Comparative Analysis of the Transcriptome of Latent Autoimmune Diabetes in Adult (LADA) Patients from Eastern China

Ji, Yuqiao; Jiang, Dongmei; Liu, Jian; Chen, Xiaolong; Xia, Tian; Yin, Zhujun; Li, Lei; Jin, Hao; Chen, Hongmei; Sun, Mingzhong

doi:10.1155/2019/8616373

Cited by 3 publications

(6 citation statements)

References 26 publications

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“…GADA is the most common biomarker used to distinguish people with LADA from those with T2DM. However, recent transcriptomics analysis has pointed to the possibility of novel LADA biomarkers [ 20 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a Prevalence Model for Latent Autoimmune Diabetes in Adults (LADA) Among Patients First Diagnosed with Type 2 Diabetes Mellitus (T2DM)

Wang

Zhang

et al. 2021

Med Sci Monit

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Background We designed this study to develop and validate a prevalence model for latent autoimmune diabetes in adults (LADA) among people initially diagnosed with type 2 diabetes mellitus (T2DM). Material/Methods The study recruited 930 patients aged ≥18 years who were diagnosed with T2DM within the past year. Demographic information, medical history, and clinical biochemistry records were collected. Logistic regression was used to develop a regression model to distinguish LADA from T2DM. Predictors of LADA were identified in a subgroup of patients (n=632) by univariate logistic regression analysis. From this we developed a prediction model using multivariate logistic regression analysis and tested its sensitivity and specificity among the remaining patients (n=298). Results Among 930 recruited patients, 880 had T2DM (96.4%) and 50 had LADA (5.4%). Compared to T2DM patients, LADA patients had fewer surviving β cells and reduced insulin production. We identified age, ketosis, history of tobacco smoking, 1-hour plasma glucose (1hPG-AUC), and 2-hour C-peptide (2hCP-AUC) as the main predictive factors for LADA (P<0.05). Based on this, we developed a multivariable logistic regression model: Y=−8.249−0.035(X1)+1.755(X2)+1.008(X3)+0.321(X4)−0.126(X5), where Y is diabetes status (0=T2DM, 1=LADA), X1 is age, X2 is ketosis (1=no, 2=yes), X3 is history of tobacco smoking (1=no, 2=yes), X4 is 1hPG-AUC, and X5 is 2hCP-AUC. The model has high sensitivity (78.57%) and selectivity (67.96%). Conclusions This model can be applied to people newly diagnosed with T2DM. When Y ≥0.0472, total autoantibody screening is recommended to assess LADA.

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Section: Discussionmentioning

confidence: 99%

Development and Validation of a Prevalence Model for Latent Autoimmune Diabetes in Adults (LADA) Among Patients First Diagnosed with Type 2 Diabetes Mellitus (T2DM)

Wang

Zhang

et al. 2021

Med Sci Monit

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“…found that patients with LADA exhibited 277 differentially expressed genes (DEGs) compared to healthy controls. Further gene ontology (GO) analysis of these DEGs indicated that many of the enriched GO terms were closely related to immune functions, including positive regulation of neutrophil chemotaxis 98 . Therefore, increased expression of neutrophil chemo‐attractants may also contribute to the augmented inflammation observed in LADA 98 .…”

Section: Innate Immune Cells In Ladamentioning

confidence: 99%

“…133 Therefore, the increased expression of these chemo-attractants for neutrophils and monocytes may contribute to the augmented pancreatic inflammation in LADA. 98…”

Section: Cytokinesmentioning

confidence: 99%

“…Further gene ontology (GO) analysis of these DEGs indicated that many of the enriched GO terms were closely related to immune functions, including positive regulation of neutrophil chemotaxis 98 . Therefore, increased expression of neutrophil chemo‐attractants may also contribute to the augmented inflammation observed in LADA 98 . Recently, our group did RNA‐seq using isolated neutrophils from LADA patients and healthy controls, finding that DEGs between LADA and healthy controls are mainly involved in leukocyte degranulation, myeloid cell differentiation and immune response‐regulating signalling, revealing an abnormality in neutrophil disposition at the transcriptional level in LADA 99 …”

Section: Innate Immune Cells In Ladamentioning

confidence: 99%

“…By performing RNA‐seq analysis from PBMCs of patients with LADA and healthy control subjects, Ji et al. found that gene expression levels of chemokine ligands including CXCL8 , CCL2 and CCL23 were upregulated in patients with LADA 98 . It is known that CXCL8 was originally identified as a potent neutrophil chemotactic factor, 132 and both CCL2 and CCL23 are potent chemo‐attractants for monocytes 133 .…”

Section: Mechanisms Of Innate Immune Activation In Ladamentioning

confidence: 99%

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Innate immunity in latent autoimmune diabetes in adults

Hao

Pearson

Wong

et al. 2021

Diabetes Metabolism Res

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Latent autoimmune diabetes in adults (LADA) is an autoimmune disease that shares some genetic, immunological and clinical features with both type 1 diabetes and type 2 diabetes. Immune cells including CD4 + T cells, CD8 + T cells, B cells, macrophages and dendritic cells (DCs) have been detected in the pancreas of patients with LADA and a rat model of LADA. Therefore, similar to type 1 diabetes, the pathogenesis of LADA may be caused by interactions between islet β-cells and innate and adaptive immune cells. However, the role of the immunity in the initiation and progression of LADA remains largely unknown. In this review, we have summarized the potential roles of innate immunity and immune-modulators in LADA development. Furthermore, we have examined the evidence and discussed potential innate immunological reasons for the slower development of LADA compared with type 1 diabetes. More in-depth mechanistic studies are needed to fully elucidate the roles of innate immune-associated genes, molecules and cells in their contributions to LADA pathogenesis. Undertaking these studies will greatly enhance the development of new strategies and optimization of current strategies for the diagnosis and treatment of the disease. K E Y W O R D Sautoimmune, diabetes mellitus, innate immune cells, innate immunity, latent autoimmune diabetes in adults | INTRODUCTIONLatent autoimmune diabetes in adults (LADA), also known as type 1.5 diabetes or slow-onset diabetes in adults, is an autoimmune disease that shares some genetic, immunological and clinical features with both type 1 diabetes and type 2 diabetes. [1][2][3][4][5] The disease was first described in 1983 6 and was defined as LADA in 1993. 7 Although LADA accounts for approximately 1.5%-14.2% of the type 2 diabetes population, 8-14 no unified criteria or management guidelines have existed for LADA. Recently, a panel of international experts defined a strategy for LADA management, which will be greatly helpful to the diagnosis and treatment of the disease in clinical practice. 15 GADA level is considered as the most valuable discriminatory parameter to predict the development of β-cell function in LADA. 16 Compared with low level of glutamic acid decarboxylase antibody (GADA), high level of GADA in LADA is associated with faster insulin progression, indicating that the presence of high level of GADA was a significant predictor of insulin requirement in LADA. 17 Our group also found that patients with high level of GADA showed a worse baseline and accelerated decline of β-cell function, 18 while the metabolic phenotypes and β-cell function in LADA patients with a low level of GADA were similar to that in type 2 diabetes patients. 19 It was reported that the presence of N-terminally truncated GAD65 autoantibody in individuals with adult-onset diabetes is associated with the clinical

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Identification of Comorbidities, Genomic Associations, and Molecular Mechanisms for COVID‐19 Using Bioinformatics Approaches

Omit

Akhter

Rana

et al. 2023

BioMed Research International

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Several studies have been done to identify comorbidities of COVID-19. In this work, we developed an analytical bioinformatics framework to reveal COVID-19 comorbidities, their genomic associations, and molecular mechanisms accomplishing transcriptomic analyses of the RNA-seq datasets provided by the Gene Expression Omnibus (GEO) database, where normal and infected tissues were evaluated. Using the framework, we identified 27 COVID-19 correlated diseases out of 7,092 collected diseases. Analyzing clinical and epidemiological research, we noticed that our identified 27 diseases are associated with COVID-19, where hypertension, diabetes, obesity, and lung cancer are observed several times in COVID-19 patients. Therefore, we selected the above four diseases and performed assorted analyses to demonstrate the association between COVID-19 and hypertension, diabetes, obesity, and lung cancer as comorbidities. We investigated genomic associations with the cross-comparative analysis and Jaccard’s similarity index, identifying shared differentially expressed genes (DEGs) and linking DEGs of COVID-19 and the comorbidities, in which we identified hypertension as the most associated illness. We also revealed molecular mechanisms by identifying statistically significant ten pathways and ten ontologies. Moreover, to understand cellular physiology, we did protein-protein interaction (PPI) analyses among the comorbidities and COVID-19. We also used the degree centrality method and identified ten biomarker hub proteins (IL1B, CXCL8, FN1, MMP9, CXCL10, IL1A, IRF7, VWF, CXCL9, and ISG15) that associate COVID-19 with the comorbidities. Finally, we validated our findings by searching the published literature. Thus, our analytical approach elicited interconnections between COVID-19 and the aforementioned comorbidities in terms of remarkable DEGs, pathways, ontologies, PPI, and biomarker hub proteins.

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Comparative Analysis of the Transcriptome of Latent Autoimmune Diabetes in Adult (LADA) Patients from Eastern China

Cited by 3 publications

References 26 publications

Development and Validation of a Prevalence Model for Latent Autoimmune Diabetes in Adults (LADA) Among Patients First Diagnosed with Type 2 Diabetes Mellitus (T2DM)

Development and Validation of a Prevalence Model for Latent Autoimmune Diabetes in Adults (LADA) Among Patients First Diagnosed with Type 2 Diabetes Mellitus (T2DM)

Innate immunity in latent autoimmune diabetes in adults

Identification of Comorbidities, Genomic Associations, and Molecular Mechanisms for COVID‐19 Using Bioinformatics Approaches

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