Type 2 diabetes is a global problem, accounting for 85% to 90% of all cases of diabetes, and the number of people with type 2 diabetes in China has reached 50 million. Diabetes is often combined with hyperlipidemia and hypertension, which brings about serious complications such as cardiovascular disease, renal impairment and limb necrosis, seriously affecting the quality of life and life expectancy of patients and imposing a heavy burden on patients and society.
Although multifactorial interventions such as lifestyle improvement, glycemic control, antihypertensive, lipid-lowering and antiplatelet therapy have been used to minimize the occurrence of complications in diabetic patients, their prognosis is still unsatisfactory. type 2 diabetes is also progressive, and studies have confirmed that the function of pancreatic β-cells in diabetic patients declines rapidly at a rate of 20% per year, so that most patients have difficulty in achieving a satisfactory outcome after 5 years of treatment with drugs, even if Combined application of hypoglycemic drugs, it is difficult to ensure that patients return to normal blood glucose and avoid the emergence of various serious complications caused by diabetes.
Insulin has benefited many patients, but insulin resistance can develop at a later stage, making treatment difficult. In order to treat diabetes, attempts have been made to achieve the goal through islet or pancreas transplantation, but the clinical treatment is very unsatisfactory, with embarrassing results, and is only at the stage of animal experiments.
New method of diabetes treatment: gastrointestinal diversion surgery to cure type 2 diabetes
In the 1980s, it was found that patients with combined type 2 diabetes who underwent bariatric surgery in the surgical treatment of morbid obesity lost significant weight while their blood sugar returned to normal, and the cure rate of type 2 diabetes reached 90%, and diabetes-related complications were controlled. There are three main surgical procedures for bariatric surgery.
①Adjustable gastric banding gastric reduction, which can cure 50% of diabetic patients;
②Sleeve gastrectomy can make 60% to 70% of the diabetic patients get cured;
③ Gastrointestinal diversion surgery (Bypass, GBP), with an efficiency of 100%, can make more than 90% of diabetic patients get cured, and has become a classic surgical way to treat type 2 diabetes.
Bariatric surgery
A, gastric septal bundle surgery: the most widely used bariatric surgery in 1980~2000
B. Laparoscopic gastric controlled banding surgery: It has gradually emerged in the past 10 years, replacing gastric septal banding, and is the standard bariatric surgery in Europe and Australia, becoming the most commonly performed bariatric surgery.
C, laparoscopic gastric bypass bariatric surgery: long history of good results, is the gold standard of obesity surgery in the United States
D.Laparoscopic pancreaticobiliary bypass surgery: still an effective surgery for super obese people
E. Laparoscopic tubular gastric reduction surgery: the latest bariatric surgery
Pories et al. in the surgical treatment of obesity “accidentally” found that after Roux-en-Y gastric bypass (gastric bypass, GBP) treatment, 91% of 298 diabetic patients with hyperglycemia was reversed, and 86% of 353 hypertensive patients with blood pressure returned to normal levels. This finding has attracted great attention from academic circles, and bariatric surgery for type 2 diabetes has become a hot issue, receiving common attention from medical and surgical practitioners.
In 2004, Buchwald et al. collected 136 English-language research papers published from 1990 to 2003 and conducted Meta-analysis, which included a total of 22,094 patients. The results showed that the total efficiency of various surgical treatments for glycemic control reached more than 80%, with a long-term complete remission rate of 76.8% and a significant improvement of 86.0%. Most patients were taken off diabetic medications and their blood glucose and glycated The majority of patients were taken off diabetic medications and their blood glucose and glycated hemoglobin levels returned to normal.
Among them, the remission rate of diabetes after biliopancreatic diversion/duodenal switch (BPD/DS) was as high as 98%, followed by Roux-en-Y gastric bypass at 84%. The combined dyslipidemia, hypertension, coronary artery disease, sleep apnea syndrome and many other metabolic abnormalities were also found to be remitted and cured. After performing biliopancreatic diversion/duodenal switch (BPD/DS), complete recovery of dyslipidemia, 81% remission of hypertension, and 95% improvement of sleep apnea syndrome were achieved. 2009 Buchwald included more updated studies and similar results were obtained. More interesting is the improvement in lipid metabolism and the reversal of fatty liver as well as the reduction in the risk of cardiovascular events brought about by gastric bypass.
The procedure: the greater and lesser curves of the stomach are freed, the gastric body is closed transversely along a joint 6 cm below the cardia on the lesser curvature side vertically to the greater curvature side, the volume of the proximal gastric cavity is about 30% of the original stomach, the length of the diverted intestinal climb is calculated according to BMI and HOMA-IR, the jejunum is dissociated at a certain site, the distal jejunum is anastomosed to the proximal gastric cavity, and the proximal jejunum is anastomosed to the distal segment of the small intestine to reconstruct the digestive tract and close the small intestinal mesentery.
The unique feature of GBP is that it alters the normal physiological flow of food and divides the digestive tract into two parts according to whether food passes through or not.
(i) Food diversion zone, i.e., most of the stomach, duodenum and proximal jejunum, a blind section of the GI tract, through which no food passes;
(ii) the food transit zone, i.e., the distal jejunum and ileum, where this part of the GI tract receives food in advance.
Mechanisms of surgery for diabetes
1.Weight loss and reduction of body fat load;
2.Correct high blood lipids and improve the function of pancreatic β-cells;
3.Change the neuroendocrine regulation function of intestine-pancreatic axis and intestine-brain axis, and after gastric diversion surgery, the glucose dependence peptide (GIP), insulin, pancreatic enzymes and YY peptide are increased, and cholecystokinin (CCK) is decreased, eliminating insulin resistance and improving insulin sensitivity;
4. Surgery can increase the secretion of peptide hormones such as Ghrelin, PYY, GLP-1 pancreatic polypeptide and other hormones that improve insulin sensitivity, thus helping to increase insulin sensitivity and lower blood glucose;
The intestine-islet axis has been a hot spot in endocrine and gastrointestinal surgery research in recent years. It has been suggested that various hormones secreted by the gastrointestinal tract are related to the regulation of glucose metabolism, including cholecystokinin (CKK), gastric inhibitory polypeptide (GIP), glucagons-like peptide-1 (GLP-1), ghrelin, leptin (Leptin), and peptide YY. Leptin), peptide YY (PYY), adiponectin (ADPN), etc.
There are 2 main hypotheses.
(1) Duodenal-jejunal hypothesis: GIP is synthesized and released by K cells in the duodenum and proximal jejunum, and there is often excessive secretion of GIP in diabetic patients, which is associated with the occurrence of insulin resistance. After GBP (or duodenojejunostomy), the stimulation of nutrients to the proximal small intestine is reduced or stopped, and the release of GIP by K cells is reduced, thus alleviating insulin resistance, and long-term cure of type 2 diabetes is obtained.
(2) Distal ileum hypothesis: GLP-1 is synthesized and released by L cells in the distal ileum and colon, which has a pro-insulin secretory effect and can increase islet regeneration and reduce apoptosis; PYY is also a hindgut hormone mainly released by L cells in the distal ileum after meals, which acts on the arcuate nucleus of the hypothalamus to inhibit the release of neuropeptide Y, producing a feeling of satiety and inhibiting gastric emptying and gastrointestinal motility, thus suppressing appetite and reducing Weight loss. After GBP or biliopancreatic diversion, undigested or partially digested food enters the distal ileum early, stimulating L cells to secrete GLP-1 and PYY, causing an increase in insulin secretion and suppressing appetite, reducing energy intake, and thus lowering blood glucose.
Some studies have shown that feeding stimulates increased GLP-1 and PYY concentrations in patients after RYGB, peaking 30 minutes after meals and significantly higher than other bariatric procedures such as BPD and GB.
5, fat-insulin axis theory First, the breakdown of triglycerides in adipose tissue produces free fatty acids. Excess free fatty acids inhibit the action of insulin and reduce the rate of glucose uptake by skeletal muscle cells. Second, adipose tissue produces a variety of proteins that affect the action of insulin. These biologically functional proteins that are specifically or abundantly expressed in adipocytes are collectively known as adipocytokines, or adipokines. The most important ones include leptin, adiponectin, visfatin, tumornecrosis factor- α (TNF- α), resistin, and interleukin-6 (IL-6). -6).
Studies have shown that TNF-α, IL-6 and resistin can reduce cellular sensitivity to insulin, resulting in insulin resistance, with TNF-α and IL-6 considered to be important cytokines in the immune inflammatory response in the body. Leptin has been shown to mediate central nervous control of feeding and to promote glucose utilization, lipolysis and fatty acid oxidation. Another adipocyte hormone, adiponectin, has been shown to enhance insulin sensitivity, not only in obese animals and insulin-impaired animals, but also in normal animals, where adiponectin has been shown to increase glucose entry into cells and fatty acid oxidation.
In metabolic syndromes such as obesity and type 2 diabetes, a significant decrease in plasma adiponectin, an anti-inflammatory and anti-insulin resistance factor, was found along with an increase in the expression of proinflammation genes such as TNF-α and IL-6 in adipose tissue. Leptin (LP) levels and adiponectin levels increase after bypass surgery, and anti-insulin hormone decreases, maintaining long-term normal blood glucose and increasing insulin sensitivity to achieve long-term blood glucose stability.
Visfatin is a newly discovered adipocytokine secreted mainly by human and mouse visceral adipose tissue, and its structure is similar to that of pre-B cell colony enhancing factor. Visfatin is closely associated with obesity and promotes adipocyte differentiation, as well as vascular smooth muscle cell maturation.
Visfatin’s expression is regulated by inflammatory response factors and a variety of hormones. visfatin may be an important molecule that links the body’s glucose and lipid metabolism, and its discovery can provide new research ideas to reveal the mechanism of the development of diabetes and obesity, and provide new solutions for the treatment of metabolic syndrome.
6, inflammatory mediator theory, clinical studies have confirmed that after GBP surgery, IL-6 and TNF levels decreased significantly, which also supports this hypothesis to some extent.
The results of surgical treatment of type 2 diabetes are encouraging. Surgery for the treatment of type 2 diabetes is now widely used around the world, and many hospitals are currently performing this work with satisfactory results for diabetic patients. Overall, this surgery is less risky and less costly. For patients with obesity combined with type 2 diabetes who may develop complications, it is a wise choice to choose surgery early. Otherwise, if complications arise, the consequences can be serious and difficult to cure. The mechanism of surgical treatment of diabetes mellitus is shown in the figure (with GLP-1 change after surgery as an example).
The text of the attached figure illustrates that after gastrointestinal diversion surgery, food enters the digestive tract
(1) Stimulation of endocrine cells in the gastrointestinal tract and increased secretion of insulin-sensitizing hormones such as GLP-1
(2) These hormones stimulate the proliferation of insulin-secreting B cells in the pancreas and decrease death
(3) These hormones also slow down the peristalsis of the gastrointestinal tract
(4) simultaneously inhibit the hunger center of the thalamus
(5) Prevent over-eating.
Risk-benefit analysis of surgery
The role of bariatric surgery in the treatment of type 2 diabetes and metabolic syndrome is unquestionable, however, all surgical procedures carry some risk, but this risk is only meaningful when compared with diabetic impairment. Risk-benefit assessment is therefore an important issue in the selection of therapeutic surgery. The first concern is the risk of death from the surgery itself, Dimick et al. reported the risk of death from seven common surgical procedures, ranging from hip arthroplasty with a 0.3% mortality rate to craniotomy with a 10.7% mortality rate, while the mortality rate from gastrointestinal diversion was comparable to that of hip arthroplasty.
In contrast, at postoperative follow-up, postoperative mortality was significantly reduced (30% to 90%) compared with non-operative diabetic patients of the same baseline age and body mass index level. in a retrospective study conducted by Adams et al. in 2007 with 18-year follow-up, 7925 obese patients who underwent RYGB compared with the same number of non-operative patients of the same baseline sex, age and body mass index had a mean The risk of total mortality was reduced by 40% over 7.1 years (3.76% and 5.71% per year, respectively; P<0.001); mortality from diabetes-related complications by 92% (0.4% and 3.4% per year, respectively; P= 0.005); risk of cardiovascular disease by 56% (2.6% and 5.9% per year, respectively; P= 0.006); and mortality from cancer by 60% (5.5% and 13.3% per year, respectively; P= 0.001).
This shows that the benefit of reduced postoperative mortality far outweighs the risk of death from the surgery itself, and that bariatric surgery remains an effective pathway for the comprehensive management of metabolic syndrome in obese diabetic patients.