicutes are dominant in human gut (75). Reduced proportions of bacteroidetes are found in obese people, while individuals with diabetes have reduced proportions of firmicutes and clostridia (75, 76). RYGB can alter microbiota populations by proportional decrease in firmicutes and increase in Gammaproteobacteria (77). Liou et al. (78) used a mouse model of gastric bypass to examine changes in the gut microbiota and its impact on metabolic parameters. Gastric bypass in mice induced essential and rapid changes to the gut microbiota that were similar to those previously observed in humans. Transfer of gut microbiota from gastric bypass mice to non-operated germ-free mice resulted in improved insulin sensitivity and reduced fasting triglyceride levels (78). However, the impact of microbiota on metabolic changes observed after RYGB is not fully understood. There is evidence that interaction between host and gut bacteria can be achieved by bacterial metabolites such as short-chain fatty acids or lipopolysaccharides from microbial membranes (79).

Further Research Directions

The surgical treatment of T2DM improves glycemic control and allows long-term remission in at least one third of the cases. However, surgical treatment appears much more beneficial in preventing rather than curing T2DM. People with IGT are at high risk for developing diabetes and macrovascular disease (80, 81). It is unknown whether treatment of IGT can delay or prevent the appearance of macrovascular disease (82). The data from SOS study show that bariatric surgery substantially decreases the incidence of T2DM especially among patients with IGT (83). Future RCTs should explore the benefits of surgical treatment among the patients with IGT.

The other important issue is impact of surgery on microvascular disease. It is known that active medical intervention can reduce the risk of microvascular complications among the patients with T2DM (84 –86). Bariatric surgery results in better glycemic control than active medical intervention and is effective in treating and preventing microvascular complications of T2DM (87). No RCT, however, has explored the effect of bariatric surgery in stopping or reversing the microvascular complications of T2DM, for example, diabetic kidney disease. Such data may improve our knowledge about the efficiency of bariatric surgery in the treatment of T2DM.

More research is needed in the field of new interventions or operations in the treatment of T2DM. DJBS has proven to be safe and effective in correcting glucose homeostasis. It is a step toward developing less invasive endoscopic procedures that can be routinely used for a broader population. However, wider usage of this technique is limited by complications such as device migration and gastrointestinal bleeding (64), as well as relatively high costs. SG with an ileal interposition must be compared to the established surgical procedures such as gastric bypass or SG in RCTs. Only in such studies the pure effect of ileal interposition may be revealed.

Footnotes

Declaration of Conflicting Interests

The authors declare that there is no conflict of interest.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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Surgery in the treatment of type 2 diabetes mellitus

Abstract

Background and Aims:

Material and Methods:

Results:

Conclusion:

Keywords

Introduction

Surgical Treatment of T2DM in Overweight and Obese Patients

Surgery versus Conventional Treatment

Long-Term Results of Surgical Treatment of T2DM

Sg versus Gastric Bypass

Possible Mechanisms of Glycemic Control after Bariatric Surgery

Hindgut Theory

Foregut Theory

Midgut Theory

Bile Acids

Microbiota

Further Research Directions

Footnotes

Declaration of Conflicting Interests

Funding

References