ObjectiveTo compare the effect of ileal transposition (IT) and Roux-en-Y gastric bypass (RYGBP) on blood glucose and expression of glucagon-like peptide-1 (GLP-1) in Goto-Kakizaki (GK) rats with non-obese type 2 diabetes mellitus (T2DM). MethodsThirty male GK rats were randomized divided into three groups:IT group (n=10), RYGBP group (n=10), and Sham group (n=10). The mortality and complication were observed after surgery. The levels of fasting blood glucose (FBG), fasting insulin (FINS), glycosylated hemoglobin (HbA1c), and GLP-1 were determined before operation, and 1 week, 2 weeks, 1 month, 2 months, 3 months, 6 months after operation in the GK rats of 3 groups. Results① Mortality and morbility. There was no death and complication occurred in IT group and Sham group, only 5 rats of RYGBP group suffered from complication, and 2 of them died. The mortality and morbility were higher in RYGBP group than those of IT group and Sham group (P < 0.05). ② FBG. Compared with before operation in the same group, the FBG levels of IT group and RYGBP group in 1 week, 2 weeks, 1 month, 2 months, 3 months, and 6 months after operation were all lower (P < 0.05). In 1 week, 2 weeks, 1 month, 2 months, 3 months, and 6 months after operation, FBG levels of IT group and RYGBP group were all lower than those of Sham group at the same time point (P < 0.05), but there was no significant difference between IT group and RYGBP group at the 6 time points (P > 0.05). ③ FINS and HbA1c. Compared with before operation in the same group, the FINS levels of IT group and RYGBP group in 3 months and 6 months after operation were higher than those of Sham group (P < 0.05), HbA1c levels of IT group and RYGBP group were both lower at the 2 time points (P < 0.05). In 3 months and 6 months after operation, FINS levels of IT group and RYGBP group were both higher, and HbA1c levels were both lower than corresponding indexes of Sham group at the same time point (P < 0.05), but there was no significant difference between IT group and RYGBP group at the 2 time points (P > 0.05). ④ GLP-1. Compared with before operation in the same group, the GLP-1 levels of IT group and RYGBP group in 1 week, 2 weeks, 1 month, 2 months, 3 months, and 6 months after operation were all higher (P < 0.05). In 1 week, 2 weeks, 1 month, 2 months, 3 months, and 6 months after operation, GLP-1 levels of IT group and RYGBP group were both higher than those of Sham group at the same time point (P < 0.05), but there was no significant difference between IT group and RYGBP group at the 6 time points (P > 0.05). ConclusionIT and RYGBP have a significant hypoglycemic effect on non-obese T2DM GK rats, but IT has lower mortality and morbility, which is more effective and safer, comparing with RYGBP.
Obesity is a chronic metabolic disease driven by multiple factors such as genetic susceptibility, environmental factors, and neuroendocrine system disorders. In recent years, the prevalence of obesity in China has been increasing year by year, and a series of obesity-induced diseases are a serious threat to public health. Glucagon-like peptide-1 receptor agonists, as a representative of the new weight loss drugs, have shown a therapeutic effect close to that of weight-loss metabolic surgery in clinical trials by targeting central appetite and metabolism and other synergistic effects, but they still face key problems such as significant differences in individual efficacy, limited evidence of the safety of long-term treatment, and regaining body weight after discontinuation of the drug. The mechanism of action and clinical evidence of several obesity drugs approved and listed in China are summarized, and the progress and challenges of obesity drug therapy in China in combination with recent advances in the development of multi-target agents internationally are discussed, with a view to providing a scientific basis for the clinical drug management of obesity and providing ideas for the research and development of obesity drugs in China as well as for the clinical transformation.
Objective To investigate and analyze the relationships among glucagon-like peptide-1 (GLP-1) level, chronic inflammation, and atherosclerosis in patients with non-alcoholic fatty liver disease (NAFLD). Methods From October 2016 to February 2017, using cross-sectional investigation, the GLP-1 level, chronic inflammation, and atherosclerosis were investigated in 80 subjects (40 NAFLD patients in NAFLD group, and 40 non-fatty liver disease participants in control group) who underwent physical examination at Xi’an Road Community Hospital. Results Compared with those in the control group, GLP-1 fasting level in patients with NAFLD [(9.09±1.03) vs. (9.15±1.06) pmol/L, P=0.807] and postprandial plasma GLP-1 [(15.96±3.37) vs. (17.46±4.76) pmol/L, P=0.108] had no changes. The correlations of GLP-1 level with chronic inflammation and insulin resistance (IR) were not significant either. The increased risk of carotid intima-media thickness related cardiovascular disease (CVD) in the NAFLD group was greater than that in the control group, and the difference was statistically significant [22 (55.0%)vs.13 (32.5%), P=0.043]. When the plasma lipoprotein-associated phospholipase A2 level increased, the risk of NAFLD increased [odd ratio (OR)=1.16, 95% confidence interval (CI) (1.02, 1.32), P=0.023]. Plasma ceramide kinase (CERK) in the NAFLD group was lower than that in the control group, and the difference was statistically significant [(12.36±2.45) vs. (18.33±3.71) ng/mL, P<0.001]. When the plasma CERK level of the fasting plasma was elevated, the risk of NAFLD decreased [OR=0.30, 95%CI (0.12, 0.78), P=0.014]. The homeostasis model assessment of insulin resistance (HOMA-IR) in the NAFLD group was higher than that in the control group, and the difference was statistically significant (2.46±2.53 vs. 1.11±0.66, P=0.002). The Matsuda index in the NAFLD group was less than that in the control group, and the difference was statistically significant (5.88±4.09 vs. 10.46±7.90, P=0.002). When HOMA-IR increased, the risk of NAFLD increased [OR=2.75, 95%CI (2.49, 3.12), P=0.036]. Conclusions Plasma GLP-1 level is not a sensitive indicator of chronic inflammation and IR in patients with NAFLD. Patients with NAFLD are in an increased risk of atherosclerosis and CVD. It suggests that NAFLD might be involved in chronic inflammation and IR. Chronic inflammation can cause IR, and then chronic inflammation and IR can cause NAFLD and subclinical atherosclerosis. In return for this, NAFLD increases chronic inflammation and IR.
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.
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.
Polycystic ovary syndrome (PCOS) affects many women of reproductive age, including ovarian and metabolic dysfunction. Major therapeutic goals include weight loss and improved insulin resistance. The effects of weight loss and increased insulin sensitivity of glucagon-like peptide-1 (GLP-1) receptor agonists provide another opportunity and pathway for the treatment of PCOS patients, especially those with metabolic abnormalities. This paper reviews the metabolism and reproductive outcomes about GLP-1 receptor agonists for PCOS by searching for literatures of clinical trials from PubMed in the past 10 years, in oder to provide new ideas and clinical evidence for clinical treatment of PCOS.
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 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.
【摘要】 目的 了解不同糖代谢状态的人群空腹及口服葡萄糖耐量实验（oral glucose tolerance test，OGTT）餐后胰高血糖素样态-1（GLP-1）和葡萄糖依赖的促胰岛素多态（GIP）水平。 方法 将受试者根据OGTT结果分为3组:正常糖耐量组（NGT，n=61例），糖耐量受损组（IGT，n=53）和2型糖尿病组（T2DM， n=66）。采空腹及糖餐后2 h静脉血检测GLP-1和GIP水平。 结果 T2DM组空腹GLP-1水平低于NGT和IGT组（Plt;0.05）。NGT和IGT的空腹GLP-1水平差异无统计学意义（Pgt;0.05）。餐后GLP-1水平三组差异无统计学意义（Pgt;0.05）。空腹及餐后GIP水平在NGT、IGT和T2DM均呈逐渐增加的趋势，而且同OGTT-0 h和OGTT-2 h血糖水平呈正相关（r=0.384，0.426；Plt;0.05）。 结论 不同的GLP-1和GIP水平也许是IGT和T2DM胰岛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