BACKGROUNDRecent studies have indicated that an imbalance of gut microbiota is associated with the development of type 1 diabetes mellitus (T1DM) and there is no literature regarding it in Chinese children yet. The aim of this study was to evaluate the alteration of gut microbiota between children with newly diagnosed T1DM and healthy controls and to determine if gut microbiota could partly explain the etiology of this disease.

METHODSA case-control study was carried out with 15 children with T1DM and 15 healthy children. The fecal bacteria composition was investigated by high-throughput sequencing of the V3-V4 region of the 16S rDNA gene and analyzed by the estimators of community richness (Chao) indexes.

RESULTSThere was a notable lower richness of fecal bacteria in T1DM group than controls (156.53 ± 36.96 vs. 130.0 ± 32.85, P = 0.047). At the genus level, the composition of Blautia was increased in T1DM group than control group whereas the composition of Haemophilus, Lachnospira, Dialister, and Acidaminococcus was decreased. In addition, we found that the percentage of Blautia was correlated positively with HbA1c (ρ = 0.40, P = 0.031), the numbers of T1DM autoantibodies (ρ = 0.42, P = 0.023), and the titers of tyrosine phosphatase autoantibodies (IA-2) (ρ = 0.82, P = 0.000) in the study.

CONCLUSIONSThis study showed that gut microbiota was associated with the development of T1DM by affecting the autoimmunity, and the results suggested a potential therapy for T1DM via modulating the gut microbiota.

Adolescent ; Autoantibodies ; immunology ; Case-Control Studies ; Child ; Computational Biology ; Diabetes Mellitus, Type 1 ; immunology ; microbiology ; Feces ; microbiology ; Female ; Gastrointestinal Microbiome ; genetics ; physiology ; Haemophilus ; genetics ; isolation & purification ; Humans ; Male ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S ; genetics

Type 1 diabetes (T1D), the most prevalent human autoimmune disease, occurs in genetically susceptible individuals. Regulatory T cells (Tregs) are defective in T1D setting. Therefore, efforts to repair or restore Tregs in T1D may prevent or reverse this autoimmune disease. Here, we studied the potential role of rgp96 in preventing T1D, using non-obese diabetic (NOD) mice as an animal model. High-dose rgp96 immunization elicited efficient protection of mice against T1D, as evidenced by stable blood glucose, decreased disease incidence. Significantly increased CD4⁺ CD25⁺ Foxp3⁺ Tregs were observed in immunized mice. In vitro co-culture experiments demonstrated that rgp96 stimulation enhanced Treg proliferation and suppressive function by up-regulation of Foxp3 and IL-10. Our work shows that activation of Tregs by high-dose rgp96 immunization protects against T1D via inducing regulatory T cells and provides preventive and therapeutic potential for the development of an rgp96-based vaccine against T1D.
Animals ; Antigens, Neoplasm ; administration & dosage ; immunology ; Coculture Techniques ; Diabetes Mellitus, Type 1 ; prevention & control ; therapy ; Forkhead Transcription Factors ; Heat-Shock Proteins ; administration & dosage ; immunology ; Interleukin-10 ; immunology ; Mice ; Mice, Inbred NOD ; T-Lymphocytes, Regulatory ; immunology ; Up-Regulation ; Vaccination

PURPOSE: Vitiligo prevalence and its associated comorbidities rate have been reported variably among different populations. We aimed to determine the prevalence of vitiligo in Korea along with the baseline rate of comorbidities and compared the risks to the general population using hospital visit information of the total population in Korea. MATERIALS AND METHODS: We assessed demographic characteristics of vitiligo patients in Korean population from 2009 to 2011 in a nationwide data from Health Insurance Review Assessment Service. Patients who had at least one visit to Korea's primary, secondary, or tertiary referral hospitals with International Classification of Diseases, 10th Revision, Clinical Modification diagnosis code for vitiligo were identified. As a supplementary study, comorbidities associated with vitiligo were selected for further review to calculate relative risks compared to the general population. RESULTS: The annual prevalence of vitiligo determined by hospital-visiting rate in Korea was 0.12% to 0.13% over a three year period. In sync with other previous epidemiological studies, there was bimodal distribution among the age groups and no difference between genders. Also, vitiligo in Korean population was associated with various autoimmune/non-autoimmune diseases such as thyroiditis, atopic dermatitis, and psoriasis. CONCLUSION: This study was by far the most comprehensive review on prevalence of vitiligo using a data of total population in Korea. The prevalence is within a range of those reported in previous literatures, and increased risk of comorbidities such as thyroid diseases and psoriasis in vitiligo might aid clinicians in the initial work up of vitiligo patients and concurrent follow ups.
Adult ; Aged ; Autoimmune Diseases/*epidemiology/immunology ; Comorbidity ; Diabetes Mellitus, Type 1/epidemiology ; Female ; Humans ; Male ; Middle Aged ; Population Surveillance ; Prevalence ; Republic of Korea/epidemiology ; Socioeconomic Factors ; Thyroid Diseases/epidemiology ; Vitiligo/*epidemiology

OBJECTIVETo evaluate the utility of zinc transporter-8 (ZnT8) in the improvement of type 1 diabetes mellitus (T1DM) diagnosis and prediction, and to explore whether ZnT8 is a potential therapeutic target in T1DM.

DATA SOURCESA search was conducted within the medical database PubMed for relevant articles published from 2001 to 2015. The search terms are as follows: "ZnT8," "type 1 diabetes," "latent autoimmune diabetes in adults," "type 2 diabetes," "islet autoantibodies," "zinc supplement," "T cells," "β cell," "immune therapy." We also searched the reference lists of selected articles.

STUDY SELECTIONEnglish-language original articles and critical reviews concerning ZnT8 and the clinical applications of islet autoantibodies in diabetes were reviewed.

RESULTSThe basic function of ZnT8 is maintaining intracellular zinc homeostasis, which modulates the process of insulin biosynthesis, storage, and secretion. Autoantibodies against ZnT8 (ZnT8A) and ZnT8-specific T cells are the reliable biomarkers for the identification, stratification, and characterization of T1DM. Additionally, the results from the animal models and clinical trials have shown that ZnT8 is a diabetogenic antigen, suggesting the possibility of ZnT8-specific immunotherapy as an alternative for T1DM therapy.

CONCLUSIONSZnT8 is a novel islet autoantigen with a widely potential for clinical applications in T1DM. However, before the large-scale clinical applications, there are still many problems to be solved.

Animals ; Autoantibodies ; immunology ; Autoantigens ; immunology ; Cation Transport Proteins ; immunology ; metabolism ; Diabetes Mellitus, Type 1 ; immunology ; metabolism ; Humans

INTRODUCTIONInsulin resistance in latent autoimmune diabetes in adults (LADA) patients is controversial. The aim of this study was to evaluate insulin resistance and its related factors (metabolic syndrome parameters) among subjects with LADA and glutamic acid decarboxylase antibodies (GADA) negative diabetes, as well as the impact of these factors on insulin resistance.

MATERIALS AND METHODSGADA levels were investigated in 1140 diabetic patients aged between 30 and 70 years. Insulin resistance and metabolic syndrome parameters were assessed in LADA and GAD-negative diabetic patients by general linear model. In addition, the impact of metabolic syndrome factors on insulin resistance was assessed in LADA and glutamic acid decarboxylase (GAD)-negative diabetic patients.

RESULTSLADA was diagnosed in 33 subjects from 1140 Malaysian diabetic patients (prevalence = 2.9%). The results showed that LADA patients had higher insulin resistance and high density lipoprotein cholesterol (HDLc) (P = 0.003 and 0.00017 respectively) and lower body mass index (BMI) (P = 0.007) compared to GAD-negative diabetic patients. The HDLc was associated with decreased insulin resistance in LADA patients (P = 0.041), whereas HbA1c, triacylglycerides (TG) and waist were associated with increased insulin resistance in GAD-negative diabetic patients (P = 3.6×10⁻¹², 1.01×10⁻⁵ and 0.004 respectively). HbA1c was highly associated with decreasing β-cell function in both LADA (P = 0.009) and GAD-negative diabetic subjects (P = 2.2×10⁻²⁸).

CONCLUSIONInsulin resistance is significantly higher in LADA than GAD-negative diabetic Malaysian subjects.

Adult ; Antibodies ; blood ; Diabetes Mellitus, Type 1 ; blood ; metabolism ; Female ; Glutamate Decarboxylase ; immunology ; Humans ; Insulin Resistance ; Male ; Middle Aged

The importance of innate immunity in host defense is becoming clear after discovery of innate immune receptors such as Toll-like receptor or Nod-like receptor. Innate immune system plays an important role in diverse pathological situations such as autoimmune diseases. Role of innate immunity in the pathogenesis of metabolic disorders such as type 2 diabetes, metabolic syndrome or atherosclerosis that has not been previously considered as inflammatory disorders, is also being appreciated. Here, the role of innate immunity in the development of type 1 diabetes, a classical organ-specific autoimmune disease, and type 2 diabetes will be discussed, focusing on the role of specific innate immune receptors involved in these disease processes.
Animals ; Cytokines/*immunology ; Diabetes Mellitus, Type 1/*immunology ; Diabetes Mellitus, Type 2/*immunology ; Humans ; Immunity, Innate/*immunology ; Inflammasomes/*immunology ; *Models, Immunological ; Pancreas/immunology

BACKGROUNDGlutamic acid decarboxylase antibody (GADA) and protein tyrosine phosphatase antibody (IA-2A) are two major autoantibodies, which exert important roles in the process of type 1 diabetes mellitus (T1D). Our study aimed to investigate the changes in positivity and titers of GADA and IA-2A during the course of Chinese acute-onset T1D patients and their relationships with clinical features.

METHODSTwo hundreds and forty-seven Chinese newly diagnosed acute-onset T1D patients were consecutively recruited. GADA and IA-2A were detected at the time of diagnosis, one year later, 3-5 years later after diagnosis during the follow-up; all the clinical data were recorded and analyzed as well.

RESULTSDuring the course of acute-onset T1D, the majority of patients remained stable for GADA or IA-2A, however, a few patients changed from positivity to negativity and fewer patients converted from negativity to positivity. The prevalence of GADA was 56.3% at diagnosis, decreasing to 50.5% one year later, and 43.3% 3-5 years later while the corresponding prevalence of IA-2A were 32.8%, 31.0% and 23.3%, respectively. The median GADA titers were 0.0825 at diagnosis, declining to 0.0585 one year later and 0.0383 3-5 years later (P < 0.001), while the corresponding median titers were 0.0016, 0.0010, 0.0014 for IA-2A, respectively. Fasting C-peptide (FCP) and postprandial C-peptide 2 hours (PCP2h) levels of GADA or IA-2A negativity persistence patients were higher than those of positivity persistence and negativity conversion patients (P < 0.05) which indicated GADA or IA-2A negativity persistence T1D patients had a less loss of β cell function.

CONCLUSIONOur data suggest that repeated detection of GADA and IA-2A are necessary for differential diagnosis of autoimmune diabetes and the indirect prediction of the β cell function in Chinese patients.

Adolescent ; Adult ; Aged ; Antibodies ; therapeutic use ; Asian Continental Ancestry Group ; Child ; Child, Preschool ; Diabetes Mellitus, Type 1 ; drug therapy ; immunology ; Female ; Glutamate Decarboxylase ; immunology ; Glycated Hemoglobin A ; metabolism ; Humans ; Infant ; Male ; Middle Aged ; Protein Tyrosine Phosphatases ; immunology ; Young Adult

OBJECTIVETo measure levels of cytokines including IL-1β, IL-12, IL-18 and TNF-α in children with newly diagnosed type 1 diabetes and to analyze their correlation with clinical indices such as infection and onset time.

METHODSA total of 33 children with newly diagnosed type 1 diabetes were assigned to the case group, and 27 healthy children to the control group. The case group was further divided into increased white blood cell (WBC) and normal WBC subgroups according to peripheral WBC level. The serum levels of cytokines including IL-1β, IL-12, IL-18 and TNF-α were measured by enzyme-linked immunosorbent assay. Blood pH, blood sugar, blood lactate, fructosamine, peripheral leukocytes and neutrophils and some other clinical indices were also measured.

RESULTSThe level of IL-12 in the case group was higher than in the control group (P<0.001). In the case group, the level of IL-18 was negatively correlated with onset time (r=0.413, P=0.015), the neutrophil count was positively correlated with IL-1β level (r=0.413, P=0.023) and the WBC count was positively correlated with IL-18 level (r=0.352, P=0.038). IL-1β, IL-12 and IL-18 levels in the increased WBC subgroup were higher than in the normal WBC subgroup (P<0.05 for all comparisons).

CONCLUSIONSCytokine secretion disorders of Th1 cells exist in children with type 1 diabetes. Infections may induce cytokine secretion and might contribute to the early onset of diabetes.

Adolescent ; Child ; Child, Preschool ; Cytokines ; blood ; Diabetes Mellitus, Type 1 ; immunology ; Female ; Humans ; Infant ; Male ; Th1 Cells ; immunology

Antibodies ; immunology ; therapeutic use ; Antigens, CD20 ; immunology ; Antilymphocyte Serum ; therapeutic use ; CD3 Complex ; immunology ; Diabetes Mellitus, Type 1 ; drug therapy ; immunology ; Humans ; Immunotherapy ; methods

Adult ; Diabetes Mellitus, Type 1 ; classification ; immunology ; Diabetes Mellitus, Type 2 ; classification ; immunology ; Humans