Gestational diabetes mellitus(GDM)is defined as any degree of hyperglycaemia that is recognized for the first time during pregnancy.This definition includes cases of undiagnosed type 2 diabetes mellitus(T2 DM)identifi...Gestational diabetes mellitus(GDM)is defined as any degree of hyperglycaemia that is recognized for the first time during pregnancy.This definition includes cases of undiagnosed type 2 diabetes mellitus(T2 DM)identified early in pregnancy and true GDM which develops later.GDM constitutes a greater impact on diabetes epidemic as it carries a major risk of developing T2 DM to the mother and foetus later in life.In addition,GDM has also been linked with cardiometabolic risk factors such as lipid abnormalities,hypertensive disorders and hyperinsulinemia.These might result in later development of cardiovascular disease and metabolic syndrome.The understanding of the different risk factors,the pathophysiological mechanisms and the genetic factors of GDM,will help us to identify the women at risk,to develop effective preventive measures and to provide adequate management of the disease.Clinical trials have shown that T2 DM can be prevented in women with prior GDM,by intensive lifestyle modification and by using pioglitazone and metformin.However,a matter of controversy surrounding both screening and management of GDM continues to emerge,despite several recent welldesigned clinical trials tackling these issues.The aim of this manuscript is to critically review GDM in a detailed and comprehensive manner,in order to provide a scientific analysis and updated write-up of different related aspects.展开更多
In 2021,approximately 537 million people suffered from diabetes mellitus(DM)globally,and this figure will increase to approximately 783 million within the next quarter-century.The increasing burden of DM is a pressing...In 2021,approximately 537 million people suffered from diabetes mellitus(DM)globally,and this figure will increase to approximately 783 million within the next quarter-century.The increasing burden of DM is a pressing global public health issue.Therefore,the early identification of high-risk groups and implementation of effective intervention measures is imperative.展开更多
Monogenic diabetes is a heterogeneous disorder characterized by hyperglycemia arising from defects in a single gene.Maturity-onset diabetes of the young(MODY)is the most common type with 14 subtypes,each linked to spe...Monogenic diabetes is a heterogeneous disorder characterized by hyperglycemia arising from defects in a single gene.Maturity-onset diabetes of the young(MODY)is the most common type with 14 subtypes,each linked to specific mutations affecting insulin synthesis,secretion and glucose regulation.Common traits across MODY subtypes include early-onset diabetes,a family history of autosomal dominant diabetes,lack of features of insulin resistance,and absent islet cell autoimmunity.Many cases are misdiagnosed as type 1 and type 2 diabetes mellitus.Biomarkers and scoring systems can help identify candidates for genetic testing.GCK-MODY,a common subtype,manifests as mild hyperglycemia and doesn’t require treatment except during pregnancy.In contrast,mutations in HNF4A,HNF1A,and HNF1B genes lead to progressive beta-cell failure and similar risks of complications as type 2 diabetes mellitus.Neonatal diabetes mellitus(NDM)is a rare form of monogenic diabetes that usually presents within the first six months.Half of the cases are lifelong,while others experience transient remission.Permanent NDM is most commonly due to activating mutations in genes encoding the adenosine triphosphate-sensitive potassium channel(KCNJ11 or ABCC8)and can be transitioned to sulfonylurea after confirmation of diagnosis.Thus,in many cases,monogenic diabetes offers an opportunity to provide precision treatment.The scope has broadened with next-generation sequencing(NGS)technologies,replacing older methods like Sanger sequencing.NGS can be for targeted gene panels,whole-exome sequencing(WES),or whole-genome sequencing.Targeted gene panels offer specific information efficiently,while WES provides comprehensive data but comes with bioinformatic challenges.The surge in testing has also led to an increase in variants of unknown significance(VUS).Deciding whether VUS is disease-causing or benign can be challenging.Computational models,functional studies,and clinical knowledge help to determine pathogenicity.Advances in genetic testing technologies offer hope for improved diagnosis and personalized treatment but also raise concerns about interpretation and ethics.展开更多
Type 1 diabetes(T1D)is an autoimmune disease that usually strikes early in life,but can affect individuals at almost any age.It is caused by autoreactive T cells that destroy insulin-producing beta cells in the pancre...Type 1 diabetes(T1D)is an autoimmune disease that usually strikes early in life,but can affect individuals at almost any age.It is caused by autoreactive T cells that destroy insulin-producing beta cells in the pancreas.Epidemiological studies estimate a prevalence of 1 in 300 children in the United States with an increasing incidence of 2%-5%annually worldwide.The daily responsibility,clinical management,and vigilance required to maintain blood sugar levels within normal range and avoid acute complications(hypoglycemic episodes and diabetic ketoacidosis)and long term micro-and macro-vascular complications significantly affects quality of life and public health care costs.Given the expansive impact of T1D,research work has accelerated and T1D has been intensively investigated with the focus to better understand,manage and cure this condition.Many advances have been made in the past decades in this regard,but key questions remain as to why certain people develop T1D,but not others,with the glaring example of discordant disease incidence among monozygotic twins.In this review,we discuss the field’s current understanding of its pathophysiology and the role of genetics and environment on the development of T1D.We examine the potential implications of these findings with an emphasis on T1D inheritance patterns,twin studies,and disease prevention.Through a better understanding of this process,interventions can be developed to prevent or halt it at early stages.展开更多
Rheumatoid arthritis(RA)is a chronic systemic autoimmune disease that extends beyond joint inflammation,affecting pulmonary and metabolic pathways.Interstitial lung disease(ILD)is one of its most serious extra-articul...Rheumatoid arthritis(RA)is a chronic systemic autoimmune disease that extends beyond joint inflammation,affecting pulmonary and metabolic pathways.Interstitial lung disease(ILD)is one of its most serious extra-articular complications,while type 2 diabetes mellitus(T2DM)frequently coexists with RA and may exacerbate inflammatory and fibrotic processes.This editorial discusses the study by Sutton et al,the largest population-based analysis to date exploring the link between T2DM and ILD in patients with RA,and reflects on its mechanistic and clinical implications.In a nationwide cohort of more than 120000 hospitalized RA patients,Sutton et al demonstrated that the coexistence of T2DM nearly doubles the odds of developing ILD(odds ratio=2.02;95%confidence interval:1.84-2.22),with additional increases in pulmonary hypertension,pneumothorax,and length of stay.These findings reinforce the concept of a metabolic-pulmonary-autoimmune axis,in which chronic inflammation promotes insulin resistance and metabolic dysfunction,while hyperglycaemia and advanced glycation end-products amplify oxidative stress and fibrogenesis.This reciprocal interaction may induce a self-perpetuating cycle of“metaflammation”,fibrosis,and organ damage.Conclusion:Recognizing diabetes as a silent amplifier of RA-associated ILD redefines the interface between rheumatology,pulmonology,and endocrinology.Early detection and integrated management of metabolic and pulmonary comorbidities should be prioritized,while future studies must determine whether optimizing glycemic control can attenuate pulmonary fibrosis and improve longterm outcomes.展开更多
Diabetes mellitus represents a major global health issue,driving the need for noninvasive alternatives to traditional blood glucose monitoring methods.Recent advancements in wearable technology have introduced skin-in...Diabetes mellitus represents a major global health issue,driving the need for noninvasive alternatives to traditional blood glucose monitoring methods.Recent advancements in wearable technology have introduced skin-interfaced biosensors capable of analyzing sweat and skin biomarkers,providing innovative solutions for diabetes diagnosis and monitoring.This review comprehensively discusses the current developments in noninvasive wearable biosensors,emphasizing simultaneous detection of biochemical biomarkers(such as glucose,cortisol,lactate,branched-chain amino acids,and cytokines)and physiological signals(including heart rate,blood pressure,and sweat rate)for accurate,personalized diabetes management.We explore innovations in multimodal sensor design,materials science,biorecognition elements,and integration techniques,highlighting the importance of advanced data analytics,artificial intelligence-driven predictive algorithms,and closed-loop therapeutic systems.Additionally,the review addresses ongoing challenges in biomarker validation,sensor stability,user compliance,data privacy,and regulatory considerations.A holistic,multimodal approach enabled by these next-generation wearable biosensors holds significant potential for improving patient outcomes and facilitating proactive healthcare interventions in diabetes management.展开更多
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
BACKGROUND The prevalence and clinical characteristics of chronic kidney disease(CKD)among patients with ketosis-onset diabetes(also known as ketosis-prone diabetes)remain unclear.Furthermore,the classification of ket...BACKGROUND The prevalence and clinical characteristics of chronic kidney disease(CKD)among patients with ketosis-onset diabetes(also known as ketosis-prone diabetes)remain unclear.Furthermore,the classification of ketosis-onset diabetes remains controversial and requires further investigation.AIM To investigate the prevalence and clinical features of CKD in patients with newly diagnosed ketosis-onset diabetes.METHODS This real-world study included 217 patients with type 1 diabetes mellitus(T1DM),698 with ketosis-onset diabetes,and 993 with non-ketotic T2DM.The prevalence and clinical characteristics of CKD were compared among the three groups.Risk factors associated with CKD were evaluated using binary logistic regression for each group.RESULTS After adjusting for age and sex,the prevalence of CKD among patients with ketosis-onset diabetes(17.8%)was significantly higher than that in those with T1DM(8.3%,P=0.007),but was not statistically different compared to those with non-ketotic T2DM(21.7%,P=0.214).Furthermore,some risk factors for CKD,including age,and serum uric acid and C-reactive protein levels,in patients with ketosis-onset diabetes were similar to those with T2DM,but significantly different from those with T1DM.CONCLUSION The prevalence,clinical characteristics,and risk factors for CKD among patients with ketosis-onset diabetes were more similar to those with non-ketotic T2DM but considerably different from those with T1DM.These findings further support the classification of ketosis-onset diabetes as a subtype of T2DM rather than idiopathic T1DM.展开更多
Type 2 diabetes(T2D)is an insidious disease associated with neural and vascular complications,acceleration of cardiovascular disease,changes in heart function,and premature death.In the newly released article of the J...Type 2 diabetes(T2D)is an insidious disease associated with neural and vascular complications,acceleration of cardiovascular disease,changes in heart function,and premature death.In the newly released article of the Journal of Sport and Health Science,Liang et al.1 describe results from the UK Biobank data showing the benefits of moderate-to-vigorous intensity physical activity(MVPA)on reducing the risks for vascular events in 11,474 adults with T2D and prediabetes.展开更多
Stem cell therapy has emerged as a groundbreaking treatment approach,particularly for type 1 diabetes,where the autoimmune destruction of beta cells necessitates regenerative strategies to restore insulin production.T...Stem cell therapy has emerged as a groundbreaking treatment approach,particularly for type 1 diabetes,where the autoimmune destruction of beta cells necessitates regenerative strategies to restore insulin production.This article focuses on the recent medical milestone in which autologous stem cell therapy led to insulin independence in a type 1 diabetes patient.This article explores the role of stem cell therapy in reversing diabetes,focusing on the recent medical milestone in which stem cell therapy successfully reversed diabetes in a patient.Stem cells,particularly induced pluripotent stem cells,are used to regenerate pancreatic cells that produce insulin,thereby potentially eliminating the need for insulin injections.The study highlights both the promises and challenges of using stem cell therapy for diabetes including concerns about durability of the response,safety and long-term functionality of generated beta cells.Clinical trials and the ethical considerations of using stem cells are also discussed,along with future directions for stem cell-based diabetes therapies.展开更多
BACKGROUND Exogenous insulin may trigger immune-mediated complications,particularly among East Asian populations.Double diabetes,characterized by overlapping features of type 1 diabetes(T1D)and type 2 diabetes(T2D),ma...BACKGROUND Exogenous insulin may trigger immune-mediated complications,particularly among East Asian populations.Double diabetes,characterized by overlapping features of type 1 diabetes(T1D)and type 2 diabetes(T2D),may arise from insulin-induced autoimmunity.This study aimed to explore the association between high-risk human leukocyte antigen(HLA)class Ⅱ genotypes and susceptibility to double diabetes in patients initially diagnosed with T2D.AIM To investigate clinical and immunogenic features of patients who develop double diabetes following exogenous insulin therapy.METHODS We retrospectively analyzed five cases from Peking Union Medical College Hospital and 18 cases identified from published literature.Patients were categorized into two groups:The T2D→T1D group,characterized by autoimmune progression,and the stable T2D(T2D→T2D).Clinical characteristics and HLA class Ⅱ genotypes were compared descriptively between the two groups.RESULTS A total of 23 patients were included in the analysis.Of these,10 progressed from theT2D→T1D with autoimmune features,while 13 remained in the stable T2D→T2D group.There was no statistically significant difference in age at diagnosis between the two groups(57.10±16.11 years vs 60.31±17.41 years).In the T2D→T1D group,70%of patients carried the HLA-DRB104:05 allele and 40%carried DRB109:01,both of which are commonly associated with a high risk of T1D.In contrast,the T2D→T2D group showed greater genetic heterogeneity,with a broader distribution of HLA-DRB1 alleles,including DRB103:02(n=4),DRB109:01(n=4),and several lower frequency alleles such as DRB1*04:05,*08:03,*03:01,*04:06,*14:01,*04:01,*12:02,*15:02 and*02:01.CONCLUSION These findings suggest that patients in the T2D→T1D group exhibit a stronger autoimmune genetic predisposition,characterized by an enrichment of high-risk HLA class II alleles.In contrast,individuals with stable T2D demonstrate greater HLA diversity and lack definitive autoimmune-associated markers.展开更多
With diabetes currently affecting 537 million people globally,innovative research approaches are urgently required.Zebrafish(Danio rerio)has emerged as a pivotal model organism in diabetes research,particularly valuab...With diabetes currently affecting 537 million people globally,innovative research approaches are urgently required.Zebrafish(Danio rerio)has emerged as a pivotal model organism in diabetes research,particularly valuable for developmental biology studies and preclinical therapeutic validation.Its rapid life cycle,optical transparency,and genetic tractability collectively enable efficient longitudinal observation of pathological progression and pharmacological responses.Utilizing zebrafish models,researchers have elucidated fundamental mechanisms governing islet development,β-cell dysfunction,and metabolic dysregulation.These experimental systems have significantly advanced our understanding of various diabetes subtypes,including type 1,type 2,gestational,and monogenic forms,while also facilitating mechanistic studies of diabetic complications such as retinopathy and nephropathy.Recent model refinements,particularly in simulating monogenic disorders and pregnancy-associated metabolic changes,promise to deepen our comprehension of disease pathophysiology and therapeutic interventions.Nevertheless,a persistent limitation lies in their incomplete recapitulation of human-specific physiological complexity and multi-organ metabolic interactions,factors that may influence translational applicability.Despite these constraints,zebrafish-based research continues to provide an indispensable platform for diabetes investigation,holding significant promise for alleviating the escalating global burden of this metabolic disorder.展开更多
Diabetes is a growing global health concern,calling for improved diagnostic and therapeutic strategies.Of the emerging possible biomarkers,microRNA 375(miR-375)has gained attention for its pivotal role in pancreaticβ...Diabetes is a growing global health concern,calling for improved diagnostic and therapeutic strategies.Of the emerging possible biomarkers,microRNA 375(miR-375)has gained attention for its pivotal role in pancreaticβcell development and function,and its altered blood levels followingβcell injury.This review summarizes the current knowledge on the role of miR-375 in insulin regulation,its correlation with diabetes,and its clinical potential.Despite its well-known role inβcell biology,literature analyses have failed to reveal a consistent correlation between the circulating levels of miR-375 and diabetes.A key limitation lies in the lack ofβcell specificity of miR-375,along with its modulation by diabetes-related complications,which influences circulating levels of the miRNA.Moreover,the absence of large-scale,standardized clinical studies undermines the comparability of existing data.Despite these limits,the literature analysis clearly indicates the need to expand research into miR-375 modulation strategies in humans,as integrating miR-375 with other diagnostic and therapeutic technologies could enhance its clinical relevance.Such strategies may support more personalized and timely interventions for treating diabetes and its complications,ultimately benefiting patient outcomes and contributing to the sustainability of global healthcare systems.展开更多
Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission ...Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders,whereas glucagon-like peptide-1 has demonstrated neuroprotective effects.However,it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells.In the present study,we used the patch-clamp technique to recordγ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats.We found that early diabetes(4 weeks of hyperglycemia)decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude,suggesting a reduction in the spontaneous release ofγ-aminobutyric acid to retinal ganglion cells.Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency,subsequently enhancing the survival of retinal ganglion cells.Concurrently,the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39,a specific glucagon-like peptide-1 receptor antagonist,or SR95531,a specific antagonist of theγ-aminobutyric acid subtype A receptor.Furthermore,extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON-and OFF-type retinal ganglion cells.This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation.Moreover,multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells.Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1.These results suggest that glucagon-like peptide-1 facilitates the release ofγ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor,leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy.Collectively,our findings indicate that theγ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy.Furthermore,the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.展开更多
BACKGROUND Type Ⅱ diabetes mellitus(T2DM)has been associated with increased risk of colon cancer(CC)and worse prognosis in patients with metastases.The effects of T2DM on postoperative chemoresistance rate(CRR)and lo...BACKGROUND Type Ⅱ diabetes mellitus(T2DM)has been associated with increased risk of colon cancer(CC)and worse prognosis in patients with metastases.The effects of T2DM on postoperative chemoresistance rate(CRR)and long-term disease-free survival(DFS)and overall survival(OS)in patients with stage Ⅲ CC who receive curative resection remain controversial.AIM To investigate whether T2DM or glycemic control is associated with worse postoperative survival outcomes in stage Ⅲ CC.METHODS This retrospective cohort study included 278 patients aged 40-75 years who underwent surgery for stage Ⅲ CC from 2018 to 2021.Based on preoperative T2DM history,the patients were categorized into non-DM(n=160)and DM groups(n=118).The latter was further divided into well-controlled(n=73)and poorly controlled(n=45)groups depending on the status of glycemic control.DFS,OS,and CRR were compared between the groups and Cox regression analysis was used to identify risk factors.RESULTS Patients in the DM and non-DM groups demonstrated similar DFS,OS,and CRR(DFS:72.03%vs 78.75%,P=0.178;OS:81.36%vs 83.12%,P=0.638;CRR:14.41%vs 7.5%,P=0.063).Poorly controlled DM was associated with a significantly worse prognosis and higher CRR than well-controlled DM(DFS:62.22%vs 78.07%,P=0.021;OS:71.11%vs 87.67%,P=0.011;CRR:24.40%vs 8.22%,P=0.015).High preoperative fasting plasma glucose[DFS:Hazard ratio(HR)=2.684,P<0.001;OS:HR=2.105,P=0.019;CRR:HR=2.214,P=0.005]and glycosylated hemoglobin levels(DFS:HR=2.344,P=0.006;OS:HR=2.119,P=0.021;CRR:HR=2.449,P=0.009)indicated significantly poor prognosis and high CRR,while T2DM history did not(DFS:HR=1.178,P=0.327;OS:HR=0.933,P=0.739;CRR:HR=0.997,P=0.581).CONCLUSION Increased preoperative fasting plasma glucose and glycosylated hemoglobin levels,but not T2DM history,were identified as risk factors associated with poor postoperative outcomes and high CRR in patients with stage Ⅲ CC.展开更多
Objective This study aimed to investigate the impact of glycemic control and diabetes duration on subsequent myocardial infarction(MI)in patients with both coronary heart disease(CHD)and type 2 diabetes(T2D).Methods W...Objective This study aimed to investigate the impact of glycemic control and diabetes duration on subsequent myocardial infarction(MI)in patients with both coronary heart disease(CHD)and type 2 diabetes(T2D).Methods We conducted a retrospective cohort study of 33,238 patients with both CHD and T2D in Shenzhen,China.Patients were categorized into 6 groups based on baseline fasting plasma glucose(FPG)levels and diabetes duration(from the date of diabetes diagnosis to the baseline date)to examine their combined effects on subsequent MI.Cox proportional hazards regression models were used,with further stratification by age,sex,and comorbidities to assess potential interactions.Results Over a median follow-up of 2.4 years,2,110 patients experienced MI.Compared to those with optimal glycemic control(FPG<6.1 mmol/L)and shorter diabetes duration(<10 years),the fullyadjusted hazard ratio(HR)(95%Confidence Interval[95%CI])for those with a diabetes duration of≥10 years and FPG>8.0 mmol/L was 1.93(95%CI:1.59,2.36).The combined effects of FPG and diabetes duration on MI were largely similar across different age,sex,and comorbidity groups,although the excess risk of MI associated with long-term diabetes appeared to be more pronounced among those with atrial fibrillation.Conclusion Our study indicates that glycemic control and diabetes duration significant influence the subsequent occurrence of MI in patients with both CHD and T2D.Tailored management strategies emphasizing strict glycemic control may be particularly beneficial for patients with longer diabetes duration and atrial fibrillation.展开更多
Osteoporosis represents a prevalent and debilitating comorbidity in patients diagnosed with type 2 diabetes mellitus(T2DM),which is characterized by suppressed osteoblast function and disrupted bone microarchitecture....Osteoporosis represents a prevalent and debilitating comorbidity in patients diagnosed with type 2 diabetes mellitus(T2DM),which is characterized by suppressed osteoblast function and disrupted bone microarchitecture.In this study,we utilized male C57BL/6 J mice to investigate the role of SIRT3 in T2DM.Decreased SIRT3 expression and impaired mitochondrial quality control mechanism are observed in both in vitro and in vivo models of T2DM.Mechanistically,SIRT3 suppression results in hyperacetylation of FOXO3,hindering the activation of the PINK1/PRKN mediated mitophagy pathway and resulting in accumulation of dysfunctional mitochondria.Genetical overexpression or pharmacological activation of SIRT3 restores deacetylation status of FOXO3,thus facilitating mitophagy and ameliorating osteogenic impairment in T2DM.Collectively,our findings highlight the fundamental regulatory function of SIRT3 in mitochondrial quality control,crucial for maintaining bone homeostasis in T2DM.These insights not only enhance our understanding of the molecular mechanisms underlying diabetic osteoporosis but also identify SIRT3 as a promising therapeutic target for diabetic osteoporosis.展开更多
Type 2 diabetes mellitus(T2DM)significantly elevates the risk of colorectal cancer(CRC)and complicates its treatment by promoting chemoresistance.Poor glycemic control has been linked to exacerbated CRC progression an...Type 2 diabetes mellitus(T2DM)significantly elevates the risk of colorectal cancer(CRC)and complicates its treatment by promoting chemoresistance.Poor glycemic control has been linked to exacerbated CRC progression and diminished chemotherapy efficacy,impacting patient outcomes through various mechanisms such as oxidative stress,activation of metabolic pathways,and altered protein modifications that hinder apoptosis and enhance tumor survival.Clinical evidence shows that T2DM patients experience higher rates of chemoresistance and reduced disease-free survival and overall survival compared to non-diabetic patients.Specifically,those with poor glycemic control exhibit increased chemo-resistance and poorer survival metrics.Antidiabetic treatments,including metformin,acarbose,and gliclazide,show promise in improving chemotherapy response and glycemic management,potentially enhancing patient outcomes.Addressing this challenge requires a comprehensive,multidisciplinary approach involving oncologists,endocrino-logists,and surgeons to optimize patient care.Integrated strategies that prioritize glycemic control are essential for reducing chemoresistance and improving survival in CRC patients with T2DM.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
BACKGROUND Inadequate glycemic control in patients with type 2 diabetes(T2DM)is a major public health problem and a significant risk factor for the progression of diabetic complications.AIM To evaluate the effects of ...BACKGROUND Inadequate glycemic control in patients with type 2 diabetes(T2DM)is a major public health problem and a significant risk factor for the progression of diabetic complications.AIM To evaluate the effects of intensive and supportive glycemic management strategies over a 12-month period in individuals with T2DM with glycated hemoglobin(HbA1c)≥10%and varying backgrounds of glycemic control.METHODS This prospective observational study investigated glycemic control in patients with poorly controlled T2DM over 12 months.Participants were categorized into four groups based on prior glycemic history:Newly diagnosed,previously well controlled with recent worsening,previously off-target but now worsening,and HbA1c consistently above 10%.HbA1c levels were monitored quarterly,and patients received medical,educational,and dietary support as needed.The analysis focused on the success rates of good glycemic control and the associated factors within each group.RESULTS The study showed significant improvements in HbA1c levels in all participants.The most significant improvement was observed in individuals newly diagnosed with diabetes:65%achieved an HbA1c target of≤7%.The results varied between participants with different glycemic control histories,followed by decreasing success rates:39%in participants with previously good glycemic control,21%in participants whose glycemic control had deteriorated compared to before,and only 10%in participants with persistently poor control,with mean HbA1c levels of 6.3%,7.7%,8.2%,and 9.7%,respectively.After one year,65.2%of the“newly diagnosed patients”,39.3%in the“previously controlled group”,21.9%in the“previously off-target but now worsened'”group and 10%in the“poorly controlled from the start”group had achieved HbA1c levels of 7 and below.CONCLUSION In poorly controlled diabetes,the rate at which treatment goals are achieved is associated with the glycemic background characteristics,emphasizing the need for tailored strategies.Therefore,different and comprehensive treatment approaches are needed for patients with persistent uncontrolled diabetes.展开更多
文摘Gestational diabetes mellitus(GDM)is defined as any degree of hyperglycaemia that is recognized for the first time during pregnancy.This definition includes cases of undiagnosed type 2 diabetes mellitus(T2 DM)identified early in pregnancy and true GDM which develops later.GDM constitutes a greater impact on diabetes epidemic as it carries a major risk of developing T2 DM to the mother and foetus later in life.In addition,GDM has also been linked with cardiometabolic risk factors such as lipid abnormalities,hypertensive disorders and hyperinsulinemia.These might result in later development of cardiovascular disease and metabolic syndrome.The understanding of the different risk factors,the pathophysiological mechanisms and the genetic factors of GDM,will help us to identify the women at risk,to develop effective preventive measures and to provide adequate management of the disease.Clinical trials have shown that T2 DM can be prevented in women with prior GDM,by intensive lifestyle modification and by using pioglitazone and metformin.However,a matter of controversy surrounding both screening and management of GDM continues to emerge,despite several recent welldesigned clinical trials tackling these issues.The aim of this manuscript is to critically review GDM in a detailed and comprehensive manner,in order to provide a scientific analysis and updated write-up of different related aspects.
基金supported by the Research Funds of the Center for Big Data and Population Health of IHM(grant number JKS2022015)the Key Scientific Research Fund of the Anhui Provincial Education Department(grant number2023AH050610)the Anhui Natural Science Foundation(grant number 1808085QH252)。
文摘In 2021,approximately 537 million people suffered from diabetes mellitus(DM)globally,and this figure will increase to approximately 783 million within the next quarter-century.The increasing burden of DM is a pressing global public health issue.Therefore,the early identification of high-risk groups and implementation of effective intervention measures is imperative.
文摘Monogenic diabetes is a heterogeneous disorder characterized by hyperglycemia arising from defects in a single gene.Maturity-onset diabetes of the young(MODY)is the most common type with 14 subtypes,each linked to specific mutations affecting insulin synthesis,secretion and glucose regulation.Common traits across MODY subtypes include early-onset diabetes,a family history of autosomal dominant diabetes,lack of features of insulin resistance,and absent islet cell autoimmunity.Many cases are misdiagnosed as type 1 and type 2 diabetes mellitus.Biomarkers and scoring systems can help identify candidates for genetic testing.GCK-MODY,a common subtype,manifests as mild hyperglycemia and doesn’t require treatment except during pregnancy.In contrast,mutations in HNF4A,HNF1A,and HNF1B genes lead to progressive beta-cell failure and similar risks of complications as type 2 diabetes mellitus.Neonatal diabetes mellitus(NDM)is a rare form of monogenic diabetes that usually presents within the first six months.Half of the cases are lifelong,while others experience transient remission.Permanent NDM is most commonly due to activating mutations in genes encoding the adenosine triphosphate-sensitive potassium channel(KCNJ11 or ABCC8)and can be transitioned to sulfonylurea after confirmation of diagnosis.Thus,in many cases,monogenic diabetes offers an opportunity to provide precision treatment.The scope has broadened with next-generation sequencing(NGS)technologies,replacing older methods like Sanger sequencing.NGS can be for targeted gene panels,whole-exome sequencing(WES),or whole-genome sequencing.Targeted gene panels offer specific information efficiently,while WES provides comprehensive data but comes with bioinformatic challenges.The surge in testing has also led to an increase in variants of unknown significance(VUS).Deciding whether VUS is disease-causing or benign can be challenging.Computational models,functional studies,and clinical knowledge help to determine pathogenicity.Advances in genetic testing technologies offer hope for improved diagnosis and personalized treatment but also raise concerns about interpretation and ethics.
文摘Type 1 diabetes(T1D)is an autoimmune disease that usually strikes early in life,but can affect individuals at almost any age.It is caused by autoreactive T cells that destroy insulin-producing beta cells in the pancreas.Epidemiological studies estimate a prevalence of 1 in 300 children in the United States with an increasing incidence of 2%-5%annually worldwide.The daily responsibility,clinical management,and vigilance required to maintain blood sugar levels within normal range and avoid acute complications(hypoglycemic episodes and diabetic ketoacidosis)and long term micro-and macro-vascular complications significantly affects quality of life and public health care costs.Given the expansive impact of T1D,research work has accelerated and T1D has been intensively investigated with the focus to better understand,manage and cure this condition.Many advances have been made in the past decades in this regard,but key questions remain as to why certain people develop T1D,but not others,with the glaring example of discordant disease incidence among monozygotic twins.In this review,we discuss the field’s current understanding of its pathophysiology and the role of genetics and environment on the development of T1D.We examine the potential implications of these findings with an emphasis on T1D inheritance patterns,twin studies,and disease prevention.Through a better understanding of this process,interventions can be developed to prevent or halt it at early stages.
文摘Rheumatoid arthritis(RA)is a chronic systemic autoimmune disease that extends beyond joint inflammation,affecting pulmonary and metabolic pathways.Interstitial lung disease(ILD)is one of its most serious extra-articular complications,while type 2 diabetes mellitus(T2DM)frequently coexists with RA and may exacerbate inflammatory and fibrotic processes.This editorial discusses the study by Sutton et al,the largest population-based analysis to date exploring the link between T2DM and ILD in patients with RA,and reflects on its mechanistic and clinical implications.In a nationwide cohort of more than 120000 hospitalized RA patients,Sutton et al demonstrated that the coexistence of T2DM nearly doubles the odds of developing ILD(odds ratio=2.02;95%confidence interval:1.84-2.22),with additional increases in pulmonary hypertension,pneumothorax,and length of stay.These findings reinforce the concept of a metabolic-pulmonary-autoimmune axis,in which chronic inflammation promotes insulin resistance and metabolic dysfunction,while hyperglycaemia and advanced glycation end-products amplify oxidative stress and fibrogenesis.This reciprocal interaction may induce a self-perpetuating cycle of“metaflammation”,fibrosis,and organ damage.Conclusion:Recognizing diabetes as a silent amplifier of RA-associated ILD redefines the interface between rheumatology,pulmonology,and endocrinology.Early detection and integrated management of metabolic and pulmonary comorbidities should be prioritized,while future studies must determine whether optimizing glycemic control can attenuate pulmonary fibrosis and improve longterm outcomes.
文摘Diabetes mellitus represents a major global health issue,driving the need for noninvasive alternatives to traditional blood glucose monitoring methods.Recent advancements in wearable technology have introduced skin-interfaced biosensors capable of analyzing sweat and skin biomarkers,providing innovative solutions for diabetes diagnosis and monitoring.This review comprehensively discusses the current developments in noninvasive wearable biosensors,emphasizing simultaneous detection of biochemical biomarkers(such as glucose,cortisol,lactate,branched-chain amino acids,and cytokines)and physiological signals(including heart rate,blood pressure,and sweat rate)for accurate,personalized diabetes management.We explore innovations in multimodal sensor design,materials science,biorecognition elements,and integration techniques,highlighting the importance of advanced data analytics,artificial intelligence-driven predictive algorithms,and closed-loop therapeutic systems.Additionally,the review addresses ongoing challenges in biomarker validation,sensor stability,user compliance,data privacy,and regulatory considerations.A holistic,multimodal approach enabled by these next-generation wearable biosensors holds significant potential for improving patient outcomes and facilitating proactive healthcare interventions in diabetes management.
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.
文摘BACKGROUND The prevalence and clinical characteristics of chronic kidney disease(CKD)among patients with ketosis-onset diabetes(also known as ketosis-prone diabetes)remain unclear.Furthermore,the classification of ketosis-onset diabetes remains controversial and requires further investigation.AIM To investigate the prevalence and clinical features of CKD in patients with newly diagnosed ketosis-onset diabetes.METHODS This real-world study included 217 patients with type 1 diabetes mellitus(T1DM),698 with ketosis-onset diabetes,and 993 with non-ketotic T2DM.The prevalence and clinical characteristics of CKD were compared among the three groups.Risk factors associated with CKD were evaluated using binary logistic regression for each group.RESULTS After adjusting for age and sex,the prevalence of CKD among patients with ketosis-onset diabetes(17.8%)was significantly higher than that in those with T1DM(8.3%,P=0.007),but was not statistically different compared to those with non-ketotic T2DM(21.7%,P=0.214).Furthermore,some risk factors for CKD,including age,and serum uric acid and C-reactive protein levels,in patients with ketosis-onset diabetes were similar to those with T2DM,but significantly different from those with T1DM.CONCLUSION The prevalence,clinical characteristics,and risk factors for CKD among patients with ketosis-onset diabetes were more similar to those with non-ketotic T2DM but considerably different from those with T1DM.These findings further support the classification of ketosis-onset diabetes as a subtype of T2DM rather than idiopathic T1DM.
文摘Type 2 diabetes(T2D)is an insidious disease associated with neural and vascular complications,acceleration of cardiovascular disease,changes in heart function,and premature death.In the newly released article of the Journal of Sport and Health Science,Liang et al.1 describe results from the UK Biobank data showing the benefits of moderate-to-vigorous intensity physical activity(MVPA)on reducing the risks for vascular events in 11,474 adults with T2D and prediabetes.
文摘Stem cell therapy has emerged as a groundbreaking treatment approach,particularly for type 1 diabetes,where the autoimmune destruction of beta cells necessitates regenerative strategies to restore insulin production.This article focuses on the recent medical milestone in which autologous stem cell therapy led to insulin independence in a type 1 diabetes patient.This article explores the role of stem cell therapy in reversing diabetes,focusing on the recent medical milestone in which stem cell therapy successfully reversed diabetes in a patient.Stem cells,particularly induced pluripotent stem cells,are used to regenerate pancreatic cells that produce insulin,thereby potentially eliminating the need for insulin injections.The study highlights both the promises and challenges of using stem cell therapy for diabetes including concerns about durability of the response,safety and long-term functionality of generated beta cells.Clinical trials and the ethical considerations of using stem cells are also discussed,along with future directions for stem cell-based diabetes therapies.
基金Supported by CAMS Innovation Fund for Medical Sciences,No.2021-I2M-1-002Healthcare Quality and Safety Incubation Programme of the Peking Union Medical Foundation,No.XHFY 2406the National High-Level Hospital Clinical Research Funding,No.2022-PUMCH-B-015.
文摘BACKGROUND Exogenous insulin may trigger immune-mediated complications,particularly among East Asian populations.Double diabetes,characterized by overlapping features of type 1 diabetes(T1D)and type 2 diabetes(T2D),may arise from insulin-induced autoimmunity.This study aimed to explore the association between high-risk human leukocyte antigen(HLA)class Ⅱ genotypes and susceptibility to double diabetes in patients initially diagnosed with T2D.AIM To investigate clinical and immunogenic features of patients who develop double diabetes following exogenous insulin therapy.METHODS We retrospectively analyzed five cases from Peking Union Medical College Hospital and 18 cases identified from published literature.Patients were categorized into two groups:The T2D→T1D group,characterized by autoimmune progression,and the stable T2D(T2D→T2D).Clinical characteristics and HLA class Ⅱ genotypes were compared descriptively between the two groups.RESULTS A total of 23 patients were included in the analysis.Of these,10 progressed from theT2D→T1D with autoimmune features,while 13 remained in the stable T2D→T2D group.There was no statistically significant difference in age at diagnosis between the two groups(57.10±16.11 years vs 60.31±17.41 years).In the T2D→T1D group,70%of patients carried the HLA-DRB104:05 allele and 40%carried DRB109:01,both of which are commonly associated with a high risk of T1D.In contrast,the T2D→T2D group showed greater genetic heterogeneity,with a broader distribution of HLA-DRB1 alleles,including DRB103:02(n=4),DRB109:01(n=4),and several lower frequency alleles such as DRB1*04:05,*08:03,*03:01,*04:06,*14:01,*04:01,*12:02,*15:02 and*02:01.CONCLUSION These findings suggest that patients in the T2D→T1D group exhibit a stronger autoimmune genetic predisposition,characterized by an enrichment of high-risk HLA class II alleles.In contrast,individuals with stable T2D demonstrate greater HLA diversity and lack definitive autoimmune-associated markers.
基金Supported by Natural Science Foundation of Zhejiang Province,China,No.LQ24H070007。
文摘With diabetes currently affecting 537 million people globally,innovative research approaches are urgently required.Zebrafish(Danio rerio)has emerged as a pivotal model organism in diabetes research,particularly valuable for developmental biology studies and preclinical therapeutic validation.Its rapid life cycle,optical transparency,and genetic tractability collectively enable efficient longitudinal observation of pathological progression and pharmacological responses.Utilizing zebrafish models,researchers have elucidated fundamental mechanisms governing islet development,β-cell dysfunction,and metabolic dysregulation.These experimental systems have significantly advanced our understanding of various diabetes subtypes,including type 1,type 2,gestational,and monogenic forms,while also facilitating mechanistic studies of diabetic complications such as retinopathy and nephropathy.Recent model refinements,particularly in simulating monogenic disorders and pregnancy-associated metabolic changes,promise to deepen our comprehension of disease pathophysiology and therapeutic interventions.Nevertheless,a persistent limitation lies in their incomplete recapitulation of human-specific physiological complexity and multi-organ metabolic interactions,factors that may influence translational applicability.Despite these constraints,zebrafish-based research continues to provide an indispensable platform for diabetes investigation,holding significant promise for alleviating the escalating global burden of this metabolic disorder.
文摘Diabetes is a growing global health concern,calling for improved diagnostic and therapeutic strategies.Of the emerging possible biomarkers,microRNA 375(miR-375)has gained attention for its pivotal role in pancreaticβcell development and function,and its altered blood levels followingβcell injury.This review summarizes the current knowledge on the role of miR-375 in insulin regulation,its correlation with diabetes,and its clinical potential.Despite its well-known role inβcell biology,literature analyses have failed to reveal a consistent correlation between the circulating levels of miR-375 and diabetes.A key limitation lies in the lack ofβcell specificity of miR-375,along with its modulation by diabetes-related complications,which influences circulating levels of the miRNA.Moreover,the absence of large-scale,standardized clinical studies undermines the comparability of existing data.Despite these limits,the literature analysis clearly indicates the need to expand research into miR-375 modulation strategies in humans,as integrating miR-375 with other diagnostic and therapeutic technologies could enhance its clinical relevance.Such strategies may support more personalized and timely interventions for treating diabetes and its complications,ultimately benefiting patient outcomes and contributing to the sustainability of global healthcare systems.
基金supported by the National Natural Science Foundation of China,Nos.32070989(to YMZ),31872766(to YMZ),81790640(to XLY),and 82070993(to SJW)the grant from Sanming Project of Medicine in Shenzhen,No.SZSM202011015(to XLY)。
文摘Diabetic retinopathy is a prominent cause of blindness in adults,with early retinal ganglion cell loss contributing to visual dysfunction or blindness.In the brain,defects inγ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders,whereas glucagon-like peptide-1 has demonstrated neuroprotective effects.However,it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells.In the present study,we used the patch-clamp technique to recordγ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats.We found that early diabetes(4 weeks of hyperglycemia)decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude,suggesting a reduction in the spontaneous release ofγ-aminobutyric acid to retinal ganglion cells.Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency,subsequently enhancing the survival of retinal ganglion cells.Concurrently,the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39,a specific glucagon-like peptide-1 receptor antagonist,or SR95531,a specific antagonist of theγ-aminobutyric acid subtype A receptor.Furthermore,extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON-and OFF-type retinal ganglion cells.This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation.Moreover,multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells.Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1.These results suggest that glucagon-like peptide-1 facilitates the release ofγ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor,leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy.Collectively,our findings indicate that theγ-aminobutyric acid system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy.Furthermore,the topical administration of glucagon-like peptide-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.
基金Supported by the Leading Innovation Specialist Support Program of Guangdong Provincethe Science and Technology Planning Project of Ganzhou,No.202101074816the National Natural Science Foundation of China,No.82260501.
文摘BACKGROUND Type Ⅱ diabetes mellitus(T2DM)has been associated with increased risk of colon cancer(CC)and worse prognosis in patients with metastases.The effects of T2DM on postoperative chemoresistance rate(CRR)and long-term disease-free survival(DFS)and overall survival(OS)in patients with stage Ⅲ CC who receive curative resection remain controversial.AIM To investigate whether T2DM or glycemic control is associated with worse postoperative survival outcomes in stage Ⅲ CC.METHODS This retrospective cohort study included 278 patients aged 40-75 years who underwent surgery for stage Ⅲ CC from 2018 to 2021.Based on preoperative T2DM history,the patients were categorized into non-DM(n=160)and DM groups(n=118).The latter was further divided into well-controlled(n=73)and poorly controlled(n=45)groups depending on the status of glycemic control.DFS,OS,and CRR were compared between the groups and Cox regression analysis was used to identify risk factors.RESULTS Patients in the DM and non-DM groups demonstrated similar DFS,OS,and CRR(DFS:72.03%vs 78.75%,P=0.178;OS:81.36%vs 83.12%,P=0.638;CRR:14.41%vs 7.5%,P=0.063).Poorly controlled DM was associated with a significantly worse prognosis and higher CRR than well-controlled DM(DFS:62.22%vs 78.07%,P=0.021;OS:71.11%vs 87.67%,P=0.011;CRR:24.40%vs 8.22%,P=0.015).High preoperative fasting plasma glucose[DFS:Hazard ratio(HR)=2.684,P<0.001;OS:HR=2.105,P=0.019;CRR:HR=2.214,P=0.005]and glycosylated hemoglobin levels(DFS:HR=2.344,P=0.006;OS:HR=2.119,P=0.021;CRR:HR=2.449,P=0.009)indicated significantly poor prognosis and high CRR,while T2DM history did not(DFS:HR=1.178,P=0.327;OS:HR=0.933,P=0.739;CRR:HR=0.997,P=0.581).CONCLUSION Increased preoperative fasting plasma glucose and glycosylated hemoglobin levels,but not T2DM history,were identified as risk factors associated with poor postoperative outcomes and high CRR in patients with stage Ⅲ CC.
基金supported by the R&D project of Pazhou Lab(Huangpu)under Grant 2023K0610the National Natural Science Foundation of China(Grants 12126602)+4 种基金the National Natural Science Foundation of China(Grants 82030102)the Shenzhen Medical Research Fund(Grants C2302001)the Shenzhen Science and Technology Innovation Committee(No.ZDSYS20200810171403013)the Chinese Postdoctoral Science Foundation(No.2022M721463)the Ministry of Science and Technology of China(Grants 2022YFC3702703).
文摘Objective This study aimed to investigate the impact of glycemic control and diabetes duration on subsequent myocardial infarction(MI)in patients with both coronary heart disease(CHD)and type 2 diabetes(T2D).Methods We conducted a retrospective cohort study of 33,238 patients with both CHD and T2D in Shenzhen,China.Patients were categorized into 6 groups based on baseline fasting plasma glucose(FPG)levels and diabetes duration(from the date of diabetes diagnosis to the baseline date)to examine their combined effects on subsequent MI.Cox proportional hazards regression models were used,with further stratification by age,sex,and comorbidities to assess potential interactions.Results Over a median follow-up of 2.4 years,2,110 patients experienced MI.Compared to those with optimal glycemic control(FPG<6.1 mmol/L)and shorter diabetes duration(<10 years),the fullyadjusted hazard ratio(HR)(95%Confidence Interval[95%CI])for those with a diabetes duration of≥10 years and FPG>8.0 mmol/L was 1.93(95%CI:1.59,2.36).The combined effects of FPG and diabetes duration on MI were largely similar across different age,sex,and comorbidity groups,although the excess risk of MI associated with long-term diabetes appeared to be more pronounced among those with atrial fibrillation.Conclusion Our study indicates that glycemic control and diabetes duration significant influence the subsequent occurrence of MI in patients with both CHD and T2D.Tailored management strategies emphasizing strict glycemic control may be particularly beneficial for patients with longer diabetes duration and atrial fibrillation.
基金supported by the National Key Research and Development Project (2021YFA1201404)National Natural Science Foundation of China Major Project (81991514)+6 种基金General Project (82272530, 82372459)Jiangsu Province Medical Innovation Center of Orthopedic Surgery (CXZX202214)Jiangsu Provincial Key Medical Center FoundationJiangsu Provincial Medical Outstanding Talent FoundationJiangsu Provincial Medical Youth Talent FoundationJiangsu Provincial Key Medical Talent Foundationthe Fundamental Research Funds for the Central Universities (14380493, 14380494)
文摘Osteoporosis represents a prevalent and debilitating comorbidity in patients diagnosed with type 2 diabetes mellitus(T2DM),which is characterized by suppressed osteoblast function and disrupted bone microarchitecture.In this study,we utilized male C57BL/6 J mice to investigate the role of SIRT3 in T2DM.Decreased SIRT3 expression and impaired mitochondrial quality control mechanism are observed in both in vitro and in vivo models of T2DM.Mechanistically,SIRT3 suppression results in hyperacetylation of FOXO3,hindering the activation of the PINK1/PRKN mediated mitophagy pathway and resulting in accumulation of dysfunctional mitochondria.Genetical overexpression or pharmacological activation of SIRT3 restores deacetylation status of FOXO3,thus facilitating mitophagy and ameliorating osteogenic impairment in T2DM.Collectively,our findings highlight the fundamental regulatory function of SIRT3 in mitochondrial quality control,crucial for maintaining bone homeostasis in T2DM.These insights not only enhance our understanding of the molecular mechanisms underlying diabetic osteoporosis but also identify SIRT3 as a promising therapeutic target for diabetic osteoporosis.
文摘Type 2 diabetes mellitus(T2DM)significantly elevates the risk of colorectal cancer(CRC)and complicates its treatment by promoting chemoresistance.Poor glycemic control has been linked to exacerbated CRC progression and diminished chemotherapy efficacy,impacting patient outcomes through various mechanisms such as oxidative stress,activation of metabolic pathways,and altered protein modifications that hinder apoptosis and enhance tumor survival.Clinical evidence shows that T2DM patients experience higher rates of chemoresistance and reduced disease-free survival and overall survival compared to non-diabetic patients.Specifically,those with poor glycemic control exhibit increased chemo-resistance and poorer survival metrics.Antidiabetic treatments,including metformin,acarbose,and gliclazide,show promise in improving chemotherapy response and glycemic management,potentially enhancing patient outcomes.Addressing this challenge requires a comprehensive,multidisciplinary approach involving oncologists,endocrino-logists,and surgeons to optimize patient care.Integrated strategies that prioritize glycemic control are essential for reducing chemoresistance and improving survival in CRC patients with T2DM.
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.
文摘BACKGROUND Inadequate glycemic control in patients with type 2 diabetes(T2DM)is a major public health problem and a significant risk factor for the progression of diabetic complications.AIM To evaluate the effects of intensive and supportive glycemic management strategies over a 12-month period in individuals with T2DM with glycated hemoglobin(HbA1c)≥10%and varying backgrounds of glycemic control.METHODS This prospective observational study investigated glycemic control in patients with poorly controlled T2DM over 12 months.Participants were categorized into four groups based on prior glycemic history:Newly diagnosed,previously well controlled with recent worsening,previously off-target but now worsening,and HbA1c consistently above 10%.HbA1c levels were monitored quarterly,and patients received medical,educational,and dietary support as needed.The analysis focused on the success rates of good glycemic control and the associated factors within each group.RESULTS The study showed significant improvements in HbA1c levels in all participants.The most significant improvement was observed in individuals newly diagnosed with diabetes:65%achieved an HbA1c target of≤7%.The results varied between participants with different glycemic control histories,followed by decreasing success rates:39%in participants with previously good glycemic control,21%in participants whose glycemic control had deteriorated compared to before,and only 10%in participants with persistently poor control,with mean HbA1c levels of 6.3%,7.7%,8.2%,and 9.7%,respectively.After one year,65.2%of the“newly diagnosed patients”,39.3%in the“previously controlled group”,21.9%in the“previously off-target but now worsened'”group and 10%in the“poorly controlled from the start”group had achieved HbA1c levels of 7 and below.CONCLUSION In poorly controlled diabetes,the rate at which treatment goals are achieved is associated with the glycemic background characteristics,emphasizing the need for tailored strategies.Therefore,different and comprehensive treatment approaches are needed for patients with persistent uncontrolled diabetes.
