scholarly journals Integrative analyses of TEDDY Omics data reveal lipid metabolism abnormalities, increased intracellular ROS and heightened inflammation prior to autoimmunity for type 1 diabetes

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Leandro Balzano-Nogueira ◽  
Ricardo Ramirez ◽  
Tatyana Zamkovaya ◽  
Jordan Dailey ◽  
Alexandria N. Ardissone ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Lipid Metabolism ◽  
Islet Autoimmunity ◽  
Matrix Remodeling ◽  
Omics Data ◽  
Multifactorial Diseases ◽  
Beta Cell Destruction ◽  
High Genetic Risk ◽  
Intracellular Ros

Abstract Background The Environmental Determinants of Diabetes in the Young (TEDDY) is a prospective birth cohort designed to study type 1 diabetes (T1D) by following children with high genetic risk. An integrative multi-omics approach was used to evaluate islet autoimmunity etiology, identify disease biomarkers, and understand progression over time. Results We identify a multi-omics signature that was predictive of islet autoimmunity (IA) as early as 1 year before seroconversion. At this time, abnormalities in lipid metabolism, decreased capacity for nutrient absorption, and intracellular ROS accumulation are detected in children progressing towards IA. Additionally, extracellular matrix remodeling, inflammation, cytotoxicity, angiogenesis, and increased activity of antigen-presenting cells are observed, which may contribute to beta cell destruction. Our results indicate that altered molecular homeostasis is present in IA-developing children months before the actual detection of islet autoantibodies, which opens an interesting window of opportunity for therapeutic intervention. Conclusions The approach employed herein for assessment of the TEDDY cohort showcases the utilization of multi-omics data for the modeling of complex, multifactorial diseases, like T1D.

Enterovirus RNA in longitudinal blood samples and risk of islet autoimmunity in children with a high genetic risk of type 1 diabetes: the MIDIA study

Diabetologia ◽  
2014 ◽  
Vol 57 (10) ◽  
pp. 2193-2200 ◽  
Author(s):  
Ondrej Cinek ◽  
Lars C. Stene ◽  
Lenka Kramna ◽  
German Tapia ◽  
Sami Oikarinen ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Genetic Risk ◽  
Islet Autoimmunity ◽  
Blood Samples ◽  
High Genetic Risk

Immunization profiles and progression of islet autoimmunity in children at type 1 diabetes risk

2012 ◽  
Vol 7 (S 01) ◽  
Author(s):  
R Chmiel ◽  
S Krause ◽  
A Knopff ◽  
C Matzke ◽  
D Höfelmann ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetes Risk ◽  
Islet Autoimmunity

Effect of lipid metabolism of mothers with type 1 diabetes and obesity on clinical and laboratory parameters of their newborns

2020 ◽  
Author(s):  
Veranika Prylutskaya ◽  
Anzhalika Solntsava ◽  
Antonina Goncharik ◽  
Marya Pavlovets ◽  
Ivan Kurlovich
Keyword(s):  
Type 1 Diabetes ◽  
Lipid Metabolism ◽  
Laboratory Parameters ◽  
Diabetes And Obesity

scholarly journals Viruses and Type 1 Diabetes: From Enteroviruses to the Virome

2021 ◽  
Vol 9 (7) ◽  
pp. 1519
Author(s):  
Sonia R. Isaacs ◽  
Dylan B. Foskett ◽  
Anna J. Maxwell ◽  
Emily J. Ward ◽  
Clare L. Faulkner ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Viral Infections ◽  
Antiviral Drug ◽  
Virus Detection ◽  
Detection Methods ◽  
Islet Autoimmunity ◽  
Comprehensive Overview ◽  
Drug Candidates

For over a century, viruses have left a long trail of evidence implicating them as frequent suspects in the development of type 1 diabetes. Through vigorous interrogation of viral infections in individuals with islet autoimmunity and type 1 diabetes using serological and molecular virus detection methods, as well as mechanistic studies of virus-infected human pancreatic β-cells, the prime suspects have been narrowed down to predominantly human enteroviruses. Here, we provide a comprehensive overview of evidence supporting the hypothesised role of enteroviruses in the development of islet autoimmunity and type 1 diabetes. We also discuss concerns over the historical focus and investigation bias toward enteroviruses and summarise current unbiased efforts aimed at characterising the complete population of viruses (the “virome”) contributing early in life to the development of islet autoimmunity and type 1 diabetes. Finally, we review the range of vaccine and antiviral drug candidates currently being evaluated in clinical trials for the prevention and potential treatment of type 1 diabetes.

scholarly journals An Age-Related Exponential Decline in the Risk of Multiple Islet Autoantibody Seroconversion During Childhood

2021 ◽  
Author(s):  
Ezio Bonifacio ◽  
Andreas Weiß ◽  
Christiane Winkler ◽  
Markus Hippich ◽  
Marian J. Rewers ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Confidence Interval ◽  
Islet Autoantibodies ◽  
Islet Autoimmunity ◽  
Islet Autoantibody ◽  
Age Related ◽  
At Risk Children ◽  
Exponential Decline ◽  
Design And Methods

<b>Objective</b>. Islet autoimmunity develops prior to clinical type 1 diabetes and includes multiple and single autoantibody phenotypes. The objective was to determine age-related risks of islet autoantibodies that reflect etiology and improve screening for pre-symptomatic type 1 diabetes. <p><b>Research Design and Methods</b>. The Environmental Determinants of Diabetes in the Young study prospectively followed 8,556 genetically at-risk children at 3–6-month intervals from birth for the development of islet autoantibodies and type 1 diabetes. The age-related change in the risk of developing islet autoantibodies was determined using landmark and regression models. </p> <p><b>Results</b>. The 5-year risk of developing multiple islet autoantibodies was 4.3% (95% confidence interval, 3.8–4.7) at 7.5 months of age and declined to 1.1% (95% confidence interval, 0.8–1.3) at a landmark age of 6.25 years (<i>P</i><0.0001). Risk decline was slight or absent in single insulin- and GAD-autoantibody phenotypes. The influence of sex, <i>HLA</i> and other susceptibility genes on risk subsided with increasing age and was abrogated by age six years. Highest sensitivity and positive predictive value of multiple islet autoantibody phenotypes for type 1 diabetes was achieved by autoantibody screening at 2 years and again at 5–7 years of age. </p> <p><b>Conclusions</b>. The risk of developing islet autoimmunity declines exponentially with age and the influence of major genetic factors on this risk is limited to the first few years of life. </p>

scholarly journals Progression from islet autoimmunity to clinical type 1 diabetes is influenced by genetic factors: results from the prospective TEDDY study

2018 ◽  
Vol 56 (9) ◽  
pp. 602-605 ◽  
Author(s):  
Andreas Beyerlein ◽  
Ezio Bonifacio ◽  
Kendra Vehik ◽  
Markus Hippich ◽  
Christiane Winkler ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Factors ◽  
Genetic Risk Score ◽  
Risk Scores ◽  
Islet Autoimmunity ◽  
Islet Autoantibody ◽  
Clinical Type

BackgroundProgression time from islet autoimmunity to clinical type 1 diabetes is highly variable and the extent that genetic factors contribute is unknown.MethodsIn 341 islet autoantibody-positive children with the human leucocyte antigen (HLA) DR3/DR4-DQ8 or the HLA DR4-DQ8/DR4-DQ8 genotype from the prospective TEDDY (The Environmental Determinants of Diabetes in the Young) study, we investigated whether a genetic risk score that had previously been shown to predict islet autoimmunity is also associated with disease progression.ResultsIslet autoantibody-positive children with a genetic risk score in the lowest quartile had a slower progression from single to multiple autoantibodies (p=0.018), from single autoantibodies to diabetes (p=0.004), and by trend from multiple islet autoantibodies to diabetes (p=0.06). In a Cox proportional hazards analysis, faster progression was associated with an increased genetic risk score independently of HLA genotype (HR for progression from multiple autoantibodies to type 1 diabetes, 1.27, 95% CI 1.02 to 1.58 per unit increase), an earlier age of islet autoantibody development (HR, 0.68, 95% CI 0.58 to 0.81 per year increase in age) and female sex (HR, 1.94, 95% CI 1.28 to 2.93).ConclusionsGenetic risk scores may be used to identify islet autoantibody-positive children with high-risk HLA genotypes who have a slow rate of progression to subsequent stages of autoimmunity and type 1 diabetes.

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