Existing bariatric surgery procedures
1.1 Vertical binding gastroplasty
Vertical banded gastroplasty (VBG) was pioneered by Mason. The procedure is as follows: the stomach is cut into two parts using a linear anastomosis and an adjustable band is installed to restrict the flow of food through the stomach. Unlike gastrointestinal bypass surgery, VBG does not alter the path of food digestion and absorption in the gastrointestinal tract. VBG was popular in the 1980s, but is now being phased out due to the high level of trauma. Niu Jianxiang, Department of General Surgery, Affiliated Hospital of Inner Mongolia Medical University
1.2 Laparoscopic adjustable gastric strapping
Laparoscopic adjustable gastric banding (LAGB) became popular in the 1990s, when the original gastric banding was improved due to the maturation of laparoscopic techniques. The principle of the procedure is as follows: a special restraint device is implanted laparoscopically. The degree of restraint is adjusted by injecting or withdrawing saline into the silicone tube, which is filled with saline and led out of the abdomen.
1.3 Roux-en-Y gastric bypass
The Roux-en-Y gastric bypass (RYGB) was first reported by Mason in 1967 and has undergone several improvements since then. RYGB is performed by cutting the stomach into two parts with a linear anastomosis – the proximal small sac-like stomach (<30mL in volume) and the distal stump stomach (<30mL in volume). After RYGB, 95% of the stomach, the entire duodenum, and a small portion of the jejunum are left open.
1.4 Biliopancreatic diversion
The concept of biliopancreatic diversion (BPD) was first introduced by Scopinaro in 1979. The procedure is as follows: a horizontal incision is made, the distal stomach is removed, 200-500 mL of the upper stomach is preserved, and then the remnant stomach is anastomosed with the distal 250 cm of the small intestine. Finally, the open small intestine (including duodenum, jejunum, and part of the proximal ileum) containing bile and pancreatic juice was anastomosed with the intestine 50 cm proximal to the ileocecal valve. In this 50-cm-long intestinal canal, digestive juices are mixed and digested with chyme, and fat and starch are absorbed.
1.5 Biliopancreatic diversion-duodenal transposition
Biliopancreatic diversion-duodenal transposition (BPD-DS) is a sleeve-shaped vertical gastrectomy rather than a BPD-style horizontal incision with a residual gastric volume of approximately 150-200 mL. The proximal duodenum is anastomosed with the ileum 2 cm distal to the pylorus (duodenal transposition) and the distal duodenum is sutured. In this way, the fundus of the stomach is almost completely removed, preserving only the cardia, pylorus, a very short section of duodenum, and the vagus nerve.
2. Surgical treatment of T2DM with BMI ≥ 35 kg/m2
2.1 Diabetes control after bariatric surgery
Several case-control studies have found significant and durable improvements in T2DM after VBG, LAGB, RYGB, and BPD in severely obese individuals (BMI ≥ 35 kg/m2). Since the descriptions of preoperative BMI, age, duration/condition of T2DM, and glycemia are not identical across studies, a direct comparison of the results of these studies is clearly inappropriate. The criteria for “remission” and “cure” of diabetes mellitus also vary, and in the case of glycosylated hemoglobin A1c (HbA1c), for example, the criteria for remission vary from < 6.0% to < 7.0%. conducted a Meta-analysis that enrolled 136 studies with 22,094 patients, with remission of T2DM defined as discontinuation of glucose-lowering medications and sustained normoglycemia, and found remission of T2DM in 77% of cases after bariatric surgery. However, the majority of the enrolled data were retrospective studies with only 1 to 3 years of postoperative follow-up. The T2DM remission rates by procedure were 48% for LAGB, 68% for VBG, 84% for RYGB, and 98% for BPD.
Two prospective studies looked at the efficacy of LAGB for glycemic control and found remission rates of 64% and 80% for postoperative T2DM, respectively. These remission rates appear to be high for LAGB, which may be related to the high number of subjects with prediabetes and mild diabetes in the study.
After RYGB, mean fasting blood glucose (FBG) decreased to 117 mg/dl versus 98 mg/dl, HbA1c decreased to 6.6% versus 5.6%, and the percentage of subjects discontinuing glucose-lowering medications was 89% versus 82%. 82%. Some of the subjects in the 2 studies were prediabetic, but the proportion of subjects with overt diabetes was higher in both studies than in the LAGB study mentioned above.
Scopinaro et al. retrospectively analyzed 201 patients with T2DM who underwent BPD. Ten years after surgery, 97% of cases remained normoglycemic (FBG < 110 mg/dl). The efficacy of laparoscopic sleeve gastrectomy (SG) versus RYGB for severely obese T2DM was compared. 39 cases were enrolled in each of the two procedures and were followed up to 1 year postoperatively, and the remaining weight loss in the SG group was found to be 63 ± 3%, with a T2DM remission rate of 85%, neither of which was significantly different from the RYGB group. In another study, 72 patients with T2DM were randomized to 3 groups with different weight loss procedures and discontinuation of glucose-lowering drugs after surgery, and the percentage of those with normal blood glucose was 17% in LAGB, 33% in SG, and 69% in RYGB.
Two prospective case-control studies observed glycemic changes before and after bariatric surgery. The Swedish Obesity Study (SOS), a large multicenter clinical study in this field, compared the efficacy of bariatric surgery (156 LAGB, 451 VBG, 34 RYGB) with oral weight loss medications for obesity. The weight loss effect after RYGB (-25.0 Kg) was better than that of LAGB (-13.2 Kg) and VBG (-16.5 Kg). Mean FBG tended to increase in the drug group (18.7% over 10 years) and decreased in the surgical group compared to preoperative (13.6% after 2 years and 2.5% after 10 years). The surgical group had a more than threefold reduction in the risk of developing diabetes at 10 years and was three times more likely to recover from diabetes.Dixon et al. conducted a randomized controlled trial designed to compare the efficacy of LAGB with conventional treatment for early (disease duration <2 years) mild type 2 diabetes with a BMI of 30-40 kg/m2 and found that LAGB resulted in significant reductions in FBG, HbA1c, and diabetes medication doses were significantly reduced.
2.2 Long-term benefits of bariatric surgery
Several retrospective studies of bariatric surgery for severe obesity with or without T2DM have found that surgery reduced overall mortality by approximately 33% to 89% compared with matched non-surgical individuals, so that such surgery prolongs patient life. In 1 large case-control study, 7,925 subjects underwent RYGB and 7,925 matched subjects underwent nonsurgical treatment with a mean follow-up of 8.4 years. Surgery resulted in a 40% reduction in all-cause mortality, a 56% reduction in cardiovascular mortality, and a 60% reduction in cancer mortality. Remarkably, diabetes-related mortality was reduced by 92%. The prospective SOS study found a 24% reduction in all-cause mortality in the surgery group, a benefit that came primarily from a reduction in cardiovascular and cancer risk.
2.3 Risks and complications of surgery
The mortality rate of bariatric surgery is low. 1 Meta-analysis of 85,048 subjects in 361 studies found a mortality rate of 0.28% (95% CI 0.22 to 0.34) within 30 days and 0.35% (95% CI 0.12 to 0.58) between 30 days and 2 years after surgery. 1 prospective clinical study involving 10 centers found A prospective clinical study involving 10 centers found that 4,776 subjects who underwent bariatric surgery had a mortality rate of 0.3% within 30 days after surgery. Another study reported that the mortality rate for bariatric surgery ranged from 0.25% to 0.5%, which is lower than that of common abdominal procedures such as laparoscopic cholecystectomy, which has a mortality rate of 0.3% to 0.6% in the United States.
Recently, data from inpatients across the United States between 1998 and 2004 were compiled, and it was found that the number of cases of bariatric surgery increased 9-fold, while the mortality rate of the surgery decreased by 79%, from 0.89% to 0.19%. In addition, Encinosa analyzed more than 9,500 bariatric surgeries performed at 652 U.S. hospitals between 2002 and 2006 and found that although the proportion of older and less well-off patients undergoing surgery increased each year, the incidence of surgical complications decreased by 38% from 24% to 15%, and the incidence of postoperative infections decreased by 58%, with abdominal hernias, anastomotic fistulas The incidence of respiratory failure and pneumonia has also decreased by 29% to 50%. Other complications such as peptic ulcer, tipping syndrome, bleeding, non-healing incision, deep vein thrombosis, pulmonary embolism, myocardial infarction and stroke did not change significantly. 1 multicenter clinical study with 4776 subjects found that the rate of serious complications of bariatric surgery was only 4.3%.
The dramatic decrease in mortality and complications of bariatric surgery is due to the widespread use of laparoscopic techniques and improved and innovative surgical methods. Common complications of bariatric surgery include anastomotic fistula (3.1%), incisional infection (2.3%), pneumonia (2.2%), and hemorrhage (1.7%). Laparoscopic techniques have led to a significant reduction in surgical complications, so the percentage of bariatric surgery abroad using laparoscopy is increasing every year.
Another adverse effect of bariatric surgery is the problem of nutritional disorders. Protein malnutrition often occurs after BPD and RYGB due to impaired postoperative absorption. Most protein deficiencies can be improved with dietary changes, and a few patients with severe protein malnutrition can be given total parenteral nutrition. The incidence of iron deficiency after RYGB ranges from 6% to 33%, while the incidence of calcium and vitamin D deficiency ranges from 10% to 51%, and can lead to reduced bone mass and secondary hyperparathyroidism. The incidence of vitamin B12 and folic acid deficiency is as high as 33% and 63%, respectively. fat-soluble vitamin deficiency is more common after BPD, and vitamin K deficiency is present in approximately 68% of patients, although it is rare to show obvious symptoms of vitamin K deficiency. It is important to note that most of the above data are from some early studies, and the incidence of postoperative nutritional deficiencies is decreasing with improvements in surgery and innovations in technology. Nutritional deficiencies due to bariatric surgery are easier to correct, especially for RYGB, and supplementation with appropriate nutrients is sufficient.
3. Surgery for T2DM with BMI <35 kg/m2
Gastrointestinal surgery can lead to remission of T2DM in obese patients. Animal experiments have found that gastrointestinal surgery can lead to remission of diabetes regardless of whether it is accompanied by obesity, suggesting that surgery may benefit non-obese patients with T2DM. Gastrointestinal surgery for T2DM with BMI <35 kg/m2 is mainly based on 1) similar procedures performed in the non-obese population, such as gastrectomy-proximal small bowel reconstruction for the treatment of gastric ulcer and gastric cancer; 2) conventional weight loss procedures performed in the mildly obese population; and 3) new gastrointestinal procedures for T2DM with BMI <35 kg/m2.
3.1 Effect of gastrectomy on diabetic condition
A large body of literature has reported significant remission of T2DM in non-obese people after gastrectomy for other diseases. Most of these procedures perform GI reconstruction, such as Bi-II gastrectomy with Roux-en-Y, in fact leaving a section of proximal small intestine open, similar to RYGB.
Nineteen patients with T2DM (13 due to peptic ulcer and 6 due to gastric cancer) underwent partial gastrectomy, with rapid glycemic normalization in 10 patients and significant improvement in glycemic control in 9 patients after surgery.1 One study found that T2DM remission from gastrointestinal surgery lasted up to 1 year postoperatively. Another study found that remission of T2DM from gastrointestinal surgery lasted up to 5 years after surgery. in 1955, Friedman observed that 3 diabetic patients who underwent subtotal gastrectomy for 3-4 days had significant remission of their diabetes and a substantial reduction in insulin requirements.
The sample sizes of the above studies were small, the methods of study were not entirely consistent, very few involved HbA1c, and provided fewer anatomical features of gastrointestinal tract reconstruction. However, gastrectomy-small bowel bypass does result in a rapid decrease in blood glucose and reduction or discontinuation of glucose-lowering medications. Thus, the procedure has similar antidiabetic effects to RYGB, BPD.
LAGB effects
In the study by Dixon et al, 60 T2DM patients with a BMI of 30 to 40 kg/m2 were randomized to receive either conventional medication/lifestyle intervention or LAGB plus conventional treatment. At 2-year follow-up, 73% of the surgical group achieved T2DM remission (defined as FBG < 126 mg/dl with discontinuation of medication and HbA1c < 6.2%), compared with only 13% of the conventional treatment group. Weight loss was more pronounced in the surgical group (20.7% Vs 1.7%). In another randomized study, 80 T2DM patients with BMI 30-35 kg/m2 were randomized to receive a combination of a very low calorie diet/lifestyle intervention/pharmacological treatment with conventional therapy versus LAGB. at enrollment, 38% of subjects in both groups suffered from metabolic syndrome. At 2 years of follow-up, the prevalence of metabolic syndrome was 24% in the non-surgical group and only 3% in the surgical group.
RYGB effects
Cohen et al. found that FBG, total cholesterol (TC), low-density lipoprotein cholesterol (LDL), and triglycerides (TG) were significantly lower and high-density lipoprotein cholesterol (HDL) levels were significantly higher in 37 T2DM patients with BMI <35 kg/m2 who underwent RYGB. Twenty months after surgery, 77% of patients lost weight. Lee et al. investigated the efficacy of RYGB in T2DM, enrolling 44 patients with a BMI <35 kg/m2 (28.3-33.7 kg/m2) and 166 patients with a BMI >35 kg/m2, with a 4-year follow-up. After RYGB, 98% of those with BMI > 35 kg/m2 had normalized blood glucose. 77% of those with BMI < 35 kg/m2 and 92% of those with BMI > 35 kg/m2 achieved the American Diabetes Association’s T2DM control goals of HbA1c < 7.0%, LDL < 100 mg/dl, and TG < 150 mg/dl. 150 mg/dl. In the BMI < 35 kg/m2 group, the mean BMI decreased from 31 kg/m2 to 23 kg/m2, with a surgical complication rate of 4.5% and a mortality rate of 0%.
Effectiveness of BPD
Mingrone reported that 1 female T2DM patient with normal weight (BMI 22 kg/m2) underwent BPD for celiac disease and normalized blood glucose and blood insulin levels 3 months after the procedure.Noya observed that 9 of 10 patients with moderate obesity (mean BMI 33.2 kg/m2) underwent BPD and showed remission of T2DM. Scopinaro performed BPD in 7 patients with T2DM with BMI <35 kg/m2 and followed them for 18 years. 2 patients remained normoglycemic (FBG <100 mg/dl) throughout the follow-up period; 5 patients had normal blood glucose for the first 5 years and then mildly elevated, but FBG never rose above 160 mg/dl even without glucose-lowering medication. All subjects maintained normal TC and TG levels over 18 years, and none showed excessive weight loss.
A prospective clinical study of BPD for T2DM with BMI <35 kg/m2 was pioneered by scholars from the Catholic University of Rome. In this study, five T2DM patients with a BMI of 27-33 kg/m2 received BPD and were followed up for 18 months. One month after the procedure, the five subjects had significantly lower blood glucose and significantly improved insulin sensitivity. lasting remission of diabetes was achieved after BPD (discontinuation of glucose-lowering drugs, HbA1c and FBG remained normal).
New gastrointestinal procedures for the treatment of type 2 diabetes
In recent years, several new gastrointestinal procedures have emerged for the treatment of type 2 diabetes, including duodeno-jejunal bypass, sleeve gastrectomy, ileal interposition, and endoscopic duodenal sleeve implantation.
Duodenal-jejunal bypass
Originally reported by Rubino, duodeno-jejunal bypass (DJB) is essentially a small section of proximal small intestine left open while the stomach is preserved, which distinguishes it from standard RYGB. there are many variations of DJB, including those that preserve the pylorus (duodeno-jejunal anastomosis) and those that do not (gastric-jejunal anastomosis). Cohen was the first to report DJB in two patients with T2DM with BMIs of 29 kg/m2 and 30 kg/m2, respectively. After 1 month of surgery, both subjects had stopped taking glucose-lowering drugs and had normal FBG (<100 mg/dl.) The HbA1c of both subjects was 8%-9% before surgery, and returned to normal 3 months after surgery, and was stable at 5%-6% at 9 months after surgery. Notably, no weight loss was observed in any of the 2 subjects, suggesting that the antidiabetic effect of surgery is independent of weight change. To date, DJB has been used for the treatment of non-obese T2DM in several countries around the world, but long-term clinical data are still lacking.
An international multicenter study involving Mexico, India, and Brazil found a rapid reduction in blood glucose to normal after DJB. Subsequently, Ramos et al. followed 20 T2DM patients with BMI < 30 kg/m2 treated with laparoscopic DJB until six months postoperatively and found that 18 discontinued glucose-lowering drugs and had a substantial reduction in FBG and HbA1c and a 25% increase in fasting C-peptide values. Another study found a significant reduction in glucose-lowering drug requirements after DJB, but not in HbA1c (from 9.4% to 8.5%) and FBG (from 209 mg/dl to 154 mg/dl).
At the time of DJB surgery, sleeve gastrectomy of the stomach can be performed simultaneously to reduce the risk of ulcer development and to increase the weight loss effect of the procedure.
Sleeve gastrectomy (SG)
To shorten the operative time for laparoscopic biliopancreatic diversion-duodenal switch (BPD-DS) in high-risk patients, Gagner proposed that BPD-DS could be broken down into two phases, and the first phase is exactly SG. duodenal-ileal anastomosis, and ileal-ileal anastomosis as the second phase is performed several months later. This improvement resulted in a significant reduction in surgical complications and mortality in severely obese patients (BMI > 60 kg/m2). Surprisingly, patients have lost significant weight after the first stage of the procedure was performed. Since then, SG has become a stand-alone bariatric procedure. In addition to reducing functional gastric volume, SG removes the fundic portion of the stomach, which is a high producer of ghrelin. Although SG may lead to remission of T2DM in patients with severe obesity, its long-term efficacy and safety remain to be seen.
Ileal interposition (IT)
The concept of “ileal interposition” (also known as “ileal transposition”) was based on extensive studies in rodent models. IT is a completely different procedure from conventional gastrointestinal bariatric surgery (gastrectomy, gastrointestinal bypass), which requires three anastomoses, compared to two for RYGB. Animal studies have found that IT results in a significant increase in glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) secretion after feeding. DePaula et al. observed the efficacy of IT and IT combined with SG in the treatment of non-obese T2DM, enrolling 60 T2DM subjects with BMI 24-34 kg/m2. 87% of the subjects showed significant improvement in glucose metabolism at 7.4 months after surgery. However, there are no data on the long-term efficacy of IT, and the long-term complications and safety of the procedure remain to be observed.
Endoscopic duodenal cuff implantation (ELS)
ELS utilizes an adjustable sleeve isolation device that prevents food in the proximal small intestine from coming in contact with the intestinal mucosa and functions similarly to standard RYGB and DJB bypass procedures. The device can be implanted endoscopically, thereby avoiding surgical anastomosis, maintaining intestinal continuity, and reducing surgical complications.Rubino tested non-obese diabetic rats and diet-induced obese rats and found significant improvements in FBG, oral versus enteral administration of glucose tolerance, and insulin sensitivity after ELS, and the procedure did not result in malabsorption.
The first ELS clinical study enrolled four obese T2DM patients, all off glucose-lowering medications at 12 weeks postoperatively and with normal FBG.1 A prospective randomized clinical trial comparing the efficacy of ELS with a low-fat diet combined with exercise for T2DM found that FBG and glucose tolerance in the ELS group improved substantially one week after duodenal cuff implantation and continued throughout the follow-up period of the study, with The long-term efficacy and long-term complications of ELS remain to be seen.
In conclusion, the available studies suggest that various gastrointestinal procedures can cure or alleviate T2DM with BMI <35 kg/m2 and maintain these efficacy at least for a short to intermediate follow-up period. However, these studies have some limitations, such as limited sample size and short postoperative follow-up. The answers to the questions of long-term outcomes and long-term complications of bariatric surgery and the suitability of gastrointestinal surgery for T2DM with a BMI < 30 kg/m2 are not yet known. However, based on the available research data, BMI 35 kg/m2 does not serve as a cut point to predict whether surgery will improve glucose metabolism. Moreover, T2DM with a BMI < 35 kg/m2 undergoing conventional weight loss surgery hardly undergoes excessive weight loss.
Mechanisms of diabetes remission after gastrointestinal surgery
As mentioned previously, gastrointestinal surgery has similar efficacy for non-obese T2DM as for obese T2DM, except that the weight loss effect of surgery is more pronounced when used for the latter, suggesting that the improvement in glucose metabolism after surgery cannot be attributed exclusively to weight loss. Research on the glucose-lowering mechanism of small bowel bypass surgery not only helps to elucidate the pathophysiology and pathogenesis of diabetes, but also facilitates the development of new glucose-lowering drugs, making a cure for diabetes possible.
What are the glucose-lowering effects of gastrointestinal surgery beyond weight loss?
T2DM remits immediately after gastrointestinal surgery, well before the change in body weight. rYGB surgery has the same weight reduction effect as simple gastric decongestion, but the former has a more pronounced improvement in glucose metabolism after surgery. In animal experiments, it was observed that glucose tolerance improved even though there was no weight loss after small bowel surgery. After small bowel surgery, a few patients may develop delayed β-cell hyperfunction. These phenomena suggest that small bowel diversion surgery can treat T2DM by mechanisms other than weight loss and reduced food intake.
What is the rate of T2DM remission after gastrointestinal surgery?
After RYGB and BPD, T2DM generally resolves within days to weeks, well before weight loss. 1,160 patients with T2DM underwent RYGB in one study, and 1/3 were off glucose-lowering medications and had normal glucose at discharge. insulin sensitivity improved only a few days after RYGB. Whether the improvement in glucose metabolism after surgery is attributable to increased insulin secretion or improved insulin sensitivity is still open to debate. Given that the mechanism of simple gastric decongestion such as LAGB and VBG for T2DM is solely due to weight loss, it does not result in rapid improvement of glucose metabolism in the short term postoperatively.
Recent studies have found that improvements in glucose metabolism after RYGB are superior to other surgical modalities while obtaining equivalent weight loss. a randomized controlled study by Laferrere et al. compared the effects of RYGB with dietary therapy for T2DM. Subjects in both groups lost 9.5 Kg, and the surgical group showed increased GLP-1 secretion, enhanced entero-insulin (incretin) effect and more pronounced improvement in glucose tolerance. Similar animal studies confirmed these findings, finding that RYGB not only enhanced the effect of entero-insulin but also led to a significant improvement in insulin sensitivity.Lee et al. compared the efficacy of SG with or without RYGB-like proximal small bowel bypass and found that both groups had the same weight loss at 6 months postoperatively, and the remission rate of T2DM in the SG with concomitant small bowel bypass (93%) was significantly better than that in the SG alone group ( 46%). In addition, one study found that the rate of improvement in glucose tolerance with T2DM remission after RYGB was much higher than that of LAGB.
The glucose lowering mechanism of gastrointestinal surgery beyond weight loss originated from studies on duodeno-jejunal bypass. In a study by Rubino et al. using non-obese T2DM rats, DJB was shown to provide rapid and durable improvements in fasting glucose and glucose tolerance. This benefit was essentially attributed to proximal small bowel openings and was independent of food intake and body weight. These findings have been validated by two rat models of T2DM as well as clinical studies.
The duodenal cuff isolates food from the duodenal mucosa without disrupting intestinal continuity, and implantation of the duodenal cuff resulted in a significant improvement in glucose tolerance in T2DM rats. The above study showed that avoiding food irritation of the proximal small intestinal mucosa produces an antidiabetic effect.
The glucose-lowering effect of ileal interposition was not proportional to the weight loss effect, suggesting that the mechanisms of the two are not entirely consistent. GLP-1, YY peptide, and enteroglucagon secretion after feeding were significantly increased after IT in experimental animals. After IT, insulin secretion and insulin sensitivity were improved in T2DM rats. The glucose metabolic benefit in rats could not be explained by weight loss alone, suggesting that surgery has a glucose-lowering mechanism other than weight loss. Apparently, increased GLP-1 secretion is one of the important mechanisms.
5.6 Delayed β-cell hyperfunction after RYGB
Fatal hyperinsulinemia with hypoglycemia has been reported to occur in a small number of subjects after RYGB. This adverse reaction appears late and occurs mostly 1 to 9 years after surgery. Hypoglycemia due to obesity-associated β-cell hypertrophy and improved postoperative insulin sensitivity should occur in the immediate postoperative period and can therefore be excluded. The persistent stimulation of β-cell secretion and growth by the internal environment after RYGB can last for several years, eventually leading to delayed hyperinsulinemia. This effect is beneficial for most patients with T2DM. In a few cases, β-cells overreact, causing hypoglycemia. after RYGB, early phase insulin secretion after glucose loading returns to normal, confirming that this characteristic defect of T2DM is reversible.
Possible glucose-lowering mechanism of gastrointestinal surgery?
Rearrangement of the gastrointestinal anatomy can antagonize hyperglycemia and diabetes through a number of different mechanisms other than reduced food intake and weight loss. However, the exact mechanism of gastrointestinal surgery for T2DM is not known. Possible mechanisms of glucose reduction other than weight loss include: 1) increased stimulation of the distal small intestine by food and increased secretion of peptides such as GLP-1 by L cells; 2) avoidance of proximal small intestine contact with food and decreased secretion of unknown glucagon; 3) decreased secretion of gastric growth promoter; 4) altered absorption of nutrients by the small intestine and increased insulin sensitivity; 5) bile acid factors; 6) other unknown intestinal factors. Procedures with more significant glucose-lowering effects, such as RYGB, can activate several of these mechanisms simultaneously to produce a coordinated effect, resulting in significant remission of T2DM. In addition to several known hormones, the intestine is capable of producing more than 100 bioactive peptides whose effects on glucose metabolism remain to be further investigated. The search for bioactive substances that can improve glucose metabolism after gastrointestinal surgery has far-reaching implications for the development of novel hypoglycemic drugs.