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 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.
The risk of cardiovascular disease in patients with type 2 diabetes mellitus is significantly increased, which is the primary cause of death. Recent studies have shown that novel hypoglycemic drugs such as sodium-glucose linked transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists have been proven to have cardiovascular protective effects through cardiovascular outcome trials. This article reviews the improvement effects of these drugs on cardiovascular outcomes and explores their possible mechanisms, such as improving myocardial metabolism and reducing inflammatory reactions, providing a reference for optimizing hypoglycemic regimens.
ObjectiveTo explore a surgery of effective weight loss concentrating on gut hormone release. MethodsWistar rats were fed with high-fat diet for inducing obesity and which randomly divided into sleeve gastrectomy plus decent jejunoileal bypass (SJB) group (n=12), sleeve gastrectomy (SG) group (n=12), and sham operation (SO) group (n=11), the body weight reduction, food intake, plasma ghrelin level, and glucagon like peptide-1 (GLP-1) level were compared among three groups. ResultsThere were no differences of the body weight and food intake before operation among three groups (Pgt;0.05). Compared with the SO group, the body weight descended and the food intake decreased obviously on 1-8 weeks after operation in the SJB group (Plt;0.05), the body weight of rats on 1-8 weeks after operation in the SJB group significantly descended as compared with the SG group (Plt;0.05), and the food intake of rats on week 3, 6, 7, and 8 in the SJB group signicantly decreased as compared with the SG group (Plt;0.05). There were no differences of the levels of the plasma ghrelin and GLP-1 before operation among three groups (Pgt;0.05). Compared with SO group, the plasma ghrelin level decreased and the GLP-1 level increased in the SJB group and the SG group, meanwhile the SJB group significantly decreased level of plasma ghrelin and elevated level of plasma GLP-1 as compared with the SG group on week 8 after operation(Plt;0.05). ConclusionThe data demonstrate that SJB could represent an effective way of losing weight by interfering with food intake and obesity related hormone levels.
目的探討胰高血糖素瘤的臨床特征及診治方法。 方法報道重慶醫科大學附一院新發胰腺胰高血糖素瘤臨床案例1例，并對該病相關文獻進行復習。 結果胰高血糖素瘤主要來源于胰腺α2細胞，少數來自于胃或十二指腸的氨前體攝取和脫羧細胞，以壞死性溶解性游走性紅斑、糖尿病、消瘦、貧血等為主要臨床表現，手術療效理想。 結論胰高血糖素瘤是一種臨床上罕見的消化道神經內分泌腫瘤，手術切除是其最為有效的治療手段。
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.
Objective To evaluate the feasibility of hyperinsulinemic normoglycemia strategy in critically ill patients. Methods Between January 2020 and October 2021, the critically ill patients with stress hyperglycemia in the Emergency Intensive Care Unit of the Fourth People’s Hospital of Langfang were randomly assigned into a trial group or a control group. The trial group adopted hyperinsulinemic normoglycemia therapy, while the control group adopted conventional glucose control therapy. The mean and variability (standard deviation) of blood glucose, incidences of severe hypoglycemia and abnormal hyperglycemia, as well as the percentage of blood glucose values within the target range were compared between the two groups, to evaluate the feasibility of hyperinsulinemic normoglycemia strategy in critically ill patients from the perspective of safety and effectiveness. The non-normally distributed measurement data were presented as median (lower quartile, upper quartile). Results A total of eighty patients were included, with forty cases in each group. The mean blood glucose level [6.00 (5.74, 6.70) vs. 9.51 (8.74, 10.01) mmol/L, P<0.001], the standard deviation of glucose level [1.58 (1.11, 2.15) vs. 2.20 (1.21, 2.76) mmol/L, P=0.028], and the glycemic lability index [175.52 (100.51, 346.69) vs. 408.51 (205.56, 651.91) mmol2/(L2·h·d), P<0.001] were all smaller in the trial group than those in the control group. The percentage of blood glucose values within the target range was 77.34% in the trial group and 5.33% in the control group, respectively, and the difference was statistically significant (P<0.001). No patients experienced severe hypoglycemia. There was a significant difference in the incidence of abnormal hyperglycemia between the two groups (5.08% vs. 36.16%, P<0.001). Conclusions Hyperinsulinemic normoglycemia strategy can effectively and safely provide normoglycemia, reduce glycemic variability, and achieve good glycemic control in critically ill patients. Hyperinsulinemic normoglycemia strategy may be a new approach to glycemic control in critically ill patients.
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.
【摘要】 目的 了解不同糖代謝狀態的人群空腹及口服葡萄糖耐量實驗（oral glucose tolerance test，OGTT）餐后胰高血糖素樣態-1（GLP-1）和葡萄糖依賴的促胰島素多態（GIP）水平。 方法 將受試者根據OGTT結果分為3組:正常糖耐量組（NGT，n=61例），糖耐量受損組（IGT，n=53）和2型糖尿病組（T2DM， n=66）。采空腹及糖餐后2 h靜脈血檢測GLP-1和GIP水平。 結果 T2DM組空腹GLP-1水平低于NGT和IGT組（Plt;0.05）。NGT和IGT的空腹GLP-1水平差異無統計學意義（Pgt;0.05）。餐后GLP-1水平三組差異無統計學意義（Pgt;0.05）。空腹及餐后GIP水平在NGT、IGT和T2DM均呈逐漸增加的趨勢，而且同OGTT-0 h和OGTT-2 h血糖水平呈正相關（r=0.384，0.426；Plt;0.05）。 結論 不同的GLP-1和GIP水平也許是IGT和T2DM胰島素分泌能力不同的原因之一。【Abstract】 Objective To investigate the fasting, and after oral glucose tolerance test (OGTT), the postprandial levels of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in Chinese people with different degrees of glucose tolerance. Methods Based on the results of OGTT, 180 subjects were divided into three groups: normal glucose tolerance group (NGT group, n=61), impaired glucose tolerance group (IGT group, n=53) and type-2 diabetes mellitus group (T2DM group, n=66). Fasting venous blood and the venous blood 2 hours after OGTT was sampled to detect GLP-1 and GIP levels. Results The fasting GLP-1 level in the T2DM group was significantly lower than that in the NGT and IGT groups (Plt;0.05). There was no significant difference in fasting GLP-1 level between NGT and IGT groups (Pgt;0.05). There was no significant difference in GLP-1 level 2 hours after OGTT among all the three groups (Pgt;0.05). GIP level gradually increased in the order of NGT, IGT and T2DM both before and after glucose load, and it was positively correlated with glucose levels just after OGTT and 2 hours after OGTT (r=0.384,0.426;Plt;0.05). Conclusion Different GLP-1 and GIP levels may be one of the reasons for different insulin secretion ability between IGT and T2DM
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.