Shuoming Luo

The Diagnostic Value of Zinc Transporter 8 Autoantibody (ZnT8A) for Type 1 Diabetes in Chinese

Zinc transporter‐8 (ZnT8) was recently identified as a novel autoantigen in human type 1 diabetes (T1D). Autoantibody to ZnT8 (ZnT8A) was detected in up to 80% of patients with new‐onset T1D and 26% of patients with T1D otherwise classified as negative on the basis of existing markers. As no data of ZnT8A in Chinese have been reported, we aim to evaluate the utility of ZnT8A for diagnosis of autoimmune T1D in Chinese relative to other autoantibody markers.

Zinc transporter 8 autoantibody (ZnT8A) could help differentiate latent autoimmune diabetes in adults (LADA) from phenotypic type 2 diabetes mellitus

The ZnT8A is an independent marker for diagnosis of type 1 diabetes mellitus. We investigated the distribution and clinical features of ZnT8A positive latent autoimmune diabetes in adult (LADA) patients to explore the potential diagnostic application.

Persistence of glutamic acid decarboxylase antibody (GADA) is associated with clinical characteristics of latent autoimmune diabetes in adults: a prospective study with 3-year follow-up.

Latent autoimmune diabetes in adults (LADA) is a form of autoimmune diabetes with heterogeneous features. This study aimed to investigate the persistent status of glutamic acid decarboxylase antibody (GADA) in patients with LADA and its association with clinical characteristics.

Fulminant type 1 diabetes: a collaborative clinical cases investigation in China

To clarify the detailed distribution, clinical and immunological features of patients with fulminant type 1 diabetes (F1D), we consecutively investigated 53 cases from nationwide 24 hospitals in China. After the clinical and immunological features were evaluated, we compared pregnancy-associated F1D (PF) with those of child-bearing age with F1D that was not associated with pregnancy in clinical characteristics. As a result, patients with F1D were reported from all over China, and there was no significant regional and seasonal preference of this disease. Around 34.0% (18/53) patients displayed low titers of autoantibodies against one or more autoantigens, including 12 cases positive for GADA, 2 for IA-2A, 4 for ZnT8A and 3 for both GADA and ZnT8A. The frequency of PF in female F1D was 34.6% (9/26). Among 9 PF patients, 8 (88.9%) developed F1D during pregnancy which resulted in stillbirth, while one had the onset of F1D after eutocia with her fetus survived. This study suggests that islet-associated autoimmunity may be involved in and contribute to the development of F1D. Pregnant women may be PF high-risk population, and the prognosis for the fetus is extremely poor in PF patients.

HLA Genetic Discrepancy Between Latent Autoimmune Diabetes in Adults and Type 1 Diabetes: LADA China Study No. 6

CONTEXT The discrepancies in terms of human leukocyte antigen (HLA)-DRB1-DQA1-DQB1 conferred risks between latent autoimmune diabetes in adults (LADA) and type 1 diabetes (T1D) patients remained almost completely unknown. The goal of the current study is to determine and compare HLA-conferred risks between LADA and T1D. DESIGN A case-control study was conducted in a representative Chinese data set containing 520 T1D patients, 562 LADA patients, and 1065 controls. The frequencies and odds ratios for HLA susceptible haplotypes and genotypes and for arginine at residue 52 in the DQ-α chain or aspartic acid at residue 57 in the DQ-β chain were analyzed. RESULTS DRB1*0405-DQA1*03-DQB1*0401 and DRB1*0901-DQA1*03-DQB1*0303 are the major LADA susceptible haplotypes, which also confer comparable risks for T1D (odds ratio 2.02 vs 2.20 and 1.61 vs 2.30, respectively). The strongly associated T1D haplotype DRB1*0301-DQA1*05-DQB1*0201 is also associated with LADA but confers only half of the T1D risk (odds ratio 2.65 vs 4.84). Interestingly, the most susceptible T1D haplotypes, DRB1*0901-DQA1*05-DQB1*0201, DRB1*0301-DQA1*03-DQB1*0201, and DRB1*0301-DQA1*03-DQB1*0303, are not associated with LADA. Genotypes for DR3/DR3, DR3/DR9, and DR9/DR9 are highly associated with T1D susceptibility, whereas only DR9/DR9 confers risk for LADA. DR3/DR3 is the high-risk genotype in Chinese T1D patients, which manifests similar risk as the DR3/DR4 genotype in Caucasians but with a lower frequency. DR9/DR9 is the high risk LADA genotype in Chinese. Alleles with DQ-α arginine at residue 52-positive, DQ-β aspartic acid at residue 57-negative, and their combination formed in cis or trans confer susceptibility to T1D but not to LADA. CONCLUSION Our results suggest that LADA risk conferred by HLA-DRB1-DQA1-DQB1 loci in Chinese differs significantly from that of T1D risk. This information would be useful for classifying Asian LADA patients, which should provides novel insight into the understanding of its pathoetiology as well.

Epigenetic regulation of Toll-like receptors and its roles in type 1 diabetes

The immune system can be divided into adaptive immunity and innate immunity. Adaptive immunity has been confirmed to be involved in the pathogenesis of autoimmune diseases, including type 1 diabetes (T1D). However, the role of innate immunity in T1D has only been studied recently. T1D is caused by selective autoimmune destruction of pancreatic islet β cells. A series of studies have suggested that TLRs play a critical role in the pathogenesis of T1D. Aberrant TLR signaling will change immune homeostasis and result in immunopathological conditions such as endotoxin shock and autoimmune responses. Thus, TLR signaling pathways are supposed to be strictly and finely regulated. Epigenetics has recently been proven to be a new regulator of TLR expression. DNA methylation, histone modification, and microRNAs are the three main epigenetic modifications. This review will mainly focus on these epigenetic mechanisms of regulation of TLRs and the role of TLRs in the pathogenesis of T1D.

Exploration of users perspectives and needs and design of a type 1 diabetes management mobile app: mixed-methods study (Preprint)

Background With the popularity of mobile phones, mobile apps have great potential for the management of diabetes, but the effectiveness of current diabetes apps for type 1 diabetes mellitus (T1DM) is poor. No study has explored the reasons for this deficiency from the users’ perspective. Objective The aims of this study were to explore the perspectives and needs of T1DM patients and diabetes experts concerning a diabetes app and to design a new T1DM management mobile app. Methods A mixed-methods design combining quantitative surveys and qualitative interviews was used to explore users’ needs and perspectives. Experts were surveyed at 2 diabetes conferences using paper questionnaires. T1DM patients were surveyed using Sojump (Changsha ran Xing InfoTech Ltd) on a network. We conducted semistructured, in-depth interviews with adult T1DM patients or parents of child patients who had ever used diabetes apps. The interviews were audio-recorded, transcribed, and coded for theme identification. Results The expert response rate was 63.5% (127/200). The respondents thought that the reasons for app invalidity were that patients did not continue using the app (76.4%, 97/127), little guidance was received from health care professionals (HCPs; 73.2%, 93/127), diabetes education knowledge was unsystematic (52.8%, 67/127), and the app functions were incomplete (44.1%, 56/127). A total of 245 T1DM patient questionnaires were collected, of which 21.2% (52/245) of the respondents had used diabetes apps. The reasons for their reluctance to use an app were limited time (39%, 20/52), complicated operations (25%, 13/52), uselessness (25%, 13/52), and cost (25%, 13/52). Both the experts and patients thought that the most important functions of the app were patient-doctor communication and the availability of a diabetes diary. Two themes that were useful for app design were identified from the interviews: (1) problems with patients’ diabetes self-management and (2) problems with current apps. In addition, needs and suggestions for a diabetes app were obtained. Patient-doctor communication, diabetes diary, diabetes education, and peer support were all considered important by the patients, which informed the development of a prototype multifunctional app. Conclusions Patient-doctor communication is the most important function of a diabetes app. Apps should be integrated with HCPs rather than stand-alone. We advocate that doctors follow up with their patients using a diabetes app. Our user-centered method explored comprehensively and deeply why the effectiveness of current diabetes apps for T1DM was poor and what T1DM patients needed for a diabetes app and provided meaningful guidance for app design.

Identification of a distinct phenotype of elderly latent autoimmune diabetes in adults: LADA China Study 8

Latent autoimmune diabetes in adults (LADA) exhibits significant clinical heterogeneity, but the underlying causes remain unclear. The aim of this study was to investigate whether age of onset of LADA contributes to the observed clinical heterogeneity by comparing the clinical, metabolic, and immunogenetic characteristics between elderly and young LADA patients.