Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not complet...Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.展开更多
BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis th...BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.展开更多
Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close rel...Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular mechanisms.Impaired insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological processes.The contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.展开更多
Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in viv...Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.展开更多
BACKGROUND Type 2 diabetes mellitus(T2DM)often leads to vascular complications,such as albuminuria.The role of insulin autoantibodies(IAA)and their interaction with D-dimer in this context remains unclear.AIM To inves...BACKGROUND Type 2 diabetes mellitus(T2DM)often leads to vascular complications,such as albuminuria.The role of insulin autoantibodies(IAA)and their interaction with D-dimer in this context remains unclear.AIM To investigate the characteristics of IAA and its effect on albuminuria in T2DM patients.METHODS We retrospectively analyzed clinical data from 115 T2DM patients with positive IAA induced by exogenous insulin,and 115 age-and sex-matched IAA-negative T2DM patients as controls.Propensity scores were calculated using multivariate logistic regression.Key variables were selected using the least absolute shrinkage and selection operator(LASSO)algorithm.We constructed a prediction model and analyzed the association between IAA and albuminuria based on demographic and laboratory parameters.RESULTS The IAA-positive group had significantly higher D-dimer levels[0.30(0.19-0.55)mg/L vs 0.21(0.19-0.33)mg/L,P=0.008]and plasma insulin levels[39.1(12.0-102.7)μU/mL vs 9.8(5.5-17.6)μU/mL,P<0.001]compared to the IAA-negative group.Increases in the insulin dose per weight ratio,diabetes duration,and urinary albumin-to-creatinine ratio(UACR)were observed but did not reach statistical significance.The LASSO model identified plasma insulin and D-dimer as key factors with larger coefficients.D-dimer was significantly associated with UACR in the total and IAA-positive groups but not in the IAA-negative group.The odds ratio for D-dimer elevation(>0.5 g/L)was 2.88(95%confidence interval:1.17-7.07)in the IAA-positive group(P interaction<0.05).CONCLUSION D-dimer elevation is an independent risk factor for abnormal albuminuria and interacts with IAA in the development of abnormal albuminuria in T2DM patients.展开更多
BACKGROUND Numerous epidemiological studies have found that pesticide exposure is associated with the incidence of type 2 diabetes(T2D);however,the underlying mechanisms remain unknown.DNA methylation may play a role ...BACKGROUND Numerous epidemiological studies have found that pesticide exposure is associated with the incidence of type 2 diabetes(T2D);however,the underlying mechanisms remain unknown.DNA methylation may play a role in this process.AIM To identify the genes associated with pesticide exposure and T2D by reviewing the current literature.METHODS We systematically searched PubMed and Embase for relevant studies that examined the association between pesticide exposure and DNA methylation,and studies on DNA methylation and T2D through January 15,2024.RESULTS We identified six genes(Alu,CABLES1,CDH1,PDX1,PTEN,PTPRN2)related to pesticide exposure and T2D.We also suggested future research directions to better define the role of DNA methylation in the association between pesticide exposure and T2D.CONCLUSION DNA methylation of specific genes may play a vital role in the association between pesticide exposure and T2D.展开更多
In this manuscript,we comment on a recent publication by Yuan et al.This article provides a detailed scientific diagnostic process for a multiple endocrine neo-plasia type 1 patient,thus offering strong guidance for c...In this manuscript,we comment on a recent publication by Yuan et al.This article provides a detailed scientific diagnostic process for a multiple endocrine neo-plasia type 1 patient,thus offering strong guidance for clinical practice.However,we believe that the authors should also provide information on the patient's long-term prognosis.展开更多
BACKGROUND The preservation of isletβ-cell function in elderly patients with type 2 diabetes mellitus(T2DM)is a top priority for diabetic control.AIM To assess the preservation of isletβ-cell function among elderly ...BACKGROUND The preservation of isletβ-cell function in elderly patients with type 2 diabetes mellitus(T2DM)is a top priority for diabetic control.AIM To assess the preservation of isletβ-cell function among elderly Chinese patients with T2DM after different anti-diabetic treatments.METHODS In this longitudinal observational study,elderly patients with T2DM treated with insulin,oral antidiabetic drugs or a combination of both were enrolled to disclose their isletβ-cell function between baseline and follow-up.Isletβ-cell function was determined by the plasma Homeostasis Model forβ-cell function(HOMA-β),Cpeptide and area under the curve(AUC)based on oral glucose tolerance test.Changes inβ-cell function(decrement or increment from baseline)between different therapy groups were the outcomes.RESULTS In total,745 elderly patients(≥60 years)with T2DM[insulin monotherapy,n=105;oral anti-diabetic drugs(OAD)monotherapy,n=321;insulin plus OAD,n=319]had their baseline and follow-upβ-cell function assessed during a median observation period of 4.5 years(range,3.0-7.2 years).Overall,isletβ-cell function(HOMA-β,fasting Cpeptide,fasting insulin,AUCc-pep,AUCins,AUCc-pep/AUCglu,AUCins/AUCglu)consistently deteriorated over time regardless of the three different antidiabetic treatments.No statistical differences in decrement were observed among the three groups regarding the isletβ-cell function indices.All three groups showed an increased ratio of delayed insulin secretion response after 4.5 years of observation.CONCLUSION In Chinese elderly patients with T2DM,isletβ-cell function progressively declines regardless of insulin supplement or insulin plus OAD treatments.展开更多
The risk factors for type 2 diabetes mellitus(T2DM)have been increasingly researched,but the lack of systematic identification and categorization makes it difficult for clinicians to quickly and accurately access and ...The risk factors for type 2 diabetes mellitus(T2DM)have been increasingly researched,but the lack of systematic identification and categorization makes it difficult for clinicians to quickly and accurately access and understand all the risk factors,which are categorized in this paper into five categories:Social determinants,lifestyle,checkable/testable risk factors,history of illness and medication,and other factors,which are discussed in a narrative review.Meanwhile,this paper points out the problems of the current research,helps to improve the systematic categorisation and practicality of T2DM risk factors,and provides a professional research basis for clinical practice and industry decision-making.展开更多
BACKGROUND The risk factors and prediction models for diabetic foot(DF)remain incompletely understood,with several potential factors still requiring in-depth investigations.AIM To identify risk factors for new-onset D...BACKGROUND The risk factors and prediction models for diabetic foot(DF)remain incompletely understood,with several potential factors still requiring in-depth investigations.AIM To identify risk factors for new-onset DF and develop a robust prediction model for hospitalized patients with type 2 diabetes.METHODS We included 6301 hospitalized patients with type 2 diabetes from January 2016 to December 2021.A univariate Cox model and least absolute shrinkage and selection operator analyses were applied to select the appropriate predictors.Nonlinear associations between continuous variables and the risk of DF were explored using restricted cubic spline functions.The Cox model was further employed to evaluate the impact of risk factors on DF.The area under the curve(AUC)was measured to evaluate the accuracy of the prediction model.RESULTS Seventy-five diabetic inpatients experienced DF.The incidence density of DF was 4.5/1000 person-years.A long duration of diabetes,lower extremity arterial disease,lower serum albumin,fasting plasma glucose(FPG),and diabetic nephropathy were independently associated with DF.Among these risk factors,the serum albumin concentration was inversely associated with DF,with a hazard ratio(HR)and 95%confidence interval(CI)of 0.91(0.88-0.95)(P<0.001).Additionally,a U-shaped nonlinear relationship was observed between the FPG level and DF.After adjusting for other variables,the HRs and 95%CI for FPG<4.4 mmol/L and≥7.0 mmol/L were 3.99(1.55-10.25)(P=0.004)and 3.12(1.66-5.87)(P<0.001),respectively,which was greater than the mid-range level(4.4-6.9 mmol/L).The AUC for predicting DF over 3 years was 0.797.CONCLUSION FPG demonstrated a U-shaped relationship with DF.Serum albumin levels were negatively associated with DF.The prediction nomogram model of DF showed good discrimination ability using diabetes duration,lower extremity arterial disease,serum albumin,FPG,and diabetic nephropathy(Clinicaltrial.gov NCT05519163).展开更多
Cumulative studies have shown that the composition of the gut microbiome is strongly associated with the development of type 2 diabetes mellitus(T2DM).Electroacupuncture(EA)therapy has been reported to alleviate vario...Cumulative studies have shown that the composition of the gut microbiome is strongly associated with the development of type 2 diabetes mellitus(T2DM).Electroacupuncture(EA)therapy has been reported to alleviate various diseases,including T2DM,by targeting specific acupuncture points and regulating metabolic homeostasis.A recent review published in the World Journal of Diabetes detailed the role of the gut microbiome in T2DM,discussing the role of therapeutic strategies developed to alleviate T2DM and its complications based on gut microbiome in ameliorating T2DM,as well as the effects of multiple diabetes medications on gut microbiome.However,the review did not elucidate the therapeutic role of EA therapy,a common non-pharmacological intervention for T2DM.This letter complemented the effect of EA therapy on glucose metabolism by adjusting the gut microbiome composition,which reveals the underlying mechanism of glucose lowering by EA therapy and provides a scientific basis for the application of EA therapy in clinical treatment.展开更多
BACKGROUND Serum retinol-binding protein(RBP)is the primary transport protein of circulating vitamin A.RBP has a crucial role in maintaining nutrient metabolism and physiologic homeostasis.Several studies have indicat...BACKGROUND Serum retinol-binding protein(RBP)is the primary transport protein of circulating vitamin A.RBP has a crucial role in maintaining nutrient metabolism and physiologic homeostasis.Several studies have indicated that serum RBP participates in the progression of diabetes and diabetes-related complications.However,the impact of serum RBP on lower limb atherosclerosis has not been determined in individuals with type 2 diabetes mellitus(T2DM).AIM To determine the association between serum RBP and lower limb atherosclerosis in individuals with T2DM.METHODS This retrospective study enrolled 4428 eligible T2DM patients and divided the patients into non-lower limb atherosclerosis(n=1913)and lower limb atherosclerosis groups(n=2515)based on lower limb arterial ultrasonography results.At hospital admission,baseline serum RBP levels were assessed,and all subjects were categorized into three groups(Q1-Q3)based on RBP tertiles.Logistic regression,restricted cubic spline regression,subgroup analysis,and machine learning were used to assess the association between RBP levels and lower limb atherosclerosis risk.RESULTS Among 4428 individuals with T2DM,2515(56.80%)had lower limb atherosclerosis.Logistic analysis showed that lower limb atherosclerosis risk increased by 1%for every 1 unit rise in serum RBP level(odds ratio=1.01,95%confidence interval:1.00-1.02,P=0.004).Patients in the highest tertile group(Q3)had a higher lower limb atherosclerosis risk compared to the lowest tertile group(Q1)(odds ratio=1.36,95%confidence interval:1.12-1.67,P=0.002).The lower limb atherosclerosis risk gradually increased with an increase in RBP tertile(P for trend=0.005).Restricted cubic spline analysis indicated a linear correlation between serum RBP levels and lower limb atherosclerosis risk(non-linear P<0.05).Machine learning demonstrated the significance and diagnostic value of serum RBP in predicting lower limb atherosclerosis risk.CONCLUSION Elevated serum RBP levels correlate with an increased lower limb atherosclerosis risk in individuals with T2DM.展开更多
BACKGROUND Although numerous single nucleotide polymorphism in multiple genes involve in the risk of type 2 diabetes mellitus(T2D),the single gene defects of T2D with strong family history is not clear yet.SPTLC1 are ...BACKGROUND Although numerous single nucleotide polymorphism in multiple genes involve in the risk of type 2 diabetes mellitus(T2D),the single gene defects of T2D with strong family history is not clear yet.SPTLC1 are causative for hereditary sensory and autonomic neuropathy,which is clinical overlapping with diabetic peripheral neuropathy.Mice with adipocyte-specific deletion of SPTLC1 had impaired glucose tolerances and insulin sensitivity.Thus,it is necessary to investigate the SPTLC1 mutations in adult-onset T2D with strong family history.AIM To analyze the role of SPTLC1 mutation on adult-onset T2D with strong family history.METHODS By whole-exome sequence analysis of a patient with T2D and his family members,an uncertain variant in SPTLC1 was identified.Bioinformation analysis was used to evaluate the influence of mutation,rare variant gene-level associations for SPTLC1 in T2D,and the relationship between SPTLC1 mRNA and T2D in human islets from GSE25724.The effect of G371R of SPTLC1 on the characteristics of inflammatory cytokines and apoptosis was also tested on human embryonic kidney(HEK)293 cells.RESULTS A single nucleotide variation in SPTLC1(c.1111G>A:p.G371R)was identified in a family with T2D.The deleterious variant was predicted by functional analysis through hidden Markov models and mendelian clinically applicable pathogenicity software.This pathogenicity might be derived from the different amino acid properties.In HEK 293T cells,p.G371R of SPTLC1 induced the expression of tumor necrosis factor-αand the percent of apoptosis.Meanwhile,rare variant gene-level associations for SPTLC1 also refer to the high risk of T2D(the overall odds ratio=2.4968,P=0.0164).Data from GSE25724 showed that SPTLC1 mRNA was lower in pancreatic islets from T2D human islets(P=0.046),and was as sociated with the decreased level of insulin mRNA expression(Spearman r=0.615,P=0.025).CONCLUSION The study classified SPTLC1 p.G371R mutation as the likely pathogenic mutation from an adult-onset T2D patients with strong family history T2D.展开更多
BACKGROUND Progressive familial intrahepatic cholestasis type 1(PFIC-1)is a genetic cholestatic disease causing end-stage liver disease,which needs liver transplantation(LT).Simultaneous biliary diversion(BD)was recom...BACKGROUND Progressive familial intrahepatic cholestasis type 1(PFIC-1)is a genetic cholestatic disease causing end-stage liver disease,which needs liver transplantation(LT).Simultaneous biliary diversion(BD)was recommended to prevent allograft steatosis after transplantation,while increasing the risk of infection.Here,an attempt was made to perform BD using appendix to prevent bacterial translocation after LT.CASE SUMMARY An 11-month-old boy diagnosed with PFIC-1 received ABO compatible living donor LT due to refractory jaundice and pruritus.His mother donated her left lateral segment with a graft-to-recipient weight ratio of 2.9%.Internal BD was constructed during LT using the appendix by connecting its proximal end with the intrahepatic biliary duct and the distal end with colon.Biliary leakage was suspected on the 5th day after transplantation and exploratory laparotomy indicated biliary leakage at the cutting surface of liver.The liver function returned to normal on the 9th day post-operation and maintained normal during the 15-month follow-up.Cholangiography at 10 months after transplantation confirmed the direct secretion of bile into colon.Computerized tomography scan(4 months and 10 months)and liver biopsy(10 months)indicated no steatosis in the allograft.No complaint of recurrent diarrhea,infection or growth retardation was reported during follow-up.CONCLUSION Internal BD using appendix during LT is effective in preventing allograft steatosis and post-transplant infection in PFIC-1 recipients.展开更多
BACKGROUND The increasing number of type 2 diabetes mellitus(T2DM)patients leads to higher rates of morbidity and mortality related to lung cancer.AIM To investigate the utility of the proliferating cell nuclear antig...BACKGROUND The increasing number of type 2 diabetes mellitus(T2DM)patients leads to higher rates of morbidity and mortality related to lung cancer.AIM To investigate the utility of the proliferating cell nuclear antigen Ki-67 in patients with lung adenocarcinoma in situ(AIS)complicated by T2DM.METHODS One hundred patients with AIS and T2DM(group A),100 patients with AIS alone(group B),and 60 patients with benign lung lesions(group C)admitted to the Department of Thoracic Surgery and Endocrinology of the First Affiliated Hospital of Soochow University from November 2021 to December 2022 were enrolled.Ki-67 expression was compared among the groups.RESULTS Group A had significantly higher levels of fasting plasma glucose(FPG),total cholesterol(TC),total triglyceride,low-density lipoprotein cholesterol,glycosylated hemoglobin(HbA1c),and insulin than groups B and C(P<0.01).Meanwhile,group B had higher insulin levels than group C(P<0.01).Group A exhibited a significantly higher average Ki-67 positivity rate than group B(P<0.01).The Ki-67 positivity rate in group A was 86.87%,while the positivity rate in group B was 77%.Ki-67 was positively correlated with FPG(P<0.01)and HbA1c levels(P<0.01).Ki-67,FBG,insulin,HbA1c,high-density lipoprotein cholesterol and TC were independent factors for patients with AIS complicated by T2DM.Chen K et al.Ki67 in patients with AIS complicated by T2DM WJD https://www.wjgnet.com 2 February 15,2025 Volume 16 Issue 2 CONCLUSION Ki-67 expression was higher in patients with AIS complicated by T2DM than in patients with AIS alone.Therefore,detecting the Ki-67 level might assist in the diagnosis of AIS in patients with T2DM.展开更多
This letter comments on a study by Jin et al,published recently in the World Journal of Diabetes.Hypoglycemia is a significant complication of diabetes,with primary defense mechanisms involving the stimulation of gluc...This letter comments on a study by Jin et al,published recently in the World Journal of Diabetes.Hypoglycemia is a significant complication of diabetes,with primary defense mechanisms involving the stimulation of glucagon secretion inα-cells and the inhibition of insulin secretion in pancreaticβ-cells,which are often compromised in type 1 diabetes mellitus(T1DM)and advanced type 2 diabetes mellitus.Recurrent hypoglycemia predisposes the development of impaired hypoglycemia awareness,a condition underpinned by complex pathophysiological processes,encompassing central nervous system adaptations and several hormonal interactions,including a potential role for glucagon-like peptide-1(GLP-1)in paracrine and endocrine vias.Experimental evidence indicates that GLP-1 may impair hypoglycemic counterregulation by disrupting the sympathoadrenal system and promoting somatostatin release in pancreaticδ-cells,which inhibits glucagon secretion from neighboringα-cells.However,current trials evaluating GLP-1 receptor agonists(GLP-1 RAs)in T1DM patients have shown promising benefits in reducing insulin requirements and body weight,without increasing the risk of hypoglycemia.Further research is essential to elucidate the specific roles of GLP-1 and GLP-1 RAs in modulating glucagon secretion and the sympathetic-adrenal reflex,and their impact on hypoglycemia unawareness in T1DM patients.展开更多
Recent advances in understanding type 1 diabetes(T1D)highlight the complexity of managing hypoglycemia,a frequent and perilous complication of diabetes therapy.This letter delves into a novel study by Jin et al,which ...Recent advances in understanding type 1 diabetes(T1D)highlight the complexity of managing hypoglycemia,a frequent and perilous complication of diabetes therapy.This letter delves into a novel study by Jin et al,which elucidates the role of intestinal glucagon-like peptide-1(GLP-1)in the counterregulatory response to hypoglycemia in T1D models.The study employed immunofluorescence,Western blotting,and enzyme-linked immunosorbent assay to track changes in GLP-1 and its receptor expression in diabetic mice subjected to recurrent hypoglycemic episodes.Findings indicate a significant increase in intestinal GLP-1 and GLP-1 receptor expression,correlating with diminished adrenal and glucagon responses,crucial for glucose stabilization during hypoglycemic events.This letter aims to explore the implications of these findings for future therapeutic strategies and the broader understanding of T1D management.展开更多
BACKGROUND Diabetic peripheral neuropathy(DPN)is a common complication of type 2 diabetes mellitus(T2DM),significantly affecting patients’quality of life and imposing a substantial economic burden.Recent studies have...BACKGROUND Diabetic peripheral neuropathy(DPN)is a common complication of type 2 diabetes mellitus(T2DM),significantly affecting patients’quality of life and imposing a substantial economic burden.Recent studies have highlighted the role of thyroid hormones in diabetes complications,particularly in elderly patients with T2DM.However,the relationship between thyroid hormone sensitivity and DPN remains unclear.AIM To investigate the correlation between thyroid hormone sensitivity and DPN in elderly patients with T2DM.METHODS In a cohort of 256 elderly patients with T2DM,propensity score matching was used to balance age,sex,and diabetes duration.Clinical data were collected to calculate thyroid hormone sensitivity and analyze its correlation with DPN.A random forest model was used to evaluate the diagnostic value of free triiodothyronine/free thyroxine(FT_(3)/FT_(4))for DPN.RESULTS Patients with DPN had a lower FT_(3)/FT_(4) ratio[(0.302±0.053)vs(0.316±0.049),P=0.040].Quartile stratification showed decreasing DPN prevalence with higher FT_(3)/FT_(4) ratios.Spearman’s correlation analysis showed that a lower FT_(3)/FT_(4) ratio was associated with higher glycated hemoglobin,fasting blood glucose,reduced nerve conduction velocity,and electrical skin conductance.Logistic regression indicated a positive relationship between the median FT_(3)/FT_(4) ratio and bilateral foot electrochemical skin conductance[odds ratio(OR):1.019;95%CI:1.005-1.034;P=0.007]and sural nerve sensory amplitude(OR:1.310;95%CI:1.008-1.703;P=0.043).Receiver operating characteristic analysis using a random forest model showed that incorporating FT_(3)/FT_(4) improved predictive performance for DPN,with an area under the curve of 0.74,sensitivity of 0.79,specificity of 0.64,and accuracy of 0.77.CONCLUSION In elderly patients with T2DM with euthyroidism,a lower FT_(3)/FT_(4) ratio is correlated with increased DPN incidence,affecting both large and small nerve fibers.FT_(3)/FT_(4) is an effective predictor of DPN.展开更多
BACKGROUND Plantamajoside(PMS)has shown potential in mitigating cell damage caused by high glucose(HG)levels.Despite this,the precise therapeutic effects of PMS on type 2 diabetes mellitus(T2DM)and the underlying regu...BACKGROUND Plantamajoside(PMS)has shown potential in mitigating cell damage caused by high glucose(HG)levels.Despite this,the precise therapeutic effects of PMS on type 2 diabetes mellitus(T2DM)and the underlying regulatory mechanisms require further exploration.AIM To investigate PMS therapeutic effects on T2DM in mice and elucidate its mechanisms of action through in vivo and in vitro experiments.METHODS An in vitro damage model of MIN6 cells was established using HG and palmitic acid(PA).PMS's protective effect on cell damage was assessed.Next,transcriptomics was employed to examine how PMS treatment affects gene expression of MIN6 cells.Furthermore,the effect of PMS on protein processing in endoplasmic reticulum and apoptosis pathways was validated.A T2DM mouse model was used to validate the therapeutic effects and mechanisms of PMS in vivo.RESULTS PMS intervention ameliorated cell injury in HG+PA-induced MIN6 cell damage.Transcriptomic analysis revealed that protein processing in the endoplasmic reticulum and apoptosis pathways were enriched in cells treated with PMS,with significant downregulation of the gene Dnajc1.Further validation indicated that PMS significantly inhibited the expression of apoptosis-related factors(Bax,CytC)and endoplasmic reticulum stress(ERS)-related factors[ATF6,XBP1,Ddit3(CHOP),GRP78],while promoting the expression of Bcl-2 and Dnajc1.Additionally,the inhibitory effects of PMS on ERS and apoptosis were abolished upon Dnajc1 silencing.Furthermore,in vivo experiments demonstrated that PMS intervention effectively improved pancreatic damage,suppressed the expression of apoptosis-related factors(Bax,CytC),and ERS-related factors[ATF6,XBP1,Ddit3(CHOP),GRP78],while promoting the expression of Bcl-2 and Dnajc1 in a T2DM model mice.CONCLUSION PMS intervention could alleviate pancreatic tissue damage effectively.The mechanism of action involves Dnajc1 activation,which subsequently inhibits apoptosis and ERS,ameliorating damage to pancreaticβ-cells.展开更多
This letter discusses the recent study by Mukherjee et al,which identifies a significant prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)among newly diagnosed type 2 diabetes mellitus(T2DM...This letter discusses the recent study by Mukherjee et al,which identifies a significant prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)among newly diagnosed type 2 diabetes mellitus(T2DM)patients in Bihar,India,and underscores the pressing need for integrated MASLD mana-gement within T2DM care.With 72.3%of the study cohort affected by MASLD,implementing routine liver function tests and ultrasound screenings is recom-mended as a standard practice in diabetes care,especially in regions with high prevalence rates.The study also advocates for dietary and lifestyle modifications,particularly the reduction of saturated fats,to slow MASLD progression.Patient education on monitoring body mass index and waist circumference,coupled with the integration of these metrics into digital health records,could enhance patient involvement and support proactive health management.Moreover,the letter emphasizes the advantages of developing a region-specific MASLD risk model that incorporates local dietary patterns and socioeconomic factors.Continued research into genetic and environmental determinants of MASLD remains es-sential for advancing our understanding of its etiology and informing targeted public health strategies.展开更多
基金supported by UniversitàCattolica(D1 intramural funds to RP)Italian Ministry of University and Research(PRIN 2022ZYLB7B,P2022YW7BP funds to CG).
文摘Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer’s disease.However,the molecular mechanisms underlying this association are not completely understood.Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role.Here,we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain,highlighting the role of interleukins and,in particular,interleukin 1βas a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.
基金Supported by The National Natural Science Foundation of China,No.82350127 and No.82241013the Shanghai Natural Science Foundation,No.20ZR1411600+2 种基金the Shanghai Shenkang Hospital Development Center,No.SHDC2020CR4039the Bethune Ethicon Excellent Surgery Foundation,No.CESS2021TC04Xuhui District Medical Research Project of Shanghai,No.SHXH201805.
文摘BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.
基金support from Region Stockholm,ALF-project(FoUI-960041)Open Access funding is provided by Karolinska Institute(both to IM)。
文摘Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular mechanisms.Impaired insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological processes.The contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.
基金supported by the Natural Science Foundation of Fujian Province,No.2020J02027the National Natural Science Foundation of China,No.31970461the Foundation of NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate,Fujian Maternity and Child Health Hospital,No.2022-NHP-05(all to WC).
文摘Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.
文摘BACKGROUND Type 2 diabetes mellitus(T2DM)often leads to vascular complications,such as albuminuria.The role of insulin autoantibodies(IAA)and their interaction with D-dimer in this context remains unclear.AIM To investigate the characteristics of IAA and its effect on albuminuria in T2DM patients.METHODS We retrospectively analyzed clinical data from 115 T2DM patients with positive IAA induced by exogenous insulin,and 115 age-and sex-matched IAA-negative T2DM patients as controls.Propensity scores were calculated using multivariate logistic regression.Key variables were selected using the least absolute shrinkage and selection operator(LASSO)algorithm.We constructed a prediction model and analyzed the association between IAA and albuminuria based on demographic and laboratory parameters.RESULTS The IAA-positive group had significantly higher D-dimer levels[0.30(0.19-0.55)mg/L vs 0.21(0.19-0.33)mg/L,P=0.008]and plasma insulin levels[39.1(12.0-102.7)μU/mL vs 9.8(5.5-17.6)μU/mL,P<0.001]compared to the IAA-negative group.Increases in the insulin dose per weight ratio,diabetes duration,and urinary albumin-to-creatinine ratio(UACR)were observed but did not reach statistical significance.The LASSO model identified plasma insulin and D-dimer as key factors with larger coefficients.D-dimer was significantly associated with UACR in the total and IAA-positive groups but not in the IAA-negative group.The odds ratio for D-dimer elevation(>0.5 g/L)was 2.88(95%confidence interval:1.17-7.07)in the IAA-positive group(P interaction<0.05).CONCLUSION D-dimer elevation is an independent risk factor for abnormal albuminuria and interacts with IAA in the development of abnormal albuminuria in T2DM patients.
文摘BACKGROUND Numerous epidemiological studies have found that pesticide exposure is associated with the incidence of type 2 diabetes(T2D);however,the underlying mechanisms remain unknown.DNA methylation may play a role in this process.AIM To identify the genes associated with pesticide exposure and T2D by reviewing the current literature.METHODS We systematically searched PubMed and Embase for relevant studies that examined the association between pesticide exposure and DNA methylation,and studies on DNA methylation and T2D through January 15,2024.RESULTS We identified six genes(Alu,CABLES1,CDH1,PDX1,PTEN,PTPRN2)related to pesticide exposure and T2D.We also suggested future research directions to better define the role of DNA methylation in the association between pesticide exposure and T2D.CONCLUSION DNA methylation of specific genes may play a vital role in the association between pesticide exposure and T2D.
基金Supported by National Natural Science Foundation of China,No.821706751·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University,No.ZYJC21011.
文摘In this manuscript,we comment on a recent publication by Yuan et al.This article provides a detailed scientific diagnostic process for a multiple endocrine neo-plasia type 1 patient,thus offering strong guidance for clinical practice.However,we believe that the authors should also provide information on the patient's long-term prognosis.
基金Medical Ethics Committee of the Nanxishan Hospital of Guangxi Zhuang Autonomous Region(Approval No.NXSYY-2024-209).
文摘BACKGROUND The preservation of isletβ-cell function in elderly patients with type 2 diabetes mellitus(T2DM)is a top priority for diabetic control.AIM To assess the preservation of isletβ-cell function among elderly Chinese patients with T2DM after different anti-diabetic treatments.METHODS In this longitudinal observational study,elderly patients with T2DM treated with insulin,oral antidiabetic drugs or a combination of both were enrolled to disclose their isletβ-cell function between baseline and follow-up.Isletβ-cell function was determined by the plasma Homeostasis Model forβ-cell function(HOMA-β),Cpeptide and area under the curve(AUC)based on oral glucose tolerance test.Changes inβ-cell function(decrement or increment from baseline)between different therapy groups were the outcomes.RESULTS In total,745 elderly patients(≥60 years)with T2DM[insulin monotherapy,n=105;oral anti-diabetic drugs(OAD)monotherapy,n=321;insulin plus OAD,n=319]had their baseline and follow-upβ-cell function assessed during a median observation period of 4.5 years(range,3.0-7.2 years).Overall,isletβ-cell function(HOMA-β,fasting Cpeptide,fasting insulin,AUCc-pep,AUCins,AUCc-pep/AUCglu,AUCins/AUCglu)consistently deteriorated over time regardless of the three different antidiabetic treatments.No statistical differences in decrement were observed among the three groups regarding the isletβ-cell function indices.All three groups showed an increased ratio of delayed insulin secretion response after 4.5 years of observation.CONCLUSION In Chinese elderly patients with T2DM,isletβ-cell function progressively declines regardless of insulin supplement or insulin plus OAD treatments.
基金National Natural Science Foundation of China,No.T2341018Science and Technology Innovation Project of Chinese Academy of Traditional Chinese Medicine,No.CI2023C049YLL.
文摘The risk factors for type 2 diabetes mellitus(T2DM)have been increasingly researched,but the lack of systematic identification and categorization makes it difficult for clinicians to quickly and accurately access and understand all the risk factors,which are categorized in this paper into five categories:Social determinants,lifestyle,checkable/testable risk factors,history of illness and medication,and other factors,which are discussed in a narrative review.Meanwhile,this paper points out the problems of the current research,helps to improve the systematic categorisation and practicality of T2DM risk factors,and provides a professional research basis for clinical practice and industry decision-making.
基金Supported by National Natural Science Foundation of China,No.81972947Academic Promotion Programme of Shandong First Medical University,No.2019LJ005.
文摘BACKGROUND The risk factors and prediction models for diabetic foot(DF)remain incompletely understood,with several potential factors still requiring in-depth investigations.AIM To identify risk factors for new-onset DF and develop a robust prediction model for hospitalized patients with type 2 diabetes.METHODS We included 6301 hospitalized patients with type 2 diabetes from January 2016 to December 2021.A univariate Cox model and least absolute shrinkage and selection operator analyses were applied to select the appropriate predictors.Nonlinear associations between continuous variables and the risk of DF were explored using restricted cubic spline functions.The Cox model was further employed to evaluate the impact of risk factors on DF.The area under the curve(AUC)was measured to evaluate the accuracy of the prediction model.RESULTS Seventy-five diabetic inpatients experienced DF.The incidence density of DF was 4.5/1000 person-years.A long duration of diabetes,lower extremity arterial disease,lower serum albumin,fasting plasma glucose(FPG),and diabetic nephropathy were independently associated with DF.Among these risk factors,the serum albumin concentration was inversely associated with DF,with a hazard ratio(HR)and 95%confidence interval(CI)of 0.91(0.88-0.95)(P<0.001).Additionally,a U-shaped nonlinear relationship was observed between the FPG level and DF.After adjusting for other variables,the HRs and 95%CI for FPG<4.4 mmol/L and≥7.0 mmol/L were 3.99(1.55-10.25)(P=0.004)and 3.12(1.66-5.87)(P<0.001),respectively,which was greater than the mid-range level(4.4-6.9 mmol/L).The AUC for predicting DF over 3 years was 0.797.CONCLUSION FPG demonstrated a U-shaped relationship with DF.Serum albumin levels were negatively associated with DF.The prediction nomogram model of DF showed good discrimination ability using diabetes duration,lower extremity arterial disease,serum albumin,FPG,and diabetic nephropathy(Clinicaltrial.gov NCT05519163).
文摘Cumulative studies have shown that the composition of the gut microbiome is strongly associated with the development of type 2 diabetes mellitus(T2DM).Electroacupuncture(EA)therapy has been reported to alleviate various diseases,including T2DM,by targeting specific acupuncture points and regulating metabolic homeostasis.A recent review published in the World Journal of Diabetes detailed the role of the gut microbiome in T2DM,discussing the role of therapeutic strategies developed to alleviate T2DM and its complications based on gut microbiome in ameliorating T2DM,as well as the effects of multiple diabetes medications on gut microbiome.However,the review did not elucidate the therapeutic role of EA therapy,a common non-pharmacological intervention for T2DM.This letter complemented the effect of EA therapy on glucose metabolism by adjusting the gut microbiome composition,which reveals the underlying mechanism of glucose lowering by EA therapy and provides a scientific basis for the application of EA therapy in clinical treatment.
基金The study was approved by the ethics committee of Southwest Hospital,the First Affiliated Hospital of Army Medical University of Chinese People's Liberation Army(No.KY2024007).
文摘BACKGROUND Serum retinol-binding protein(RBP)is the primary transport protein of circulating vitamin A.RBP has a crucial role in maintaining nutrient metabolism and physiologic homeostasis.Several studies have indicated that serum RBP participates in the progression of diabetes and diabetes-related complications.However,the impact of serum RBP on lower limb atherosclerosis has not been determined in individuals with type 2 diabetes mellitus(T2DM).AIM To determine the association between serum RBP and lower limb atherosclerosis in individuals with T2DM.METHODS This retrospective study enrolled 4428 eligible T2DM patients and divided the patients into non-lower limb atherosclerosis(n=1913)and lower limb atherosclerosis groups(n=2515)based on lower limb arterial ultrasonography results.At hospital admission,baseline serum RBP levels were assessed,and all subjects were categorized into three groups(Q1-Q3)based on RBP tertiles.Logistic regression,restricted cubic spline regression,subgroup analysis,and machine learning were used to assess the association between RBP levels and lower limb atherosclerosis risk.RESULTS Among 4428 individuals with T2DM,2515(56.80%)had lower limb atherosclerosis.Logistic analysis showed that lower limb atherosclerosis risk increased by 1%for every 1 unit rise in serum RBP level(odds ratio=1.01,95%confidence interval:1.00-1.02,P=0.004).Patients in the highest tertile group(Q3)had a higher lower limb atherosclerosis risk compared to the lowest tertile group(Q1)(odds ratio=1.36,95%confidence interval:1.12-1.67,P=0.002).The lower limb atherosclerosis risk gradually increased with an increase in RBP tertile(P for trend=0.005).Restricted cubic spline analysis indicated a linear correlation between serum RBP levels and lower limb atherosclerosis risk(non-linear P<0.05).Machine learning demonstrated the significance and diagnostic value of serum RBP in predicting lower limb atherosclerosis risk.CONCLUSION Elevated serum RBP levels correlate with an increased lower limb atherosclerosis risk in individuals with T2DM.
文摘BACKGROUND Although numerous single nucleotide polymorphism in multiple genes involve in the risk of type 2 diabetes mellitus(T2D),the single gene defects of T2D with strong family history is not clear yet.SPTLC1 are causative for hereditary sensory and autonomic neuropathy,which is clinical overlapping with diabetic peripheral neuropathy.Mice with adipocyte-specific deletion of SPTLC1 had impaired glucose tolerances and insulin sensitivity.Thus,it is necessary to investigate the SPTLC1 mutations in adult-onset T2D with strong family history.AIM To analyze the role of SPTLC1 mutation on adult-onset T2D with strong family history.METHODS By whole-exome sequence analysis of a patient with T2D and his family members,an uncertain variant in SPTLC1 was identified.Bioinformation analysis was used to evaluate the influence of mutation,rare variant gene-level associations for SPTLC1 in T2D,and the relationship between SPTLC1 mRNA and T2D in human islets from GSE25724.The effect of G371R of SPTLC1 on the characteristics of inflammatory cytokines and apoptosis was also tested on human embryonic kidney(HEK)293 cells.RESULTS A single nucleotide variation in SPTLC1(c.1111G>A:p.G371R)was identified in a family with T2D.The deleterious variant was predicted by functional analysis through hidden Markov models and mendelian clinically applicable pathogenicity software.This pathogenicity might be derived from the different amino acid properties.In HEK 293T cells,p.G371R of SPTLC1 induced the expression of tumor necrosis factor-αand the percent of apoptosis.Meanwhile,rare variant gene-level associations for SPTLC1 also refer to the high risk of T2D(the overall odds ratio=2.4968,P=0.0164).Data from GSE25724 showed that SPTLC1 mRNA was lower in pancreatic islets from T2D human islets(P=0.046),and was as sociated with the decreased level of insulin mRNA expression(Spearman r=0.615,P=0.025).CONCLUSION The study classified SPTLC1 p.G371R mutation as the likely pathogenic mutation from an adult-onset T2D patients with strong family history T2D.
基金Supported by the National Natural Science Foundation of China,No.82471804.
文摘BACKGROUND Progressive familial intrahepatic cholestasis type 1(PFIC-1)is a genetic cholestatic disease causing end-stage liver disease,which needs liver transplantation(LT).Simultaneous biliary diversion(BD)was recommended to prevent allograft steatosis after transplantation,while increasing the risk of infection.Here,an attempt was made to perform BD using appendix to prevent bacterial translocation after LT.CASE SUMMARY An 11-month-old boy diagnosed with PFIC-1 received ABO compatible living donor LT due to refractory jaundice and pruritus.His mother donated her left lateral segment with a graft-to-recipient weight ratio of 2.9%.Internal BD was constructed during LT using the appendix by connecting its proximal end with the intrahepatic biliary duct and the distal end with colon.Biliary leakage was suspected on the 5th day after transplantation and exploratory laparotomy indicated biliary leakage at the cutting surface of liver.The liver function returned to normal on the 9th day post-operation and maintained normal during the 15-month follow-up.Cholangiography at 10 months after transplantation confirmed the direct secretion of bile into colon.Computerized tomography scan(4 months and 10 months)and liver biopsy(10 months)indicated no steatosis in the allograft.No complaint of recurrent diarrhea,infection or growth retardation was reported during follow-up.CONCLUSION Internal BD using appendix during LT is effective in preventing allograft steatosis and post-transplant infection in PFIC-1 recipients.
文摘BACKGROUND The increasing number of type 2 diabetes mellitus(T2DM)patients leads to higher rates of morbidity and mortality related to lung cancer.AIM To investigate the utility of the proliferating cell nuclear antigen Ki-67 in patients with lung adenocarcinoma in situ(AIS)complicated by T2DM.METHODS One hundred patients with AIS and T2DM(group A),100 patients with AIS alone(group B),and 60 patients with benign lung lesions(group C)admitted to the Department of Thoracic Surgery and Endocrinology of the First Affiliated Hospital of Soochow University from November 2021 to December 2022 were enrolled.Ki-67 expression was compared among the groups.RESULTS Group A had significantly higher levels of fasting plasma glucose(FPG),total cholesterol(TC),total triglyceride,low-density lipoprotein cholesterol,glycosylated hemoglobin(HbA1c),and insulin than groups B and C(P<0.01).Meanwhile,group B had higher insulin levels than group C(P<0.01).Group A exhibited a significantly higher average Ki-67 positivity rate than group B(P<0.01).The Ki-67 positivity rate in group A was 86.87%,while the positivity rate in group B was 77%.Ki-67 was positively correlated with FPG(P<0.01)and HbA1c levels(P<0.01).Ki-67,FBG,insulin,HbA1c,high-density lipoprotein cholesterol and TC were independent factors for patients with AIS complicated by T2DM.Chen K et al.Ki67 in patients with AIS complicated by T2DM WJD https://www.wjgnet.com 2 February 15,2025 Volume 16 Issue 2 CONCLUSION Ki-67 expression was higher in patients with AIS complicated by T2DM than in patients with AIS alone.Therefore,detecting the Ki-67 level might assist in the diagnosis of AIS in patients with T2DM.
基金Industrial Technological Initiation Scholarship of National Council for Scientific and Technological Development,CNPq,No.0932204294929829CNPq Research Productivity Fellow,No.4357511882624145.
文摘This letter comments on a study by Jin et al,published recently in the World Journal of Diabetes.Hypoglycemia is a significant complication of diabetes,with primary defense mechanisms involving the stimulation of glucagon secretion inα-cells and the inhibition of insulin secretion in pancreaticβ-cells,which are often compromised in type 1 diabetes mellitus(T1DM)and advanced type 2 diabetes mellitus.Recurrent hypoglycemia predisposes the development of impaired hypoglycemia awareness,a condition underpinned by complex pathophysiological processes,encompassing central nervous system adaptations and several hormonal interactions,including a potential role for glucagon-like peptide-1(GLP-1)in paracrine and endocrine vias.Experimental evidence indicates that GLP-1 may impair hypoglycemic counterregulation by disrupting the sympathoadrenal system and promoting somatostatin release in pancreaticδ-cells,which inhibits glucagon secretion from neighboringα-cells.However,current trials evaluating GLP-1 receptor agonists(GLP-1 RAs)in T1DM patients have shown promising benefits in reducing insulin requirements and body weight,without increasing the risk of hypoglycemia.Further research is essential to elucidate the specific roles of GLP-1 and GLP-1 RAs in modulating glucagon secretion and the sympathetic-adrenal reflex,and their impact on hypoglycemia unawareness in T1DM patients.
文摘Recent advances in understanding type 1 diabetes(T1D)highlight the complexity of managing hypoglycemia,a frequent and perilous complication of diabetes therapy.This letter delves into a novel study by Jin et al,which elucidates the role of intestinal glucagon-like peptide-1(GLP-1)in the counterregulatory response to hypoglycemia in T1D models.The study employed immunofluorescence,Western blotting,and enzyme-linked immunosorbent assay to track changes in GLP-1 and its receptor expression in diabetic mice subjected to recurrent hypoglycemic episodes.Findings indicate a significant increase in intestinal GLP-1 and GLP-1 receptor expression,correlating with diminished adrenal and glucagon responses,crucial for glucose stabilization during hypoglycemic events.This letter aims to explore the implications of these findings for future therapeutic strategies and the broader understanding of T1D management.
基金National Natural Science Foundation of China,No.82270881 and No.82200928National High-Level Hospital Clinical Research Funding,No.BJ-2023-124 and No.BJ-2023-130.
文摘BACKGROUND Diabetic peripheral neuropathy(DPN)is a common complication of type 2 diabetes mellitus(T2DM),significantly affecting patients’quality of life and imposing a substantial economic burden.Recent studies have highlighted the role of thyroid hormones in diabetes complications,particularly in elderly patients with T2DM.However,the relationship between thyroid hormone sensitivity and DPN remains unclear.AIM To investigate the correlation between thyroid hormone sensitivity and DPN in elderly patients with T2DM.METHODS In a cohort of 256 elderly patients with T2DM,propensity score matching was used to balance age,sex,and diabetes duration.Clinical data were collected to calculate thyroid hormone sensitivity and analyze its correlation with DPN.A random forest model was used to evaluate the diagnostic value of free triiodothyronine/free thyroxine(FT_(3)/FT_(4))for DPN.RESULTS Patients with DPN had a lower FT_(3)/FT_(4) ratio[(0.302±0.053)vs(0.316±0.049),P=0.040].Quartile stratification showed decreasing DPN prevalence with higher FT_(3)/FT_(4) ratios.Spearman’s correlation analysis showed that a lower FT_(3)/FT_(4) ratio was associated with higher glycated hemoglobin,fasting blood glucose,reduced nerve conduction velocity,and electrical skin conductance.Logistic regression indicated a positive relationship between the median FT_(3)/FT_(4) ratio and bilateral foot electrochemical skin conductance[odds ratio(OR):1.019;95%CI:1.005-1.034;P=0.007]and sural nerve sensory amplitude(OR:1.310;95%CI:1.008-1.703;P=0.043).Receiver operating characteristic analysis using a random forest model showed that incorporating FT_(3)/FT_(4) improved predictive performance for DPN,with an area under the curve of 0.74,sensitivity of 0.79,specificity of 0.64,and accuracy of 0.77.CONCLUSION In elderly patients with T2DM with euthyroidism,a lower FT_(3)/FT_(4) ratio is correlated with increased DPN incidence,affecting both large and small nerve fibers.FT_(3)/FT_(4) is an effective predictor of DPN.
基金Yuansong Wang National Famous Traditional Chinese Medicine Expert Heritage Studio,No.4(2022).
文摘BACKGROUND Plantamajoside(PMS)has shown potential in mitigating cell damage caused by high glucose(HG)levels.Despite this,the precise therapeutic effects of PMS on type 2 diabetes mellitus(T2DM)and the underlying regulatory mechanisms require further exploration.AIM To investigate PMS therapeutic effects on T2DM in mice and elucidate its mechanisms of action through in vivo and in vitro experiments.METHODS An in vitro damage model of MIN6 cells was established using HG and palmitic acid(PA).PMS's protective effect on cell damage was assessed.Next,transcriptomics was employed to examine how PMS treatment affects gene expression of MIN6 cells.Furthermore,the effect of PMS on protein processing in endoplasmic reticulum and apoptosis pathways was validated.A T2DM mouse model was used to validate the therapeutic effects and mechanisms of PMS in vivo.RESULTS PMS intervention ameliorated cell injury in HG+PA-induced MIN6 cell damage.Transcriptomic analysis revealed that protein processing in the endoplasmic reticulum and apoptosis pathways were enriched in cells treated with PMS,with significant downregulation of the gene Dnajc1.Further validation indicated that PMS significantly inhibited the expression of apoptosis-related factors(Bax,CytC)and endoplasmic reticulum stress(ERS)-related factors[ATF6,XBP1,Ddit3(CHOP),GRP78],while promoting the expression of Bcl-2 and Dnajc1.Additionally,the inhibitory effects of PMS on ERS and apoptosis were abolished upon Dnajc1 silencing.Furthermore,in vivo experiments demonstrated that PMS intervention effectively improved pancreatic damage,suppressed the expression of apoptosis-related factors(Bax,CytC),and ERS-related factors[ATF6,XBP1,Ddit3(CHOP),GRP78],while promoting the expression of Bcl-2 and Dnajc1 in a T2DM model mice.CONCLUSION PMS intervention could alleviate pancreatic tissue damage effectively.The mechanism of action involves Dnajc1 activation,which subsequently inhibits apoptosis and ERS,ameliorating damage to pancreaticβ-cells.
文摘This letter discusses the recent study by Mukherjee et al,which identifies a significant prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)among newly diagnosed type 2 diabetes mellitus(T2DM)patients in Bihar,India,and underscores the pressing need for integrated MASLD mana-gement within T2DM care.With 72.3%of the study cohort affected by MASLD,implementing routine liver function tests and ultrasound screenings is recom-mended as a standard practice in diabetes care,especially in regions with high prevalence rates.The study also advocates for dietary and lifestyle modifications,particularly the reduction of saturated fats,to slow MASLD progression.Patient education on monitoring body mass index and waist circumference,coupled with the integration of these metrics into digital health records,could enhance patient involvement and support proactive health management.Moreover,the letter emphasizes the advantages of developing a region-specific MASLD risk model that incorporates local dietary patterns and socioeconomic factors.Continued research into genetic and environmental determinants of MASLD remains es-sential for advancing our understanding of its etiology and informing targeted public health strategies.