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.
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 investigate the association between the stress-induced hyperglycemia ratio (SHR) and all-cause, cardiovascular, and diabetes-related mortality in patients with advanced cardiovascular-kidney-metabolic (CKM) syndrome, and to evaluate the value of SHR as an independent prognostic marker. MethodsThis retrospective cohort study used data from the 1999–2018 U.S. National Health and Nutrition Examination Survey (NHANES). A total of 2 135 patients with advanced CKM (stages 3 and 4) were included. Kaplan-Meier analysis and multivariable Cox regression models were applied to assess the relationship between SHR and mortality outcomes. Restricted cubic spline (RCS) analysis was employed to explore potential non-linear associations. Subgroup analyses were conducted to identify possible effect modifiers. ResultsOver a mean follow-up of 248 months, 674 all-cause, 198 cardiovascular, and 31 diabetes-related deaths occurred. Elevated SHR was significantly associated with diabetes-related mortality (HR=3.48, P<0.001) in a dose-response manner. SHR exhibited a U-shaped relationship with both all-cause and cardiovascular mortality (non-linearity P<0.001), indicating increased risk at both low and high SHR levels. Subgroup analyses revealed that sex, BMI, and hyperlipidemia significantly modified the association between SHR and diabetes-related death. ConclusionSHR is an independent predictor of mortality risk in patients with advanced CKM syndrome, particularly for diabetes-related death. These findings support the integration of SHR into risk stratification of high-risk CKM populations and provide a basis for metabolic stress-targeted interventions.
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.
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.
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.
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 impact of elevated fasting blood glucose (FBG) level after open radical hepatectomy on the early recurrence of hepatocellular carcinoma (HCC).MethodsThe clinical data of 112 patients with HCC who underwent the open radical hepatecomy from January 2013 to December 2014 in the Affiliated Hospital of Qingdao University were retrospectively analyzed. After the radical resection of HCC, 86 patients with level of FBG 3.9–6.1 mmol/L and 26 patients with level of FBG≥6.1 mmol/L were design into a normal FBG group and an elevated FBG group, respectively. The recurrence rates of HCC were compared between the two groups at 1- and 2-year after the opreation.ResultsThere were no significant differences between the 2 groups in the gender, age, history of alcohol drinking, hepatitis B history, preoperative ALT, AST, AFP and Child-Pugh classification, scope of hepatectomy, intraoperative hemorrhage, hepatic blood flow occlusion, diameter of maximal tumor, histopathological differentiation, tumor number, cirrhosis, satellite lesion, postoperative adjuvant TACE treatment or not (P>0.05). The postoperative 1- and 2-year recurrence rates of HCC were 19.8% (17/86) and 33.7% (29/86) in the normal FBG group and 42.3% (11/26) and 61.5% (16/26) in the elevated FBG group, respectively, showing significant differences between the 2 groups (P<0.05). The results of multivariate analysis showed that the level of FBG≥6.1 mmol/L, low histopathological differentiation, and no postoperative TACE treatment were the independent risk factors affecting tumor-free survival rate after the open radical resection of HCC (P<0.05). ConclusionsElevated FBG level after open radical resection has a stimulative effect on early recurrence of HCC. As a result, monitoring and controlling of FBG level after operation is helpful in decreasing early recurrence rate of patients with HCC.