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 investigate the effects of single anastomosis sleeve ileal (SASI) bypass on weight loss, metabolic improvements, and postoperative safety in patients with obesity and its metabolic comorbidities (such as type 2 diabetes and hyperlipidemia). MethodsA retrospective analysis was conducted. The clinical data of patients with obesity [body mass index (BMI) ≥32.5 kg/m² or BMI ≥27.5 kg/m² with metabolic diseases] who underwent SASI bypass in the Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School from January 2023 to December 2023. Weight loss outcomes, including the percentage of total weight loss (%TWL), percentage of excess weight loss (%EWL), and percentage of excess BMI loss (%EBMIL), were recorded at 6 and 12 months postoperatively. Metabolic disease remission and complications at 12 months postoperatively were also documented. ResultsA total of 82 patients were included in the study. At 12 months postoperatively, the reductions in %TWL, %EWL, and %EBMIL were significantly greater than those observed at 6 months postoperatively [%TWL: (27.1±4.6)% vs. (23.6±3.8)%, t=2.379, P=0.026; %EWL: (72.1±5.8)% vs. (56.6±7.3)%, t=2.593, P<0.001; %EBMIL: (71.6±6.7)% vs. (58.3±4.9)%, t=2.607, P<0.001], remission was observed in 40 out of 48 patients (83.3%) with comorbid hypertension, 49 out of 51 patients (96.1%) with comorbid type 2 diabetes mellitus, and all patients with comorbid hyperlipidemia (33 cases) and obstructive sleep apnea syndrome (29 cases) achieved complete remission. Within 12 months after SASI bypass, 3 patients (3.7%) experienced melena, 2 patients (2.4%) developed incomplete intestinal obstruction, and 10 patients (12.1%) showed malnutrition. ConclusionThe findings of this study indicate that SASI bypass demonstrates significant weight loss and metabolic improvement effects in patients with obesity and metabolic diseases, with a controllable safety profile.
Objective To construct, validate and evaluate a nomogram prediction model based on triglyceride-glucose index for predicting the risk of type 2 diabetes mellitus (T2DM) in patients with obstructive sleep apnea (OSA). Methods A total of 414 patients diagnosed with OSA who were hospitalized in the Second Affiliated Hospital of Kunming Medical University from July 2013 to July 2023 were retrospectively analyzed. They were randomly divided into training set (n=289) and validation set (n=125) at a ratio of 7:3 using R software. In the training set, univariate logistic regression, best subsets regression (BSR) and multivariate Logistic regression were used to determine the independent predictors of OSA combined with T2DM and construct a nomogram. The area under the receiver operating characteristic curve (AUC), calibration curve, Hosmer-Lemeshow goodness of fit test, decision curve analysis (DCA) and clinical impact curve (CIC) were used to evaluate the discrimination, calibration and clinical applicability of the nomogram prediction model. Finally, the internal validation of the nomogram prediction model was carried out on the validation set. Results In the training set, the results of univariate logistic regression, BSR and multivariate logistic regression analysis showed that hypertension (OR=2.413, 95%CI 1.276-4.563, P=0.007), apnea hypopnea index (OR=1.034, 95%CI 1.014-1.053, P=0.001), triglyceride-glucose index( OR=12.065, 95%CI 5.735-25.379, P<0.001), triglyceride/high density lipoprotein cholesterol (OR=0.736, 95%CI 0.634-0.855, P<0.001) were independent predictors of T2DM in OSA patients. A nomogram prediction model was constructed based on the above four predictors. In the training set and validation set, the AUC, sensitivity, and specificity of the nomogram prediction model for predicting the risk of T2DM in OSA patients were 0.820 (95%CI 0.771-0.869), 75.7%, 75.9% and 0.778 (95%CI 0.696-0.861), 74.5%, 73.0%, respectively, indicating that the nomogram had good discrimination. The calibration curve showed that the nomogram had a good calibration for predicting T2DM in OSA patients. DCA and CIC also showed that the nomogram prediction model had certain clinical utility. Conclusions A simple, fast and effective nomogram prediction model with good discrimination, calibration and clinical applicability was successfully constructed, validated and evaluated. It can be used to predict the risk of T2DM in OSA patients and help clinicians to identify patients with high risk of T2DM in OSA patients.
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.
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.
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 explore the risk factors affecting occurrence of arteriosclerosis obliterans (ASO) for patients with type 2 diabetes mellitus (T2DM) and to develop a nomogram predictive model using these risk factors. MethodsA case-control study was conducted. The patients with T2DM accompanied with ASO and those with T2DM alone, admitted to the First Affiliated Hospital of Xinjiang Medical University from January 2017 to December 2022, were retrospectively collected according to the inclusion and exclusion criteria. The basic characteristics, blood, thyroid hormones, and other relevant indicators of the paitents in two groups were compared. The multivariate logistic regression analysis was used to identify the risk factors for the occurrence of ASO in the patients with T2DM, and then a nomogram predictive model was developed. ResultsThere were 119 patients with T2DM alone and 114 patients with T2DM accompanied with lower extremity ASO in this study. The significant differences were observed between the two groups in terms of smoking history, white blood cell count, neutrophil count, lymphocyte count, platelet count, systemic immune-inflammation index, systemic inflammatory response index (SIRI), high-density lipoprotein cholesterol, apolipoprotein A1 (ApoA1), apolipoprotein α (Apoα), serum cystatin C, free-triiodothyronine (FT3), total triiodothyronine, FT3/total triiodothyronine ratio, fibrinogen (Fib), fibrinogen degradation products, and plasma D-dimer (P<0.05). Further the results of the multivariate logistic regression analysis revealed that the history of smoking, increased Fib level and SIRI value increased the probabilities of ASO occurrence in the patients with T2DM [OR (95%CI)=2.921 (1.023, 4.227), P=0.003; OR (95%CI)=2.641 (1.810, 4.327), P<0.001; OR (95%CI)=1.020 (1.004, 1.044), P=0.018], whereas higher levels of ApoA1 and FT3 were associated with reduced probabilities of ASO occurrence in the patients with T2DM [OR (95%CI)=0.231 (0.054, 0.782), P=0.021; OR (95%CI)=0.503 (0.352, 0.809), P=0.002]. The nomogram predictive model based on these factors demonstrated a good discrimination for predicting the ASO occurrence in the T2DM patients [area under the receiver operating characteristic curve (95%CI)=0.788 (0.730, 0.846)]. The predicted curve closely matched the ideal curve (Hosmer-Lemeshow goodness-of-fit test, χ2=5.952, P=0.653). The clinical decision analysis curve showed that the clinical net benefit of intervention based on the nomogram model was higher within a threshold probability range of 0.18 to 0.80 compared to no intervention or universal intervention. ConclusionsThe analysis results indicate that T2DM patients with a smoking history, elevated Fib level and SIRI value, as well as decreased ApoA1 and FT3 levels should be closely monitored for ASO risk. The nomogram predictive model based on these features has a good discriminatory power for ASO occurrence in T2DM patients, though its value warrants further investigation.
Objective To investigate the clinical characteristics and pathogen distribution of community-acquired pneumonia (CAP) combined with type 2 diabetes mellitus (T2DM), based on bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) test. Methods In this cross-sectional study, CAP patients with BALF mNGS test were screened from April 2023 to April 2024. The patients were divided into a single CAP group (CAP group) and a CAP combine with T2DM group (CAP+T2DM group). The data of demographics, underlying diseases, complications, and laboratory tests including blood routine, inflammatory parameters, liver and renal functions, random blood glucose (RGB), hemoglobin A1C (HbA1c), and BALF mNGS tests were collected and compared between the two groups. Results Ultimately, 86 patients were included, with 45 in the CAP group and 41 in the CAP+T2DM group. Compared with the CAP group, the CAP+T2DM group had higher platelet count [(272.44±128.57)×109/L vs. (215.00±100.06)×109/L], erythrocyte sedimentation rate [(75.63±35.19) vs. (59.69±34.47) mm/h], RGB [10.8 (9.1, 13.5) vs. 6.5 (5.8, 7.8) mmol/L], HbA1c [8.2% (7.3%, 8.5%) vs. 5.7% (5.5%, 6.1%)], and fungi infection rate (65.9% vs. 40.0%), and the differences were statistically significant between the two groups (P<0.05). Conclusion CAP patients with T2DM have increased levels of platelet and erythrocyte sedimentation rate, and are at higher risk for fungi infection, which potentially leads to worse outcome.
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.
Patients with type 2 diabetes mellitus often face significant treatment burden, which substantially impacts their quality of life and health outcomes. Reducing treatment burden represents a critical component for improving patient prognosis and enhancing treatment adherence. Based on the cumulative complexity model, this article systematically examines the conceptual connotation and multidimensional characteristics of treatment burden in type 2 diabetes mellitus patients, explores the theoretical extension and application value of cumulative complexity model in the type 2 diabetes mellitus field, elucidates its specific applications and recent advances in treatment burden research, evaluates the limitations of existing assessment tools while proposing a multidimensional assessment framework, and ultimately develops cumulative complexity model based intervention strategies. The findings provide theoretical references for optimizing patient-centered diabetes management approaches and offer novel perspectives for treatment burden intervention.