BACKGROUND Cardiovascular disease is a major complication of diabetes mellitus(DM).Type-2 DM(T2DM)is associated with an increased risk of cardiovascular events and mortality,while serum biomarkers may facilitate the p...BACKGROUND Cardiovascular disease is a major complication of diabetes mellitus(DM).Type-2 DM(T2DM)is associated with an increased risk of cardiovascular events and mortality,while serum biomarkers may facilitate the prediction of these outcomes.Early differential diagnosis of T2DM complicated with acute coronary syndrome(ACS)plays an important role in controlling disease progression and improving safety.AIM To investigate the correlation of serum bilirubin andγ-glutamyltranspeptidase(γ-GGT)with major adverse cardiovascular events(MACEs)in T2DM patients with ACS.METHODS The clinical data of inpatients from January 2022 to December 2022 were analyzed retrospectively.According to different conditions,they were divided into the T2DM complicated with ACS group(T2DM+ACS,n=96),simple T2DM group(T2DM,n=85),and simple ACS group(ACS,n=90).The clinical data and laboratory indices were compared among the three groups,and the correlations of serum total bilirubin(TBIL)levels and serumγ-GGT levels with other indices were discussed.T2DM+ACS patients received a 90-day follow-up after discharge and were divided into event(n=15)and nonevent(n=81)groups according to the occurrence of MACEs;Univariate and multivariate analyses were further used to screen the independent influencing factors of MACEs in patients.RESULTS The T2DM+ACS group showed higherγ-GGT,total cholesterol,low-density lipoprotein cholesterol(LDL-C)and glycosylated hemoglobin(HbA1c)and lower TBIL and high-density lipoprotein cholesterol levels than the T2DM and ACS groups(P<0.05).Based on univariate analysis,the event and nonevent groups were significantly different in age(t=3.3612,P=0.0011),TBIL level(t=3.0742,P=0.0028),γ-GGT level(t=2.6887,P=0.0085),LDL-C level(t=2.0816,P=0.0401),HbA1c level(t=2.7862,P=0.0065)and left ventricular ejection fraction(LEVF)levels(t=3.2047,P=0.0018).Multivariate logistic regression analysis further identified that TBIL level and LEVF level were protective factor for MACEs,and age andγ-GGT level were risk factors(P<0.05).CONCLUSION Serum TBIL levels are decreased andγ-GGT levels are increased in T2DM+ACS patients,and the two indices are significantly negatively correlated.TBIL andγ-GGT are independent influencing factors for MACEs in such patients.展开更多
BACKGROUND The lack of specific predictors for type-2 diabetes mellitus(T2DM)severely impacts early intervention/prevention efforts.Elevated branched-chain amino acids(BCAAs:Isoleucine,leucine,valine)and aromatic amin...BACKGROUND The lack of specific predictors for type-2 diabetes mellitus(T2DM)severely impacts early intervention/prevention efforts.Elevated branched-chain amino acids(BCAAs:Isoleucine,leucine,valine)and aromatic amino acids(AAAs:Tyrosine,tryptophan,phenylalanine)show high sensitivity and specificity in predicting diabetes in animals and predict T2DM 10-19 years before T2DM onset in clinical studies.However,improvement is needed to support its clinical utility.AIM To evaluate the effects of body mass index(BMI)and sex on BCAAs/AAAs in new-onset T2DM individuals with varying body weight.METHODS Ninety-seven new-onset T2DM patients(<12 mo)differing in BMI[normal weight(NW),n=33,BMI=22.23±1.60;overweight,n=42,BMI=25.9±1.07;obesity(OB),n=22,BMI=31.23±2.31]from the First People’s Hospital of Yunnan Province,Kunming,China,were studied.One-way and 2-way ANOVAs were conducted to determine the effects of BMI and sex on BCAAs/AAAs.RESULTS Fasting serum AAAs,BCAAs,glutamate,and alanine were greater and high-density lipoprotein(HDL)was lower(P<0.05,each)in OB-T2DM patients than in NW-T2DM patients,especially in male OB-T2DM patients.Arginine,histidine,leucine,methionine,and lysine were greater in male patients than in female patients.Moreover,histidine,alanine,glutamate,lysine,valine,methionine,leucine,isoleucine,tyrosine,phenylalanine,and tryptophan were significantly correlated with abdominal adiposity,body weight and BMI,whereas isoleucine,leucine and phenylalanine were negatively correlated with HDL.CONCLUSION Heterogeneously elevated amino acids,especially BCAAs/AAAs,across new-onset T2DM patients in differing BMI categories revealed a potentially skewed prediction of T2DM development.The higher BCAA/AAA levels in obese T2DM patients would support T2DM prediction in obese individuals,whereas the lower levels of BCAAs/AAAs in NW-T2DM individuals may underestimate T2DM risk in NW individuals.This potentially skewed T2DM prediction should be considered when BCAAs/AAAs are to be used as the T2DM predictor.展开更多
This editorial synthesizes insights from a series of studies examining the interplay between metabolic and oxidative stress biomarkers in cardiovascular disease(CVD),focusing particularly on type-2 diabetes mellitus(T...This editorial synthesizes insights from a series of studies examining the interplay between metabolic and oxidative stress biomarkers in cardiovascular disease(CVD),focusing particularly on type-2 diabetes mellitus(T2DM)and acute coronary syndrome(ACS).The central piece of this synthesis is a study that investigates the balance between oxidative stress and antioxidant systems in the body through the analysis of serum bilirubin andγ-glutamyltranspeptidase(γ-GGT)levels in T2DM patients with ACS.This study highlights serum bilirubin as a protective antioxidant factor,while elevatedγ-GGT levels indicate increased oxidative stress and correlate with major adverse cardiovascular events.Complementary to this,other research contributions revealγ-GGT’s role as a risk factor in ACS,its association with cardiovascular mortality in broader populations,and its link to metabolic syndrome,further elucidating the metabolic dysregulation in CVDs.The collective findings from these studies underscore the critical roles ofγ-GGT and serum bilirubin in cardiovascular health,especially in the context of T2DM and ACS.By providing a balanced view of the body’s oxidative and antioxidative mechanisms,these insights suggest potential pathways for targeted interventions and improved prognostic assessments in patients with T2DM and ACS.This synthesis not only corroborates the pivotal role ofγ-GGT in cardiovascular pathology but also introduces the protective potential of antioxidants like bilirubin,illuminating the complex interplay between T2DM and heart disease.These studies collectively underscore the critical roles of serum bilirubin andγ-GGT as biomarkers in cardiovascular health,particularly in T2DM and ACS contexts,offering insights into the body’s oxidative and antioxidative mechanisms.This synthesis of research supports the potential of these biomarkers in guiding therapeutic strategies and improving prognostic assessments for patients with T2DM and some CVD.展开更多
TypeⅡdiabetes mellitus(T2DM)has experienced a dramatic increase globally across countries of various income levels over the past three decades.The persistent prevalence of T2DM is attributed to a complex interplay of...TypeⅡdiabetes mellitus(T2DM)has experienced a dramatic increase globally across countries of various income levels over the past three decades.The persistent prevalence of T2DM is attributed to a complex interplay of genetic and environmental factors.While numerous pharmaceutical therapies have been developed,there remains an urgent need for innovative treatment approaches that offer effectiveness without significant adverse effects.In this context,the exploration of the gut microbiome presents a promising avenue.Research has increasingly shown that the gut microbiome of individuals with T2DM exhibits distinct differences compared to healthy individuals,suggesting its potential role in the disease’s pathogenesis and progression.This emerging field offers diverse applications,particularly in modifying the gut environment through the administration of prebiotics,probiotics,and fecal microbiome transfer.These interventions aim to restore a healthy microbiome balance,which could potentially alleviate or even reverse the metabolic dysfunctions associated with T2DM.Although current results from clinical trials have not yet shown dramatic effects on diabetes management,the groundwork has been laid for deeper investigation.Ongoing and future clinical trials are critical to advancing our understanding of the microbiome’s impact on diabetes.By further elucidating the mechanisms through which microbiome alterations influence insulin resistance and glucose metabolism,researchers can develop more targeted interventions.The potential to harness the gut microbiome in developing new therapeutic strategies offers a compelling prospect to transform the treatment landscape of T2DM,potentially reducing the disease’s burden significantly with approaches that are less reliant on traditional pharmaceuticals and more focused on holistic,systemic health improvements.展开更多
This published Meta-Analysis by Lin et al is an indirect comparison between two drugs Chiglitazar and Thiazolidinedione which are commonly used for glycemic control in type-Ⅱ diabetes mellitus.In terms of safety and ...This published Meta-Analysis by Lin et al is an indirect comparison between two drugs Chiglitazar and Thiazolidinedione which are commonly used for glycemic control in type-Ⅱ diabetes mellitus.In terms of safety and efficacy,this Meta-Analysis is inconclusive.展开更多
BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis...BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis(HT).While single symptomatic drug treatment of the two diseases is less effective,combined drug treatment may improve efficacy.AIM To investigate the effect of a combination of vitamin D,selenium,and hypoglycemic agents in T2DM with HT.METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023.Fifty patients were assigned to the control group,test group A,and test group B according to different treatment methods.The control group received low-iodine diet guidance and hypoglycemic drug treatment.Test group A received the control treatment plus vitamin D treatment.Test group B received the group A treatment plus selenium.Blood levels of markers of thyroid function[free T3(FT3),thyroid stimulating hormone(TSH),free T4(FT4)],autoantibodies[thyroid peroxidase antibody(TPOAB)and thyroid globulin antibody(TGAB)],blood lipid index[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triacylglycerol(TG)],blood glucose index[fasting blood glucose(FBG),and hemoglobin A1c(HbA1c)]were measured pre-treatment and 3 and 6 months after treatment.The relationships between serum 25-hydroxyvitamin D3[25(OH)D3]level and each of these indices were analyzed.RESULTS The levels of 25(OH)D3,FT3,FT4,and LDL-C increased in the order of the control group,test group A,and test group B(all P<0.05).The TPOAB,TGAB,TC,TG,FBG,HbA1c,and TSH levels increased in the order of test groups B,A,and the control group(all P<0.05).All the above indices were compared after 3 and 6 months of treatment.Pre-treatment,there was no divergence in serum 25(OH)D3 level,thyroid function-related indexes,autoantibodies level,blood glucose,and blood lipid index between the control group,test groups A and B(all P>0.05).The 25(OH)D3 levels in test groups A and B were negatively correlated with FT4 and TGAB(all P<0.05).CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function,autoantibody,and blood glucose and lipid levels.展开更多
BACKGROUND Islets of Langerhans beta cells diminish in autoimmune type 1 diabetes mellitus(T1DM).Teplizumab,a humanized anti-CD3 monoclonal antibody,may help T1DM.Its long-term implications on clinical T1DM developmen...BACKGROUND Islets of Langerhans beta cells diminish in autoimmune type 1 diabetes mellitus(T1DM).Teplizumab,a humanized anti-CD3 monoclonal antibody,may help T1DM.Its long-term implications on clinical T1DM development,safety,and efficacy are unknown.AIM To assess the effectiveness and safety of teplizumab as a therapeutic intervention for individuals with T1DM.METHODS A systematic search was conducted using four electronic databases(PubMed,Embase,Scopus,and Cochrane Library)to select publications published in peerreviewed journals written in English.The odds ratio(OR)and risk ratio(RR)were calculated,along with their 95%CI.We assessed heterogeneity using Cochrane Q and I2 statistics and the appropriate P value.RESULTS There were 8 randomized controlled trials(RCTs)in the current meta-analysis with a total of 1908 T1DM patients from diverse age cohorts,with 1361 patients receiving Teplizumab and 547 patients receiving a placebo.Teplizumab was found to have a substantial link with a decrease in insulin consumption,with an OR of 4.13(95%CI:1.72 to 9.90).Teplizumab is associated with an improved Cpeptide response(OR 2.49;95%CI:1.62 to 3.81)and a significant change in Glycated haemoglobin A1c(HbA1c)levels in people with type 1 diabetes[OR 1.75(95%CI:1.03 to 2.98)],and it has a RR of 0.71(95%CI:0.53 to 0.95).CONCLUSION In type 1 diabetics,teplizumab decreased insulin consumption,improved C-peptide response,and significantly changed HbA1c levels with negligible side effects.Teplizumab appears to improve glycaemic control and diabetes management with good safety and efficacy.展开更多
Diabetes mellitus is associated with foot ulcers,which frequently pave the way to lower-extremity amputation.Neuropathy,trauma,deformity,high plantar pressures,and peripheral vascular disease are the most common under...Diabetes mellitus is associated with foot ulcers,which frequently pave the way to lower-extremity amputation.Neuropathy,trauma,deformity,high plantar pressures,and peripheral vascular disease are the most common underlying causes.Around 15%of diabetic patients are affected by diabetic foot ulcer in their lifetime.64 million people are affected by diabetics in India and 40000 amputations are done every year.Foot ulcers are evaluated and classified in a systematic and thorough manner to assist in determining the best course of therapy.This paper proposes a novel model which predicts the threat of diabetic foot ulcer using independent agents for various input values and a combination of fuzzy expert systems.The proposed model uses a classification system to distinguish between each fuzzy framework and its parameters.Based on the severity levels necessary prevention,treatment,and medication are recommended.Combining the results of all the fuzzy frameworks derived from its constituent parameters,a risk-specific medication is recommended.The work also has higher accuracy when compared to other related models.展开更多
AIM To examine the changes of the ghrelin/ghrelin O-acyltransferase(GOAT) axis and the mammalian target of rapamycin(m TOR) pathway in the hypothalamus after sleeve gastrectomy.METHODS A total of 30 obese type-2 diabe...AIM To examine the changes of the ghrelin/ghrelin O-acyltransferase(GOAT) axis and the mammalian target of rapamycin(m TOR) pathway in the hypothalamus after sleeve gastrectomy.METHODS A total of 30 obese type-2 diabetes Sprague-Dawley(SD) rats, 6 wk of age, fed with high-sugar and highfat fodder for 2 mo plus intraperitoneal injection of streptozotocin were randomly divided into three groups: non-operation group(S0 group, n = 10), sham operation group(Sh group, n = 10) and sleeve gastrectomy group(SG group, n = 10). Data of body mass, food intake, oral glucose tolerance test(OGTT), acylated ghrelin(AG) and total ghrelin(TG) were collected and measured at the first day(when the rats were 6 wk old), preoperative day 3 and postoperative week 8. The m RNA expression of preproghrelin, GOAT and neuropeptide Y(NPY), and protein expression of ghrelin, GOAT, GHSR and the m TOR pathway(p-Akt, p-m TOR and p-S6) were measured in the hypothalamus.RESULTS SG can significantly improve metabolic symptoms by reducing body mass and food intake. The obese rats showed lower serum TG levels and no change in AG, but the ratio of AG/TG was increased. When compared with the S0 and Sh groups, the SG group showed decreased TG(1482.03 ± 26.55, 1481.49 ± 23.30 and 1206.63 ± 52.02 ng/L, respectively, P < 0.05), but unchanged AG(153.06 ± 13.74, 155.37 ± 19.30 and 144.44 ± 16.689 ng/L, respectively, P > 0.05). As a result, the ratio of AG/TG further increased in the SG group(0.103 ± 0.009, 0.105 ± 0.013 and 0.12 ± 0.016, respectively, P < 0.05). When compared with the S0 group, SG suppressed m RNA and protein levels of preproghrelin(0.63 ± 0.12 vs 0.5 ± 0.11, P < 0.05) and GOAT(0.96 ± 0.09 vs 0.87 ± 0.08, P < 0.05), but did not change NPY m RNA expression(0.61 ± 0.04 vs 0.65 ± 0.07, P > 0.05) in the hypothalamus. The protein levels of p-Akt, p-m TOR and p-S6 were higher in the SG group, which indicated that the hypothalamic m TOR pathway was activated after SG at the postoperative week 8. CONCLUSION The reduction of ghrelin expression and activation of the m TOR pathway might have opposite effects on food intake, as SG improves obesity and T2 DM.展开更多
Objective:The aim of this study was to assess the status of diabetes self-management(DSM)among Omanis with type-2 diabetes and its relationship with glycemic control and demographic variables.Methods:A correlational d...Objective:The aim of this study was to assess the status of diabetes self-management(DSM)among Omanis with type-2 diabetes and its relationship with glycemic control and demographic variables.Methods:A correlational descriptive design using questionnaire was conducted with a convenience sample of 266 Omani patients with type-2 diabetes to collect the data.Results:The findings indicated that DSM among the study subject is sub-optimal.Only 1%of them were regular on SMBG;9.5%of them exercise regularly;and 18%of them maintain healthy diet practices.No significant relationship between DSM and glycemic control(p>0.05)was found.DSM was found to be associated with age,gender,level of education,and duration of diabetes.Examining the differences between two regions in Oman(Muscat&Aldhakiliyah)indicated that participants from Muscat differ only in practicing SMBG.Conclusion:Results indicated that many Omani patients with type-2 diabetes do not perform DSM consistently.Practice implications:The findings of this study set the stage to develop teaching strategies that will improve DSM and subsequently improve diabetes management in patient with type-2 diabetes in Oman.展开更多
Objective Isletαcells input is essential for insulin secretion fromβcells.The present study aims to investigate the association between 25-hydroxyvitamin D[25(OH)D]and islet function homeostasis in type-2 diabetes(T...Objective Isletαcells input is essential for insulin secretion fromβcells.The present study aims to investigate the association between 25-hydroxyvitamin D[25(OH)D]and islet function homeostasis in type-2 diabetes(T2D)patients.Methods A total of 4670 T2D patients from seven communities in Shanghai,China were enrolled.The anthropometric indices,biochemical parameters,serum 25(OH)D,and islet function[including C-peptide(C-p)and glucagon]were measured.Results The fasting plasma glucose(FPG),glycated hemoglobin(HbA1c),glucagon,and C-p levels exhibited a significantly decreasing trend in T2D patients as the 25(OH)D levels increased.Next,the population was divided into two groups:abdominal obesity and non-abdominal obesity groups.After adjustment,the 25(OH)D level was found to be associated with HbA1c,glucagon,and homeostasis model assessment ofβ(HOMA-β)in the non-abdominal obesity group.There was a significant relationship between 25(OH)D and HbA1c,glucagon,HOMA-IR,baseline insulin or C-p in the abdominal obesity group.In the abdominal obesity group,the ordinary least squares(OLS)regression and quantile regression revealed that 25(OH)D was obviously associated with glucagon and fasting C-p levels.In the abdominal obesity group,the moderate analysis revealed a significant interaction effect of 25(OH)D and glucagon on C-p(P=0.0124).Furthermore,the conditional indirect effect of 25(OH)D on the glucagon/C-p ratio was significantly lower at 1 standard deviation(SD)below the mean(P=0.0002),and lower at the mean of the course of diabetes(P=0.0007).Conclusion 25(OH)D was found to be negatively correlated to glucagon and C-p in T2D patients with abdominal obesity.The 25(OH)D influenced C-p in part by influencing glucagon.The effect of 25(OH)D on the glucagon/C-p ratio in T2D patients with abdominal obesity,in terms of islet homeostasis,is influenced by the course of diabetes.展开更多
Obesity and type-2 diabetes mellitus(T2DM)are metabolic disorders.Obesity increases the risk of T2DM,and as obesity is becoming increasingly common,more individuals suffer from T2DM,which poses a considerable burden o...Obesity and type-2 diabetes mellitus(T2DM)are metabolic disorders.Obesity increases the risk of T2DM,and as obesity is becoming increasingly common,more individuals suffer from T2DM,which poses a considerable burden on health systems.Traditionally,pharmaceutical therapy together with lifestyle changes is used to treat obesity and T2DM to decrease the incidence of comorbidities and allcause mortality and to increase life expectancy.Bariatric surgery is increasingly replacing other forms of treatment of morbid obesity,especially in patients with refractory obesity,owing to its many benefits including good long-term outcomes and almost no weight regain.The bariatric surgery options have markedly changed recently,and laparoscopic sleeve gastrectomy(LSG)is gradually gaining popularity.LSG has become an effective and safe treatment for type-2 diabetes and morbid obesity,with a high cost-benefit ratio.Here,we review the mechanism associated with LSG treatment of T2DM,and we discuss clinical studies and animal experiments with regard to gastrointestinal hormones,gut microbiota,bile acids,and adipokines to clarify current treatment modalities for patients with obesity and T2DM.展开更多
The worldwide epidemic of obesity and its medical complications are being dealt with a combination of life style changes(e.g.,healthier diet and exercise),medications and a variety of surgical interventions.The Roux-e...The worldwide epidemic of obesity and its medical complications are being dealt with a combination of life style changes(e.g.,healthier diet and exercise),medications and a variety of surgical interventions.The Roux-en Y gastric bypass(RYGB) and laparoscopic adjustable gastric banding(LAGB) are two of the most common weight loss surgeries for morbid obesityassociated metabolic syndrome and insulin resistance.A vast majority of patients that undergo RYGB and LAGB are known to experience marked weight loss and attenuation of diabetes.A number of recent studies have indicated that the rates of remission in glycemic control and insulin sensitivity are significantly greater in patients that have undergone RYGB.A plausible hypothesis to explain this observation is that the gastric bypass surgery as opposed to the gastric banding procedure impinges on glucose homeostasis by a weight loss-independent mechanism.In a recent paper,Bradley et al have experimentally explored this hypothesis.The authors compared several clinical and laboratory parameters of insulin sensitivity and β-cell function in cohorts of RYGB and LAGB patients before and after they lost approximately 20% of their body mass.Afterweight loss,both groups of patients underwent similar changes in their intra-abdominal and total adipose tissue volume,hepatic triglyceride and circulating leptin levels.The RYGB patients who lost 20% body mass,manifested higher postprandial output of glucose,insulin and glucagon-like peptide-1;these laboratory parameters remained unchanged in LABG patients.Irrespective of the observed differences in transient responses of RYGB and LAGB patients to mixed meal,the overall glycemic control as judged by glucose tolerance,multi-organ insulin sensitivity and β-cell function were nearly identical in the two groups.Both RYGB and LAGB patient cohorts also experienced similar changes in the expression of a number of pro-and anti-inflammatory markers.Based on these analyses,Bradley et al concluded that similar restoration of insulin sensitivity and b-cell function in non-diabetic obese patients that have undergone RYGB and LAGB were directly due to marked weight loss.These data have important implications for the risk/benefit analysis of weight loss therapy by bariatric procedures.展开更多
Glucagon-like peptide-1 receptor agonists(GLP-1 RA)are a series of polypeptides broadly applied in the long-term treatment of typeⅡdiabetes.However,administration of GLP-RA is mainly through repetitive subcutaneous i...Glucagon-like peptide-1 receptor agonists(GLP-1 RA)are a series of polypeptides broadly applied in the long-term treatment of typeⅡdiabetes.However,administration of GLP-RA is mainly through repetitive subcutaneous injection,which may seriously decrease the compliance and safety.Herein,a bio-inspired oral delivery system was designed to enhance the oral absorption of liraglutide(Lira),a kind of GLP-1 RA,by mimicking the natural cholesterol assimilation.25-hydroxycholesterol(25HC),a cholesterol derivative,was modified on the surfaced of Lira-loaded PLGA nanoparticles(Lira 25HC NPs)and functioned as a“top-down”actuator to facilitate unidirectional transcytosis across the intestinal epithelium.After oral delivery,Lira 25HC NPs displayed improved therapeutic effect as compared with oral free Lira on typeⅡdiabetes db/db mice,as evidenced by multiple relieved diabetic symptoms including the enhanced glucose tolerance,repressed weight growth,improved liver glucose metabolism,decreased fasting blood glucose,HbA 1c,serum lipid,and increasedβcells activity.Surprisingly,the fasting blood glucose,liver glucose metabolism,and HbA1c of oral Lira-loaded 25HC NPs were comparable to subcutaneous injection of free Lira.Further mechanisms revealed that 25HC ligand could mediate the nanoparticles to mimic natural cholesterol absorption by exerting high affinity towards apical Niemann-Pick C1 Like 1(NPC1L1)and then basolateral ATP binding cassette transporter A1(ABCA1)overexpressed on the opposite side of intestinal epithelium.This cholesterol assimilation-mimicking strategy achieve the unidirectional transport across the intestinal epithelium,thus improving the oral absorption of liraglutide.In general,this study established a cholesterol simulated platform and provide promising insight for the oral delivery of GLP-1 RA.展开更多
Aim: We demonstrated the risk of developing islet autoantibodies-Insulin Autoanti-bodies (IAAs) and Islets cell Autoantibodies (ICAs)-in type-1 diabetic relatives and newly diagnosed type-1 patients compared to non-di...Aim: We demonstrated the risk of developing islet autoantibodies-Insulin Autoanti-bodies (IAAs) and Islets cell Autoantibodies (ICAs)-in type-1 diabetic relatives and newly diagnosed type-1 patients compared to non-diabetic controls. We also aimed to determine the predictive strengths of both autoantibodies in the development of type-1 diabetes mellitus, and which of the two autoantibodies is a better predictive marker of type-1 diabetes mellitus among Nigerian adults. Methodology: A total number of four hundred and fifty five (455) subjects (211 (46%) males, and 244 (54%) females) aged between 35 - 76 years were recruited for the study. IAA and ICA levels were estimated using ELISA reagents from Biomerica Inc. Other parameters such as fasting blood sugar, urine glucose, and urine protein were assessed using standard biochemical techniques. Results: Relatives of type-1 diabetic patients and newly diagnosed type-1 diabetic patients were at greater risk (p < 0.05) of testing positive for more than one autoantibody (ICA and IAA) compared to non-diabetic controls. In addition, IAAs appeared to be better predictors or markers of type-1 diabetes mellitus compared to ICAs. Conclusion: The present study indicated a greater risk of autoim-mune destruction of the insulin producing beta cells of the pancrease of the type-1 relatives and newly diagnosed type-1 patients and suggests the need for periodic re-cruitment of individuals in the general population, siblings and relatives of type-1 diabetic patients for planned intervention trials. In addition, IAAs appeared to be better autoimmune markers of type-1 diabetes compared to ICAs.展开更多
Objective To explore the pharmacological mechanism of active saponin compounds of Tuchao Baibiandouren(Lablab Semen Album fried with earth,TCBBDR)in treating type 2 diabetes(T2DM)using UHPLC-Q-Exactive Orbitrap MS and...Objective To explore the pharmacological mechanism of active saponin compounds of Tuchao Baibiandouren(Lablab Semen Album fried with earth,TCBBDR)in treating type 2 diabetes(T2DM)using UHPLC-Q-Exactive Orbitrap MS and network pharmacology.Methods UHPLC-Q-Exactive Orbitrap MS was used for a qualitative analysis of saponin compounds in TCBBDR.PharmMapper and CTD were used to screen drug active compounds and disease targets,and an active compound-target network was constructed via Cytoscape 3.8.0.Molecular docking was applied with the drug active compounds and key targets using AutoDock Vina 1.1.2,and a trajectory for the molecular dynamics simulation was completed by GROMACS 2019-3.Results Sixteen saponin compounds were identified from TCBBDR,along with 292 saponin compoud targets and 792 T2DM targets.Through Venn analysis of target saponin constituents and T2DM related targets,a total of 91 intersection targets were screened out in the treatment of T2DM with saponin.The mean values of degree,betweenness centrality and closeness centrality were taken as the thresholds to screen out 22 key genes,among which 4 key proteins namely MAPK1,IGF1 EGFR,PIK3R1 were selected in the top 10 key genes.On this basis,the saponin active constituent-target-signaling pathway network was established.The Gene Ontology(GO)enrichment analysis showed that the related biological modules included activity of steroid hormone receptor,steroid binding,and insulin receptor binding,etc.;the related signaling pathways were EGFR,PI3K-Akt and MAPK,etc.;regulating signaling pathways like MAPK could induce the proliferation,inhibition and apoptosis of pancreaticβcells,increase the quantity of pancreaticβcells,improve the functions of pancreaticβcells and stimulate the insulin secretion.Docking experiment analysis showed that all selected saponin compounds could enter the active sites of targets and form 3–14 hydrogen bonds with residues of the active sites.Moreover,van der Waals forces were present between chemical compounds and active sites.By combining the docking binding energy,we determined that the chemical compounds showed strong binding energy to the targets.Conclusion TCBBDR exerts therapeutic effects on diabetes through multi-compound and multi-target collaboration.Specifically,saponin components mediate pathways including inflammatory reaction and signal transduction to treat T2DM by regulating several key proteins that interact with EGFR and a series of signaling pathways related to disease development.展开更多
Diabetes mellitus is one of the world's most prevalent and complex metabolic disorders,and it is a rapidly growing global public health issue.It is characterized by hyperglycemia,a condition involving a high blood...Diabetes mellitus is one of the world's most prevalent and complex metabolic disorders,and it is a rapidly growing global public health issue.It is characterized by hyperglycemia,a condition involving a high blood glucose level brought on by deficiencies in insulin secretion,decreased activity of insulin,or both.Prolonged effects of diabetes include cardiovascular problems,retinopathy,neuropathy,nephropathy,and vascular alterations in both macro-and micro-blood vessels.In vivo and in vitro models have always been important for investigating and characterizing disease pathogenesis,identifying targets,and reviewing novel treatment options and medications.Fully understanding these models is crucial for the researchers so this review summarizes the different experimental in vivo and in vitro model options used to study diabetes and its consequences.The most popular in vivo studies involves the small animal models,such as rodent models,chemically induced diabetogens like streptozotocin and alloxan,and the possibility of deleting or overexpressing a specific gene by knockout and transgenic technologies on these animals.Other models include virally induced models,diet/nutrition induced diabetic animals,surgically induced models or pancreatectomy models,and non-obese models.Large animals or non-rodent models like porcine(pig),canine(dog),nonhuman primate,and Zebrafish models are also outlined.The in vitro models discussed are murine and human beta-cell lines and pancreatic islets,human stem cells,and organoid cultures.The other enzymatic in vitro tests to assess diabetes include assay of amylase inhibition and inhibition ofα-glucosidase activity.展开更多
Background: Diabetes mellitus (DM) has become a serious chronic disease.Self-management strategies help persons with DM make choices which will develop skills needed to reach their goal of blood glucose control and al...Background: Diabetes mellitus (DM) has become a serious chronic disease.Self-management strategies help persons with DM make choices which will develop skills needed to reach their goal of blood glucose control and allow them to be successful in reaching goals.Objective: To examine the impact of self-management activities on HbA1c for persons with DM and to examine the impact of social support,self-efficacy and Buddhist values as moderators on the relationship between the self-management activities and HbA1c.Method: This study is a cross-sectional design.The sample included 401 Thai adults diagnosed with type 2 diabetes,aged 20-65 years old who had at least one HbA1c test in the last three months were recruited.Participants completed four questionnaires to measure self-management activities,as well as self-efficacy,Buddhist values and social support as moderating factors on self-management activities and HbA1 c,Results: The self-management activities were negatively associated (β =-2.05,p ≤ 0.001) with HbA1c.The Social support,self-efficacy and Buddhist values had a significant interaction effect between selfmanagement activities and HbA1c (β =-0.97,p ≤ 0.05,β =-0.18,p ≤ 0.05 and β =-2.76,p ≤ 0.001).Conclusion: The diabetes self-management activities were more strongly associated with HbA1c under conditions of high social support,self-efficacy and health beliefs with Buddhist values.Future interventions for T2DM self-management programs should incorporate mechanisms to measure and support these factors.展开更多
基金Supported by Science and Technology Major Project of Changzhou Science and Technology Bureau,No.CE20205047Natural Science Foundation of Xinjiang Uygur Autonomo us Region,No.ZD202220Changzhou A major scientific research project of the Municipal Health Commission,No.2022D01F52.
文摘BACKGROUND Cardiovascular disease is a major complication of diabetes mellitus(DM).Type-2 DM(T2DM)is associated with an increased risk of cardiovascular events and mortality,while serum biomarkers may facilitate the prediction of these outcomes.Early differential diagnosis of T2DM complicated with acute coronary syndrome(ACS)plays an important role in controlling disease progression and improving safety.AIM To investigate the correlation of serum bilirubin andγ-glutamyltranspeptidase(γ-GGT)with major adverse cardiovascular events(MACEs)in T2DM patients with ACS.METHODS The clinical data of inpatients from January 2022 to December 2022 were analyzed retrospectively.According to different conditions,they were divided into the T2DM complicated with ACS group(T2DM+ACS,n=96),simple T2DM group(T2DM,n=85),and simple ACS group(ACS,n=90).The clinical data and laboratory indices were compared among the three groups,and the correlations of serum total bilirubin(TBIL)levels and serumγ-GGT levels with other indices were discussed.T2DM+ACS patients received a 90-day follow-up after discharge and were divided into event(n=15)and nonevent(n=81)groups according to the occurrence of MACEs;Univariate and multivariate analyses were further used to screen the independent influencing factors of MACEs in patients.RESULTS The T2DM+ACS group showed higherγ-GGT,total cholesterol,low-density lipoprotein cholesterol(LDL-C)and glycosylated hemoglobin(HbA1c)and lower TBIL and high-density lipoprotein cholesterol levels than the T2DM and ACS groups(P<0.05).Based on univariate analysis,the event and nonevent groups were significantly different in age(t=3.3612,P=0.0011),TBIL level(t=3.0742,P=0.0028),γ-GGT level(t=2.6887,P=0.0085),LDL-C level(t=2.0816,P=0.0401),HbA1c level(t=2.7862,P=0.0065)and left ventricular ejection fraction(LEVF)levels(t=3.2047,P=0.0018).Multivariate logistic regression analysis further identified that TBIL level and LEVF level were protective factor for MACEs,and age andγ-GGT level were risk factors(P<0.05).CONCLUSION Serum TBIL levels are decreased andγ-GGT levels are increased in T2DM+ACS patients,and the two indices are significantly negatively correlated.TBIL andγ-GGT are independent influencing factors for MACEs in such patients.
基金Supported by the Open Project Grant for Clinical Medical Center of Yunnan Province,No.2019LCZXKF-NM03Medical Leader Training Grant,No.L-201624and Yunnan Province Ten Thousand Talents:“Medical Expert”grant,No.YNWR-MY-2019-020.
文摘BACKGROUND The lack of specific predictors for type-2 diabetes mellitus(T2DM)severely impacts early intervention/prevention efforts.Elevated branched-chain amino acids(BCAAs:Isoleucine,leucine,valine)and aromatic amino acids(AAAs:Tyrosine,tryptophan,phenylalanine)show high sensitivity and specificity in predicting diabetes in animals and predict T2DM 10-19 years before T2DM onset in clinical studies.However,improvement is needed to support its clinical utility.AIM To evaluate the effects of body mass index(BMI)and sex on BCAAs/AAAs in new-onset T2DM individuals with varying body weight.METHODS Ninety-seven new-onset T2DM patients(<12 mo)differing in BMI[normal weight(NW),n=33,BMI=22.23±1.60;overweight,n=42,BMI=25.9±1.07;obesity(OB),n=22,BMI=31.23±2.31]from the First People’s Hospital of Yunnan Province,Kunming,China,were studied.One-way and 2-way ANOVAs were conducted to determine the effects of BMI and sex on BCAAs/AAAs.RESULTS Fasting serum AAAs,BCAAs,glutamate,and alanine were greater and high-density lipoprotein(HDL)was lower(P<0.05,each)in OB-T2DM patients than in NW-T2DM patients,especially in male OB-T2DM patients.Arginine,histidine,leucine,methionine,and lysine were greater in male patients than in female patients.Moreover,histidine,alanine,glutamate,lysine,valine,methionine,leucine,isoleucine,tyrosine,phenylalanine,and tryptophan were significantly correlated with abdominal adiposity,body weight and BMI,whereas isoleucine,leucine and phenylalanine were negatively correlated with HDL.CONCLUSION Heterogeneously elevated amino acids,especially BCAAs/AAAs,across new-onset T2DM patients in differing BMI categories revealed a potentially skewed prediction of T2DM development.The higher BCAA/AAA levels in obese T2DM patients would support T2DM prediction in obese individuals,whereas the lower levels of BCAAs/AAAs in NW-T2DM individuals may underestimate T2DM risk in NW individuals.This potentially skewed T2DM prediction should be considered when BCAAs/AAAs are to be used as the T2DM predictor.
文摘This editorial synthesizes insights from a series of studies examining the interplay between metabolic and oxidative stress biomarkers in cardiovascular disease(CVD),focusing particularly on type-2 diabetes mellitus(T2DM)and acute coronary syndrome(ACS).The central piece of this synthesis is a study that investigates the balance between oxidative stress and antioxidant systems in the body through the analysis of serum bilirubin andγ-glutamyltranspeptidase(γ-GGT)levels in T2DM patients with ACS.This study highlights serum bilirubin as a protective antioxidant factor,while elevatedγ-GGT levels indicate increased oxidative stress and correlate with major adverse cardiovascular events.Complementary to this,other research contributions revealγ-GGT’s role as a risk factor in ACS,its association with cardiovascular mortality in broader populations,and its link to metabolic syndrome,further elucidating the metabolic dysregulation in CVDs.The collective findings from these studies underscore the critical roles ofγ-GGT and serum bilirubin in cardiovascular health,especially in the context of T2DM and ACS.By providing a balanced view of the body’s oxidative and antioxidative mechanisms,these insights suggest potential pathways for targeted interventions and improved prognostic assessments in patients with T2DM and ACS.This synthesis not only corroborates the pivotal role ofγ-GGT in cardiovascular pathology but also introduces the protective potential of antioxidants like bilirubin,illuminating the complex interplay between T2DM and heart disease.These studies collectively underscore the critical roles of serum bilirubin andγ-GGT as biomarkers in cardiovascular health,particularly in T2DM and ACS contexts,offering insights into the body’s oxidative and antioxidative mechanisms.This synthesis of research supports the potential of these biomarkers in guiding therapeutic strategies and improving prognostic assessments for patients with T2DM and some CVD.
文摘TypeⅡdiabetes mellitus(T2DM)has experienced a dramatic increase globally across countries of various income levels over the past three decades.The persistent prevalence of T2DM is attributed to a complex interplay of genetic and environmental factors.While numerous pharmaceutical therapies have been developed,there remains an urgent need for innovative treatment approaches that offer effectiveness without significant adverse effects.In this context,the exploration of the gut microbiome presents a promising avenue.Research has increasingly shown that the gut microbiome of individuals with T2DM exhibits distinct differences compared to healthy individuals,suggesting its potential role in the disease’s pathogenesis and progression.This emerging field offers diverse applications,particularly in modifying the gut environment through the administration of prebiotics,probiotics,and fecal microbiome transfer.These interventions aim to restore a healthy microbiome balance,which could potentially alleviate or even reverse the metabolic dysfunctions associated with T2DM.Although current results from clinical trials have not yet shown dramatic effects on diabetes management,the groundwork has been laid for deeper investigation.Ongoing and future clinical trials are critical to advancing our understanding of the microbiome’s impact on diabetes.By further elucidating the mechanisms through which microbiome alterations influence insulin resistance and glucose metabolism,researchers can develop more targeted interventions.The potential to harness the gut microbiome in developing new therapeutic strategies offers a compelling prospect to transform the treatment landscape of T2DM,potentially reducing the disease’s burden significantly with approaches that are less reliant on traditional pharmaceuticals and more focused on holistic,systemic health improvements.
文摘This published Meta-Analysis by Lin et al is an indirect comparison between two drugs Chiglitazar and Thiazolidinedione which are commonly used for glycemic control in type-Ⅱ diabetes mellitus.In terms of safety and efficacy,this Meta-Analysis is inconclusive.
基金Supported by Science and Technology Plan Project of Shaoyang City,No.2022GX4139.
文摘BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis(HT).While single symptomatic drug treatment of the two diseases is less effective,combined drug treatment may improve efficacy.AIM To investigate the effect of a combination of vitamin D,selenium,and hypoglycemic agents in T2DM with HT.METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023.Fifty patients were assigned to the control group,test group A,and test group B according to different treatment methods.The control group received low-iodine diet guidance and hypoglycemic drug treatment.Test group A received the control treatment plus vitamin D treatment.Test group B received the group A treatment plus selenium.Blood levels of markers of thyroid function[free T3(FT3),thyroid stimulating hormone(TSH),free T4(FT4)],autoantibodies[thyroid peroxidase antibody(TPOAB)and thyroid globulin antibody(TGAB)],blood lipid index[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triacylglycerol(TG)],blood glucose index[fasting blood glucose(FBG),and hemoglobin A1c(HbA1c)]were measured pre-treatment and 3 and 6 months after treatment.The relationships between serum 25-hydroxyvitamin D3[25(OH)D3]level and each of these indices were analyzed.RESULTS The levels of 25(OH)D3,FT3,FT4,and LDL-C increased in the order of the control group,test group A,and test group B(all P<0.05).The TPOAB,TGAB,TC,TG,FBG,HbA1c,and TSH levels increased in the order of test groups B,A,and the control group(all P<0.05).All the above indices were compared after 3 and 6 months of treatment.Pre-treatment,there was no divergence in serum 25(OH)D3 level,thyroid function-related indexes,autoantibodies level,blood glucose,and blood lipid index between the control group,test groups A and B(all P>0.05).The 25(OH)D3 levels in test groups A and B were negatively correlated with FT4 and TGAB(all P<0.05).CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function,autoantibody,and blood glucose and lipid levels.
文摘BACKGROUND Islets of Langerhans beta cells diminish in autoimmune type 1 diabetes mellitus(T1DM).Teplizumab,a humanized anti-CD3 monoclonal antibody,may help T1DM.Its long-term implications on clinical T1DM development,safety,and efficacy are unknown.AIM To assess the effectiveness and safety of teplizumab as a therapeutic intervention for individuals with T1DM.METHODS A systematic search was conducted using four electronic databases(PubMed,Embase,Scopus,and Cochrane Library)to select publications published in peerreviewed journals written in English.The odds ratio(OR)and risk ratio(RR)were calculated,along with their 95%CI.We assessed heterogeneity using Cochrane Q and I2 statistics and the appropriate P value.RESULTS There were 8 randomized controlled trials(RCTs)in the current meta-analysis with a total of 1908 T1DM patients from diverse age cohorts,with 1361 patients receiving Teplizumab and 547 patients receiving a placebo.Teplizumab was found to have a substantial link with a decrease in insulin consumption,with an OR of 4.13(95%CI:1.72 to 9.90).Teplizumab is associated with an improved Cpeptide response(OR 2.49;95%CI:1.62 to 3.81)and a significant change in Glycated haemoglobin A1c(HbA1c)levels in people with type 1 diabetes[OR 1.75(95%CI:1.03 to 2.98)],and it has a RR of 0.71(95%CI:0.53 to 0.95).CONCLUSION In type 1 diabetics,teplizumab decreased insulin consumption,improved C-peptide response,and significantly changed HbA1c levels with negligible side effects.Teplizumab appears to improve glycaemic control and diabetes management with good safety and efficacy.
文摘Diabetes mellitus is associated with foot ulcers,which frequently pave the way to lower-extremity amputation.Neuropathy,trauma,deformity,high plantar pressures,and peripheral vascular disease are the most common underlying causes.Around 15%of diabetic patients are affected by diabetic foot ulcer in their lifetime.64 million people are affected by diabetics in India and 40000 amputations are done every year.Foot ulcers are evaluated and classified in a systematic and thorough manner to assist in determining the best course of therapy.This paper proposes a novel model which predicts the threat of diabetic foot ulcer using independent agents for various input values and a combination of fuzzy expert systems.The proposed model uses a classification system to distinguish between each fuzzy framework and its parameters.Based on the severity levels necessary prevention,treatment,and medication are recommended.Combining the results of all the fuzzy frameworks derived from its constituent parameters,a risk-specific medication is recommended.The work also has higher accuracy when compared to other related models.
基金Supported by the National Natural Science Foundation of China,No.81270969(to Wei Zhang)and No.81300723(to Cheng-Xiang Shan)Shanghai Science and Technology Commission,No.12ZR1439100(to Wei Zhang)
文摘AIM To examine the changes of the ghrelin/ghrelin O-acyltransferase(GOAT) axis and the mammalian target of rapamycin(m TOR) pathway in the hypothalamus after sleeve gastrectomy.METHODS A total of 30 obese type-2 diabetes Sprague-Dawley(SD) rats, 6 wk of age, fed with high-sugar and highfat fodder for 2 mo plus intraperitoneal injection of streptozotocin were randomly divided into three groups: non-operation group(S0 group, n = 10), sham operation group(Sh group, n = 10) and sleeve gastrectomy group(SG group, n = 10). Data of body mass, food intake, oral glucose tolerance test(OGTT), acylated ghrelin(AG) and total ghrelin(TG) were collected and measured at the first day(when the rats were 6 wk old), preoperative day 3 and postoperative week 8. The m RNA expression of preproghrelin, GOAT and neuropeptide Y(NPY), and protein expression of ghrelin, GOAT, GHSR and the m TOR pathway(p-Akt, p-m TOR and p-S6) were measured in the hypothalamus.RESULTS SG can significantly improve metabolic symptoms by reducing body mass and food intake. The obese rats showed lower serum TG levels and no change in AG, but the ratio of AG/TG was increased. When compared with the S0 and Sh groups, the SG group showed decreased TG(1482.03 ± 26.55, 1481.49 ± 23.30 and 1206.63 ± 52.02 ng/L, respectively, P < 0.05), but unchanged AG(153.06 ± 13.74, 155.37 ± 19.30 and 144.44 ± 16.689 ng/L, respectively, P > 0.05). As a result, the ratio of AG/TG further increased in the SG group(0.103 ± 0.009, 0.105 ± 0.013 and 0.12 ± 0.016, respectively, P < 0.05). When compared with the S0 group, SG suppressed m RNA and protein levels of preproghrelin(0.63 ± 0.12 vs 0.5 ± 0.11, P < 0.05) and GOAT(0.96 ± 0.09 vs 0.87 ± 0.08, P < 0.05), but did not change NPY m RNA expression(0.61 ± 0.04 vs 0.65 ± 0.07, P > 0.05) in the hypothalamus. The protein levels of p-Akt, p-m TOR and p-S6 were higher in the SG group, which indicated that the hypothalamic m TOR pathway was activated after SG at the postoperative week 8. CONCLUSION The reduction of ghrelin expression and activation of the m TOR pathway might have opposite effects on food intake, as SG improves obesity and T2 DM.
基金This work received funding from the University of Nizwa,Oman.
文摘Objective:The aim of this study was to assess the status of diabetes self-management(DSM)among Omanis with type-2 diabetes and its relationship with glycemic control and demographic variables.Methods:A correlational descriptive design using questionnaire was conducted with a convenience sample of 266 Omani patients with type-2 diabetes to collect the data.Results:The findings indicated that DSM among the study subject is sub-optimal.Only 1%of them were regular on SMBG;9.5%of them exercise regularly;and 18%of them maintain healthy diet practices.No significant relationship between DSM and glycemic control(p>0.05)was found.DSM was found to be associated with age,gender,level of education,and duration of diabetes.Examining the differences between two regions in Oman(Muscat&Aldhakiliyah)indicated that participants from Muscat differ only in practicing SMBG.Conclusion:Results indicated that many Omani patients with type-2 diabetes do not perform DSM consistently.Practice implications:The findings of this study set the stage to develop teaching strategies that will improve DSM and subsequently improve diabetes management in patient with type-2 diabetes in Oman.
基金supported by the National Natural Science Foundation of China(No.82120108008,No.91857117)the Project of Biobank(No.YBKA201909)from Shanghai Ninth People’s Hospital,Shanghai Jiaotong University School of Medicinea grant from Shanghai Jiaotong University School of Medicine(No.19XJ11007).
文摘Objective Isletαcells input is essential for insulin secretion fromβcells.The present study aims to investigate the association between 25-hydroxyvitamin D[25(OH)D]and islet function homeostasis in type-2 diabetes(T2D)patients.Methods A total of 4670 T2D patients from seven communities in Shanghai,China were enrolled.The anthropometric indices,biochemical parameters,serum 25(OH)D,and islet function[including C-peptide(C-p)and glucagon]were measured.Results The fasting plasma glucose(FPG),glycated hemoglobin(HbA1c),glucagon,and C-p levels exhibited a significantly decreasing trend in T2D patients as the 25(OH)D levels increased.Next,the population was divided into two groups:abdominal obesity and non-abdominal obesity groups.After adjustment,the 25(OH)D level was found to be associated with HbA1c,glucagon,and homeostasis model assessment ofβ(HOMA-β)in the non-abdominal obesity group.There was a significant relationship between 25(OH)D and HbA1c,glucagon,HOMA-IR,baseline insulin or C-p in the abdominal obesity group.In the abdominal obesity group,the ordinary least squares(OLS)regression and quantile regression revealed that 25(OH)D was obviously associated with glucagon and fasting C-p levels.In the abdominal obesity group,the moderate analysis revealed a significant interaction effect of 25(OH)D and glucagon on C-p(P=0.0124).Furthermore,the conditional indirect effect of 25(OH)D on the glucagon/C-p ratio was significantly lower at 1 standard deviation(SD)below the mean(P=0.0002),and lower at the mean of the course of diabetes(P=0.0007).Conclusion 25(OH)D was found to be negatively correlated to glucagon and C-p in T2D patients with abdominal obesity.The 25(OH)D influenced C-p in part by influencing glucagon.The effect of 25(OH)D on the glucagon/C-p ratio in T2D patients with abdominal obesity,in terms of islet homeostasis,is influenced by the course of diabetes.
文摘Obesity and type-2 diabetes mellitus(T2DM)are metabolic disorders.Obesity increases the risk of T2DM,and as obesity is becoming increasingly common,more individuals suffer from T2DM,which poses a considerable burden on health systems.Traditionally,pharmaceutical therapy together with lifestyle changes is used to treat obesity and T2DM to decrease the incidence of comorbidities and allcause mortality and to increase life expectancy.Bariatric surgery is increasingly replacing other forms of treatment of morbid obesity,especially in patients with refractory obesity,owing to its many benefits including good long-term outcomes and almost no weight regain.The bariatric surgery options have markedly changed recently,and laparoscopic sleeve gastrectomy(LSG)is gradually gaining popularity.LSG has become an effective and safe treatment for type-2 diabetes and morbid obesity,with a high cost-benefit ratio.Here,we review the mechanism associated with LSG treatment of T2DM,and we discuss clinical studies and animal experiments with regard to gastrointestinal hormones,gut microbiota,bile acids,and adipokines to clarify current treatment modalities for patients with obesity and T2DM.
文摘The worldwide epidemic of obesity and its medical complications are being dealt with a combination of life style changes(e.g.,healthier diet and exercise),medications and a variety of surgical interventions.The Roux-en Y gastric bypass(RYGB) and laparoscopic adjustable gastric banding(LAGB) are two of the most common weight loss surgeries for morbid obesityassociated metabolic syndrome and insulin resistance.A vast majority of patients that undergo RYGB and LAGB are known to experience marked weight loss and attenuation of diabetes.A number of recent studies have indicated that the rates of remission in glycemic control and insulin sensitivity are significantly greater in patients that have undergone RYGB.A plausible hypothesis to explain this observation is that the gastric bypass surgery as opposed to the gastric banding procedure impinges on glucose homeostasis by a weight loss-independent mechanism.In a recent paper,Bradley et al have experimentally explored this hypothesis.The authors compared several clinical and laboratory parameters of insulin sensitivity and β-cell function in cohorts of RYGB and LAGB patients before and after they lost approximately 20% of their body mass.Afterweight loss,both groups of patients underwent similar changes in their intra-abdominal and total adipose tissue volume,hepatic triglyceride and circulating leptin levels.The RYGB patients who lost 20% body mass,manifested higher postprandial output of glucose,insulin and glucagon-like peptide-1;these laboratory parameters remained unchanged in LABG patients.Irrespective of the observed differences in transient responses of RYGB and LAGB patients to mixed meal,the overall glycemic control as judged by glucose tolerance,multi-organ insulin sensitivity and β-cell function were nearly identical in the two groups.Both RYGB and LAGB patient cohorts also experienced similar changes in the expression of a number of pro-and anti-inflammatory markers.Based on these analyses,Bradley et al concluded that similar restoration of insulin sensitivity and b-cell function in non-diabetic obese patients that have undergone RYGB and LAGB were directly due to marked weight loss.These data have important implications for the risk/benefit analysis of weight loss therapy by bariatric procedures.
基金financial support from National Natural Science Foundation of China (81872818)National Key R&D Program of China (2021YFE0115200)
文摘Glucagon-like peptide-1 receptor agonists(GLP-1 RA)are a series of polypeptides broadly applied in the long-term treatment of typeⅡdiabetes.However,administration of GLP-RA is mainly through repetitive subcutaneous injection,which may seriously decrease the compliance and safety.Herein,a bio-inspired oral delivery system was designed to enhance the oral absorption of liraglutide(Lira),a kind of GLP-1 RA,by mimicking the natural cholesterol assimilation.25-hydroxycholesterol(25HC),a cholesterol derivative,was modified on the surfaced of Lira-loaded PLGA nanoparticles(Lira 25HC NPs)and functioned as a“top-down”actuator to facilitate unidirectional transcytosis across the intestinal epithelium.After oral delivery,Lira 25HC NPs displayed improved therapeutic effect as compared with oral free Lira on typeⅡdiabetes db/db mice,as evidenced by multiple relieved diabetic symptoms including the enhanced glucose tolerance,repressed weight growth,improved liver glucose metabolism,decreased fasting blood glucose,HbA 1c,serum lipid,and increasedβcells activity.Surprisingly,the fasting blood glucose,liver glucose metabolism,and HbA1c of oral Lira-loaded 25HC NPs were comparable to subcutaneous injection of free Lira.Further mechanisms revealed that 25HC ligand could mediate the nanoparticles to mimic natural cholesterol absorption by exerting high affinity towards apical Niemann-Pick C1 Like 1(NPC1L1)and then basolateral ATP binding cassette transporter A1(ABCA1)overexpressed on the opposite side of intestinal epithelium.This cholesterol assimilation-mimicking strategy achieve the unidirectional transport across the intestinal epithelium,thus improving the oral absorption of liraglutide.In general,this study established a cholesterol simulated platform and provide promising insight for the oral delivery of GLP-1 RA.
文摘Aim: We demonstrated the risk of developing islet autoantibodies-Insulin Autoanti-bodies (IAAs) and Islets cell Autoantibodies (ICAs)-in type-1 diabetic relatives and newly diagnosed type-1 patients compared to non-diabetic controls. We also aimed to determine the predictive strengths of both autoantibodies in the development of type-1 diabetes mellitus, and which of the two autoantibodies is a better predictive marker of type-1 diabetes mellitus among Nigerian adults. Methodology: A total number of four hundred and fifty five (455) subjects (211 (46%) males, and 244 (54%) females) aged between 35 - 76 years were recruited for the study. IAA and ICA levels were estimated using ELISA reagents from Biomerica Inc. Other parameters such as fasting blood sugar, urine glucose, and urine protein were assessed using standard biochemical techniques. Results: Relatives of type-1 diabetic patients and newly diagnosed type-1 diabetic patients were at greater risk (p < 0.05) of testing positive for more than one autoantibody (ICA and IAA) compared to non-diabetic controls. In addition, IAAs appeared to be better predictors or markers of type-1 diabetes mellitus compared to ICAs. Conclusion: The present study indicated a greater risk of autoim-mune destruction of the insulin producing beta cells of the pancrease of the type-1 relatives and newly diagnosed type-1 patients and suggests the need for periodic re-cruitment of individuals in the general population, siblings and relatives of type-1 diabetic patients for planned intervention trials. In addition, IAAs appeared to be better autoimmune markers of type-1 diabetes compared to ICAs.
基金We thank for the funding support from the Program of Survey of Chinese Medicines of China(No.[2017]66).
文摘Objective To explore the pharmacological mechanism of active saponin compounds of Tuchao Baibiandouren(Lablab Semen Album fried with earth,TCBBDR)in treating type 2 diabetes(T2DM)using UHPLC-Q-Exactive Orbitrap MS and network pharmacology.Methods UHPLC-Q-Exactive Orbitrap MS was used for a qualitative analysis of saponin compounds in TCBBDR.PharmMapper and CTD were used to screen drug active compounds and disease targets,and an active compound-target network was constructed via Cytoscape 3.8.0.Molecular docking was applied with the drug active compounds and key targets using AutoDock Vina 1.1.2,and a trajectory for the molecular dynamics simulation was completed by GROMACS 2019-3.Results Sixteen saponin compounds were identified from TCBBDR,along with 292 saponin compoud targets and 792 T2DM targets.Through Venn analysis of target saponin constituents and T2DM related targets,a total of 91 intersection targets were screened out in the treatment of T2DM with saponin.The mean values of degree,betweenness centrality and closeness centrality were taken as the thresholds to screen out 22 key genes,among which 4 key proteins namely MAPK1,IGF1 EGFR,PIK3R1 were selected in the top 10 key genes.On this basis,the saponin active constituent-target-signaling pathway network was established.The Gene Ontology(GO)enrichment analysis showed that the related biological modules included activity of steroid hormone receptor,steroid binding,and insulin receptor binding,etc.;the related signaling pathways were EGFR,PI3K-Akt and MAPK,etc.;regulating signaling pathways like MAPK could induce the proliferation,inhibition and apoptosis of pancreaticβcells,increase the quantity of pancreaticβcells,improve the functions of pancreaticβcells and stimulate the insulin secretion.Docking experiment analysis showed that all selected saponin compounds could enter the active sites of targets and form 3–14 hydrogen bonds with residues of the active sites.Moreover,van der Waals forces were present between chemical compounds and active sites.By combining the docking binding energy,we determined that the chemical compounds showed strong binding energy to the targets.Conclusion TCBBDR exerts therapeutic effects on diabetes through multi-compound and multi-target collaboration.Specifically,saponin components mediate pathways including inflammatory reaction and signal transduction to treat T2DM by regulating several key proteins that interact with EGFR and a series of signaling pathways related to disease development.
文摘Diabetes mellitus is one of the world's most prevalent and complex metabolic disorders,and it is a rapidly growing global public health issue.It is characterized by hyperglycemia,a condition involving a high blood glucose level brought on by deficiencies in insulin secretion,decreased activity of insulin,or both.Prolonged effects of diabetes include cardiovascular problems,retinopathy,neuropathy,nephropathy,and vascular alterations in both macro-and micro-blood vessels.In vivo and in vitro models have always been important for investigating and characterizing disease pathogenesis,identifying targets,and reviewing novel treatment options and medications.Fully understanding these models is crucial for the researchers so this review summarizes the different experimental in vivo and in vitro model options used to study diabetes and its consequences.The most popular in vivo studies involves the small animal models,such as rodent models,chemically induced diabetogens like streptozotocin and alloxan,and the possibility of deleting or overexpressing a specific gene by knockout and transgenic technologies on these animals.Other models include virally induced models,diet/nutrition induced diabetic animals,surgically induced models or pancreatectomy models,and non-obese models.Large animals or non-rodent models like porcine(pig),canine(dog),nonhuman primate,and Zebrafish models are also outlined.The in vitro models discussed are murine and human beta-cell lines and pancreatic islets,human stem cells,and organoid cultures.The other enzymatic in vitro tests to assess diabetes include assay of amylase inhibition and inhibition ofα-glucosidase activity.
文摘Background: Diabetes mellitus (DM) has become a serious chronic disease.Self-management strategies help persons with DM make choices which will develop skills needed to reach their goal of blood glucose control and allow them to be successful in reaching goals.Objective: To examine the impact of self-management activities on HbA1c for persons with DM and to examine the impact of social support,self-efficacy and Buddhist values as moderators on the relationship between the self-management activities and HbA1c.Method: This study is a cross-sectional design.The sample included 401 Thai adults diagnosed with type 2 diabetes,aged 20-65 years old who had at least one HbA1c test in the last three months were recruited.Participants completed four questionnaires to measure self-management activities,as well as self-efficacy,Buddhist values and social support as moderating factors on self-management activities and HbA1 c,Results: The self-management activities were negatively associated (β =-2.05,p ≤ 0.001) with HbA1c.The Social support,self-efficacy and Buddhist values had a significant interaction effect between selfmanagement activities and HbA1c (β =-0.97,p ≤ 0.05,β =-0.18,p ≤ 0.05 and β =-2.76,p ≤ 0.001).Conclusion: The diabetes self-management activities were more strongly associated with HbA1c under conditions of high social support,self-efficacy and health beliefs with Buddhist values.Future interventions for T2DM self-management programs should incorporate mechanisms to measure and support these factors.
