摘要:目的: 观察格列美脲对2型糖尿病患者心血管的保护作用并探讨其可能的机制。 方法 :112例T2DM患者随机分为格列美脲组(格列美脲+二甲双胍)和对照组(格列本脲+二甲双胍),观察治疗前后两者空腹及餐后两小时血糖(FBG,2hPBG)、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)、HOMA模型胰岛素抵抗指数(HOMAIR)、甘油三脂(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDLC)、低密度脂蛋白胆固醇(LDLC)、同型半胱氨酸(HCY)、血浆脂联素的变化。 结果 :两组患者的TC、LDLC、TG、FBG、2hPBG都较治疗前降低,连续服用6个月以上格列美脲的T2DM患者其血浆HCY、HOMAIR、血糖水平明显下降,血浆脂联素水平明显升高,与对照组相比差异有统计学意义(〖WTBX〗P lt;005)。 结论 :格列美脲能降低多项心血管危险因子水平,对血脂、HCY和动脉粥样硬化都有良性调节作用,其作用基础可能与改善胰岛素抵抗,增加血浆脂联素相关。Abstract: Objective: To observe the protective effects and to explore mechanisms of glimepiride on cardiovascular system of Type 2 Diabetes Mellitus. Methods : 112 patients with type 2 diabetes mellitus were randomly divided into treatment group (glimepiride combined with metformin) and control group (glibenclamide combined with metformin). The fasting blood glucose (FBG), 2hPBG, hemoglobin A1c (HbA1c), FINS, HOMAIR, blood lipid (TC, TG, LDLC and HDLC), HCY (homocysteine) and adiponectin were detected before and after treatment. Results : In all cases, the level of TC、LDLC、TG、FBG、2hPBG were decreased after treated with glimepiride or glibenclamide combined with metformin for 6 monthes. Moreover, the level of HCY, HOMAIR and blood glucose were decreased and the level of adiponectin was increased significantly than that of in control group (Plt;005). Conclusion : Glimepiride showed the effective on decreasing the risk factor of cardiovascular system disease with regulation of blood lipid, HCY, and improve the atherosclerosis. The effective of glimepiride on cardiovascular system was relation to improved the insulin resistance and increase the adiponectin.
Objective To investigate effect of metabolic surgery on type 2 diabetes mellitus (T2DM) patients with body mass index (BMI) 27.5–32.5 kg/m2. Methods The clinical data of 43 T2DM patients with BMI 27.5–32.5 kg/m2 underwent metabolic surgery from October 2014 to October 2016 in the Third Xiangya Hospital of Central South University were analyzed retrospectively. The related indexes such as BMI, blood glucose level, blood lipid level were analyzed before and after metabolic surgery. Results All the patients underwent metabolic surgery successfully. Among them, 35 cases underwent laparoscopic gastric bypass surgery while 8 cases underwent laparoscopic sleeve gastrectomy without related complications after operation. Compared with preoperative indexes, the BMI, fasting blood glucose, HbA1c, triglyceride, and total cholesterol on the postoperative different time were all significantly decreased (P<0.05) except for the HbA1c on the postoperative 1-week, the high density lipoprotein level on the postoperative 12-month was significantly increased (P<0.05). The OGTT 30, 60, and 120 min blood glucose levels on the postoperative 1-week and 3-month, and 60 and 120 min blood glucose levels on the postoperative 6-month and 12-month were all significantly decreased (P<0.05). The OGTT-IRT 60 min insulin level on the postoperative 3-month and the 30 min insulin levels on the postoperative 6- and 12-month were all significantly increased (P<0.05). The levels of OGTT-CRT 30 and 60 min C peptide on the postoperative 6-month and the level of 30 min C peptide on the postoperative 12-month were all significantly increased (P<0.05). Conclusions Metabolic surgery is effective in treatment of T2DM patients with BMI 27.5–32.5 kg/m2, and levels of blood glucose and blood lipids can be improved significantly. Synthesis and release of insulin by islet cells can be ameliorated.
Objective To explore mechanism of gastric bypass in treating obesity with type 2 diabetes mellitus (T2DM) and its relationship with c-Jun N-terminal kinase (JNK) signaling pathway. Methods The INS-1 cells were divided into 4 groups according to the different treatment: control group (complete medium), high glucose group (30 mmol/L glucose medium), exendin-4 group (high glucose+100 nmol/L exendin-4), and JNK agonist group (high glucose+100 nmol/L exendin-4+JNK agonist). When these cells were cultured on day 7, the cell activity was assessed by the MTT staining. The cell apoptosis was determined by the fluorescence microscopy analysis after the Hoechst/PI staining and flow cytometric assay after the Annexin V-FITC/PI staining. The expressions of the human immunoglobulin binding protein (Bip), CCAAT/enhancer-binding protein homologous protein (CHOP), P-SAPK/JNK, and caspase-3 protein were detected by the Western blot. Results Compared with the control group, the cell activities were significantly decreased (P<0.05), the cell apoptosis rates and the P-SAPK/JNK and caspase-3 protein expression levels were significantly increased (P<0.01) in the high glucose group and the JNK agonist group, but the Bip and CHOP protein expression levels were significantly increased (P<0.01) in the high glucose group. Compared with the high glucose group, the cell activity was significantly increased (P<0.05), the cell apoptosis rate and the Bip, CHOP, P-SAPK/JNK, and caspase-3 protein expression levels were significantly decreased (P<0.01) in the exendin-4 group, the Bip and CHOP protein expression levels were significantly decreased (P<0.01) in the JNK agonist group. Compared with the exendin-4 group, the cell activity was significantly decreased (P<0.05), the cell apoptosis rate and the P-SAPK/JNK and caspase-3 protein expression levels were significantly increased (P<0.01) in the JNK agonist group. Conclusion Gastric bypass can inhibit endoplasmic reticulum stress of pancreatic islet β-cells by regulating secretion of glucagon like peptide-1, thereby inhibiting JNK signaling pathway, protecting pancreatic islet β-cells and inhibiting apoptosis, so as to achieve effect of treating T2DM.
ObjectiveTo observe expressions of E3 ubiquitin ligase—mitsugmin53 (MG53) protein, MG53 mRNA, and insulin receptor substrate 1 (IRS-1) mRNA in skeletal muscle of non-obese type 2 diabetic mellitus (T2DM) rats after gastric bypass operation (GBP), and to investigate possible mechanism of GBP in improving insulin resistance.MethodsTwenty-four healthy male GK rats were randomly divided into diabetic operation group, diabetic sham operation group, and diabetic control group, 8 rats in each group; besides, 8 male Wistar rats were served as normal control group. The expressions of MG53 protein in skeletal muscle tissue were detected by using Western blot method on week8 after operation. The mRNA levels of IRS-1 and MG53 in skeletal muscles tissue were measured by RT-PCR methods on week 8 after operation.Results① The expressions of MG53 protein and MG53 mRNA in the diabetic sham operation group and diabetic control group were significantly higher than those in the diabetic operation group and the normal control group on week 8 after operation (P<0.05), respectively, which had no significant differences between the diabetic operation group and the normal control group (P>0.05), and between the diabetic sham operation group and the diabetic control group (P>0.05) on week 8 after surgery. ② Compared with the normal control group, the expression of IRS-1 mRNA was significantly decreased in the diabetic operation group, the diabetic sham operation group, and the diabetic control group (P<0.05), while there were no significant differences between the diabetic operation group, diabetic sham operation group, and the diabetic control group on week 8 after operation (P>0.05).ConclusionExpression of E3 ubiquitin ligase—MG53 protein in skeletal muscle tissue in T2DM rats following GBP is decreased, thus reduces the IRS-1 ubiquitin-degradation, increase the expression of IRS-1 protein in insulin signaling pathway of skeletal muscle tissue, and improve insulin resistance of skeletal muscle.
ObjectiveTo systematically evaluate effect of metformin on prognosis of colorectal cancer patients with type 2 diabetes mellitus (T2DM).MethodsThe PubMed, Embase, Web of Science, Cochrane Library, CNKI, VIP, Wangfang, etc. databases for cohort studies over the past 10 years were systematically searched. The relationship between the metformin and the prognosis in the colorectal cancer patients with T2DM was assessed with RevMan 5.3 software.ResultsA total of 12 articles with 13 694 patients were included in this study, of which 9 069 patients treated by the metformin (metformin group) and 4 625 patients treated by the other antidiabetic agent (control group). The results of meta-analysis showed that the metformin group had higher over survival [HR=0.74, 95%CI (0.66, 0.82), P<0.000 01] and cancer-specific survival [HR=0.77, 95%CI (0.69, 0.86), P<0.000 01] as compared with the control group. The sensitivity analysis of the heterogeneity showed that the research results did not be changed when the study which might cause heterogeneity was excluded. ConclusionMetformin treatment could improve prognosis of colorectal cancer patients with T2DM and improve overall survival and cancer-specific survival.
ObjectiveTo investigate the effect of the remnant stomach after gastric bypass (GB) surgery on the weight loss and glucose metabolism in rats with obese and type 2 diabetes mellitus (T2DM).MethodsHigh fat feeding for one month combined with intraperitoneal injection of low-dose streptozotocin was used to induce obese rats with T2DM. Twenty-four rats with obese and type T2DM successfully established were randomly divided into resectional gastric bypass (R-GB) group, GB surgery (GB group), and sham operation (SO) group, eight rats in each group. The weight loss and anti-diabetic effect of the R-GB and GB were compared. Body weight, food intake, and fasting blood glucose (FBG) were measured at week 1 before operation and week 1–8 after the operation. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed using tail venous blood at week 1 before operation and on week 8 after operation (at 0, 30, 60, 90, and 120 min). The levels of serum glucagon like peptide-1 (GLP-1), gastrin, insulin, and glucagon at week 1 before operation and at week 8 after operation were detected, meanwhile the homeostasis model assessment insulin resistance (HOMA-IR) index was calculated.Results① The body weight and food intake of the rats in the R-GB group and GB group were lower than those in the SO group after operation (P<0.05) and which were lower than before operation (P<0.05), but the differences were not significant between the R-GB group and GB group after operation (P>0.05). ② The levels of FBG in the R-GB group only at week 1–4 after operation were lower than those before operation (P<0.05), while which in the GB group at week 1–8 after operation were lower than those before operation and were lower than in the SO group (P<0.05), but which in the R-GB group only at week 2–4 after operation were lower than in the SO group and which were higher than that in the GB group from 3 to 8 weeks after operation (P<0.05). ③ The area under receiver operating characteristic curves (AUCs) of blood glucoses of OGTT and ITT and HOMA-IR index at week 8 after operation were lower than those before operation (P<0.05) in the GB group and which were lower than those the other two groups (P<0.05). ④ The AUC of gastrin level at week 8 after operation was lower than that before operation in the R-GB group and which lower than that in the other two groups (P<0.05). The AUC values of insulin and glucagon levels at week 8 after operation were lower than those before operation in the GB group and which lower than those in the other two groups (P<0.05). The AUC of GLP-1 level at week 8 after operation was higher than that before operation in the GB group and which higher than that in the other two groups (P<0.05).ConclusionsGB could remarkably improve glucose metabolism and weight loss in obese rat with T2DM. Gastric remnant gastrectomy following GB has a remarkable anti-diabetic effect, but it doesn’t effect on weight loss.
ObjectiveTo investigate effects of sleeve gastrectomy (SG)-transit bipartition (SG-TB) and simple SG on bariatric and anti-diabetic and protective effect on esophagus reflux. MethodsA total of 36 male Sprague-Dawley rats were used to successfully induce the obesity with type 2 diabetes mellitus (T2DM) model by dietary feeding and receiving intraperitoneal injection of streptozotocin (35 mg/kg), then were randomly averagely divided into SG, SG-TB, and sham operation (SO) groups according to the surgical methods, and 8 rats from each procedure were randomly selected and included to use for experimental observation. The observation period was 12 weeks. The changes of terminal esophageal mucosa were observed at the 12th week after operation. The body weight and food intake were measured every 2 weeks after operation. The fasting blood glucose (FBG), oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) blood glucose levels were measured before operation and at the 4th and 12th week after operation. And the changes of glucagon like peptide-1 (GLP-1) and insulin levels were measured before operation and at the 12th week after operation. ResultsThere were no significant differences in all indexes among the 3 groups before operation (P>0.05). ① No esophageal papillomatosis was observed in the SG-TB group at the 12th week after operation, but more severe esophageal papillomatosis was observed in the SG group, and the mucosal height in the SG-TB group was lower than that in the SG group (P<0.05). ② From the 4th week after operation, the body weight and food intake of the SG-TB group and SG group were lower than the SO group (P<0.05), and their changes of these two groups over time were generally stable. While no significant difference was found in the reduction of body weight between the SG-TB group and the SG group (P>0.05), however the food intakes of the SG-TB group were higher than the SG group at the 10th and 12th week after operation (P<0.05). ③ The levels of FBG, OGTT and ITT blood glucoses in the SG-TB group and SG group were lower than in the SO group at the 4th and 12th week after operation (P<0.05) and remained stable after operation. However, no significant difference was found in the FBG and ITT blood glucose level between the SG-TB group and the SG group (P>0.05), while the level of OGTT blood glucose in the SG-TB group was lower than that in the SG group at the 12th week after operation (P<0.05). ④ The levels of GLP-1 in the SG-TB group and SG group were higher than in the SO group and still higher than before operation (P<0.05), while the insulin levels were lower than in the SO group and lower than before operation (P<0.05). ConclusionsFrom preliminary results of this study, change of terminal esophageal mucosa after SG-TB is weaker than that of SG operation, and it is found that SG-TB surgery shows a better trend in blood glucose control as compared with SG operation. However, due to the limitations of sample size, further research and anti-reflux effect of SG-TB operation still need to be verified.
Objective To explore the potential molecular mechanism of Rhodiola crenulata (RC) for type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) by network pharmacology and molecular docking. Methods The target genes of T2DM and AD, the effective active components and targets of RC were identified through multiple public databases during March to August, 2022. The main active components and core genes of RC anti T2DM-AD were screened. The key genes were enrichment analyzed by gene ontology function and Kyoto gene and Kyoto Encyclopedia of Genes and Genomes. AutoDock Vina was used for molecular docking and binding energy calculation. Results A total of 5189 T2DM related genes and 1911 AD related genes were obtained, and the intersection result showed that there were 1418 T2DM-AD related genes. There were 48 active components of RC and 617 corresponding target genes. There were 220 crossing genes between RC and T2DM-AD. The main active components of RC anti T2DM-AD included kaempferol, velutin, and crenulatin. The key genes for regulation include ESR1, EGFR, and AKT1, which were mainly enriched in the hypoxia-inducible factor-1 signal pathway, estrogen signal pathway, and vascular endothelial growth factor signal pathway. The docking binding energies of the main active components of RC and key gene molecules were all less than −1.2 kcal/mol (1 kcal=4.2 kJ). Conclusions RC may play a role in influencing T2DM and AD by regulating the hypoxia-inducible factor-1 signaling pathway, estrogen signaling pathway, and vascular endothelial growth factor signaling pathway.
Objective To assess the improvement of different resistance training regimens on blood lipid metabolism and insulin resistance in patients with type 2 diabetes mellitus (T2DM). Methods PubMed, ProQuest, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang, and VIP databases were searched to collect randomized controlled trials of resistance training intervention to improve blood lipids and insulin resistance in patients with T2DM. The search time range was from the establishment of the databases to May 2023. Two reviewers assessed the risk of bias of the included studies using the Physiotherapy Evidence Database scale, and performed a network meta-analysis of the extracted data using Stata 16.0 software. Results In the end, 24 articles were included, and a total of 983 participants were enrolled. The result of network meta-analysis showed that high-frequency and moderate-intensity resistance exercise significantly improved the levels of insulin resistance [standardized mean difference=−1.71, 95% confidence interval (CI) (−2.75, −0.67)], triglycerides [weighted mean difference (WMD)=−0.27 mmol/L, 95%CI (−0.51, −0.04) mmol/L], and total cholesterol [WMD=−0.16 mmol/L, 95%CI (−0.20, −0.12) mmol/L], but had no significant effect on improving the level of high-density lipoprotein [WMD=0.05 mmol/L, 95%CI (−0.02, 0.11) mmol/L] or low-density lipoprotein [WMD=−0.20 mmol/L, 95%CI (−0.42, 0.03) mmol/L]. The results of cumulative probability ranking showed that high-frequency and moderate-intensity resistance exercise was the best in improving insulin resistance, triglycerides, high-density lipoprotein and low-density lipoprotein levels. Conclusion Based on current evidence, high-frequency and moderate-intensity resistance exercise may be the best resistance exercise regimen to improve insulin resistance and lipid metabolism in patients with T2DM.
Sleeve gastrectomy with transit bipartition (SG-TB) was a novel bariatric and metabolic surgery that had received preliminary approval for its effectiveness and safety in reducing weight, improving diabetes, and other metabolic diseases. It showed promising prospects in clinical applications. However, SG-TB also faced some challenges including a small number of cases, insufficient clinical evidence, issues with anastomotic stoma and common channel design, bile reflux, gastroesophageal reflux disease, and malnutrition. Further research is needed to enhance the standardization of SG-TB procedures and provides reference for its wider implementation.