Current understandings of the pathogenesis of type 1 diabetes:Genetics to environment

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.

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

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

Intestinal glucagon-like peptide-1:A new regulator of impaired counterregulatory responses to hypoglycemia in type 1 diabetes mellitus

In this article,we review the study by Jin et al,which examined the role of intestinal glucagon-like peptide-1(GLP-1)in counterregulatory responses to hypoglycemia in patients with type 1 diabetes mellitus(T1DM).With the global rise of T1DM,there is an increased burden on society and healthcare systems.Due to insulin therapy and islet dysfunction,T1DM patients are highly vulnerable to severe hypoglycemia,a leading cause of mortality.In healthy individuals,counterregulatory mechanisms restore blood glucose during hypoglycemia,but repeated episodes impair these responses.Jin et al demonstrated that overexpression of GLP-1 attenuates the sympathetic-adrenal reflex and disrupts the secretion of counterregulatory hormones such as glucagon during hypoglycemia,leading to counterregulatory dysfunction.These findings highlight the critical role of GLP-1 in the impaired counterregulatory response to hypoglycemia in T1DM patients and provide new insights into the potential application of GLP-1-related therapies in T1DM patients.

Current perspectives and the future of disease-modifying therapies in type 1 diabetes

Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,immunologic vaccination and anti-inflammatory agents targeting specific immune cells or cytokines.Teplizumab is an anti-CD3-molecule that binds to and leads to the disappearance of the CD3/TCR complex and rendering the T cell anergic to its target antigen.Preclinical and clinical trials have demonstrated its efficacy in reducing the decline in serum C-peptide levels and the need for insulin therapy if used early in the disease process of T1DM.The benefits have been apparent as early as six months to as long as seven years after therapy.It has recently been approved by the Food and Drug Administration to delay the onset of clinical(stage 3)type 1 diabetes in children above 8 years of age.In their recent metaanalysis published in the World Journal of Diabetes,Ma et al found that those in the teplizumab treatment group have a greater likelihood of reduction in insulin use,change in C-peptide response,and better glycemic control compared to the control group with a good safety profile.However,all the included randomized control trials have been conducted in high-income countries.High cost of therapy and unknown utility of the molecule in stage 3 disease limit its widespread use.

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

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.

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

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

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

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

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

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.

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

●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.P<0.05),and 328 of these were identified with a significance of Adj.P<0.01.Among these,319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls.Pyrosequencing revealed that the transcription elongation regulator 1 like(TCERG1L,cg07684215)gene was hypermethylated in the four T1DM children with DR(P=0.018),which was consistent with the result from the first survey.The methylation status of the other three DMS(cg26389052,cg25192647,and cg05413694)showed no difference(all P>0.05)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.

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

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.

COVID-19 infection and inactivated vaccination:Impacts on clinical and immunological profiles in Chinese children with type 1 diabetes

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic has been linked to an increased incidence of diabetes and diabetic ketoacidosis(DKA).However,the relationship between COVID-19 infection and progression to type 1 diabetes(T1D)in children has not been well defined.AIM To evaluate the influence of COVID-19 infection and inactivated vaccine adminis-tration on the progression of T1D among Chinese children.METHODS A total of 197 newly diagnosed patients with T1D were retrospectively enrolled from Children's Hospital of Fudan University between September 2020 and December 2023.The patients were divided into three groups based on their history of COVID-19 infection and vaccination:the infection group,the vacci-nation-only group,and the non-infection/non-vaccination group.Comprehensive clinical assessments and detailed immunological evaluations were performed to delineate the characteristics and immune responses of these groups.RESULTS The incidence of DKA was significantly higher in the COVID-19 infection group(70.2%)compared to the non-infection/non-vaccination group(62.5%)and vac-scination-only group(45.6%;P=0.015).Prior COVID-19 infection was correlated with increased DKA risk(OR:1.981,95%CI:1.026-3.825,P=0.042),while vacci-nation was associated with a reduced risk(OR:0.558,95%CI:0.312-0.998,P=0.049).COVID-19 infection mildly altered immune profiles,with modest dif-ferences in autoantibody positivity,lymphocyte distribution,and immunoglobulin levels.Notably,HLA-DR3 po-sitive children with a history of COVID-19 infection had an earlier T1D onset and lower fasting C-peptide levels than the HLA-DR3 negative children with a history of infection(both P<0.05).CONCLUSION COVID-19 infection predisposes children to severe T1D,characterized by enhanced DKA risk.Inactivated vaccination significantly lowers DKA incidence at T1D onset.These findings are valuable for guiding future vaccination and T1D risk surveillance strategies in epidemic scenarios in the general pediatric population.

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

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.

Intestinal glucagon-like peptide-1 in hypoglycemic counterregulation for type 1 diabetes management

Type 1 diabetes(T1D)is characterized by the autoimmune destruction of pan-creatic beta cells,leading to absolute insulin deficiency and the need for exoge-nous insulin.A significant concern in T1D management is hypoglycemia,which is worsened by impaired counterregulatory mechanisms.Effective counterregu-lation involves hormones such as glucagon and adrenaline,which work to restore normal blood glucose levels.However,in T1D,these mechanisms often fail,par-ticularly after recurrent hypoglycemia,resulting in hypoglycemia-associated au-tonomic failure.Recent research indicates that elevated levels of intestinal glu-cagon-like peptide-1(GLP-1)impair counterregulatory responses by reducing the secretion of glucagon and adrenaline.This editorial underscores GLP-1’s role be-yond its incretin effects,contributing to impaired hypoglycemic counterregu-lation.This understanding necessitates a nuanced approach to GLP-1-based the-rapies in T1D,balancing the benefits of glycemic control with potential risks.Future research should delve into the mechanisms behind GLP-1’s effects and explore potential interventions to improve hypoglycemic counterregulation.The goal is to enhance the safety and quality of life for T1D patients.

Adiposity in Chinese people with type 1 diabetes

Adiposity,synonymous with obesity,is prevalent among both children and adults with type 1 diabetes in China.Recent literature underscored the pathophysiological and socioeconomic factors associated with adiposity,and consistently highlighted its impact on cardiovascular,kidney,and metabolic diseases among Chinese individuals with type 1 diabetes.Addressing and managing adiposity in individuals with type 1 diabetes are complicated and entail comprehensive approaches including lifestyle modifications,cognitive-behavioral therapy,insulin dose titration,and other diabetes treatment medications.The condition calls for coordination among policymakers,researchers,clinicians,and patients.

Role of intestinal glucagon-like peptide-1 in hypoglycemia response impairment in type 1 diabetes

This study critically examines the novel findings presented by Jin et al,which explores the role of intestinal glucagon-like peptide-1(GLP-1)in impaired counterregulatory responses to hypoglycemia in mice with type 1 diabetes.The study identifies intestinal GLP-1 as a significant determinant in the physiological responses to hypoglycemia,offering new insights into its potential implications for diabetes management.The editorial synthesizes these findings,discusses their relevance in the context of current diabetes research,and outlines potential avenues for future investigation of intestinal GLP-1 as a therapeutic target.This analysis underscores the need for continued research into the complex mechanisms underlying impaired hypoglycemia responses and highlights the potential of targeting intestinal GLP-1 pathways in therapeutic strategies for type 1 diabetes.

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

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

Glucagon-like peptide-1 agonists:Role of the gut in hypoglycemia unawareness,and the rationale in type 1 diabetes

Type 1 diabetes is increasing and the majority of patients have poor glycemic control.Although advanced technology and nanoparticle use have greatly enhanced insulin delivery and glucose monitoring,weight gain and hypoglycemia remain major challenges and a constant source of concern for patients with type 1 diabetes.Type 1 diabetes shares some pathophysiology with type 2 diabetes,and an overlap has been reported.The above observation created great interest in glucagon-like peptide-1 receptor agonists(GLP-1)as adjuvants for type 1 diabetes.Previous trials confirmed the positive influence of GLP-1 agonists onβcell function.However,hypoglycemia unawareness and dysregulated glucagon response have been previously reported in patients with recurrent hypoglycemia using GLP-1 agonists.Jin et al found that the source of glucagon dysregulation due to GLP-1 agonists resides in the gut.Plausible explanations could be gut nervous system dysregulation or gut microbiota disruption.This review evaluates the potential of GLP-1 agonists in managing type 1 diabetes,particularly focusing on their impact on glycemic control,weight management,and glucagon dysregulation.We provide a broader insight into the problem of type 1 diabetes mellitus management in the light of recent findings and provide future research directions.

Immunotherapy in type 1 diabetes:Novel pathway to the future ahead

Since the discovery of insulin over 100 years ago,the focus of research in the management of type 1 diabetes(T1D)has centered around glycemic control and management of complications rather than the prevention of autoimmune destruc-tion of pancreaticβcells.Fortunately,in recent years,there has been significant advancement in immune-targeted pharmacotherapy to halt the natural progres-sion of T1D.The immune-targeted intervention aims to alter the underlying pa-thogenesis of T1D by targeting different aspects of the immune system.The im-munotherapy can either antagonize the immune mediators like T cells,B cells or cytokines(antibody-based therapy),or reinduce self-tolerance to pancreaticβcells(antigen-based therapy)or stem-cell treatment.Recently,the US Food and Drug Administration approved the first immunotherapy teplizumab to be used only in stage 2 of T1D.However,the window of opportunity to practically implement this approved molecule in the selected target population is limited.In this Edito-rial,we briefly discuss the various promising recent developments in the field of immunotherapy research in T1D.However,further studies of these newer thera-peutic agents are needed to explore their true potential for prevention or cure of T1D.

Safety of teplizumab in patients with high-risk for diabetes mellitus type 1:A systematic review

BACKGROUND The incidence of diabetes mellitus type 1(DM1)has been rising worldwide because of improvements in diagnostic techniques and improved access to care in countries with lower socioeconomic status.A new anti-CD4 antibody,Teplizumab,has been shown to delay the progression of DM1 and is the only medication approved for this indication.However,more information is needed about the safety profile of this drug.AIM To identify the odds ratios(OR)of systems-based adverse effects for Teplizumab when compared to Placebo.METHODS An extensive systematic review was conducted from the inception of the medication until December 31,2023.All clinical trials and studies that evaluated Teplizumab vs placebo were included in the initial review.The study protocol was designed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines guidelines and was registered in PROSPERO(ID:CRD42024496169).Crude OR were generated using RevMan Software version 5.4.RESULTS After screening and review,5 studies were selected to determine the risk of adverse effects of teplizumab compared to placebo.A total of 561 patients were included in the study population.Total adverse effects and system-based adverse effects were studied and reported.We determined that patients receiving Teplizumab had a higher risk of developing gastrointestinal(GI)(OR=1.60,95%CI:1.01-2.52,P=0.04),dermatological(OR=6.33,95%CI:4.05-9.88,P<0.00001)and hematological adverse effects(OR=19.03,95%CI:11.09-32.66,P<0.00001).These patients were also significantly likely to have active Epstein-Barr Virus infection(OR=3.16,95%CI:1.51-6.64,P<0.002).While our data showed that patients receiving Teplizumab did have a higher incidence of total adverse effects vs placebo,this finding did not reach statistical significance(OR=2.25,95%CI:0.80-6.29,P=0.12).CONCLUSION Our systematic review suggests that Teplizumab patients are at risk for significant adverse effects,primarily related to GI,dermatological,and hematological systems.The total adverse effect data is limited as study populations are small.More studies should be conducted on this medication to better inform the target population of potential adverse effects.

Association between glucose levels of children with type 1 diabetes and parental economic status in mobile health application

BACKGROUND The glycemic control of children with type 1 diabetes(T1D)may be influenced by the economic status of their parents.AIM To investigate the association between parental economic status and blood glucose levels of children with T1D using a mobile health application.METHODS Data from children with T1D in China's largest T1D online community,Tang-TangQuan■.Blood glucose levels were uploaded every three months and parental economic status was evaluated based on annual household income.Children were divided into three groups:Low-income(<30000 Yuan),middle-income(30000-100000 Yuan),and high-income(>100000 yuan)(1 Yuan=0.145 United States Dollar approximately).Blood glucose levels were compared among the groups and associations were explored using Spearman’s correlation analysis and multivariable logistic regression.RESULTS From September 2015 to August 2022,1406 eligible children with T1D were included(779 female,55.4%).Median age was 8.1 years(Q1-Q3:4.6-11.6)and duration of T1D was 0.06 years(0.02-0.44).Participants were divided into three groups:Low-income(n=320),middle-income(n=724),and high-income(n=362).Baseline hemoglobin A1c(HbA1c)levels were comparable among the three groups(P=0.072).However,at month 36,the low-income group had the highest HbA1c levels(P=0.036).Within three years after registration,glucose levels increased significantly in the low-income group but not in the middle-income and high-income groups.Parental economic status was negatively correlated with pre-dinner glucose(r=-0.272,P=0.012).After adjustment for confounders,parental economic status remained a significant factor related to pre-dinner glucose levels(odds ratio=13.02,95%CI:1.99 to 126.05,P=0.002).CONCLUSION The blood glucose levels of children with T1D were negatively associated with parental economic status.It is suggested that parental economic status should be taken into consideration in the management of T1D for children.