Gut microbiome:A revolution in typeⅡdiabetes mellitus

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.

Icariin accelerates bone regeneration by inducing osteogenesisangiogenesis coupling in rats with type 1 diabetes mellitus

BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To explore the role and potential mechanism of ICA on bone defect in the context of T1DM.METHODS The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining,alizarin red S staining,quantitative real-time polymerase chain reaction,Western blot,and immunofluorescence.Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis.A bone defect model was established in T1DM rats.The model rats were then treated with ICA or placebo and micron-scale computed tomography,histomorphometry,histology,and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area.RESULTS ICA promoted bone marrow mesenchymal stem cell(BMSC)proliferation and osteogenic differentiation.The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers(alkaline phosphatase and osteocalcin)and angiogenesis-related markers(vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1)compared to the untreated group.ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs.In the bone defect model T1DM rats,ICA facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation.Lastly,ICA effectively accelerated the rate of bone formation in the defect area.CONCLUSION ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.

Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy

Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is scarce.This study aimed to demonstrate and identify predictors of DM control under the influence of CST.Methods:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM group.The incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM groups.Of the 52 patients with DM,CST was administered in 48 cases.Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control improvement.Conclusions:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis.CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

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.

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.

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.

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.

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.

Gestational diabetes mellitus combined with fulminant type 1 diabetes mellitus, four cases of double diabetes: A case report

BACKGROUND Fulminant type 1 diabetes mellitus(FT1DM)that occurs during pregnancy or the perinatal period is known as pregnancy-related FT1DM(PF),always without history of abnormal glucose metabolism.Here,we present four patients who developed FT1DM during treatment but were first diagnosed with gestational diabetes mellitus(GDM).CASE SUMMARY The clinical data of four patients with GDM combined with FT1DM admitted to our hospital between July 2018 and April 2021 were collected,and the patients and their infants were followed up.All patients were diagnosed with GDM during the second trimester and were treated.The blood glucose level elevated suddenly during the third trimester and then were diagnosed with FT1DM.Two patients had an insulin allergy,and two had symptoms of upper respiratory tract infection before onset.One patient developed ketoacidosis,and three developed ketosis.Two patients had cesarean section deliveries,and two had vaginal deliveries.The growth and development of the infants were normal.C-peptide levels were lower than those at onset,suggesting progressive impairment of islet function.The frequencies of the DRB109:01,DQB103:03,DQA103:02,DPA101:03,DPA102:02,DPB105:01,DRB401:03,G 01:01,and G 01:04 human leukocyte antigen(HLA)-G alleles were high in the present study.CONCLUSION In comparison with pregnancy-associated FT1DM(PF),patients with GDM combined with FT1DM had an older age of onset,higher body mass index,slower onset,fewer prodromal symptoms,and less acidosis.The pathogenesis may be due to various factors affecting the already fragileβ-cells of GDM patients with genetically susceptible class II HLA genotypes.We speculate that GDM combined with FT1DM during pregnancy,referred to as“double diabetes,”is a subtype of PF with its own unique characteristics that should be investigated further.

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.

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.

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.

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.

Emerging and multifaceted potential contributions of polyphenols in the management of type 2 diabetes mellitus

Type 2 diabetes mellitus(T2DM)is recognized as a serious public health concern with a considerable impact on human life,long-term health expenditures,and substantial health losses.In this context,the use of dietary polyphenols to prevent and manage T2DM is widely documented.These dietary compounds exert their beneficial effects through several actions,including the protection of pancreatic islet β-cell,the antioxidant capacities of these molecules,their effects on insulin secretion and actions,the regulation of intestinal microbiota,and their contribution to ameliorate diabetic complications,particularly those of vascular origin.In the present review,we intend to highlight these multifaceted actions and the molecular mechanisms by which these plant-derived secondary metabolites exert their beneficial effects on type 2 diabetes patients.

Association of autoimmune thyroid disease with type 1 diabetes mellitus and its ultrasonic diagnosis and management

As a common hyperglycemic disease,type 1 diabetes mellitus(T1DM)is a complicated disorder that requires a lifelong insulin supply due to the immunemediated destruction of pancreaticβcells.Although it is an organ-specific autoimmune disorder,T1DM is often associated with multiple other autoimmune disorders.The most prevalent concomitant autoimmune disorder occurring in T1DM is autoimmune thyroid disease(AITD),which mainly exhibits two extremes of phenotypes:hyperthyroidism[Graves'disease(GD)]and hypothyroidism[Hashimoto's thyroiditis,(HT)].However,the presence of comorbid AITD may negatively affect metabolic management in T1DM patients and thereby may increase the risk for potential diabetes-related complications.Thus,routine screening of thyroid function has been recommended when T1DM is diagnosed.Here,first,we summarize current knowledge regarding the etiology and pathogenesis mechanisms of both diseases.Subsequently,an updated review of the association between T1DM and AITD is offered.Finally,we provide a relatively detailed review focusing on the application of thyroid ultrasonography in diagnosing and managing HT and GD,suggesting its critical role in the timely and accurate diagnosis of AITD in T1DM.

Advancing cardiovascular outcomes with dapagliflozin and sacubitril in post-acute myocardial infarction heart failure and type 2 diabetes mellitus

Coronary heart disease and type 2 diabetes mellitus(T2DM)often co-occur,presenting substantial health risks,particularly following acute myocardial infarction(AMI).While percutaneous coronary intervention(PCI)is a prevalent treatment,complications such as microvascular dysfunction may lead to heart failure,necessitating additional therapies.This editorial examines the emerging roles of sacubitril/valsartan and sodium-glucose co-transporter 2 inhibitors in managing post-PCI.Recent research investigates the combined effects of dapag-liflozin and telmisartan on myocardial microperfusion in post-AMI heart failure patients with T2DM.The findings suggest that this combination enhances myo-cardial microcirculation,improves cardiac function,and achieves better glycemic control,with a reduced incidence of major adverse cardiovascular events.Despite ongoing challenges,the integration of dapagliflozin and sacubitril/valsartan re-presents a significant advancement in post-AMI care.Further investigation in larger cohorts and more diverse patient populations is required to confirm its long-term clinical outcomes.