Application of Dorzagliatin in peritoneal dialysis patients with type 2 diabetes mellitus:A case report

BACKGROUND Treating diabetes in dialysis patients remains a challenge,with many hypoglycemic drugs requiring dose adjustments or avoidance in these patients.CASE SUMMARY This report describes an 83-year-old female patient with a 30-year history of type 2 diabetes(T2DM)who had struggled to control her blood sugar for more than a year.She had a history of high blood pressure for 30 years,had undergone continuous ambulatory peritoneal dialysis for more than two years,was 163 cm tall,weighed 77 kg,and had a body mass index of 28.98 kg/m2.Despite intensive insulin therapy at a daily dose of 150 units,adding Dorzagliatin at a dosage of 75 mg orally twice daily led to immediate blood sugar improvement and a gradual reduction in insulin dosage.After one month of follow-up,the fasting plasma glucose was 6-8 mmol/L,and the 2-hour postprandial glucose was 8-12 mmol/L.CONCLUSION To our knowledge,this report is the first to use Dorzagliatin to treat type 2 diabetes peritoneal dialysis patients with challenging glucose control.Dorzagliatin,a novel glucokinase activator primarily metabolized by the liver,exhibits no pharmacokinetic differences among patients with varying degrees of chronic kidney disease.It has a high plasma protein binding rate and may not be cleared by peritoneal dialysis,potentially offering a new glycemic control option for Type 2 diabetic patients on peritoneal dialysis.

Unveiling mitochondrial mysteries:Exploring novel tRNA variants in type 2 diabetes mellitus

The recent study of Ding et al provides valuable insights into the functional implications of novel mitochondrial tRNATrp and tRNASer(AGY)variants in type 2 diabetes mellitus(T2DM).This editorial explores their findings,highlighting the role of mitochondrial dysfunction in the pathogenesis of T2DM.By examining the molecular mechanisms through which these tRNA variants contribute to disease progression,the study introduces new targets for therapeutic strategies.We discuss the broader implications of these results,emphasizing the importance of understanding mitochondrial genetics in addressing T2DM.

Correlation between type 2 diabetes mellitus remission and intrapancreatic fat deposition

BACKGROUND Intrapancreatic fat deposition(IPFD)exerts a significant negative impact on patients with type 2 diabetes mellitus(T2DM),accelerates disease deterioration,and may lead to impairedβ-cell quality and function.AIM To investigate the correlation between T2DM remission and IPFD.METHODS We enrolled 80 abdominally obese patients with T2DM admitted to our institution from January 2019 to October 2023,including 40 patients with weight lossinduced T2DM remission(research group)and 40 patients with short-term intensive insulin therapy-induced T2DM remission(control group).We comparatively analyzed improvements in IPFD[differential computed tomography(CT)values of the spleen and pancreas and average CT value of the pancreas];levels of fasting blood glucose(FBG),2-h postprandial blood glucose(2hPBG),and insulin;and homeostasis model assessment of insulin resistance(HOMA-IR)scores.Correlation analysis was performed to explore the association between T2DM remission and IPFD.RESULTS After treatment,the differential CT values of the spleen and pancreas,FBG,2hPBG,and HOMA-IR in the research group were significantly lower than those before treatment and in the control group,and the average CT value of the pancreas and insulin levels were significantly higher.Correlation analysis revealed that the greater the T2DM remission,the lower the amount of IPFD.

Vitamin D,selenium,and antidiabetic drugs in the treatment of type 2 diabetes mellitus 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.

Clinical study of different prediction models in predicting diabetic nephropathy in patients with type 2 diabetes mellitus

BACKGROUND Among older adults,type 2 diabetes mellitus(T2DM)is widely recognized as one of the most prevalent diseases.Diabetic nephropathy(DN)is a frequent com-plication of DM,mainly characterized by renal microvascular damage.Early detection,aggressive prevention,and cure of DN are key to improving prognosis.Establishing a diagnostic and predictive model for DN is crucial in auxiliary diagnosis.AIM To investigate the factors that impact T2DM complicated with DN and utilize this information to develop a predictive model.METHODS The clinical data of 210 patients diagnosed with T2DM and admitted to the First People’s Hospital of Wenling between August 2019 and August 2022 were retrospectively analyzed.According to whether the patients had DN,they were divided into the DN group(complicated with DN)and the non-DN group(without DN).Multivariate logistic regression analysis was used to explore factors affecting DN in patients with T2DM.The data were randomly split into a training set(n=147)and a test set(n=63)in a 7:3 ratio using a random function.The training set was used to construct the nomogram,decision tree,and random forest models,and the test set was used to evaluate the prediction performance of the model by comparing the sensitivity,specificity,accuracy,recall,precision,and area under the receiver operating characteristic curve.RESULTS Among the 210 patients with T2DM,74(35.34%)had DN.The validation dataset showed that the accuracies of the nomogram,decision tree,and random forest models in predicting DN in patients with T2DM were 0.746,0.714,and 0.730,respectively.The sensitivities were 0.710,0.710,and 0.806,respectively;the specificities were 0.844,0.875,and 0.844,respectively;the area under the receiver operating characteristic curve(AUC)of the patients were 0.811,0.735,and 0.850,respectively.The Delong test results revealed that the AUC values of the decision tree model were lower than those of the random forest and nomogram models(P<0.05),whereas the difference in AUC values of the random forest and column-line graph models was not statistically significant(P>0.05).CONCLUSION Among the three prediction models,random forest performs best and can help identify patients with T2DM at high risk of DN.

Comparative efficacy of sodium glucose cotransporter-2 inhibitors in the management of type 2 diabetes mellitus:A real-world experience

BACKGROUND Sodium glucose cotransporter-2 inhibitors(SGLT-2i)are a class of drugs with modest antidiabetic efficacy,weight loss effect,and cardiovascular benefits as proven by multiple randomised controlled trials(RCTs).However,real-world data on the comparative efficacy and safety of individual SGLT-2i medications is sparse.AIM To study the comparative efficacy and safety of SGLT-2i using real-world clinical data.METHODS We evaluated the comparative efficacy data of 3 SGLT-2i drugs(dapagliflozin,canagliflozin,and empagliflozin)used for treating patients with type 2 diabetes mellitus.Data on the reduction of glycated hemoglobin(HbA1c),body weight,blood pressure(BP),urine albumin creatinine ratio(ACR),and adverse effects were recorded retrospectively.RESULTS Data from 467 patients with a median age of 64(14.8)years,294(62.96%)males and 375(80.5%)Caucasians were analysed.Median diabetes duration was 16.0(9.0)years,and the duration of SGLT-2i use was 3.6(2.1)years.SGLT-2i molecules used were dapagliflozin 10 mg(n=227;48.6%),canagliflozin 300 mg(n=160;34.3%),and empagliflozin 25 mg(n=80;17.1).Baseline median(interquartile range)HbA1c in mmol/mol were:dapagliflozin-78.0(25.3),canagliflozin-80.0(25.5),and empagliflozin-75.0(23.5)respectively.The respective median HbA1c reduction at 12 months and the latest review(just prior to the study)were:66.5(22.8)&69.0(24.0),67.0(16.3)&66.0(28.0),and 67.0(22.5)&66.5(25.8)respectively(P<0.001 for all comparisons from baseline).Significant improvements in body weight(in kilograms)from baseline to study end were noticed with dapagliflozin-101(29.5)to 92.2(25.6),and canagliflozin 100(28.3)to 95.3(27.5)only.Significant reductions in median systolic and diastolic BP,from 144(21)mmHg to 139(23)mmHg;(P=0.015),and from 82(16)mmHg to 78(19)mmHg;(P<0.001)respectively were also observed.A significant reduction of microalbuminuria was observed with canagliflozin only[ACR 14.6(42.6)at baseline to 8.9(23.7)at the study end;P=0.043].Adverse effects of SGLT-2i were as follows:genital thrush and urinary infection-20(8.8%)&17(7.5%)with dapagliflozin;9(5.6%)&5(3.13%)with canagliflozin;and 4(5%)&4(5%)with empagliflozin.Diabetic ketoacidosis was observed in 4(1.8%)with dapagliflozin and 1(0.63%)with canagliflozin.CONCLUSION Treatment of patients with SGLT-2i is associated with statistically significant reductions in HbA1c,body weight,and better than those reported in RCTs,with low side effect profiles.A review of large-scale real-world data is needed to inform better clinical practice decision making.

KCNQ1 rs2237895 gene polymorphism increases susceptibility to type 2 diabetes mellitus in Asian populations

BACKGROUND The association of single nucleotide polymorphism of KCNQ1 gene rs2237895 with type 2 diabetes mellitus(T2DM)is currently controversial.It is unknown whether this association can be gene realized across different populations.AIM To determine the association of KCNQ1 rs2237895 with T2DM and provide reliable evidence for genetic susceptibility to T2DM.METHODS We searched PubMed,Embase,Web of Science,Cochrane Library,Medline,Baidu Academic,China National Knowledge Infrastructure,China Biomedical Literature Database,and Wanfang to investigate the association between KCNQ1 gene rs2237895 and the risk of T2DM up to January 12,2022.Review Manager 5.4 was used to analyze the association of the KCNQ1 gene rs2237895 polymorphism with T2DM and to evaluate the publication bias of the selected literature.RESULTS Twelve case–control studies(including 11273 cases and 11654 controls)met our inclusion criteria.In the full population,allelic model[odds ratio(OR):1.19;95%confidence interval(95%CI):1.09–1.29;P<0.0001],recessive model(OR:1.20;95%CI:1.11–1.29;P<0.0001),dominant model(OR:1.27.95%CI:1.14–1.42;P<0.0001),and codominant model(OR:1.36;95%CI:1.15–1.60;P=0.0003)(OR:1.22;95%CI:1.10–1.36;P=0.0002)indicated that the KCNQ1 gene rs2237895 polymorphism was significantly correlated with susceptibility to T2DM.In stratified analysis,this association was confirmed in Asian populations:allelic model(OR:1.25;95%CI:1.13–1.37;P<0.0001),recessive model(OR:1.29;95%CI:1.11–1.49;P=0.0007),dominant model(OR:1.35;95%CI:1.20–1.52;P<0.0001),codominant model(OR:1.49;95%CI:1.22–1.81;P<0.0001)(OR:1.26;95%CI:1.16–1.36;P<0.0001).In non-Asian populations,this association was not significant:Allelic model(OR:1.06,95%CI:0.98–1.14;P=0.12),recessive model(OR:1.04;95%CI:0.75–1.42;P=0.83),dominant model(OR:1.06;95%CI:0.98–1.15;P=0.15),codominant model(OR:1.08;95%CI:0.82–1.42;P=0.60.OR:1.15;95%CI:0.95–1.39;P=0.14).CONCLUSION KCNQ1 gene rs2237895 was significantly associated with susceptibility to T2DM in an Asian population.Carriers of the C allele had a higher risk of T2DM.This association was not significant in non-Asian populations.

Functional analysis of the novel mitochondrial tRNA^(Trp)and tRNA^(Ser(AGY))variants associated with type 2 diabetes mellitus

BACKGROUND Mutations in mitochondrial tRNA(mt-tRNA)genes that result in mitochondrial dysfunction play important roles in type 2 diabetes mellitus(T2DM).We previously reported a large Chinese pedigree with maternally inherited T2DM that harbors novel mt-tRNA^(Trp)A5514G and tRNA^(Ser(AGY))C12237T variants,however,the effects of these mt-tRNA variants on T2DM progression are largely unknown.AIM To assess the potential pathogenicity of T2DM-associated m.A5514G and m.C12237T variants at genetic,molecular,and biochemical levels.METHODS Cytoplasmic hybrid(cybrid)cells carrying both m.A5514G and m.C12237T variants,and healthy control cells without these mitochondrial DNA(mtDNA)variants were generated using trans-mitochondrial technology.Mitochondrial features,including mt-tRNA steady-state level,levels of adenosine triphosphate(ATP),mitochondrial membrane potential(MMP),reactive oxygen species(ROS),mtDNA copy number,nicotinamide adenine dinucleotide(NAD+)/NADH ratio,enzymatic activities of respiratory chain complexes(RCCs),8-hydroxy-deoxyguanine(8-OhdG),malondialdehyde(MDA),and superoxide dismutase(SOD)were examined in cell lines with and without these mt-tRNA variants.RESULTS Compared with control cells,the m.A5514G variant caused an approximately 35%reduction in the steady-state level of mt-tRNA^(Trp)(P<0.0001);however,the m.C12237T variant did not affect the mt-tRNA^(Ser(AGY))steady-state level(P=0.5849).Biochemical analysis revealed that cells with both m.A5514G and m.C12237T variants exhibited more severe mitochondrial dysfunctions and elevated oxidative stress than control cells:ATP,MMP,NAD+/NADH ratio,enzyme activities of RCCs and SOD levels were markedly decreased in mutant cells(P<0.05 for all measures).By contrast,the levels of ROS,8-OhdG and MDA were significantly increased(P<0.05 for all measures),but mtDNA copy number was not affected by m.A5514G and m.C12237T variants(P=0.5942).CONCLUSION The m.A5514G variant impaired mt-tRNA^(Trp)metabolism,which subsequently caused mitochondrial dysfunction.The m.C12237T variant did not alter the steady-state level of mt-tRNA^(Ser(AGY)),indicating that it may be a modifier of the m.A5514G variant.The m.A5514G variant may exacerbate the pathogenesis and progression of T2DM in this Chinese pedigree.

Identification of hub genes associated with Helicobacter pylori infection and type 2 diabetes mellitus:A pilot bioinformatics study

BACKGROUND Helicobacter pylori(H.pylori)infection is related to various extragastric diseases including type 2 diabetes mellitus(T2DM).However,the possible mechanisms connecting H.pylori infection and T2DM remain unknown.AIM To explore potential molecular connections between H.pylori infection and T2DM.METHODS We extracted gene expression arrays from three online datasets(GSE60427,GSE27411 and GSE115601).Differentially expressed genes(DEGs)commonly present in patients with H.pylori infection and T2DM were identified.Hub genes were validated using human gastric biopsy samples.Correlations between hub genes and immune cell infiltration,miRNAs,and transcription factors(TFs)were further analyzed.RESULTS A total of 67 DEGs were commonly presented in patients with H.pylori infection and T2DM.Five significantly upregulated hub genes,including TLR4,ITGAM,C5AR1,FCER1G,and FCGR2A,were finally identified,all of which are closely related to immune cell infiltration.The gene-miRNA analysis detected 13 miRNAs with at least two gene cross-links.TF-gene interaction networks showed that TLR4 was coregulated by 26 TFs,the largest number of TFs among the 5 hub genes.CONCLUSION We identified five hub genes that may have molecular connections between H.pylori infection and T2DM.This study provides new insights into the pathogenesis of H.pylori-induced onset of T2DM.

Serum tumor markers expression(CA199,CA242,and CEA)and its clinical implications in type 2 diabetes mellitus

BACKGROUND Glucose and lipid metabolic disorder in patients with type 2 diabetes mellitus(T2DM)is associated with the levels of serum tumor markers of the digestive tract,such as cancer antigen(CA)199.Therefore,tumor markers in T2DM are important.AIM To evaluate the expression of serum tumor markers[CA199,CA242,and carcinoembryonic antigen(CEA)]and the clinical implications of the expression in T2DM.METHODS For this observational study conducted at Hefei BOE Hospital,China,we enrolled 82 patients with first-onset T2DM and 51 controls between April 2019 and December 2020.Levels of fasting blood glucose(FBG),tumor markers(CA199,CEA,and CA242),glycosylated hemoglobin(HbA1c),etc.were measured and group index levels were compared.Moreover,FBG and HbA1c levels were correlated with tumor marker levels.Tumor markers were tested for diagnostic accuracy in patients with>9%HbA1c using the receiver operating curve(ROC)curve.RESULTS The T2DM group had high serum FBG,HbA1c,CA199,and CEA levels(P<0.05).A comparative analysis of the two groups based on HbA1c levels(Group A:HbA1c≤9%;Group B:HbA1c>9%)revealed significant differences in CEA and CA199 levels(P<0.05).The areas under the ROC curve for CEA and CA199 were 0.853 and 0.809,respectively.CA199,CEA,and CA242 levels positively correlated with HbA1c(r=0.308,0.426,and 0.551,respectively)and FBG levels(r=0.236,0.231,and 0.298,respectively).CONCLUSION As compared to controls,serum CEA and CA199 levels were higher in patients with T2DM.HbA1c and FBG levels correlated with CA199,CEA,and CA242 levels.Patients with poorly controlled blood sugar must be screened for tumor markers.

Predictive value of bilirubin and serum γ-glutamyltranspeptidase levels in type-2 diabetes mellitus patients with acute coronary syndrome

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.

Association of plasma vitamin A level with type 2 diabetes mellitus:a community aging population-based cross-sectional study

Recent studies indicated that vitamin A(VA)might be involved in the pathology of type 2 diabetes mellitus(T2DM).This cross-sectional study was conducted to explore the association between circulating VA level and T2DM.A total of 1818 subjects aged 50 years old and above were recruited from the community.Binomial logistic regression and restricted cubic spline(RCS)were applied to analyze the association of plasma VA level with the risk of T2DM.Serum VA and lipid-adjusted VA levels of T2DM patients were significantly higher than that of non-T2DM subjects(P<0.05).The ratios of plasma VA/total cholesterol(TC),VA/high-density lipoprotein cholesterol(HDL-c)and VA/low-density lipoprotein cholesterol(LDL-c)were positively associated with the risk of T2DM in the aging population(P<0.05).Compared with the Q1 level,subjects with Q2 to Q3 levels of plasma VA/triglyceride(TG)have decreased risk of T2DM(odds ratio(OR)Q2=0.68,P_(Q2)=0.021;ORQ3=0.59,P_(Q3)<0.01).Our results indicated that the imbalance of circulating lipids and VA might affect the relationship between VA and T2DM.The middle and aging subjects with higher ratios of plasma VA/TC,VA/HDL-c,and VA/LDL-c displayed increased risk for T2DM,but the moderate ratio of VA/TG might protect against risk of T2DM.

Prevalence and Risk Factors of Stroke in Inpatients with Type 2 Diabetes Mellitus in China

Objective The prevalence and the cluster characteristics of risk factors of stroke were assessed in a Chinese diabetic population.Methods Clinical data of 30693 inpatients who were diagnosed with type 2 diabetes mellitus(T2DM)and admitted between 2013 and 2018 were retrospectively analyzed.The age-standardized prevalence of stroke was estimated using the 2010 Chinese population census data,and risk factors were analyzed by multiple imputation and regression.Results The crude and standardized prevalence rates of stroke in patients with T2DM were 34.4%and 21.5%,respectively,and 85.2%of the stroke patients had ischemic stroke.Nearly half of the patients who experienced stroke had clusters of more than 4 risk factors.Compared with no-risk-factor clustering,the risk of stroke significantly increased 3-4 times in the presence of more than 4 risk-factor clusters(P<0.001).Hypertension was the most common major risk factor for ischemic stroke[odds ratio(OR),2.34;95%confidence interval(CI),2.18-2.50]and hemorrhagic stroke(OR,3.68;95%CI 2.95-4.59;P<0.001).Moreover,a 1-standard-deviation increase in fasting blood glucose(FBG)was significantly negatively correlated with ischemic stroke risk,and the same change in FBG was significantly associated with an 8%increased risk of hemorrhagic stroke.Conclusion The prevalence of stroke in patients with T2DM is rather high,and the clustering of risk factors is associated with the development of stroke in T2DM patients.Risk factors differ in different stroke subtypes.Identifying risk factors for a specific high-risk group is necessary.

Effects of axylitol-casein complex on insulin resistance and gut microbiota composition in high-fat-diet+streptozotocin-induced type 2 diabetes mellitus mice

This study investigated the effects of a xylitol-casein non-covalent complex(XC)on parameters related to type 2 diabetes mellitus(T2DM),in addition to related changes in gut microbiome composition and functions.High-fat-diet(HFD)+streptozotocin(STZ)-induced T2DM mice were treated with xylitol(XY),casein(CN),and XC,after which fecal samples were collected for gut microbiota composition and diversity analyses based on 16S rRNA high-throughput sequencing and multivariate statistics.XC decreased body weight and improved glucose tolerance,insulin sensitivity,pancreas impairment,blood lipid levels,and liver function in T2DM mice compared to XY-and CN-treated mice.Furthermore,XC modulated theα-diversity,β-diversity and gut microbiota composition.Based on Spearman’s correlation analysis,the relative abundances of Alistipes,Bacteroides,and Faecalibaculum were positively correlated and those of Akkermansia,Lactobacillus,Bifidobacterium,and Turicibacter were negatively correlated with the phenotypes related to the improvement of T2DM.In conclusion,we found that XC alleviated insulin resistance by restoring the gut microbiota of T2DM mice.Our results provide strong evidence for the beneficial effects of XC on T2DM and motivation for further investigation in animal models and,eventually,human trials.

Asiaticoside ameliorates type 2 diabetes mellitus in rats by modulating carbohydrate metabolism and regulating insulin signaling

Objective:To evaluate the effect of asiaticoside on streptozotocin(STZ)and nicotinamide(NAD)-induced carbohydrate metabolism abnormalities and deregulated insulin signaling pathways in rats.Methods:Asiaticoside(50 and 100 mg/kg body weight)was administered to STZ-NAD-induced diabetic rats for 45 days,and its effects on hyperglycaemic,carbohydrate metabolic,and insulin signaling pathway markers were examined.Results:Asiaticoside increased insulin production,lowered blood glucose levels,and enhanced glycolysis by improving hexokinase activity and suppressing glucose-6-phosphatase and fructose-1,6-bisphosphatase activities.Abnormalities in glycogen metabolism were mitigated by increasing glycogen synthase activity and gluconeogenesis was decreased by decreasing glycogen phosphorylase activity.Furthermore,asiaticoside upregulated the mRNA expressions of IRS-1,IRS-2,and GLUT4 in STZ-NAD-induced diabetic rats and restored the beta cell morphology to normal.Conclusions:Asiaticoside has the potential to ameliorate type 2 diabetes by improving glycolysis,gluconeogenesis,and insulin signaling pathways.

Effects of needling at Sanyinjiao(SP6)acupuncture point on blood glucose levels and cardiovascular functions in patients with type 2 diabetes mellitus:a randomized placebo-controlled study

Objective To determine the effect of needling at Sanyinjiao(SP6)on random blood glucose(RBG)levels and cardiovascular function in patients with type 2 diabetes mellitus(T2DM).Methods In this randomized placebo-controlled study,T2DM patients(aged 35-65 years)were recruited from the Government Yoga and Naturopathy Medical College and Hospital,Chennai,India,between January 5,2022 and March 15,2023.Participants were randomly as-signed to either acupuncture group or sham acupuncture group.The acupuncture group re-ceived bilateral needling at Sanyinjiao(SP6)while sham acupuncture group received needling at a non-acupuncture point[1.5 cun lateral to Sanyinjiao(SP6)]for 30 min.Primary outcome was RBG,and secondary outcomes included systolic blood pressure(SBP),diastolic blood pressure(DBP),pulse rate(PR),pulse pressure(PP),mean arterial pressure(MAP),rate pressure product(RPP),and double product(Do-P).All parameters were assessed imme-diately before and after intervention.Results A total of 100 patients with T2DM were enrolled in the study,and blinded to acupuncture group(n=50)and sham acupuncture group(n=50).Intergroup analysis showed that significant reductions in RBG(P<0.001),SBP(P=0.035),DBP(P=0.008),and MAP(P=0.009)were found in acupuncture group compared with sham acupuncture group.Within-group analysis showed significant reductions in RBG(P<0.001),SBP(P<0.001),DBP(P=0.008),PP(P=0.023),MAP(P<0.001),RPP(P<0.001),and Do-P(P=0.002)in acupunc-ture group,whereas sham acupuncture group showed a significant decrease in PR(P=0.023)only in the post-test assessment compared with pre-test assessment.Conclusion A period of 30 min of needling at the Sanyinjiao(SP6)acupuncture point re-duces RBG and promotes cardiovascular function in patients with T2DM as compared with needling at non-acupuncture points.Sanyinjiao(SP6)acupuncture may offer an immediate,non-pharmacological intervention to strengthen glycemic control management and cardio-vascular health in T2DM patients.

Gut-targeted therapies for type 2 diabetes mellitus: A review

Type 2 diabetes mellitus(T2DM)is a chronic metabolic disorder characterized by hyperglycemia and insulin resistance.The global prevalence of T2DM has reached epidemic proportions,affecting approximately 463 million adults worldwide in 2019.Current treatments for T2DM include lifestyle modifications,oral antidiabetic agents,and insulin therapy.However,these therapies may carry side effects and fail to achieve optimal glycemic control in some patients.Therefore,there is a growing interest in the role of gut microbiota and more gut-targeted therapies in the management of T2DM.The gut microbiota,which refers to the community of microorganisms that inhabit the human gut,has been shown to play a crucial role in the regulation of glucose metabolism and insulin sensitivity.Alterations in gut microbiota composition and diversity have been observed in T2DM patients,with a reduction in beneficial bacteria and an increase in pathogenic bacteria.This dysbiosis may contribute to the pathogenesis of the disease by promoting inflammation and impairing gut barrier function.Several gut-targeted therapies have been developed to modulate the gut microbiota and improve glycemic control in T2DM.One potential approach is the use of probio-tics,which are live microorganisms that confer health benefits to the host when administered in adequate amounts.Several randomized controlled trials have demonstrated that certain probiotics,such as Lactobacillus and Bifidobacterium species,can improve glycemic control and insulin sensitivity in T2DM patients.Mechanisms may include the production of short-chain fatty acids,the improvement of gut barrier function,and the reduction of inflammation.Another gut-targeted therapy is fecal microbiota transplantation(FMT),which involves the transfer of fecal material from a healthy donor to a recipient.FMT has been used successfully in the treatment of Clostridioides difficile infection and is now being investigated as a potential therapy for T2DM.A recent randomized controlled trial showed that FMT from lean donors improved glucose metabolism and insulin sensitivity in T2DM patients with obesity.However,FMT carries potential risks,including transmission of infectious agents and alterations in the recipient's gut microbiota that may be undesirable.In addition to probiotics and FMT,other gut-targeted therapies are being investigated for the management of T2DM,such as prebiotics,synbiotics,and postbiotics.Prebiotics are dietary fibers that promote the growth of beneficial gut bacteria,while synbiotics combine probiotics and prebiotics.Postbiotics refer to the metabolic products of probiotics that may have beneficial effects on the host.The NIH SPARC program,or the Stimulating Peripheral Activity to Relieve Conditions,is a research initiative aimed at developing new therapies for a variety of health conditions,including T2DM.The SPARC program focuses on using electrical stimulation to activate peripheral nerves and organs,in order to regulate glucose levels in the body.The goal of this approach is to develop targeted,non-invasive therapies that can help patients better manage their diabetes.One promising area of research within the SPARC program is the use of electrical stimulation to activate the vagus nerve,which plays an important role in regulating glucose metabolism.Studies have shown that vagus nerve stimulation can improve insulin sensitivity and lower blood glucose levels in patients with T2DM.Gut-targeted therapies,such as probiotics and FMT,have shown potential for improving glycemic control and insulin sensitivity in T2DM patients.However,further research is needed to determine the optimal dose,duration,and safety of these therapies.

Limitations and suggestions for type 2 diabetes mellitus and pancreatic neuroendocrine tumors based on meta-analysis

We read with great interest the systematic review and meta-analysis by Cigrovski Berkovic et al published recently,which evaluated the association between type 2 diabetes mellitus(T2DM)and pancreatic neuroendocrine tumors(pNETs).The study identified T2DM as a risk factor for the development of pNETs and linked it to poor tumor-free survival.However,due to the limited number of studies and high heterogeneity,the role of metformin in the diagnosis and prognosis of pNETs remained inconclusive.We believe the study has some limitations regarding literature search,risk of bias assessment,and analysis of heterogeneity and publication bias.Expanding the search to more databases,applying more appropriate bias assessment tools,and using better statistical methods to evaluate heterogeneity and publication bias would strengthen the study’s conclusions.Addressing these concerns could provide more robust evidence for understanding the diagnostic and prognostic impact of T2DM in pNETs.

Platelet indices as predictors of poor glucoregulation in type 2 diabetes mellitus adults at Bishoftu General Hospital,Ethiopia

BACKGROUND Diabetes is a chronic metabolic syndrome that has become a global public health problem with significant morbidity and mortality.It is a pro-inflammatory and pro-thrombotic condition characterized by increased platelet activation and alterations in platelet indices.However,the use of platelet indices as predictors of poor glucoregulation has not been fully evaluated in this context,and evidence for their role as predictors of poor glycemic status in diabetic patients is limited.AIM To evaluate platelet indices and determine their prognostic significance in relation to inadequate glucoregulation among individuals diagnosed with type 2 diabetes at Bishoftu General Hospital in Ethiopia,from June 15 to August 12,2022.METHODS A comparative cross-sectional study was conducted in 261 participants including 174 individuals with type 2 diabetes mellitus(T2DM)and 87 non-diabetic controls.The systematic random sampling technique was used to select participants.Data were collected using structured questionnaires,physical measurements,checklists,and laboratory tests.Platelet parameters and fasting blood glucose levels were determined from blood samples using Sysmex-XN550 and CobasC311 analyzers,respectively.The hematology analyzer output was checked and participants were also screened for malaria parasites using a prepared blood smear.Collected data were entered into Epi-data version 3.1 and exported to SPSS version 25 for analysis.Theχ^(2) test,Mann-Whitney U test,Kruskal-Wallis test,post hoc test,Spearman correlation,and receiver operating characteristic curve were used for analysis.A P value<0.05 was considered statistically significant.RESULTS The results of our study indicate that diabetic patients have significantly higher levels of platelet distribution width(PDW),mean platelet volume(MPV),platelet large cell ratio(PLCR),and plateletcrit(PCT)compared to healthy individuals(P<0.001).Furthermore,these indices were found to be significantly elevated in individuals with poor glycemic control in T2DM compared to those with good glycemic control and healthy controls.We also observed significant correlations between these indices and various anthropometric and clinical variables.Our findings suggest that PDW,with a cut-off value of 15.75 fL and an area under the curve(AUC)of 0.803,MPV,with a cut-off value of 12.25 fL and an AUC of 0.774,PLCR,with a cut-off value of 36.3%and an AUC of 0.775,and PCT,with a cut-off value of 0.24%and an AUC of 0.761,can serve as predictors of poor glycemic control in patients with diabetes mellitus.CONCLUSION The observed correlation between diabetic patients and a significant increase in platelet indices has highlighted their potential as predictors of poor glycemic control in diabetes.Therefore,regular screening and profiling of platelet indices is recommended as part of the follow-up process for individuals with diabetes mellitus.

Novel insights into immune-related genes associated with type 2 diabetes mellitus-related cognitive impairment

BACKGROUND The cognitive impairment in type 2 diabetes mellitus(T2DM)is a multifaceted and advancing state that requires further exploration to fully comprehend.Neu-roinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the disease.AIM To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive impairment.METHODS To identify differentially expressed genes(DEGs)between T2DM and controls,we used data from the Gene Expression Omnibus database GSE125387.To identify T2DM module genes,we used Weighted Gene Co-Expression Network Analysis.All the genes were subject to Gene Set Enrichment Analysis.Protein-protein interaction network construction and machine learning were utilized to identify three hub genes.Immune cell infiltration analysis was performed.The three hub genes were validated in GSE152539 via receiver operating characteristic curve analysis.Validation experiments including reverse transcription quantitative real-time PCR,Western blotting and immunohistochemistry were conducted both in vivo and in vitro.To identify potential drugs associated with hub genes,we used the Comparative Toxicogenomics Database(CTD).RESULTS A total of 576 DEGs were identified using GSE125387.By taking the intersection of DEGs,T2DM module genes,and immune-related genes,a total of 59 genes associated with the immune system were identified.Afterward,machine learning was utilized to identify three hub genes(H2-T24,Rac3,and Tfrc).The hub genes were associated with a variety of immune cells.The three hub genes were validated in GSE152539.Validation experiments were conducted at the mRNA and protein levels both in vivo and in vitro,consistent with the bioinformatics analysis.Additionally,11 potential drugs associated with RAC3 and TFRC were identified based on the CTD.CONCLUSION Immune-related genes that differ in expression in the hippocampus are closely linked to microglia.We validated the expression of three hub genes both in vivo and in vitro,consistent with our bioinformatics results.We discovered 11 compounds associated with RAC3 and TFRC.These findings suggest that they are co-regulatory molecules of immunometabolism in diabetic cognitive impairment.