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TCERG1L hypermethylation is a risk factor of diabetic retinopathy in Chinese children with type 1 diabetes

International Journal of Ophthalmology(English edition) 2024年第3期17卷 537-544页

作者： Yu Qian Ying Xiao Qiu-Rong Lin Zhao-Yu Xiang Li-Pu Cui Jia-Qi Sun Si-Cong Li Xin-Ran Qin Hai-Dong Zou Chen-Hao Yang Pei-Yao Jin Department of Ophthalmology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai First People’s HospitalShanghai 200080China Shanghai Eye Diseases Prevention&Treatment Center Shanghai Eye HospitalShanghai 200040China National Clinical Research Center for Eye Diseases Shanghai Clinical Research Center for Eye DiseasesShanghai Key Clinical SpecialtyShanghai Key Laboratory of Ocular Fundus DiseasesShanghai Engineering Center for Visual Science and PhotomedicineShanghai Engineering Center for Precise Diagnosis and Treatment of Eye DiseasesShanghai 200080China Department of Ophthalmology Children’s Hospital of Fudan UniversityShanghai 201102China

●AIM:To identify the differential methylation sites(DMS)and their according genes associated with diabetic retinopathy(DR)development in type 1 diabetes(T1DM)children.●METHODS:This study consists of two surveys.A total of 40 T1DM children was included in the first survey.Because no participant has DR,retina thinning was used as a surrogate indicator for DR.The lowest 25%participants with the thinnest macular retinal thickness were included into the case group,and the others were controls.The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay,and compared between the case and control groups.Four DMS with a potential role in diabetes were identified.The second survey included 27 T1DM children,among which four had DR.The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing.●RESULTS:In the first survey,the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls(|Δβ|>0.1 and Adj.P0.05)between participants with and without DR.●CONCLUSION:The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.

关键词： DNA methylation 850K array pyrosequencing diabetic retinopathy type 1 diabetes children

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Evaluation of hybrid closed-loop insulin delivery system in type 1 diabetes in real-world clinical practice:One-year observational study

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World Journal of diabetes 2024年第3期15卷 455-462页

作者： Ahmed Eldib Shilton Dhaver Karim Kibaa Astrid Atakov-Castillo Tareq Salah Marwa Al-Badri Abdelrahman Khater Ryan McCarragher Omnia Elenani Elena Toschi Osama Hamdy Department of Clinical Behavioral&Outcomes ResearchJoslin Diabetes CenterBostonMA 02215United States Department of Medicine Harvard Medical SchoolBostonMA 02115United States

BACKGROUND In 2016,the Food and Drug Administration approved the first hybrid closed-loop(HCL)insulin delivery system for adults with type 1 diabetes(T1D).There is limited information on the impact of using HCL systems on patient-reported outcomes(PROs)in patients with T1D in real-world clinical practice.In this independent study,we evaluated glycemic parameters and PROs over one year of continuous use of Medtronic’s 670G HCL in real-world clinical practice.AIM To assess the effects of hybrid closed loop system on glycemic control and quality of life in adults with T1D.METHODS We evaluated 71 patients with T1D(mean age:45.5±12.1 years;59%females;body weight:83.8±18.7 kg,body mass index:28.7±5.6 kg/m2,A1C:7.6%±0.8%)who were treated with HCL at Joslin Clinic from 2017 to 2019.We measured A1C and percent of glucose time-in-range(%TIR)at baseline and 12 months.We measured percent time in auto mode(%TiAM)for the last two weeks preceding the final visit and assessed PROs through several validated quality-of-life surveys related to general health and diabetes management.RESULTS At 12 mo,A1C decreased by 0.3%±0.1%(P=0.001)and%TIR increased by 8.1%±2.5%(P=0.002).The average%TiAM was only 64.3%±32.8%and was not associated with A1C,%TIR or PROs.PROs,provided at baseline and at the end of the study,showed that the physical functioning submodule of 36Item Short-Form Health Survey increased significantly by 22.9%(Pdiabetes reduced significantly by-17.2%(P=0.002).The emotional burden submodules of dietary diversity score reduced significantly by-44.7%(P=0.001).Furthermore,analysis of Clarke questionnaire showed no increase in awareness of hypoglycemic episodes.WHO-5 showed no improvements in subject’s wellbeing among participants after starting the 670G HCL system.Finally,analysis of Pittsburgh Sleep Quality Index showed no difference in sleep quality,sleep latency,or duration of sleep from baseline to 12 mo.CONCLUSION The us

关键词： Artificial pancreas Continuous blood glucose monitor type 1 diabetes Hybrid closed-loop insulin delivery Quality of life

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Glucagon-like peptide-1 receptor agonists as a possible intervention to delay the onset of type 1 diabetes:A new horizon

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World Journal of diabetes 2024年第2期15卷 133-136页

作者： Mahmoud Nassar Ajay Chaudhuri Husam Ghanim Paresh Dandona Department of Internal Medicine Division of EndocrinologyDiabetes and MetabolismJacobs School of Medicine and Biomedical SciencesUniversity of BuffaloBuffaloNY 14221United States

type 1 diabetes(T1D)is a chronic autoimmune condition that destroys insulinproducing beta cells in the pancreas,leading to insulin deficiency and hyperglycemia.The management of T1D primarily focuses on exogenous insulin replacement to control blood glucose levels.However,this approach does not address the underlying autoimmune process or prevent the progressive loss of beta cells.Recent research has explored the potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)as a novel intervention to modify the disease course and delay the onset of T1D.GLP-1RAs are medications initially developed for treating type 2 diabetes.They exert their effects by enhancing glucose-dependent insulin secretion,suppressing glucagon secretion,and slowing gastric emptying.Emerging evidence suggests that GLP-1RAs may also benefit the treatment of newly diagnosed patients with T1D.This article aims to highlight the potential of GLP-1RAs as an intervention to delay the onset of T1D,possibly through their potential immunomodulatory and anti-inflammatory effects and preservation of beta-cells.This article aims to explore the potential of shifting the paradigm of T1D management from reactive insulin replacement to proactive disease modification,which should open new avenues for preventing and treating T1D,improving the quality of life and long-term outcomes for individuals at risk of T1D.

关键词： type 1 diabetes Semaglutide Glucagon-like peptide-1 receptor agonists Insulin therapy Autoimmune response Blood glucose monitoring Β-cell preservation Early screening Teplizumab Randomized controlled trials

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Drawing lines in the sand: The growing threat of obesity in type 1 diabetes

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World Journal of diabetes 2024年第5期15卷 823-827页

作者： Theocharis Koufakis Dimitrios Patoulias Ioanna Zografou Nikolaos Papanas Djordje S Popovic Second Propedeutic Department of Internal Medicine Aristotle University of ThessalonikiThessaloniki 54642Greece diabetes Centre Second Department of Internal MedicineDemocritus University of ThraceAlexandroupolis 68100Greece Clinic for Endocrinology Diabetes and Metabolic DisordersClinical Center of VojvodinaMedical FacultyUniversity of Novi SadNovi Sad 21000Serbia

In this editorial,we comment on the article by Zeng et al published in the recent issue of the World Journal of diabetes in 2024.We focus on the epidemiological,pathophysiological,and clinical interplay between obesity and type 1 diabetes mellitus(T1DM).Overweight and obesity represent a growing threat for modern societies and people with T1DM could not be an exception to this rule.Chronic exogenous insulin administration,genetic and epigenetic factors,and psy-chosocial and behavioral parameters,along with the modern way of life that incorporates unhealthy eating patterns and physical inactivity,set the stage for the increasing obesity rates in T1DM.As our knowledge of the underlying mechanisms that lead to the development of obesity and hyperglycemia expands,it becomes clear that there are overlap zones in the pathophysiology of the two main types of diabetes.Stereotypes regarding strict dividing lines between“autoimmune”and“metabolic”phenotypes increase the risk of trapping physicians into ineffective therapeutic approaches,instead of individualized diabetes care.In this context,the use of adjuncts to insulin therapy that have the potential to alleviate cardiorenal risk and decrease body weight can reduce the burden of obesity in patients with T1DM.

关键词： Obesity Overweight type 1 diabetes Metabolic syndrome

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Mesenchymal stromal cells modulate unfolded protein response and preserve β-cell mass in type 1 diabetes

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BIOCELL 2024年第7期48卷 1115-1126页

作者： SIYUAN LIU YUAN ZHAO YU YU DOU YE QIAN WANG ZHAOYAN WANG ZUO LUAN Department of Pediatrics The Sixth Medical CenterChinese PLA General HospitalBeijing100037China

Introduction:Transplantation of mesenchymal stromal cells(MSCs)is a promising therapy for type 1 diabetes(T1D).However,whether the infused MSCs affect the endoplasmic reticulum stress or subsequent unfolded protein response inβcells remains unclear.Methods:To investigate this,we induced early-onset T1D in non-obese diabetic mice using streptozotocin.Subsequently,T1D mice were randomly assigned to receive either MSCs or phosphate-buffered saline.We observed the in vivo homing of MSCs and assessed their effectiveness by analyzing blood glucose levels,body weight,histopathology,pancreatic protein expression,and serum levels of cytokines,proinsulin,and C-peptide.Results:Infused MSCs were found in the lungs,liver,spleen,and pancreas of T1D mice.They exhibited various effects,including reducing blood glucose levels,regulating immunity,inhibiting inﬂammation,increasingβ-cell areas,and reducing the expression of key proteins in the unfolded protein response pathway.Fasting serum proinsulin and C-peptide levels were signiﬁcantly higher in the MSCs treatment group than in the T1D model group.However,there was no signiﬁcant difference in the biomarker ofβ-cell endoplasmic reticulum stress,the ratio of fasting serum proinsulin to C-peptide,between the two groups.Conclusion:Ourﬁndings reveal that MSCs infusion does not alleviate endoplasmic reticulum stress inβcells directly but modulates the unfolded protein response pathway to preserveβ-cell mass and function in T1D mice.

关键词： type 1 diabetes Mesenchymal stromal cells Endoplasmic reticulum stress Unfolded protein response Non-obese diabetic mice

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Honeymoon phase in type 1 diabetes mellitus: A window of opportunity for diabetes reversal?

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World Journal of Clinical Cases 2024年第1期12卷 9-14页

作者： Madhukar Mittal Pradakshna Porchezhian Nitin Kapoor Department of Endocrinology and Metabolism All India Institute of Medical Sciences JodhpurJodhpur 342005India Department of Endocrinology Diabetes and MetabolismChristian Medical College and HospitalVellore 632004Tamil NaduIndia

The knowledge of the pathogenesis of type 1 diabetes mellitus(T1DM)continues to rapidly evolve.The natural course of the disease can be described in four clinical stages based on the autoimmune markers and glycemic status.Not all individuals of T1DM progress in that specific sequence.We hereby present a case of T1DM with a classical third phase(honeymoon phase)and discuss the intri-cacies of this interesting phase along with a possible future promise of“cure”with the use of immunotherapies.We now know that the course of T1DM may not be in only one direction towards further progression;rather the disease may have a waxing and waning course with even reversal of type 1 diabetes concept being discussed.The third phase popularly called the“honeymoon phase”,is of special interest as this phase is complex in its pathogenesis.The honeymoon phase of T1DM seems to provide the best window of opportunity for using targeted therapies using various immunomodulatory agents leading to the possibility of achieving the elusive“diabetes reversal”in T1DM.Identifying this phase is therefore the key,with a lot of varying criteria having been proposed.

关键词： diabetes reversal diabetes remission type 1 diabetes Honeymoon phase Immunomodulation

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Pressure pain sensitivity: A new stress measure in children and adolescents with type 1 diabetes?

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World Journal of Clinical Pediatrics 2024年第1期13卷 150-154页

作者： Annemarie Cecilie Grauslund Emilie Bundgaard Lindkvist Steffen Ullitz Thorsen Søren Ballegaard Jens Faber Jannet Svensson Anna Korsgaard Berg Department of Pediatrics Herlev and Gentofte HospitalHerlev 2730Denmark Copenhagen University Hospital Steno Diabetes Center CopenhagenHerlev 2730Denmark Department of Clinical Immunology RigshospitaletUniversity of CopenhagenCopenhagen 2100Denmark Department of Endocrinology Herlev and Gentofte HospitalHerlev 2730Denmark Department of Clinical Medicine Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagen 2200Denmark

type 1 diabetes(T1D)is associated with general-and diabetes-specific stress which has multiple adverse effects.Hence measuring stress is of great importance.An algometer measuring pressure pain sensitivity(PPS)has been shown to correlate to certain stress measures in adults.However,it has never been investigated in children and adolescents.The aim of our study was to examine associations between PPS and glycated hemoglobin(HbA1c),salivary cortisol and two questionnaires as well as to identify whether the algometer can be used as a clinical tool among children and adolescents with T1D.Eighty-three participants aged 6-18 years and diagnosed with T1D were included in this study with data from two study visits.Salivary cortisol,PPS and questionnaires were collected,measured,and answered on site.HbA1c was collected from medical files.We found correlations between PPS and HbA1c(rho=0.35,P=0.046),cortisol(rho=-0.25,P=0.02)and Perceived Stress Scale(rho=-0.44,P=0.02)in different subgroups based on age.Males scored higher in PPS than females(P<0.001).We found PPS to be correlated to HbA1c but otherwise inconsistent in results.High PPS values indicated either measurement difficulties or hypersensibility towards pain.

关键词： Stress Children and adolescents type 1 diabetes Autonomic dysfunction

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Roles of fibroblast growth factors in the treatment of diabetes

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World Journal of diabetes 2024年第3期15卷 392-402页

作者： Chun-Ye Zhang Ming Yang Bond Life Sciences Center University of MissouriColumbiaMO 65211United States Department of Surgery University of MissouriColumbiaMO 65212United States NextGen Precision Health Institution University of MissouriColumbiaMO 65212United States

diabetes affects about 422 million people worldwide,causing 1.5 million deaths each year.However,the incidence of diabetes is increasing,including several types of diabetes.type 1 diabetes(5%-10%of diabetic cases)and type 2 diabetes(90%-95%of diabetic cases)are the main types of diabetes in the clinic.Accumulating evidence shows that the fibroblast growth factor(FGF)family plays important roles in many metabolic disorders,including type 1 and type 2 diabetes.FGF consists of 23 family members(FGF-1-23)in humans.Here,we review current findings of FGFs in the treatment of diabetes and management of diabetic complications.Some FGFs(e.g.,FGF-15,FGF-19,and FGF-21)have been broadly investigated in preclinical studies for the diagnosis and treatment of diabetes,and their therapeutic roles in diabetes are currently under investigation in clinical trials.Overall,the roles of FGFs in diabetes and diabetic complications are involved in numerous processes.First,FGF intervention can prevent high-fat diet-induced obesity and insulin resistance and reduce the levels of fasting blood glucose and triglycerides by regulating lipolysis in adipose tissues and hepatic glucose production.Second,modulation of FGF expression can inhibit renal and cardiac fibrosis by regulating the expression of extracellular matrix components,promote diabetic wound healing process and bone repair,and inhibit cancer cell proliferation and migration.Finally,FGFs can regulate the activation of glucoseexcited neurons and the expression of thermogenic genes.

关键词： Fibroblast growth factors type 1 diabetes type 2 diabetes Metabolic disorders Treatment Clinical trials

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Enzyme-linked immunosorbent assay of 3 Screen Islet Cell Autoantibody in patients with autoimmune thyroid disease

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World Journal of diabetes 2024年第5期15卷 935-944页

作者： Eiji Kawasaki Hidekazu Tamai Takahiro Fukuyama Yoko Sagara Ryutaro Hidaka Aira Uchida Masayuki Tojikubo Narihito Tatsumoto Yuko Akehi Yuji Hiromatsu The diabetes Thyroid and Endocrine CenterShin-Koga HospitalKurume 830-8577Japan

BACKGROUND In recent years,the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediated type 1 diabetes(T1D).While it has been established that 20%-30%of T1D patients suffer from autoimmune thyroid disease(AITD),there is limited available data regarding the presence of anti-islet autoantibodies in AITD patients.Among commercially available anti-islet autoantibodies,glutamic acid decarboxylase 65 autoantibodies(GADAs)are often the first marker measured in general clinical practice.AIM To investigate the frequency of anti-islet autoantibodies in AITD patients.METHODS Our study involved four hundred ninety-five AITD patients,categorized into three distinct groups:AITD with T1D(n=18),AITD with phenotypic type 2 diabetes(T2D)(n=81),and AITD without diabetes(n=396),and the enzyme-linked immunosorbent assay(ELISA)was employed to determine the frequencies of 3 Screen Islet Cell Autoantibody(3 Screen ICA),GADA,insulinoma-associated antigen-2 autoantibodies(IA-2As),and zinc transporter 8 autoantibodies(ZnT8As)within these groups.RESULTS The frequency of 3 Screen ICA in AITD patients with T1D,T2D,and those without diabetes were 88.9%,6.2%,and 5.1%,respectively,with no significant difference seen between the latter two groups.Notably,the frequency of 3 Screen ICA was 11.1%higher in AITD patients with T1D,1.3%higher in AITD patients with T2D,and 1.1%higher in AITD patients without diabetes compared to GADA,respectively.Furthermore,12.5%,20.0%,and 20.0%of the 3 Screen ICA-positive patients were negative for GADA.Additionally,1.3%of the AITD patients who tested negative for 3 Screen ICA in both the AITD with T2D and non-diabetic AITD groups were found to be positive for individual autoantibodies.Among the 3 Screen ICA-positive patients,there was a significantly higher proportion of individuals with multiple autoantibodies in AITD patients with T1D compared to those without diabetes(37.5%vs 5.0%,P<0

关键词： Anti-islet autoantibodies Autoimmune thyroid disease Real-world practice Retrospective study type 1 diabetes

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Therapeutic effects of menstrual blood-derived endometrial stem cells on mouse models of streptozotocin-induced type 1 diabetes

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World Journal of Stem Cells 2022年第1期14卷 104-116页

作者： Yu-Liang Sun Ling-Rui Shang Rui-Hong Liu Xin-Yi Li Sheng-Hui Zhang Ya-Kun Ren Kang Fu Hong-Bin Cheng Badrul Hisham Yahaya Yan-Li Liu Jun-Tang Lin Stem Cell and Biotherapy Technology Research Center Xinxiang Medical UniversityXinxiang 453000Henan ProvinceChina Regenerative Medicine Cluster Advanced Medical and Dental Institute(IPPT)Universiti Sains MalaysiaKepala Batas 13200PenangMalaysia College of Biomedical Engineering Xinxiang Medical UniversityXinxiang 453000Henan ProvinceChina The Third Affiliated Hospital of Xinxiang Medical University Xinxiang Medical UniversityXinxiang 453000Henan ProvinceChina Henan Key Laboratory of Medical Tissue Regeneration Xinxiang Medical UniversityXinxiang 453000Henan ProvinceChina Department of Technical Henan Intercell Biotechnology co.LTDXinxiang 453000Henan ProvinceChina

BACKGROUND type 1 diabetes(T1D),a chronic metabolic and autoimmune disease,seriously endangers human health.In recent years,mesenchymal stem cell(MSC)transplantation has become an effective treatment for diabetes.Menstrual bloodderived endometrial stem cells(MenSC),a novel MSC type derived from the decidual endometrium during menstruation,are expected to become promising seeding cells for diabetes treatment because of their noninvasive collection procedure,high proliferation rate and high immunomodulation capacity.AIM To comprehensively compare the effects of MenSC and umbilical cord-derived MSC(UcMSC)transplantation on T1D treatment,to further explore the potential mechanism of MSC-based therapies in T1D,and to provide support for the clinical application of MSC in diabetes treatment.METHODS A conventional streptozotocin-induced T1D mouse model was established,and the effects of MenSC and UcMSC transplantation on their blood glucose and serum insulin levels were detected.The morphological and functional changes in the pancreas,liver,kidney,and spleen were analyzed by routine histological and immunohistochemical examinations.Changes in the serum cytokine levels in the model mice were assessed by protein arrays.The expression of target proteins related to pancreatic regeneration and apoptosis was examined by western blot.RESULTS MenSC and UcMSC transplantation significantly improved the blood glucose and serum insulin levels in T1D model mice.Immunofluorescence analysis revealed that the numbers of insulin+and CD31+cells in the pancreas were significantly increased in MSC-treated mice compared with control mice.Subsequent western blot analysis also showed that vascular endothelial growth factor(VEGF),Bcl2,Bcl-xL and Proliferating cell nuclear antigen in pancreatic tissue was significantly upregulated in MSC-treated mice compared with control mice.Additionally,protein arrays indicated that MenSC and UcMSC transplantation significantly downregulated the serum levels of interferonγand tumor necrosis factorαand upregu

关键词： type 1 diabetes Menstrual blood-derived endometrial stem cell Umbilical cord mesenchymal stem cells Improvement Complication

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