Background:To determine whether initiating a glucagon-like peptide-1 receptor agonist(GLP-1 RA)within 3 months of type 2 diabetes(T2DM)diagnosis alters the subsequent risk of overall and site-specific cancer and wheth...Background:To determine whether initiating a glucagon-like peptide-1 receptor agonist(GLP-1 RA)within 3 months of type 2 diabetes(T2DM)diagnosis alters the subsequent risk of overall and site-specific cancer and whether this association differs by baseline body-mass index(BMI).Methods:This retrospective cohort study used electronic health records from the TriNetX U.S.research network.Adults aged 20 years or older diagnosed with T2DM between 2016 and 2024 were included if they received any hypoglycemic agents within 3 months before and after diagnosis.Following 1:1 propensity score matching,both the GLP-1 RA user and non-user groups included 183,264 patients.The study outcome was defined as a diagnosis of malignant neoplasms.Hazard ratios(HRs)for overall and site-specific cancer risk were estimated using Cox proportional hazards models.Kaplan–Meier analysis and stratified analysis by BMI were performed.Results:Early GLP-1 RA use demonstrated a modest but significant association with reduced overall cancer risk(HR 0.93;95%CI:0.90–0.96).Reduced risks were noted for cancers of the digestive(HR 0.81),respiratory(HR 0.66),and female genital(HR 0.87)systems.In stratified analysis,benefits were more pronounced in patients with BMI≥30,particularly for pancreatic and colorectal cancers.Conclusion:Early initiation of GLP-1 receptor agonists in patients with diagnosed T2DM was associated with a modest reduction in overall cancer risk,particularly among individuals with obesity.These findings highlight the dual metabolic and oncologic value of prompt GLP-1 RA therapy.展开更多
AIM:To investigate the sex-specific correlation between systemic factors and retinal neurovascular alterations in individuals with type 1 diabetes mellitus(T1DM)who do not exhibit signs of diabetic retinopathy(DR).MET...AIM:To investigate the sex-specific correlation between systemic factors and retinal neurovascular alterations in individuals with type 1 diabetes mellitus(T1DM)who do not exhibit signs of diabetic retinopathy(DR).METHODS:A cohort participant without DR diagnosed with T1DM,underwent comprehensive ophthalmologic evaluation,optical coherence tomography angiography retinal structural and microvascular density analysis,and systemic parameter assessment.Multiple linear regression analysis was used to investigate the impact of systemic parameters on retinal alterations in distinct gender groups.RESULTS:A total of 182 individuals were included,consisting of 85 males(mean age 23.28±12.75y)and 97 females(mean age 22.98±13.68y).Males exhibited significantly greater thickness in both the internal retinal layer and the entire retina compared to females(P<0.01),whereas females had higher densities of deep retinal vessels and choroidal capillaries(P<0.05).Additionally,glycemic control was found to have a notable influence on retinal thickness in males(P<0.05),while insulin function had a more pronounced impact on retinal structure in females(P<0.01).Furthermore,a significant correlation was observed between thyroid function markers and retinal parameters in both male and female(P<0.05).CONCLUSION:Sex differences in alterations in retinal structure and microcirculation are observed in individuals with T1DM prior to the development of clinical DR,with a noted association between these changes and systemic parameters.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
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 Diabetes has become a widespread metabolic disease affecting multiple organs.Among diabetic complications,cardiovascular complications are the main cause of patient morbidity and mortality.Diabetic cardiomy...BACKGROUND Diabetes has become a widespread metabolic disease affecting multiple organs.Among diabetic complications,cardiovascular complications are the main cause of patient morbidity and mortality.Diabetic cardiomyopathy is a diabetes-specific cardiomyopathy in the absence of other cardiovascular disease and occurs more frequently in type 1 diabetes(T1D)than in type 2 diabetes.Previous studies on diabetic cardiomyopathy have predominantly focused on the effects of diabetes on left ventricular(LV)dysfunction,while studies of right ventricular(RV)dysfunction have been sparse but are gaining attention.Although T1D accounts for only 5%-10%of the total diabetic population,diabetic cardiomyopathy is a major cause of morbidity and mortality in children with life-long,long-term complications.AIM To evaluate longitudinal RV and LV functional changes in female transgenic OVE26,T1D mice and wild-type FVB mice over a 30-week period.METHODS RV and LV structure and function were evaluated by transthoracic echocardiography.RV systolic pressure was measured by a transducer-tipped pressure catheter.Sirius-red staining was used to quantify collagen and fibrosis,wheat germ agglutinin staining was utilized to measure cardiomyocyte size,and quantitative real-time polymerase chain reaction and Western blotting were used to quantify miRNA expression and protein abundance,respectively.RESULTS RV systolic function,measured by tricuspid valve annular plane systolic excursion and RV systolic velocity,was similar between control and T1D mice,but LV systolic function decreased in T1D mice at 30 weeks of age.RV diastolic dysfunction in T1D mice significantly increased by 18 weeks and progressed until 30 weeks,while LV diastolic dysfunction trended towards abnormal at 12 weeks,significantly increased by 18 weeks,and continued to progress by 30 weeks.Furthermore,RV diastolic dysfunction was accompanied by RV cardiac fibrosis and hypertrophy in T1D mice,occurring later than that in the LV.Pulmonary arterial hypertension developed in T1D mice,evidenced by increased pulmonary acceleration time to pulmonary ejection time ratio and increased RV peak systolic pressure at 30 weeks.These results suggest the development of early LV diastolic dysfunction followed by LV systolic dysfunction and RV diastolic dysfunction at 30 weeks in T1D mice.CONCLUSION RV diastolic dysfunction develops later than LV dysfunction in OVE26 T1D mice.Mild pulmonary arterial hypertension appear at later stages of T1D and could contribute to RV systolic impairment and remodeling.展开更多
BACKGROUND Glycated hemoglobin(HbA1c),the gold standard for assessing glycemic control,has limited ability to reflect the risks of hypoglycemia and glycemic variability,raising great concerns,especially in patients wi...BACKGROUND Glycated hemoglobin(HbA1c),the gold standard for assessing glycemic control,has limited ability to reflect the risks of hypoglycemia and glycemic variability,raising great concerns,especially in patients with type 1 diabetes(T1D).The glycemia risk index(GRI),a composite metric derived from continuous glucose monitoring(CGM),has emerged as a potential solution by systematically in-tegrating both hypoglycemia and hyperglycemia risks into a single interpretable score.The GRI exhibited linear correlations with HbA1c(r=0.53),time in range(r=-0.90),time above range(r=0.63),time below range(TBR)(r=0.37),and co-efficient of variation(CV)(r=0.71).It correlated strongly with TBR and CV than HbA1c.The association between HbA1c levels and GRI was influenced by TBR and CV.At a given HbA1c,each 1%increase in TBR or CV raised GRI by 1.87[95%confidence interval(CI):1.72-2.01]and 1.94(95%CI:1.80-2.10),respectively(P<0.001).Clustering of the CGM data identified four subgroups:Moderate-risk glycemic fluctuations,high-risk hypoglycemia,optimal glycemic control,and high-risk hyperglycemia.The GRI and its components for hypoglycemia and hyperglycemia could distinguish between these subgroups.CONCLUSION The GRI offers a comprehensive view of glycemic control in T1D.Combining HbA1c with the GRI enables accurate assessment for managing glycemic control in patients with T1D.展开更多
ACKGROUND The hemoglobin glycation index(HGI)represents the discrepancy between the glucose management indicator(GMI)based on mean blood glucose levels and laboratory values of glycated hemoglobin(HbA1c).The HGI is a ...ACKGROUND The hemoglobin glycation index(HGI)represents the discrepancy between the glucose management indicator(GMI)based on mean blood glucose levels and laboratory values of glycated hemoglobin(HbA1c).The HGI is a promising indicator for identifying individuals with excessive glycosylation,facilitating personalized evaluation and prediction of diabetic complications.However,the factors influencing the HGI in patients with type 1 diabetes(T1D)remain unclear.Autoimmune destruction of pancreaticβcells is central in T1D pathogenesis,yet insulin resistance can also be a feature of patients with T1D and their coexistence is called“double diabetes”(DD).However,knowledge regarding the relationship between DD features and the HGI in T1D is limited.AIM To assess the association between the HGI and DD features in adults with T1D.METHODS A total of 83 patients with T1D were recruited for this cross-sectional study.Laboratory HbA1c and GMI from continuous glucose monitoring data were collected to calculate the HGI.DD features included a family history of type 2 diabetes,overweight/obesity/central adiposity,hypertension,atherogenic dyslipidemia,an abnormal percentage of body fat(PBF)and/or visceral fat area(VFA)and decreased estimated insulin sensitivity.Skin autofluorescence of advanced glycation end products(SAF-AGEs),diabetic complications,and DD features were assessed,and their association with the HGI was analyzed.RESULTS A discrepancy was observed between HbA1c and GMI among patients with T1D and DD.A higher HGI was associated with an increased number of SAF-AGEs and a higher prevalence of diabetic microangiopathy(P=0.030),particularly retinopathy(P=0.031).Patients with three or more DD features exhibited an eight-fold increased risk of having a high HGI,compared with those without DD features(adjusted odds ratio=8.12;95%confidence interval:1.52-43.47).Specifically,an elevated PBF and/or VFA and decreased estimated insulin sensitivity were associated with high HGI.Regression analysis identified estimated insulin sensitivity and VFA as factors independently associated with HGI.CONCLUSION In patients with T1D,DD features are associated with a higher HGI,which represents a trend toward excessive glycosylation and is associated with a higher prevalence of chronic diabetic complications.展开更多
In this article,we review the study by Jin et al,which examined the role of intestinal glucagon-like peptide-1(GLP-1)in counterregulatory responses to hypoglycemia in patients with type 1 diabetes mellitus(T1DM).With ...In this article,we review the study by Jin et al,which examined the role of intestinal glucagon-like peptide-1(GLP-1)in counterregulatory responses to hypoglycemia in patients with type 1 diabetes mellitus(T1DM).With the global rise of T1DM,there is an increased burden on society and healthcare systems.Due to insulin therapy and islet dysfunction,T1DM patients are highly vulnerable to severe hypoglycemia,a leading cause of mortality.In healthy individuals,counterregulatory mechanisms restore blood glucose during hypoglycemia,but repeated episodes impair these responses.Jin et al demonstrated that overexpression of GLP-1 attenuates the sympathetic-adrenal reflex and disrupts the secretion of counterregulatory hormones such as glucagon during hypoglycemia,leading to counterregulatory dysfunction.These findings highlight the critical role of GLP-1 in the impaired counterregulatory response to hypoglycemia in T1DM patients and provide new insights into the potential application of GLP-1-related therapies in T1DM patients.展开更多
Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,im...Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,immunologic vaccination and anti-inflammatory agents targeting specific immune cells or cytokines.Teplizumab is an anti-CD3-molecule that binds to and leads to the disappearance of the CD3/TCR complex and rendering the T cell anergic to its target antigen.Preclinical and clinical trials have demonstrated its efficacy in reducing the decline in serum C-peptide levels and the need for insulin therapy if used early in the disease process of T1DM.The benefits have been apparent as early as six months to as long as seven years after therapy.It has recently been approved by the Food and Drug Administration to delay the onset of clinical(stage 3)type 1 diabetes in children above 8 years of age.In their recent metaanalysis published in the World Journal of Diabetes,Ma et al found that those in the teplizumab treatment group have a greater likelihood of reduction in insulin use,change in C-peptide response,and better glycemic control compared to the control group with a good safety profile.However,all the included randomized control trials have been conducted in high-income countries.High cost of therapy and unknown utility of the molecule in stage 3 disease limit its widespread use.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
基金financial support fromthe Chung Shan Medical University Hospital,Taiwan(CSH-2022-A-009).
文摘Background:To determine whether initiating a glucagon-like peptide-1 receptor agonist(GLP-1 RA)within 3 months of type 2 diabetes(T2DM)diagnosis alters the subsequent risk of overall and site-specific cancer and whether this association differs by baseline body-mass index(BMI).Methods:This retrospective cohort study used electronic health records from the TriNetX U.S.research network.Adults aged 20 years or older diagnosed with T2DM between 2016 and 2024 were included if they received any hypoglycemic agents within 3 months before and after diagnosis.Following 1:1 propensity score matching,both the GLP-1 RA user and non-user groups included 183,264 patients.The study outcome was defined as a diagnosis of malignant neoplasms.Hazard ratios(HRs)for overall and site-specific cancer risk were estimated using Cox proportional hazards models.Kaplan–Meier analysis and stratified analysis by BMI were performed.Results:Early GLP-1 RA use demonstrated a modest but significant association with reduced overall cancer risk(HR 0.93;95%CI:0.90–0.96).Reduced risks were noted for cancers of the digestive(HR 0.81),respiratory(HR 0.66),and female genital(HR 0.87)systems.In stratified analysis,benefits were more pronounced in patients with BMI≥30,particularly for pancreatic and colorectal cancers.Conclusion:Early initiation of GLP-1 receptor agonists in patients with diagnosed T2DM was associated with a modest reduction in overall cancer risk,particularly among individuals with obesity.These findings highlight the dual metabolic and oncologic value of prompt GLP-1 RA therapy.
基金Supported by Natural Science Foundation of Hunan Province(No.2023JJ70017No.2025JJ50627)Peak Climbing Project of Optometry Hospital Affiliated to Wenzhou Medical University。
文摘AIM:To investigate the sex-specific correlation between systemic factors and retinal neurovascular alterations in individuals with type 1 diabetes mellitus(T1DM)who do not exhibit signs of diabetic retinopathy(DR).METHODS:A cohort participant without DR diagnosed with T1DM,underwent comprehensive ophthalmologic evaluation,optical coherence tomography angiography retinal structural and microvascular density analysis,and systemic parameter assessment.Multiple linear regression analysis was used to investigate the impact of systemic parameters on retinal alterations in distinct gender groups.RESULTS:A total of 182 individuals were included,consisting of 85 males(mean age 23.28±12.75y)and 97 females(mean age 22.98±13.68y).Males exhibited significantly greater thickness in both the internal retinal layer and the entire retina compared to females(P<0.01),whereas females had higher densities of deep retinal vessels and choroidal capillaries(P<0.05).Additionally,glycemic control was found to have a notable influence on retinal thickness in males(P<0.05),while insulin function had a more pronounced impact on retinal structure in females(P<0.01).Furthermore,a significant correlation was observed between thyroid function markers and retinal parameters in both male and female(P<0.05).CONCLUSION:Sex differences in alterations in retinal structure and microcirculation are observed in individuals with T1DM prior to the development of clinical DR,with a noted association between these changes and systemic parameters.
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 University of Louisville-China Pediatric Research Exchange Program(Cai L,Tan Y,Huang J,and Keller B,no salary support)University of Louisville Executive Vice President for Research and Innovation Internal Grant(Huang J and Cai L)University of Louisville School of Medicine Basic Grant(Huang J and Cai L).
文摘BACKGROUND Diabetes has become a widespread metabolic disease affecting multiple organs.Among diabetic complications,cardiovascular complications are the main cause of patient morbidity and mortality.Diabetic cardiomyopathy is a diabetes-specific cardiomyopathy in the absence of other cardiovascular disease and occurs more frequently in type 1 diabetes(T1D)than in type 2 diabetes.Previous studies on diabetic cardiomyopathy have predominantly focused on the effects of diabetes on left ventricular(LV)dysfunction,while studies of right ventricular(RV)dysfunction have been sparse but are gaining attention.Although T1D accounts for only 5%-10%of the total diabetic population,diabetic cardiomyopathy is a major cause of morbidity and mortality in children with life-long,long-term complications.AIM To evaluate longitudinal RV and LV functional changes in female transgenic OVE26,T1D mice and wild-type FVB mice over a 30-week period.METHODS RV and LV structure and function were evaluated by transthoracic echocardiography.RV systolic pressure was measured by a transducer-tipped pressure catheter.Sirius-red staining was used to quantify collagen and fibrosis,wheat germ agglutinin staining was utilized to measure cardiomyocyte size,and quantitative real-time polymerase chain reaction and Western blotting were used to quantify miRNA expression and protein abundance,respectively.RESULTS RV systolic function,measured by tricuspid valve annular plane systolic excursion and RV systolic velocity,was similar between control and T1D mice,but LV systolic function decreased in T1D mice at 30 weeks of age.RV diastolic dysfunction in T1D mice significantly increased by 18 weeks and progressed until 30 weeks,while LV diastolic dysfunction trended towards abnormal at 12 weeks,significantly increased by 18 weeks,and continued to progress by 30 weeks.Furthermore,RV diastolic dysfunction was accompanied by RV cardiac fibrosis and hypertrophy in T1D mice,occurring later than that in the LV.Pulmonary arterial hypertension developed in T1D mice,evidenced by increased pulmonary acceleration time to pulmonary ejection time ratio and increased RV peak systolic pressure at 30 weeks.These results suggest the development of early LV diastolic dysfunction followed by LV systolic dysfunction and RV diastolic dysfunction at 30 weeks in T1D mice.CONCLUSION RV diastolic dysfunction develops later than LV dysfunction in OVE26 T1D mice.Mild pulmonary arterial hypertension appear at later stages of T1D and could contribute to RV systolic impairment and remodeling.
基金Supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project,No.2023ZD0508201the National Key R and D Program of China,No.2022YFC2010100+3 种基金the National Natural Science Foundation of China,No.82070812the Natural Science Foundation of Hunan Province,No.2024JJ9049,No.2023JJ30762 and No.2021JC0003Sinocare Diabetes Foundation,No.2020SD08the National Clinical Research Center for Metabolic Diseases Clinical Diagnosis and Treatment Capacity Enhancement Program,No.2023ZLNL003.
文摘BACKGROUND Glycated hemoglobin(HbA1c),the gold standard for assessing glycemic control,has limited ability to reflect the risks of hypoglycemia and glycemic variability,raising great concerns,especially in patients with type 1 diabetes(T1D).The glycemia risk index(GRI),a composite metric derived from continuous glucose monitoring(CGM),has emerged as a potential solution by systematically in-tegrating both hypoglycemia and hyperglycemia risks into a single interpretable score.The GRI exhibited linear correlations with HbA1c(r=0.53),time in range(r=-0.90),time above range(r=0.63),time below range(TBR)(r=0.37),and co-efficient of variation(CV)(r=0.71).It correlated strongly with TBR and CV than HbA1c.The association between HbA1c levels and GRI was influenced by TBR and CV.At a given HbA1c,each 1%increase in TBR or CV raised GRI by 1.87[95%confidence interval(CI):1.72-2.01]and 1.94(95%CI:1.80-2.10),respectively(P<0.001).Clustering of the CGM data identified four subgroups:Moderate-risk glycemic fluctuations,high-risk hypoglycemia,optimal glycemic control,and high-risk hyperglycemia.The GRI and its components for hypoglycemia and hyperglycemia could distinguish between these subgroups.CONCLUSION The GRI offers a comprehensive view of glycemic control in T1D.Combining HbA1c with the GRI enables accurate assessment for managing glycemic control in patients with T1D.
基金Supported by the National Key R D Program of China,No.2022YFC2010102Natural Science Foundation of Hunan Province,No.2021JC0003+1 种基金National Natural Science Foundation of China,No.82070812the Sinocare Diabetes Foundation,No.LYF2022039.
文摘ACKGROUND The hemoglobin glycation index(HGI)represents the discrepancy between the glucose management indicator(GMI)based on mean blood glucose levels and laboratory values of glycated hemoglobin(HbA1c).The HGI is a promising indicator for identifying individuals with excessive glycosylation,facilitating personalized evaluation and prediction of diabetic complications.However,the factors influencing the HGI in patients with type 1 diabetes(T1D)remain unclear.Autoimmune destruction of pancreaticβcells is central in T1D pathogenesis,yet insulin resistance can also be a feature of patients with T1D and their coexistence is called“double diabetes”(DD).However,knowledge regarding the relationship between DD features and the HGI in T1D is limited.AIM To assess the association between the HGI and DD features in adults with T1D.METHODS A total of 83 patients with T1D were recruited for this cross-sectional study.Laboratory HbA1c and GMI from continuous glucose monitoring data were collected to calculate the HGI.DD features included a family history of type 2 diabetes,overweight/obesity/central adiposity,hypertension,atherogenic dyslipidemia,an abnormal percentage of body fat(PBF)and/or visceral fat area(VFA)and decreased estimated insulin sensitivity.Skin autofluorescence of advanced glycation end products(SAF-AGEs),diabetic complications,and DD features were assessed,and their association with the HGI was analyzed.RESULTS A discrepancy was observed between HbA1c and GMI among patients with T1D and DD.A higher HGI was associated with an increased number of SAF-AGEs and a higher prevalence of diabetic microangiopathy(P=0.030),particularly retinopathy(P=0.031).Patients with three or more DD features exhibited an eight-fold increased risk of having a high HGI,compared with those without DD features(adjusted odds ratio=8.12;95%confidence interval:1.52-43.47).Specifically,an elevated PBF and/or VFA and decreased estimated insulin sensitivity were associated with high HGI.Regression analysis identified estimated insulin sensitivity and VFA as factors independently associated with HGI.CONCLUSION In patients with T1D,DD features are associated with a higher HGI,which represents a trend toward excessive glycosylation and is associated with a higher prevalence of chronic diabetic complications.
基金Supported by the National Natural Science Foundation of China,No.82400966Guangdong Basic and Applied Basic Research Foundation,No.2021A1515111025Science and Technology Projects in Guangzhou,No.2024A04J5170.
文摘In this article,we review the study by Jin et al,which examined the role of intestinal glucagon-like peptide-1(GLP-1)in counterregulatory responses to hypoglycemia in patients with type 1 diabetes mellitus(T1DM).With the global rise of T1DM,there is an increased burden on society and healthcare systems.Due to insulin therapy and islet dysfunction,T1DM patients are highly vulnerable to severe hypoglycemia,a leading cause of mortality.In healthy individuals,counterregulatory mechanisms restore blood glucose during hypoglycemia,but repeated episodes impair these responses.Jin et al demonstrated that overexpression of GLP-1 attenuates the sympathetic-adrenal reflex and disrupts the secretion of counterregulatory hormones such as glucagon during hypoglycemia,leading to counterregulatory dysfunction.These findings highlight the critical role of GLP-1 in the impaired counterregulatory response to hypoglycemia in T1DM patients and provide new insights into the potential application of GLP-1-related therapies in T1DM patients.
文摘Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,immunologic vaccination and anti-inflammatory agents targeting specific immune cells or cytokines.Teplizumab is an anti-CD3-molecule that binds to and leads to the disappearance of the CD3/TCR complex and rendering the T cell anergic to its target antigen.Preclinical and clinical trials have demonstrated its efficacy in reducing the decline in serum C-peptide levels and the need for insulin therapy if used early in the disease process of T1DM.The benefits have been apparent as early as six months to as long as seven years after therapy.It has recently been approved by the Food and Drug Administration to delay the onset of clinical(stage 3)type 1 diabetes in children above 8 years of age.In their recent metaanalysis published in the World Journal of Diabetes,Ma et al found that those in the teplizumab treatment group have a greater likelihood of reduction in insulin use,change in C-peptide response,and better glycemic control compared to the control group with a good safety profile.However,all the included randomized control trials have been conducted in high-income countries.High cost of therapy and unknown utility of the molecule in stage 3 disease limit its widespread use.
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.
