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 fo...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.展开更多
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-spec...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.展开更多
Managing diabetes during pregnancy is challenging,given the significant risk it poses for both maternal and foetal health outcomes.While traditional methods involve capillary self-monitoring of blood glucose level mon...Managing diabetes during pregnancy is challenging,given the significant risk it poses for both maternal and foetal health outcomes.While traditional methods involve capillary self-monitoring of blood glucose level monitoring and periodic HbA1c tests,the advent of continuous glucose monitoring(CGM)systems has revolutionized the approach.These devices offer a safe and reliable means of tracking glucose levels in real-time,benefiting both women with diabetes during pregnancy and the healthcare providers.Moreover,CGM systems have shown a low rate of side effects and high feasibility when used in pregnancies complicated by diabetes,especially when paired with continuous subcutaneous insulin infusion pump as hybrid closed loop device.Such a combined approach has been demonstrated to improve overall blood sugar control,lessen the occurrence of preeclampsia and neonatal hypoglycaemia,and minimize the duration of neonatal intensive care unit stays.This paper aims to offer a comprehensive evaluation of CGM metrics specifically tailored for pregnancies impacted by type 1 diabetes mellitus.展开更多
Type 1 diabetes mellitus(T1DM)is a chronic endocrine disease that results from autoimmune destruction of pancreatic insulin-producingβcells,which can lead to microvascular(e.g.,retinopathy,neuropathy,and nephropathy)...Type 1 diabetes mellitus(T1DM)is a chronic endocrine disease that results from autoimmune destruction of pancreatic insulin-producingβcells,which can lead to microvascular(e.g.,retinopathy,neuropathy,and nephropathy)and macrovascular complications(e.g.,coronary arterial disease,peripheral artery disease,stroke,and heart failure)as a consequence of chronic hyperglycemia.Despite the widely available and compelling evidence that regular exercise is an efficient strategy to prevent cardiovascular disease and to improve functional capacity and psychological well-being in people with T1DM,over 60%of individuals with T1DM do not exercise regularly.It is,therefore,crucial to devise approaches to motivate patients with T1DM to exercise,to adhere to a training program,and to inform them of its specific characteristics(e.g.,exercise mode,intensity,volume,and frequency).Moreover,given the metabolic alterations that occur during acute bouts of exercise in T1DM patients,exercise prescription in this population should be carefully analyzed to maximize its benefits and to reduce its potential risks.展开更多
Type 1 diabetes mellitus(T1DM)is one of the important causes of chronic kidney disease(CKD)and end-stage renal failure(ESRF).Even with the best available treatment options,management of T1DM poses significant challeng...Type 1 diabetes mellitus(T1DM)is one of the important causes of chronic kidney disease(CKD)and end-stage renal failure(ESRF).Even with the best available treatment options,management of T1DM poses significant challenges for clinicians across the world,especially when associated with CKD and ESRF.Substantial increases in morbidity and mortality along with marked rise in treatment costs and marked reduction of quality of life are the usual consequences of onset of CKD and progression to ESRF in patients with T1DM.Simultaneous pancreas-kidney transplant(SPK)is an attractive and promising treatment option for patients with advanced CKD/ESRF and T1DM for potential cure of these diseases and possibly several complications.However,limited availability of the organs for transplantation,the need for long-term immunosuppression to prevent rejection,peri-and post-operative complications of SPK,lack of resources and the expertise for the procedure in many centers,and the cost implications related to the surgery and postoperative care of these patients are major issues faced by clinicians across the globe.This clinical update review compiles the latest evidence and current recommendations of SPK for patients with T1DM and advanced CKD/ESRF to enable clinicians to care for these diseases.展开更多
Background: Diabetic retinopathy is among the most common diabetic complications, and is one of the leading causes of blindness in the world. Recent studies have linked vitamin D to the pathogenesis of diabetes and th...Background: Diabetic retinopathy is among the most common diabetic complications, and is one of the leading causes of blindness in the world. Recent studies have linked vitamin D to the pathogenesis of diabetes and there is growing evidence that vitamin D can interfere with the mechanisms involved in diabetes and its complications. Despite improvements in treatment, diabetic retinopathy remains a significant complication of type 1 diabetes mellitus. Identification of early treatable predictors of diabetic retinopathy such as vitamin D deficiency, may allow more aggressive management of those at high risk. Purpose: To assess the association of vitamin D deficiency with diabetic retinopathy in young people with type 1 diabetes mellitus. Design: Observational study with case control design. Method: 60 young people with type 1 diabetes aged between 11 to 24 years were included in this study. Among them, 30-young people have diabetic retinopathy and 30-young people do not have diabetic retinopathy. Purposive sampling technique was applied as per inclusion criteria. Statistical analysis of the results was done by using computer-based software, SPSS version 26. P value of less than 0.05 was considered as statistically significant. Results: Vitamin D deficiency was present in 83% of the young people with diabetic retinopathy and in 53% without diabetic retinopathy. The mean vitamin D level in young people with and without diabetic retinopathy was 17.38 ± 3.77 ng/ml and 20.15 ± 5.06 ng/ml respectively and the difference was statistically significant (p = 0.019). Vitamin D deficiency was increased with the severity of diabetic retinopathy. Univariate and multivariate logistic regression showed vitamin D deficiency was independently associated with diabetic retinopathy with a crude odds ratio of 5.69 with a p value of 0.008 and adjusted odds ratio of 16.08 with a p value of 0.002 respectively. Conclusion: Result of the study revealed that vitamin D deficiency was strongly associated with diabetic retinopathy in young people with type 1 diabetes mellitus.展开更多
BACKGROUND Gut microbiota dysbiosis is reportedly actively involved in autoimmune diseases such as type 1 diabetes mellitus(T1DM).However,the alterations in the gut microbiota and their correlation with fasting blood ...BACKGROUND Gut microbiota dysbiosis is reportedly actively involved in autoimmune diseases such as type 1 diabetes mellitus(T1DM).However,the alterations in the gut microbiota and their correlation with fasting blood glucose(FBG)in Chinese children with T1DM remain unclear.AIM To investigate alterations in the gut microbiota in Chinese children with T1DM and their associations with clinical indicators.METHODS Samples from 51 children with T1DM and 47 age-matched and gender-matched healthy controls were obtained,to explore the structural and functional alterations in the fecal microbiota.The V3-V4 regions of the 16S rRNA gene were sequenced on a MiSeq instrument,and the association with FBG were analyzed.RESULTS We found that the bacterial diversity was significantly increased in the T1DMassociated fecal microbiota,and changes in the microbial composition were observed at different taxonomic levels.The T1DM-reduced differential taxa,such as Bacteroides vulgatus ATCC8482,Bacteroides ovatus,Bacteroides xylanisolvens,and Flavonifractor plautii,were negatively correlated with FBG,while the T1DMenriched taxa,such as Blautia,Eubacterium hallii group,Anaerostipes hadrus,and Dorea longicatena,were positively correlated with FBG.Bacteroides vulgatus ATCC8482,Bacteroides ovatus,the Eubacterium hallii group,and Anaerostipes hadrus,either alone or in combination,could be used as noninvasive diagnostic biomarkers to discriminate children with T1DM from healthy controls.In addition,the functional changes in the T1DM-associated fecal microbiota also suggest that these fecal microbes were associated with altered functions and metabolic activities,such as glycan biosynthesis and metabolism and lipid metabolism,which might play vital roles in the pathogenesis and development of T1DM.CONCLUSION Our present comprehensive investigation of the T1DM-associated fecal microbiota provides novel insights into the pathogenesis of the disease and sheds light on the diagnosis and treatment of T1DM.展开更多
As a T cell-mediated autoimmune disease,type 1 diabetes mellitus(T1DM)is marked by insulin defect resulting from the destruction of pancreaticβ-cells.The understanding of various aspects of T1DM,such as its epidemiol...As a T cell-mediated autoimmune disease,type 1 diabetes mellitus(T1DM)is marked by insulin defect resulting from the destruction of pancreaticβ-cells.The understanding of various aspects of T1DM,such as its epidemiology,pathobiology,pathogenesis,clinical manifestations,and complications,has been greatly promoted by valuable research performed during the past decades.However,these findings have not been translated into an effective treatment.The ideal treatment should safely repair the destroyed immune balance in a longlasting manner,preventing or stopping the destruction ofβ-cells.As a type of immune hypo-responsiveness to the orally administrated antigen,oral tolerance may be induced by enhancement of regulatory T cells(Tregs)or by anergy/deletion of T cells,depending on the dosage of orally administrated antigen.Acting as an antigen-specific immunotherapy,oral tolerance therapy for T1DM has been mainly performed using animal models and some clinical trials have been completed or are still ongoing.Based on the review of the proposed mechanism of the development of T1DM and oral tolerance,we give a current overview of oral tolerance therapy for T1DM conducted in both animal models and clinical trials.展开更多
Hypoglycemia limits optimal glycemic management of patients with type 1 diabetes mellitus(T1DM).Fear of hypoglycemia(FoH)is a significant psychosocial consequence that negatively impacts the willingness of T1DM patien...Hypoglycemia limits optimal glycemic management of patients with type 1 diabetes mellitus(T1DM).Fear of hypoglycemia(FoH)is a significant psychosocial consequence that negatively impacts the willingness of T1DM patients to engage in and profit from the health benefits of regular physical activity(e.g.,cardiometabolic health,improved body composition,cardiovascular fitness,quality of life).Technological advances,improved insulin regimens,and a better understanding of the physiology of various types of exercise could help ameliorate FoH.This narrative review summarizes the available literature on FoH in children and adults and tools to avoid it.展开更多
Type 1 Diabetes Mellitus remains one of the most complex chronic diseases in childhood. Although advances in knowledge and technology, as the use of insulin pumps or glucose sensors, have improved the quality of life ...Type 1 Diabetes Mellitus remains one of the most complex chronic diseases in childhood. Although advances in knowledge and technology, as the use of insulin pumps or glucose sensors, have improved the quality of life of patients, the onset of the disease, as well as long-term treatment and diet, are pitfalls for families and clinicians. It is important to bear in mind that acute, life-threatening consequences of uncontrolled diabetes are hyperglycemia with ketoacidosis, both in new diagnosis and in patients already on treatment, and may be hidden by other symptoms. Moreover, treatment with insulin and diet should always be tailored on lifestyle habits and age of the patient. Aim of this work is to briefly summarise and comment what are the worst insidious aspects of Diabetes and what are the best strategies to improve the management of the disease in childhood.展开更多
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 e...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.展开更多
Type 2 diabetes mellitus(T2DM)is a lifelong condition and a threat to human health.Thorough understanding of its pathogenesis is acutely needed in order to devise innovative,preventative,and potentially curative pharm...Type 2 diabetes mellitus(T2DM)is a lifelong condition and a threat to human health.Thorough understanding of its pathogenesis is acutely needed in order to devise innovative,preventative,and potentially curative pharmacological interventions.MicroRNAs(miRNA),are small,non-coding,one-stranded RNA molecules,that can target and silence around 60%of all human genes through translational repression.MiR-155 is an ancient,evolutionarily well-conserved miRNA,with distinct expression profiles and multifunctionality,and a target repertoire of over 241 genes involved in numerous physiological and pathological processes including hematopoietic lineage differentiation,immunity,inflammation,viral infections,cancer,cardiovascular conditions,and particularly diabetes mellitus.MiR-155 Levels are progressively reduced in aging,obesity,sarcopenia,and T2DM.Thus,the loss of coordinated repression of multiple miR-155 targets acting as negative regulators,such as C/EBPβ,HDAC4,and SOCS1 impacts insulin signaling,deteriorating glucose homeostasis,and causing insulin resistance(IR).Moreover,deranged regulation of the renin angiotensin aldosterone system(RAAS)through loss of Angiotensin II Type 1 receptor downregulation,and negated repression of ETS-1,results in unopposed detrimental Angiotensin II effects,further promoting IR.Finally,loss of BACH1 and SOCS1 repression abolishes cytoprotective,anti-oxidant,anti-apoptotic,and anti-inflam matory cellular pathways,and promotesβ-cell loss.In contrast to RAAS inhibitor treatments that further decrease already reduced miR-155 Levels,strategies to increase an ailing miR-155 production in T2DM,e.g.,the use of metformin,mineralocorticoid receptor blockers(spironolactone,eplerenone,finerenone),and verapamil,alone or in various combinations,represent current treatment options.In the future,direct tissue delivery of miRNA analogs is likely.展开更多
A century has passed since the Nobel Prize winning discovery of insulin,which still remains the mainstay treatment for type 1 diabetes mellitus(T1DM)to this day.True to the words of its discoverer Sir Frederick Banti...A century has passed since the Nobel Prize winning discovery of insulin,which still remains the mainstay treatment for type 1 diabetes mellitus(T1DM)to this day.True to the words of its discoverer Sir Frederick Banting,“insulin is not a cure for diabetes,it is a treatment”,millions of people with T1DM are dependent on daily insulin medications for life.Clinical donor islet transplantation has proven that T1DM is curable,however due to profound shortages of donor islets,it is not a mainstream treatment option for T1DM.Human pluripotent stem cell derived insulin-secreting cells,pervasively known as stem cell-derivedβcells(SC-βcells),are a promising alternative source and have the potential to become a T1DM treatment through cell replacement therapy.Here we briefly review how isletβcells develop and mature in vivo and several types of reported SC-βcells produced using different ex vivo protocols in the last decade.Although some markers of maturation were expressed and glucose stimulated insulin secretion was shown,the SC-βcells have not been directly compared to their in vivo counterparts,generally have limited glucose response,and are not yet fully matured.Due to the presence of extra-pancreatic insulin-expressing cells,and ethical and technological issues,further clarification of the true nature of these SC-βcells is required.展开更多
Type 2 diabetes mellitus(T2DM)is a lifelong condition and a grave threat to human health.Innovative efforts to relieve its detrimental effects are acutely needed.The sine qua non in T2DM management is consistent adher...Type 2 diabetes mellitus(T2DM)is a lifelong condition and a grave threat to human health.Innovative efforts to relieve its detrimental effects are acutely needed.The sine qua non in T2DM management is consistent adherence to a prudent lifestyle and nutrition,combined with aerobic and resistance exercise regimens,together repeatedly shown to lead to complete reversal and even longterm remission.Non-adherence to the above lifestyle adjustments condemns any treatment effort and ultimately the patient to a grim fate.It is thus imperative that every study evaluating the effects of innovative interventions in T2DM objectively compares the novel treatment modality to lifestyle modifications,preferably through double-blind controlled randomization,before claiming efficacy.展开更多
Type 1 diabetes mellitus(T1D)is a chronic autoimmune condition in which the immune system destroys insulin-producing pancreatic β cells.In addition to well-established pathogenic effector T cells,regulatory T cells(T...Type 1 diabetes mellitus(T1D)is a chronic autoimmune condition in which the immune system destroys insulin-producing pancreatic β cells.In addition to well-established pathogenic effector T cells,regulatory T cells(Tregs)have also been shown to be defective in T1D.Thus,an increasing number of therapeutic approaches are being developed to target Tregs.However,the role and mechanisms of TGF-β-induced Tregs(iTregs)in T1D remain poorly understood.Here,using a streptozotocin(STZ)-induced preclinical T1D mouse model,we found that iTregs could ameliorate the development of T1D and preserve β cell function.The preventive effect was associated with the inhibition of type 1 cytotoxic T(Tel)cell function and rebalancing the Treg/Tc1 cell ratio in recipients.Furthermore,we showed that the underlying mechanisms were due to the TGF-β-mediated combinatorial actions of mTOR and TCF1.In addition to the preventive role,the therapeutic effects of iTregs on the established STZ-T1D and nonobese diabetic(NOD)mouse models were tested,which revealed improved β cell function.Our findings therefore provide key new insights into the basic mechanisms involved in the therapeutic role of iTregs in T1D.展开更多
Autoantibodies and inflammation are the hallmarks of autoimmune diseases(ADs).Organ-specific and nonorgan-specific ADs are divided according to whether the autoimmune reaction is directed against a specific tissue(e.g...Autoantibodies and inflammation are the hallmarks of autoimmune diseases(ADs).Organ-specific and nonorgan-specific ADs are divided according to whether the autoimmune reaction is directed against a specific tissue(e.g.,thyroid in Hashimoto's thyroiditis)or widely expressed antigens(e.g.,cell nuclei in systemic lupus erythematosus[SLE]).SLE is distinguished by the presence of circulating autoantibodies and immune complex deposition,both of which can induce inflammatory damage to many organs.Rheumatoid arthritis(RA),sometimes called inflammatory arthritis,is a systemic AD that affects the joints and causes synovitis.Multiple sclerosis(MS)is a central nervous system inflammatory disease with various neurological and autoimmune symptoms.Links have been reported between RA and SLE as well as between Type 1 diabetes mellitus and MS.Identification of shared genes and biological processes could aid in the discovery of possible treatment targets in these dual ADs.This review article explores the molecular nature and familial inheritance of dual ADs.展开更多
The magnitude of diabetes mellitus(DM)has increased in recent decades,where the number of cases and the proportion of the disease have been gradually increasing over the past few decades.The chronic complications of D...The magnitude of diabetes mellitus(DM)has increased in recent decades,where the number of cases and the proportion of the disease have been gradually increasing over the past few decades.The chronic complications of DM affect many organ systems and account for the majority of morbidity and mortality associated with the disease.The prevalence of type 1 DM(T1DM)is increasing globally,and it has a very significant burden on countries and at an individual level.T1DM is a chronic illness that requires ongoing medical care and patient self-management to prevent complications.This study aims to discuss the health benefits of physical activity(PA)in T1DM patients.The present review article was performed following a comprehensive literature search.The search was conducted using the following electronic databases:“Cochrane Library”,Web of Science,PubMed,HINARI,EMBASE,Google for grey literature,Scopus,African journals Online,and Google Scholar for articles published up to June 21,2021.The present review focused on the effects of PA on many outcomes such as blood glucose(BG)control,physical fitness,endothelial function,insulin sensitivity,well-being,the body defense system,blood lipid profile,insulin resistance,cardiovascular diseases(CVDs),insulin requirements,blood pressure(BP),and mortality.It was found that many studies recommended the use of PA for the effective management of T1DM.PA is a component of comprehensive lifestyle modifications,which is a significant approach for the management of T1DM.It provides several health benefits,such as improving BG control,physical fitness,endothelial function,insulin sensitivity,well-being,and the body defense system.Besides this,it reduces the blood lipid profile,insulin resistance,CVDs,insulin requirements,BP,and mortality.Overall,PA has significant and essential protective effects against the health risks associated with T1DM.Even though PA has several health benefits for patients with T1DM,these patients are not well engaged in PA due to barriers such as a fear of exercise-induced hypoglycemia in particular.However,several effective strategies have been identified to control exercise-induced hypoglycemia in these patients.Finally,the present review concludes that PA should be recommended for the management of patients with T1DM due to its significant health benefits and protective effects against associated health risks. Italso provides suggestions for the future direction of research in this field.展开更多
Type 1 diabetes mellitus(T1DM)is a chronic autoimmune disease caused by the specific destruction of pancreatic isletβcells and is characterized as the absolute insufficiency of insulin secretion.Current insulin repla...Type 1 diabetes mellitus(T1DM)is a chronic autoimmune disease caused by the specific destruction of pancreatic isletβcells and is characterized as the absolute insufficiency of insulin secretion.Current insulin replacement therapy supplies insulin in a non-physiological way and is associated with devastating complications.Experimental islet transplantation therapy has been proven to restore glucose homeostasis in people with severe T1DM.However,it is restricted by many factors such as severe shortage of donor sources,progressive loss of donor cells,high cost,etc.As pluripotent stem cells have the potential to give rise to all cells including isletβcells in the body,stem cell therapy for diabetes has attracted great attention in the academic community and the general public.Transplantation of isletβ-like cells differentiated from human pluripotent stem cells(hPSCs)has the potential to be an excellent alternative to islet transplantation.In stem cell therapy,obtainingβcells with complete insulin secretion in vitro is crucial.However,after much research,it has been found that theβ-like cells obtained by in vitro differentiation still have many defects,including lack of adult-type glucose stimulated insulin secretion,and multihormonal secretion,suggesting that in vitro culture does not allows for obtaining fully matureβ-like cells for transplantation.A large number of studies have found that many transcription factors play important roles in the process of transforming immature to mature human isletβcells.Furthermore,PDX1,NKX6.1,SOX9,NGN3,PAX4,etc.,are important in inducing hPSC differentiation in vitro.The absent or deficient expression of any of these key factors may lead to the islet development defect in vivo and the failure of stem cells to differentiate into genuine functionalβ-like cells in vitro.This article reviewsβcell maturation in vivo and in vitro and the vital roles of key molecules in this process,in order to explore the current problems in stem cell therapy for diabetes.展开更多
BACKGROUND Type 1 diabetes(DT1)in adolescents brings behavioural changes,altered nutritional habits,and eating disorders.AIM To identify and analyze the validated instruments that examine the disordered eating behavio...BACKGROUND Type 1 diabetes(DT1)in adolescents brings behavioural changes,altered nutritional habits,and eating disorders.AIM To identify and analyze the validated instruments that examine the disordered eating behaviour and eating disorders among adolescents with DT1.METHODS An integrative review was accomplished based on the following databases:PubMed,LILACS,CINAHL,Scopus,Web of Science,and Reference Citation Analysis(RCA),including publications in Portuguese,English,or Spanish,without time limit and time published.RESULTS The main instruments to evaluate disordered eating behaviour were The Diabetes Eating Problem Survey-Revised,The Diabetes Eating Problem Survey,and the eating attitudes test-26,and for eating disorders the main instruments used were The Bulimic Investigation Test of Edinburgh,The Binge Eating Scale,The Child Eating Disorder Examination,The five questions of the(Sick,Control,One,Fat and Food),and The Mind Youth Questionnaire.These instruments showed an effect in evaluating risks regarding nutritional habits or feeding grievances,with outcomes related to weight control,inadequate use of insulin,and glycaemia unmanageability.We did not identify publication bias.CONCLUSION Around the world,the most used scale to study the risk of disordered eating behaviour or eating disorder is The Diabetes Eating Problem Survey-Revised.International researchers use this scale to identify high scores in adolescents with DT1 and a relationship with poorer glycemic control and psychological problems related to body image.展开更多
Genetic linkage analyses, genome-wide association studies of single nucleotide polymorphisms, copy number variation surveys, and mutation screenings found the human chromosomal 12q24 locus, with the genes SH2B3 and AT...Genetic linkage analyses, genome-wide association studies of single nucleotide polymorphisms, copy number variation surveys, and mutation screenings found the human chromosomal 12q24 locus, with the genes SH2B3 and ATXN2 in its core, to be associated with an exceptionally wide spectrum of disease susceptibilities. Hematopoietic traits of red and white blood cells(like erythrocytosis and myeloproliferative disease), autoimmune disorders(like type 1 diabetes, coeliac disease, juvenile idiopathic arthritis, rheumatoid arthritis, thrombotic antiphospholipid syndrome, lupus erythematosus, multiple sclerosis, hypothyroidism and vitiligo), also vascular pathology(like kidney glomerular filtration rate deficits, serum urate levels, plasma beta-2-microglobulin levels, retinal microcirculation problems, diastolic and systolic blood pressure and hypertension, cardiovascular infarction), furthermore obesity, neurodegenerative conditions(like the polyglutamine-expansion disorder spinocerebellar ataxia type 2, Parkinson's disease, the motor-neuron disease amyotrophic lateral sclerosis, and progressive supranuclear palsy), andfinally longevity were reported. Now it is important to clarify, in which ways the loss or gain of function of the locally encoded proteins SH2B3/LNK and ataxin-2, respectively, contribute to these polygenic health problems. SH2B3/LNK is known to repress the JAK2/ABL1 dependent proliferation of white blood cells. Its null mutations in human and mouse are triggers of autoimmune traits and leukemia(acute lymphoblastic leukemia or chronic myeloid leukemia-like), while missense mutations were found in erythrocytosis-1 patients. Ataxin-2 is known to act on RNA-processing and trophic receptor internalization. While its polyglutamine-expansion mediated gain-of-function causes neuronal atrophy in human and mouse, its deletion leads to obesity and insulin resistance in mice. Thus, it is conceivable that the polygenic pathogenesis of type 1 diabetes is enhanced by an SH2B3-dysregulation-mediated predisposition to autoimmune diseases that conspires with an ATXN2-deficiency-mediated predisposition to lipid and glucose metabolism pathology.展开更多
基金Supported by National Natural Science Foundation of China,No.82270864.
文摘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.
文摘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.
文摘Managing diabetes during pregnancy is challenging,given the significant risk it poses for both maternal and foetal health outcomes.While traditional methods involve capillary self-monitoring of blood glucose level monitoring and periodic HbA1c tests,the advent of continuous glucose monitoring(CGM)systems has revolutionized the approach.These devices offer a safe and reliable means of tracking glucose levels in real-time,benefiting both women with diabetes during pregnancy and the healthcare providers.Moreover,CGM systems have shown a low rate of side effects and high feasibility when used in pregnancies complicated by diabetes,especially when paired with continuous subcutaneous insulin infusion pump as hybrid closed loop device.Such a combined approach has been demonstrated to improve overall blood sugar control,lessen the occurrence of preeclampsia and neonatal hypoglycaemia,and minimize the duration of neonatal intensive care unit stays.This paper aims to offer a comprehensive evaluation of CGM metrics specifically tailored for pregnancies impacted by type 1 diabetes mellitus.
文摘Type 1 diabetes mellitus(T1DM)is a chronic endocrine disease that results from autoimmune destruction of pancreatic insulin-producingβcells,which can lead to microvascular(e.g.,retinopathy,neuropathy,and nephropathy)and macrovascular complications(e.g.,coronary arterial disease,peripheral artery disease,stroke,and heart failure)as a consequence of chronic hyperglycemia.Despite the widely available and compelling evidence that regular exercise is an efficient strategy to prevent cardiovascular disease and to improve functional capacity and psychological well-being in people with T1DM,over 60%of individuals with T1DM do not exercise regularly.It is,therefore,crucial to devise approaches to motivate patients with T1DM to exercise,to adhere to a training program,and to inform them of its specific characteristics(e.g.,exercise mode,intensity,volume,and frequency).Moreover,given the metabolic alterations that occur during acute bouts of exercise in T1DM patients,exercise prescription in this population should be carefully analyzed to maximize its benefits and to reduce its potential risks.
文摘Type 1 diabetes mellitus(T1DM)is one of the important causes of chronic kidney disease(CKD)and end-stage renal failure(ESRF).Even with the best available treatment options,management of T1DM poses significant challenges for clinicians across the world,especially when associated with CKD and ESRF.Substantial increases in morbidity and mortality along with marked rise in treatment costs and marked reduction of quality of life are the usual consequences of onset of CKD and progression to ESRF in patients with T1DM.Simultaneous pancreas-kidney transplant(SPK)is an attractive and promising treatment option for patients with advanced CKD/ESRF and T1DM for potential cure of these diseases and possibly several complications.However,limited availability of the organs for transplantation,the need for long-term immunosuppression to prevent rejection,peri-and post-operative complications of SPK,lack of resources and the expertise for the procedure in many centers,and the cost implications related to the surgery and postoperative care of these patients are major issues faced by clinicians across the globe.This clinical update review compiles the latest evidence and current recommendations of SPK for patients with T1DM and advanced CKD/ESRF to enable clinicians to care for these diseases.
文摘Background: Diabetic retinopathy is among the most common diabetic complications, and is one of the leading causes of blindness in the world. Recent studies have linked vitamin D to the pathogenesis of diabetes and there is growing evidence that vitamin D can interfere with the mechanisms involved in diabetes and its complications. Despite improvements in treatment, diabetic retinopathy remains a significant complication of type 1 diabetes mellitus. Identification of early treatable predictors of diabetic retinopathy such as vitamin D deficiency, may allow more aggressive management of those at high risk. Purpose: To assess the association of vitamin D deficiency with diabetic retinopathy in young people with type 1 diabetes mellitus. Design: Observational study with case control design. Method: 60 young people with type 1 diabetes aged between 11 to 24 years were included in this study. Among them, 30-young people have diabetic retinopathy and 30-young people do not have diabetic retinopathy. Purposive sampling technique was applied as per inclusion criteria. Statistical analysis of the results was done by using computer-based software, SPSS version 26. P value of less than 0.05 was considered as statistically significant. Results: Vitamin D deficiency was present in 83% of the young people with diabetic retinopathy and in 53% without diabetic retinopathy. The mean vitamin D level in young people with and without diabetic retinopathy was 17.38 ± 3.77 ng/ml and 20.15 ± 5.06 ng/ml respectively and the difference was statistically significant (p = 0.019). Vitamin D deficiency was increased with the severity of diabetic retinopathy. Univariate and multivariate logistic regression showed vitamin D deficiency was independently associated with diabetic retinopathy with a crude odds ratio of 5.69 with a p value of 0.008 and adjusted odds ratio of 16.08 with a p value of 0.002 respectively. Conclusion: Result of the study revealed that vitamin D deficiency was strongly associated with diabetic retinopathy in young people with type 1 diabetes mellitus.
基金National Natural Science Foundation of China,No.31700800,No.81771724,and No.81790631National S&T Major Project of China,No.2018YFC2000500.
文摘BACKGROUND Gut microbiota dysbiosis is reportedly actively involved in autoimmune diseases such as type 1 diabetes mellitus(T1DM).However,the alterations in the gut microbiota and their correlation with fasting blood glucose(FBG)in Chinese children with T1DM remain unclear.AIM To investigate alterations in the gut microbiota in Chinese children with T1DM and their associations with clinical indicators.METHODS Samples from 51 children with T1DM and 47 age-matched and gender-matched healthy controls were obtained,to explore the structural and functional alterations in the fecal microbiota.The V3-V4 regions of the 16S rRNA gene were sequenced on a MiSeq instrument,and the association with FBG were analyzed.RESULTS We found that the bacterial diversity was significantly increased in the T1DMassociated fecal microbiota,and changes in the microbial composition were observed at different taxonomic levels.The T1DM-reduced differential taxa,such as Bacteroides vulgatus ATCC8482,Bacteroides ovatus,Bacteroides xylanisolvens,and Flavonifractor plautii,were negatively correlated with FBG,while the T1DMenriched taxa,such as Blautia,Eubacterium hallii group,Anaerostipes hadrus,and Dorea longicatena,were positively correlated with FBG.Bacteroides vulgatus ATCC8482,Bacteroides ovatus,the Eubacterium hallii group,and Anaerostipes hadrus,either alone or in combination,could be used as noninvasive diagnostic biomarkers to discriminate children with T1DM from healthy controls.In addition,the functional changes in the T1DM-associated fecal microbiota also suggest that these fecal microbes were associated with altered functions and metabolic activities,such as glycan biosynthesis and metabolism and lipid metabolism,which might play vital roles in the pathogenesis and development of T1DM.CONCLUSION Our present comprehensive investigation of the T1DM-associated fecal microbiota provides novel insights into the pathogenesis of the disease and sheds light on the diagnosis and treatment of T1DM.
基金Supported by National Natural Science Foundation of China,No.81803418Natural Science Foundation of the Jiangsu Higher Education Institutions,No.18KJD350001and Project for Youth Scholar of Jiangsu Collaborative Innovation Center of Regional Modern Agriculture and Environmental Projection,No.HSXT2-314.
文摘As a T cell-mediated autoimmune disease,type 1 diabetes mellitus(T1DM)is marked by insulin defect resulting from the destruction of pancreaticβ-cells.The understanding of various aspects of T1DM,such as its epidemiology,pathobiology,pathogenesis,clinical manifestations,and complications,has been greatly promoted by valuable research performed during the past decades.However,these findings have not been translated into an effective treatment.The ideal treatment should safely repair the destroyed immune balance in a longlasting manner,preventing or stopping the destruction ofβ-cells.As a type of immune hypo-responsiveness to the orally administrated antigen,oral tolerance may be induced by enhancement of regulatory T cells(Tregs)or by anergy/deletion of T cells,depending on the dosage of orally administrated antigen.Acting as an antigen-specific immunotherapy,oral tolerance therapy for T1DM has been mainly performed using animal models and some clinical trials have been completed or are still ongoing.Based on the review of the proposed mechanism of the development of T1DM and oral tolerance,we give a current overview of oral tolerance therapy for T1DM conducted in both animal models and clinical trials.
文摘Hypoglycemia limits optimal glycemic management of patients with type 1 diabetes mellitus(T1DM).Fear of hypoglycemia(FoH)is a significant psychosocial consequence that negatively impacts the willingness of T1DM patients to engage in and profit from the health benefits of regular physical activity(e.g.,cardiometabolic health,improved body composition,cardiovascular fitness,quality of life).Technological advances,improved insulin regimens,and a better understanding of the physiology of various types of exercise could help ameliorate FoH.This narrative review summarizes the available literature on FoH in children and adults and tools to avoid it.
文摘Type 1 Diabetes Mellitus remains one of the most complex chronic diseases in childhood. Although advances in knowledge and technology, as the use of insulin pumps or glucose sensors, have improved the quality of life of patients, the onset of the disease, as well as long-term treatment and diet, are pitfalls for families and clinicians. It is important to bear in mind that acute, life-threatening consequences of uncontrolled diabetes are hyperglycemia with ketoacidosis, both in new diagnosis and in patients already on treatment, and may be hidden by other symptoms. Moreover, treatment with insulin and diet should always be tailored on lifestyle habits and age of the patient. Aim of this work is to briefly summarise and comment what are the worst insidious aspects of Diabetes and what are the best strategies to improve the management of the disease in childhood.
基金Supported by the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation,No.GZC20231088President Foundation of The Third Affiliated Hospital of Southern Medical University,China,No.YP202210.
文摘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.
文摘Type 2 diabetes mellitus(T2DM)is a lifelong condition and a threat to human health.Thorough understanding of its pathogenesis is acutely needed in order to devise innovative,preventative,and potentially curative pharmacological interventions.MicroRNAs(miRNA),are small,non-coding,one-stranded RNA molecules,that can target and silence around 60%of all human genes through translational repression.MiR-155 is an ancient,evolutionarily well-conserved miRNA,with distinct expression profiles and multifunctionality,and a target repertoire of over 241 genes involved in numerous physiological and pathological processes including hematopoietic lineage differentiation,immunity,inflammation,viral infections,cancer,cardiovascular conditions,and particularly diabetes mellitus.MiR-155 Levels are progressively reduced in aging,obesity,sarcopenia,and T2DM.Thus,the loss of coordinated repression of multiple miR-155 targets acting as negative regulators,such as C/EBPβ,HDAC4,and SOCS1 impacts insulin signaling,deteriorating glucose homeostasis,and causing insulin resistance(IR).Moreover,deranged regulation of the renin angiotensin aldosterone system(RAAS)through loss of Angiotensin II Type 1 receptor downregulation,and negated repression of ETS-1,results in unopposed detrimental Angiotensin II effects,further promoting IR.Finally,loss of BACH1 and SOCS1 repression abolishes cytoprotective,anti-oxidant,anti-apoptotic,and anti-inflam matory cellular pathways,and promotesβ-cell loss.In contrast to RAAS inhibitor treatments that further decrease already reduced miR-155 Levels,strategies to increase an ailing miR-155 production in T2DM,e.g.,the use of metformin,mineralocorticoid receptor blockers(spironolactone,eplerenone,finerenone),and verapamil,alone or in various combinations,represent current treatment options.In the future,direct tissue delivery of miRNA analogs is likely.
基金Supported by the Juvenile Diabetes Research Foundation,No.4-2006-1025Diabetes Australia Research TrustTelethon Perth Children’s Hospital Research Fund(TPCHRF)grant to Jiang FX.
文摘A century has passed since the Nobel Prize winning discovery of insulin,which still remains the mainstay treatment for type 1 diabetes mellitus(T1DM)to this day.True to the words of its discoverer Sir Frederick Banting,“insulin is not a cure for diabetes,it is a treatment”,millions of people with T1DM are dependent on daily insulin medications for life.Clinical donor islet transplantation has proven that T1DM is curable,however due to profound shortages of donor islets,it is not a mainstream treatment option for T1DM.Human pluripotent stem cell derived insulin-secreting cells,pervasively known as stem cell-derivedβcells(SC-βcells),are a promising alternative source and have the potential to become a T1DM treatment through cell replacement therapy.Here we briefly review how isletβcells develop and mature in vivo and several types of reported SC-βcells produced using different ex vivo protocols in the last decade.Although some markers of maturation were expressed and glucose stimulated insulin secretion was shown,the SC-βcells have not been directly compared to their in vivo counterparts,generally have limited glucose response,and are not yet fully matured.Due to the presence of extra-pancreatic insulin-expressing cells,and ethical and technological issues,further clarification of the true nature of these SC-βcells is required.
文摘Type 2 diabetes mellitus(T2DM)is a lifelong condition and a grave threat to human health.Innovative efforts to relieve its detrimental effects are acutely needed.The sine qua non in T2DM management is consistent adherence to a prudent lifestyle and nutrition,combined with aerobic and resistance exercise regimens,together repeatedly shown to lead to complete reversal and even longterm remission.Non-adherence to the above lifestyle adjustments condemns any treatment effort and ultimately the patient to a grim fate.It is thus imperative that every study evaluating the effects of innovative interventions in T2DM objectively compares the novel treatment modality to lifestyle modifications,preferably through double-blind controlled randomization,before claiming efficacy.
基金supported by the National Key R&D Program of China(2017YFAO105803)the general program of the National Natural Science Foundation of China(81770826)+2 种基金the Science and Technology Plan Projects of Guangdong Province(2019B020227003)the Key Special Projects of Medical and Health of Guangzhou City(202007040003)the 5010 Clinical Research Projects of Sun Yatsen University(2015015).
文摘Type 1 diabetes mellitus(T1D)is a chronic autoimmune condition in which the immune system destroys insulin-producing pancreatic β cells.In addition to well-established pathogenic effector T cells,regulatory T cells(Tregs)have also been shown to be defective in T1D.Thus,an increasing number of therapeutic approaches are being developed to target Tregs.However,the role and mechanisms of TGF-β-induced Tregs(iTregs)in T1D remain poorly understood.Here,using a streptozotocin(STZ)-induced preclinical T1D mouse model,we found that iTregs could ameliorate the development of T1D and preserve β cell function.The preventive effect was associated with the inhibition of type 1 cytotoxic T(Tel)cell function and rebalancing the Treg/Tc1 cell ratio in recipients.Furthermore,we showed that the underlying mechanisms were due to the TGF-β-mediated combinatorial actions of mTOR and TCF1.In addition to the preventive role,the therapeutic effects of iTregs on the established STZ-T1D and nonobese diabetic(NOD)mouse models were tested,which revealed improved β cell function.Our findings therefore provide key new insights into the basic mechanisms involved in the therapeutic role of iTregs in T1D.
文摘Autoantibodies and inflammation are the hallmarks of autoimmune diseases(ADs).Organ-specific and nonorgan-specific ADs are divided according to whether the autoimmune reaction is directed against a specific tissue(e.g.,thyroid in Hashimoto's thyroiditis)or widely expressed antigens(e.g.,cell nuclei in systemic lupus erythematosus[SLE]).SLE is distinguished by the presence of circulating autoantibodies and immune complex deposition,both of which can induce inflammatory damage to many organs.Rheumatoid arthritis(RA),sometimes called inflammatory arthritis,is a systemic AD that affects the joints and causes synovitis.Multiple sclerosis(MS)is a central nervous system inflammatory disease with various neurological and autoimmune symptoms.Links have been reported between RA and SLE as well as between Type 1 diabetes mellitus and MS.Identification of shared genes and biological processes could aid in the discovery of possible treatment targets in these dual ADs.This review article explores the molecular nature and familial inheritance of dual ADs.
文摘The magnitude of diabetes mellitus(DM)has increased in recent decades,where the number of cases and the proportion of the disease have been gradually increasing over the past few decades.The chronic complications of DM affect many organ systems and account for the majority of morbidity and mortality associated with the disease.The prevalence of type 1 DM(T1DM)is increasing globally,and it has a very significant burden on countries and at an individual level.T1DM is a chronic illness that requires ongoing medical care and patient self-management to prevent complications.This study aims to discuss the health benefits of physical activity(PA)in T1DM patients.The present review article was performed following a comprehensive literature search.The search was conducted using the following electronic databases:“Cochrane Library”,Web of Science,PubMed,HINARI,EMBASE,Google for grey literature,Scopus,African journals Online,and Google Scholar for articles published up to June 21,2021.The present review focused on the effects of PA on many outcomes such as blood glucose(BG)control,physical fitness,endothelial function,insulin sensitivity,well-being,the body defense system,blood lipid profile,insulin resistance,cardiovascular diseases(CVDs),insulin requirements,blood pressure(BP),and mortality.It was found that many studies recommended the use of PA for the effective management of T1DM.PA is a component of comprehensive lifestyle modifications,which is a significant approach for the management of T1DM.It provides several health benefits,such as improving BG control,physical fitness,endothelial function,insulin sensitivity,well-being,and the body defense system.Besides this,it reduces the blood lipid profile,insulin resistance,CVDs,insulin requirements,BP,and mortality.Overall,PA has significant and essential protective effects against the health risks associated with T1DM.Even though PA has several health benefits for patients with T1DM,these patients are not well engaged in PA due to barriers such as a fear of exercise-induced hypoglycemia in particular.However,several effective strategies have been identified to control exercise-induced hypoglycemia in these patients.Finally,the present review concludes that PA should be recommended for the management of patients with T1DM due to its significant health benefits and protective effects against associated health risks. Italso provides suggestions for the future direction of research in this field.
基金the National Natural Science Foundation of China,No.81471081the Natural Science Foundation of Fujian Province,China,No.2019J010 10+1 种基金Xiamen Research Foundation for Science and Technology Project No.3502Z20194037and Scientific Research Foundation for Advanced Talents,Xiang’an Hospital of Xiamen University,No.PM201809170005.
文摘Type 1 diabetes mellitus(T1DM)is a chronic autoimmune disease caused by the specific destruction of pancreatic isletβcells and is characterized as the absolute insufficiency of insulin secretion.Current insulin replacement therapy supplies insulin in a non-physiological way and is associated with devastating complications.Experimental islet transplantation therapy has been proven to restore glucose homeostasis in people with severe T1DM.However,it is restricted by many factors such as severe shortage of donor sources,progressive loss of donor cells,high cost,etc.As pluripotent stem cells have the potential to give rise to all cells including isletβcells in the body,stem cell therapy for diabetes has attracted great attention in the academic community and the general public.Transplantation of isletβ-like cells differentiated from human pluripotent stem cells(hPSCs)has the potential to be an excellent alternative to islet transplantation.In stem cell therapy,obtainingβcells with complete insulin secretion in vitro is crucial.However,after much research,it has been found that theβ-like cells obtained by in vitro differentiation still have many defects,including lack of adult-type glucose stimulated insulin secretion,and multihormonal secretion,suggesting that in vitro culture does not allows for obtaining fully matureβ-like cells for transplantation.A large number of studies have found that many transcription factors play important roles in the process of transforming immature to mature human isletβcells.Furthermore,PDX1,NKX6.1,SOX9,NGN3,PAX4,etc.,are important in inducing hPSC differentiation in vitro.The absent or deficient expression of any of these key factors may lead to the islet development defect in vivo and the failure of stem cells to differentiate into genuine functionalβ-like cells in vitro.This article reviewsβcell maturation in vivo and in vitro and the vital roles of key molecules in this process,in order to explore the current problems in stem cell therapy for diabetes.
文摘BACKGROUND Type 1 diabetes(DT1)in adolescents brings behavioural changes,altered nutritional habits,and eating disorders.AIM To identify and analyze the validated instruments that examine the disordered eating behaviour and eating disorders among adolescents with DT1.METHODS An integrative review was accomplished based on the following databases:PubMed,LILACS,CINAHL,Scopus,Web of Science,and Reference Citation Analysis(RCA),including publications in Portuguese,English,or Spanish,without time limit and time published.RESULTS The main instruments to evaluate disordered eating behaviour were The Diabetes Eating Problem Survey-Revised,The Diabetes Eating Problem Survey,and the eating attitudes test-26,and for eating disorders the main instruments used were The Bulimic Investigation Test of Edinburgh,The Binge Eating Scale,The Child Eating Disorder Examination,The five questions of the(Sick,Control,One,Fat and Food),and The Mind Youth Questionnaire.These instruments showed an effect in evaluating risks regarding nutritional habits or feeding grievances,with outcomes related to weight control,inadequate use of insulin,and glycaemia unmanageability.We did not identify publication bias.CONCLUSION Around the world,the most used scale to study the risk of disordered eating behaviour or eating disorder is The Diabetes Eating Problem Survey-Revised.International researchers use this scale to identify high scores in adolescents with DT1 and a relationship with poorer glycemic control and psychological problems related to body image.
文摘Genetic linkage analyses, genome-wide association studies of single nucleotide polymorphisms, copy number variation surveys, and mutation screenings found the human chromosomal 12q24 locus, with the genes SH2B3 and ATXN2 in its core, to be associated with an exceptionally wide spectrum of disease susceptibilities. Hematopoietic traits of red and white blood cells(like erythrocytosis and myeloproliferative disease), autoimmune disorders(like type 1 diabetes, coeliac disease, juvenile idiopathic arthritis, rheumatoid arthritis, thrombotic antiphospholipid syndrome, lupus erythematosus, multiple sclerosis, hypothyroidism and vitiligo), also vascular pathology(like kidney glomerular filtration rate deficits, serum urate levels, plasma beta-2-microglobulin levels, retinal microcirculation problems, diastolic and systolic blood pressure and hypertension, cardiovascular infarction), furthermore obesity, neurodegenerative conditions(like the polyglutamine-expansion disorder spinocerebellar ataxia type 2, Parkinson's disease, the motor-neuron disease amyotrophic lateral sclerosis, and progressive supranuclear palsy), andfinally longevity were reported. Now it is important to clarify, in which ways the loss or gain of function of the locally encoded proteins SH2B3/LNK and ataxin-2, respectively, contribute to these polygenic health problems. SH2B3/LNK is known to repress the JAK2/ABL1 dependent proliferation of white blood cells. Its null mutations in human and mouse are triggers of autoimmune traits and leukemia(acute lymphoblastic leukemia or chronic myeloid leukemia-like), while missense mutations were found in erythrocytosis-1 patients. Ataxin-2 is known to act on RNA-processing and trophic receptor internalization. While its polyglutamine-expansion mediated gain-of-function causes neuronal atrophy in human and mouse, its deletion leads to obesity and insulin resistance in mice. Thus, it is conceivable that the polygenic pathogenesis of type 1 diabetes is enhanced by an SH2B3-dysregulation-mediated predisposition to autoimmune diseases that conspires with an ATXN2-deficiency-mediated predisposition to lipid and glucose metabolism pathology.
