Objective To observe the curative effect on non-obese type 2 diabetes and the effect on change of glucagon-like peptide-1 (GLP-1) of gastric bypass operation. Methods Thirty-two cases of gastric ulcer with non-obese type 2 diabetes were suffered gastric bypass operation. Plasma glucose concentrations, insulin and GLP-1 were measured respectively in fasting and postprandial conditions before operation and in week 1, 2, 3 and month 1, 3, 6 after gastric bypass operation, and the body mass index (BMI), homeostasis model assessment β cell function index (HBCI) and glycosylated hemoglobin (HbA1c， the index was detected only before operation and in month 3, 6 after operation) were also measured. The turnover of the diabetes condition in the 6th month after surgery was observed. Results Compared with the levels before operation, the fasting and postprandial plasma glucose levels were descending (P＜0.05), fasting and postprandial plasma insulin and GLP-1 levels were ascending (P＜0.05), HBCI was ascending and HbA1c was descending significantly after operation respectively (P＜0.05), while BMI changed un-significantly after operation (Pgt;0.05). The diabetes control rate was 78.1%(25/32) overall six months after operation. Level of GLP-1 was negatively correlated with level of plasma glucose (P＜0.05) and positively correlated with level of insulin (P＜0.05). Conclusions Gastric bypass operation can markedly reduce plasma glucose level on the type 2 diabetes patients with non-obese, and the hypoglycemic effect may be contributed by more GLP-1 secretion that caused more insulin secretion, which doesn’t depend on the loss of weight.
Diabetic retinopathy (DR) is one of the most frequent complications of diabetes (T2DM), which is the main eye disease causing blindness in adults in recent years. At present, glucagon-like peptide-1 receptor agonists (GLP-1RA) have become the main drugs used in the treatment of diabetes due to its superior hypoglycemic, lipid-lowering, hypertensive and cardiovascular effects. A large number of studies have shown that GLP-1RA drugs can protect retinal microvascular and optic nerves in the treatment of diabetes through various ways, but some studies have found that GLP-1RA drugs represented by semaglutide may lead to the progress of DR. Therefore, GLP-1RA should be used cautiously for patients who with severe non-proliferative DR or proliferative DR. Regardless of whether T2DM patients are complicated with DR, the fundus retinal condition should be monitored regularly after the use of GLP-1RA drugs, and timely countermeasures should be taken when DR occurs and develops. The benefits of GLP-1RA used by diabetes patients are obvious to all, and scientific and rational drug use can prevent the occurrence and progress of DR, which can better benefit DR Patients.
ObjectiveTo observe the influence and interaction of duodenal jejunal bypass (DJB) and hepatic branch of vagus on glucose metabolism, and fasting serum glucagon like peptide-1 (GLP-1), peptide YY (PYY) in non-obese rat with type 2 diabetes mellitus (T2DM). MethodsForty non-obese Wistar rats (GK) with T2DM were randomly divided into four groups: sham operation group (SO group), sham operation plus hepatic branch of vagus resection (HBVR) group (SO+HBVR group), DJB group, and DJB+ HBVR group. The changes of preoperative and postoperative body weight, fasting blood glucose level, fasting serum insulin level, fasting serum GLP-1 and PYY contents among four groups were observed. ResultsIn the DJB group, the postoperative body weight and fasting blood glucose level were decreased significantly (P < 0.05) and the fasting insulin level, fasting serum GLP-1 and PYY contents were increased significantly (P < 0.05) as compared with the preoperative corresponding values in the same group, and it was found that the hepatic branch of vagus could more lastingly maintain postoperative lower body weight (P < 0.05), improve the level of insulin (P < 0.05), increase the fasting serum GLP-1 and PYY contents (P < 0.05) as compared with the DJB+HBVR group. ConclusionDJB could improve glucose metabolism effect of GK rats, the hepatic branch of vagus might play a role in it, too.
ObjectiveTo investigate the effect and mechanism of gastric bypass surgery (GBP) on fasting bloo-glucose (FBG) in type 2 diabetic rats. MethodsThe models of type 2 diabetic rats were induced by stretozotocin and 20 diabetic rats were randomly divided into two groups: diabetes-operation group (DO group, n=10) and diabetes-control group (DC group, n=10). Another twenty normal rats were randomly divided into two groups: normaloperation group (NO group, n=10) and normal-control group (NC group, n=10). The rats underwent GBP in DO group and NO group and sham operation in DC group and NC group. The FBG levels, serum dipeptidyl peptidase Ⅳ (DPPⅣ), and glucagon-like peptide-1 (GLP-1) concentrations of rats in each group were detected before operation and at 72 h, on 1 week, 4 weeks, and 8 weeks after operation. ResultsThe FBG levels of rats before operation were not significantly different between DO group and DC group or between NO group and NCgroup (Pgt;0.05). After operation, the FBG levels of rats in DO group gradually declined, reached the bottom on 4 weeks after operation and rose slightly on 8 weeks; The FBG levels of rats in DO group were lower after operation than before operation (Plt;0.05); After operation the FBG levels of rats in DO group were higher than that in NO group and NC group at the same time point (Plt;0.05); In DC group, the difference of FBG levels of rats at different time point was not statistically significant (Pgt;0.05); The inter-group and intra-group difference of FPG levels of rats for NO group and NC group was not statistically significant (Pgt;0.05). The concentrations of serum DPP-Ⅳ of rats before operation were not significantly different in each group (Pgt;0.05). After operation, the concentrations of serum DPP-Ⅳ of rats in DO group and NO group gradually decreased and markedly lower than that before operation, respectively (Plt;0.05). The concentrations of serum DPP-Ⅳ of rats after operation in DO group and NO group were significantly lower than that at the same time point in DC group and NC group, respectively (Plt;0.05); The intragroup difference of serum DPP-Ⅳ concentrations of rats for DC group and NC group was not statistically significant (Pgt;0.05). The concentrations of serum GLP-1 of rats before operation were not significantly different between DO group and DC group or between NO group and NC group (Pgt;0.05). After operation, the concentrations of serum GLP-1 of rats in DO group and NO group gradually increased, reached the top on 4 weeks after operation and declined slightly on 8 weeks; The concentrations of serum GLP-1 of rats in DO group and NO group were higher after operation than before operation (Plt;0.05);After operation, the concentrations of serum GLP-1 of rats in NO group were higher than that in NC group (Plt;0.05), but the concentrations of serum GLP-1 of rats at different time point in NO group were not different (Pgt;0.05). The intragroup difference of serum GLP-1 concentrations of rats for DC group and NC group was not statistically significant (Pgt;0.05). ConclusionsThere is obvious hypoglycemic effect of GBP on FBG levels of type 2 diabetic rats other than normal rats, in which high secretion of GLP-1 and low secretion of DPP-Ⅳ may be play an important role.
Objectives To summarize the regulation of glucagon-like peptide-1（GLP-1） level by metabolism of gastrointestinal nutrients. Methods Domestic and international publications online involving regulation of GLP-1 level by metabolism of gastrointestinal nutrients in recent years were collected and reviewed. Results GLP-1 influenced insulin secretion and sensitivity， and played a leading role in recovery of glucose metabolism. Metabolism of gastrointestinal nutrients regulated GLP-1 level. Studies had shown that GLP-1 was a candidate mediator of the effects of gastric bypass （GBP） for type 2 diabetes mellitus（T2DM）. Conclusions It plays an important role in anti-T2DM effects of GBP that metabolism of gastrointestinal nutrients regulated GLP-1 level. The corresponding studies can provide a novel clinical field to treat T2DM.
Both bariatric surgery and pharmacotherapy, particularly glucagon-like peptide-1 receptor agonist (GLP-1RA), are effective interventions for obesity, yet each has its own advantages and limitations. Drawing on the “bridging” concept from cancer therapy, this commentary explores an innovative obesity management strategy that involves the combined application of GLP-1RA and bariatric surgery during the perioperative period, with the aim of optimizing treatment outcomes. The present analysis focuses specifically on the potential value of this approach: preoperatively, GLP-1RAs serve as a “bridging therapy” to promote weight loss and reduce surgical risks in severely obese patients; postoperatively, they might be used to manage weight rebound or insufficient weight loss. This multimodal integrated strategy is designed to overcome the inherent limitations of single therapies and offer patients more comprehensive treatment options. Emphasizing that future research must urgently focus on optimizing treatment parameters (e.g., timing, dosage), evaluating long-term safety and efficacy, and establishing patient selection criteria for combination therapy. Integrating surgical and pharmacological treatments, this comprehensive strategy based on the oncological “bridging” concept represents a highly promising paradigm shift in obesity management.
ObjectiveTo investigate the effect and mechanism of sleeve gastrectomy (SG) on reducing blood glucose level. MethodsThirty GK rats were randomly divided into SG group, sham operation (SO) group, pair-fed (PF) group, and blank control (BC) group. The changes of weight, fasting blood glucose, glucose tolerance (oral glucose tolerance test, OGTT), insulin tolerance (insulin tolerance test, ITT), plasma insulin, ghrelin, and glucagon like peptide-1 (GLP-1) were monitored before and 24 weeks after operation respectively. ResultsFrom the 4th week after operation, weight gain in SG group and PF group began to decrease significantly compared with SO group (Plt;0.01). From the 2nd week after operation, fasting blood glucose level in SG group was lower than that in SO, PF, and BC groups (Plt;005), and the glucose tolerance in SG group obviously improved compared with preoperation and the other 3 groups (Plt;0.01). On the 6th week after operation, the insulin sensitivity in SG group obviously improved compared with SO group (Plt;0.05, Plt;0.01). There was no significant difference of insulin level between SG group and SO group (Pgt;0.05), ghrelin level significantly decreased (Plt;0.01) while GLP-1 level significantly increased (Plt;0.01) in SG group compared with SO group during 2-24 weeks after operation. ConclusionsThe effect of SG on reducing blood glucose is definite. SG can directly lower blood glucose independent with weight loss. Postoperative decreased ghrelin level and increased GLP-1 level may be its primary mechanism.
ObjectiveTo systematically evaluate the effects of weight-loss interventions on hormone levels and sexual function in patients with obesity. MethodsThis review was conducted in accordance with PRISMA guidelines. A systematic search of PubMed, Embase, and other databases was performed for studies published within the past decade that investigated the effects of bariatric surgery, glucagon-like peptide 1 (GLP-1) receptor agonists, and lifestyle interventions on sex hormones and sexual function. ResultsBariatric surgery (e.g., sleeve gastrectomy, gastric bypass) demonstrated the most pronounced improvements in hormonal balance and sexual function. In males, total testosterone levels doubled postoperatively, with marked increase in erectile function score. In females with polycystic ovary syndrome, androgen levels were reduced by 50%, with significant amelioration in the female sexual function index. GLP-1 receptor agonists (e.g., semaglutide, liraglutide) partially improved sperm quality and testosterone levels, but were also associated with a higher risk of erectile dysfunction (with a hazard ratio of approximately 4.5). Lifestyle interventions (e.g., low-calorie diet, exercise) could increase sex hormone-binding globulin levels and improve sexual function score, although their efficacy remained inferior to that of surgery. ConclusionsWeight-loss interventions can alleviate hormonal imbalances and sexual dysfunction in obesity, with bariatric surgery demonstrating the most significant effects. Pharmacological and lifestyle interventions have shown variable efficacy. Future research should further investigate mechanisms underlying effects of different weight-loss modalities on sexual health.
ObjectiveTo explore therapeutic mechanisms and clinical application prospects of novel weight-loss medications in patients with obesity complicated by cardiovascular-kidney-metabolic (CKM) syndrome, aiming to provide theoretical support and therapeutic strategies for personalized precision management of CKM syndrome. MethodsRecent domestic and international studies were retrospectively reviewed, focusing on the mechanisms of action, clinical research outcomes, and application progress of novel weight-loss medications, including glucagon-like peptide 1 (GLP-1) receptor agonists, dual glucose-dependent insulinotropic peptide (GIP)/GLP-1 receptor agonists, triple GIP/GLP-1/glucagon receptor agonists, and amylin analogues. Special emphasis was placed on their comprehensive effects on cardiovascular, renal, and metabolic parameters. ResultsNovel weight-loss medications have demonstrated significant weight reduction and multisystem benefits through precise regulation of central appetite pathways, insulin sensitivity, and lipid metabolism. Among these medications, GLP-1 receptor agonists (e.g., semaglutide) and dual receptor agonists (e.g., tirzepatide) have been confirmed in phase Ⅲ clinical trials to effectively reduce cardiovascular event risks, slow renal function deterioration, and markedly improve glycemic control in obese patients with CKM syndrome. Triple receptor agonists (e.g., retatrutide) and combination medication regimen (e.g., CagriSema regimen) have further enhanced weight-loss efficacy, providing novel therapeutic avenues for obesity-related diseases. Additionally, these medications usually require combined application with traditional chronic disease medications, such as sodium-glucose linked transporter 2 inhibitors and renin-angiotensin-aldosterone system blockers, to achieve comprehensive therapeutic outcomes in CKM syndrome patients. However, further studies are needed to address long-term safety in real-world settings, optimization of drug formulations, and application in precision medicine. ConclusionsNovel weight-loss medications offer promising strategies for personalized precision treatment of obesity with CKM syndrome due to their significant weight-loss efficacy and multisystem synergistic effects. Although current clinical trials demonstrate substantial therapeutic potential, the complexity of CKM syndrome and individual patient variability necessitate additional in-depth research to facilitate broader clinical adoption and optimization of these medications.
Diabetic retinopathy (DR) is one of the most serious complications of diabetes mellitus. Severe diabetic macular edema or proliferative retinopathy may lead to impaired vision or even blindness in diabetic patients. The glucagon-like peptide-1 receptor agonist (GLP-1RA) is now commonly used as novel glucose-lowering agents in the clinical management of type 2 diabetes, but the rapid glycaemic changes associated with the use of the GLP-1RA may aggravate the risk of an increase in the occurrence of short-term potential DR. Potential effects and mechanisms of DR include oxidative stress, vascular endothelial growth factor, inflammation, retinal neurodegeneration, and other cytokines.Whether GLP-1RA leads to the increased risk of DR remains controversial. More basic and clinical studies are needed with the aim of further clarifying the correlation between GLP-1RA and DR risk.