SARS-CoV-2 - No Increased Islet Autoimmunity or Type 1 Diabetes in Teens.
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ABSTRACT:
SUBMITTER: Krischer JP
PROVIDER: S-EPMC10481371 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
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SARS-CoV-2 - No Increased Islet Autoimmunity or Type 1 Diabetes in Teens.
Krischer Jeffrey P JP Lernmark Åke Å Hagopian William A WA Rewers Marian J MJ McIndoe Richard R Toppari Jorma J Ziegler Anette-Gabriele AG Akolkar Beena B
The New England journal of medicine 20230801 5
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Project description:BackgroundType 1 diabetes (TID) is characterized by a loss of pancreatic islet beta cell function resulting in loss of insulin production. Genetic and environmental factors may trigger immune responses targeting beta cells thus generating islet antibodies (IA). Immune response pathways involve a cascade of events, initiated by cytokines and chemokines, producing inflammation which can result in tissue damage.MethodsA nested case-control study was performed to identify temporal changes in cytokine levels in 75 DAISY subjects: 25 diagnosed T1D, 25 persistent IA, and 25 controls. Serum samples were selected at four time points: (T1) earliest, (T2) just prior to IA, (T3) just after IA, and (T4) prior to T1D diagnosis or most recent. Cytokines (IFN-α2a, IL-6, IL-17, IL-1β, IP-10, MCP-1, IFN-γ, IL-1α, and IL-1ra) were measured using the Meso Scale Discovery system Human Custom Cytokine 9-Plex assay.ResultsMultivariate mixed models adjusting for HLA risk, first-degree relative status, age, and gender, showed MCP-1 and IFN-үto be significantly higher at T3 in T1D compared to IA subjects. At T4, IP-10 was significantly higher in IA subjects than controls.ConclusionsThis repeated measures nested case-control study identified increased inflammatory markers in IA children who developed T1D compared to IA children who had not progressed to clinical disease. It also showed increased inflammation in both T1D and IA children when compared to controls. Results suggest inflammation may be related to both the development of IA and progression to T1D.
| S-EPMC5381877 | biostudies-literature
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| S-EPMC11877402 | biostudies-literature
Project description:BackgroundProspective longitudinal evidence considering the entire childhood food consumption in relation to the development of islet autoimmunity (IA or) type 1 diabetes is lacking.ObjectivesWe studied the associations of consumption of various foods and their combinations with IA and type 1 diabetes risk.MethodsChildren with genetic susceptibility to type 1 diabetes born in 1996-2004 were followed from birth up to ≤6 y of age in the prospective birth cohort type 1 diabetes prediction and prevention study (n = 5674). Exposure variables included 34 food groups covering the entire diet based on repeated 3-d food records at ages 3 mo to 6 y. Endpoints were islet cell antibodies plus biochemical IA (n = 247), multiple biochemical IA (n = 206), and type 1 diabetes (n = 94). We analyzed associations between longitudinally observed foods and risk of IA/type 1 diabetes using a Bayesian approach to joint models in 1-food and multi-food models adjusted for energy intake, sex, human leukocyte antigen genotype, and familial diabetes.ResultsThe final multi-food model for islet cell antibodies plus biochemical IA included oats [hazard ratio (HR): 1.09; 95% credible interval (CI): 1.04, 1.14], banana (HR: 1.07; 95% CI: 1.03, 1.11), and cruciferous vegetables (HR: 0.83; 95% CI: 0.73, 0.94). The final model for multiple biochemical IA included, in addition to the above-mentioned foods, fermented dairy (HR: 1.42; 95% CI: 1.12, 1.78) and wheat (HR: 1.10; 95% CI: 1.03, 1.18). The final multi-food model for type 1 diabetes included rye (HR: 1.27; 95% CI: 1.07, 1.50), oats (HR: 1.15; 95% CI: 1.03, 1.26), fruits (HR: 1.05; 95% CI: 1.01, 1.09), and berries (HR: 0.67; 95% CI: 0.50, 0.93).ConclusionsHigher consumption of oats, gluten-containing cereals, and fruits was associated with increased that of cruciferous vegetables with decreased risk of several type 1 diabetes-related endpoints when considering all the foods in combination. Further etiological and mechanistic studies are warranted.
| S-EPMC11600112 | biostudies-literature
Project description:Larger childhood body size and rapid growth have been associated with increased type 1 diabetes risk. We analysed height, weight, BMI and velocities of growth in height, weight and BMI, for association with development of islet autoimmunity (IA) and type 1 diabetes.Since 1993, the Diabetes Autoimmunity Study in the Young (DAISY) has followed children at increased type 1 diabetes risk, based on HLA-DR, -DQ genotype or family history, for the development of IA and type 1 diabetes. IA was defined as the presence of autoantibodies to insulin, GAD or protein tyrosine phosphatase islet antigen 2 twice in succession, or autoantibody-positive on one visit and diabetic at the next consecutive visit within 1 year. Type 1 diabetes was diagnosed by a physician. Height and weight were collected starting at age 2 years. Of 1,714 DAISY children <11.5 years of age, 143 developed IA and 21 progressed to type 1 diabetes. We conducted Cox proportional hazards analysis to explore growth velocities and size measures for association with IA and type 1 diabetes development.Greater height growth velocity was associated with IA development (HR 1.63, 95% CI 1.31-2.05) and type 1 diabetes development (HR 3.34, 95% CI 1.73-6.42) for a 1 SD difference in velocity.Our study suggests that greater height growth velocity may be involved in the progression from genetic susceptibility to autoimmunity and then to type 1 diabetes in pre-pubertal children.
| S-EPMC2813468 | biostudies-literature
Project description:The metabolome is sensitive to genetic and environmental factors contributing to complex diseases such as type 1 diabetes (T1D). Metabolomics is the study of biochemical and physiological processes involving metabolites. It is therefore one of the key platforms for the discovery and study of pathophysiological phenomena leading to T1D and the development of T1D-associated complications. Although the application of metabolomics in T1D research is still rare, metabolomic research has already advanced across the full spectrum, from disease progression to the development of diabetic complications. Metabolomic studies in T1D have contributed to an improved etiopathogenic understanding and demonstrated their potential in the clinic. For example, metabolomic data from recent T1D studies suggest that a specific metabolic profile, or metabotype, precedes islet autoimmunity and the development of overt T1D. These early metabolic changes are attributed to many biochemical pathways, thus suggesting a systemic change in metabolism which may be inborn. Based on this evidence, the role of the metabolome in the progression to T1D is therefore to facilitate specific biochemical processes associated with T1D, and to contribute to the development of a vulnerable state in which disease is more likely to be triggered. This may have important implications for the understanding of T1D pathophysiology and early disease detection and prevention.
| S-EPMC3740693 | biostudies-literature
Project description:Aims/hypothesisMetabolic dysregulation may precede the onset of type 1 diabetes. However, these metabolic disturbances and their specific role in disease initiation remain poorly understood. In this study, we examined whether children who progress to type 1 diabetes have a circulatory polar metabolite profile distinct from that of children who later progress to islet autoimmunity but not type 1 diabetes and a matched control group.MethodsWe analysed polar metabolites from 415 longitudinal plasma samples in a prospective cohort of children in three study groups: those who progressed to type 1 diabetes; those who seroconverted to one islet autoantibody but not to type 1 diabetes; and an antibody-negative control group. Metabolites were measured using two-dimensional GC high-speed time of flight MS.ResultsIn early infancy, progression to type 1 diabetes was associated with downregulated amino acids, sugar derivatives and fatty acids, including catabolites of microbial origin, compared with the control group. Methionine remained persistently upregulated in those progressing to type 1 diabetes compared with the control group and those who seroconverted to one islet autoantibody. The appearance of islet autoantibodies was associated with decreased glutamic and aspartic acids.Conclusions/interpretationOur findings suggest that children who progress to type 1 diabetes have a unique metabolic profile, which is, however, altered with the appearance of islet autoantibodies. Our findings may assist with early prediction of the disease.
| S-EPMC6861356 | biostudies-literature
Project description:ImportanceThe incidence of diabetes in childhood has increased during the COVID-19 pandemic. Elucidating whether SARS-CoV-2 infection is associated with islet autoimmunity, which precedes type 1 diabetes onset, is relevant to disease etiology and future childhood diabetes trends.ObjectiveTo determine whether there is a temporal relationship between SARS-CoV-2 infection and the development of islet autoimmunity in early childhood.Design, setting, and participantsBetween February 2018 and March 2021, the Primary Oral Insulin Trial, a European multicenter study, enrolled 1050 infants (517 girls) aged 4 to 7 months with a more than 10% genetically defined risk of type 1 diabetes. Children were followed up through September 2022.ExposureSARS-CoV-2 infection identified by SARS-CoV-2 antibody development in follow-up visits conducted at 2- to 6-month intervals until age 2 years from April 2018 through June 2022.Main outcomes and measuresThe development of multiple (≥2) islet autoantibodies in follow-up in consecutive samples or single islet antibodies and type 1 diabetes. Antibody incidence rates and risk of developing islet autoantibodies were analyzed.ResultsConsent was obtained for 885 (441 girls) children who were included in follow-up antibody measurements from age 6 months. SARS-CoV-2 antibodies developed in 170 children at a median age of 18 months (range, 6-25 months). Islet autoantibodies developed in 60 children. Six of these children tested positive for islet autoantibodies at the same time as they tested positive for SARS-CoV-2 antibodies and 6 at the visit after having tested positive for SARS-CoV-2 antibodies. The sex-, age-, and country-adjusted hazard ratio for developing islet autoantibodies when the children tested positive for SARS-CoV-2 antibodies was 3.5 (95% CI, 1.6-7.7; P = .002). The incidence rate of islet autoantibodies was 3.5 (95% CI, 2.2-5.1) per 100 person-years in children without SARS-CoV-2 antibodies and 7.8 (95% CI, 5.3-19.0) per 100 person-years in children with SARS-CoV-2 antibodies (P = .02). Islet autoantibody risk in children with SARS-CoV-2 antibodies was associated with younger age (<18 months) of SARS-CoV-2 antibody development (HR, 5.3; 95% CI, 1.5-18.3; P = .009).Conclusion and relevanceIn young children with high genetic risk of type 1 diabetes, SARS-CoV-2 infection was temporally associated with the development of islet autoantibodies.
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Project description:PURPOSE OF REVIEW:Regulatory T cells (Tregs) are critical contributors to immune homeostasis and their dysregulation can lead to the loss of immune tolerance and autoimmune diseases like type 1 diabetes (T1D). Recent studies have highlighted microRNAs (miRNAs) as important regulators of the immune system, by fine-tuning relevant genes in various immune cell types. In this review article, we discuss recent insights into miRNA regulation of immune tolerance and activation. Specifically, we discuss how the dysregulation of miRNAs in T cells contributes to their aberrant function and the onset of islet autoimmunity, as well as their potential as targets of novel intervention strategies to interfere with autoimmune activation. RECENT FINDINGS:Several studies have shown that the dysregulation of individual miRNAs in T cells can contribute to impaired immune tolerance, contributing to onset and progression of islet autoimmunity. Importantly, the targeting of these miRNAs, including miR-92a, miR-142-3p and miR-181a, resulted in relevant effects on downstream pathways, improved Treg function and reduced islet autoimmunity in murine models. miRNAs are critical regulators of immune homeostasis and the dysregulation of individual miRNAs in T cells contributes to aberrant T cell function and autoimmunity. The specific targeting of individual miRNAs could improve Treg homeostasis and therefore limit overshooting T cell activation and islet autoimmunity.
| S-EPMC7387371 | biostudies-literature
Project description:Previous studies suggest that children who progress to type 1 diabetes (T1D) later in life already have an altered serum lipid molecular profile at birth. Here, we compared cord blood lipidome across the three study groups: children who progressed to T1D (PT1D; n = 30), children who developed at least one islet autoantibody but did not progress to T1D during the follow-up (P1Ab; n = 33), and their age-matched controls (CTR; n = 38). We found that phospholipids, specifically sphingomyelins, were lower in T1D progressors when compared to P1Ab and the CTR. Cholesterol esters remained higher in PT1D when compared to other groups. A signature comprising five lipids was predictive of the risk of progression to T1D, with an area under the receiver operating characteristic curve (AUROC) of 0.83. Our findings provide further evidence that the lipidomic profiles of newborn infants who progress to T1D later in life are different from lipidomic profiles in P1Ab and CTR.
| S-EPMC6359525 | biostudies-literature
Project description:To investigate whether enterovirus infections predict progression to type 1 diabetes in genetically predisposed children repeatedly positive for islet autoantibodies.Since 1993, the Diabetes and Autoimmunity Study in the Young (DAISY) has followed 2,365 genetically predisposed children for islet autoimmunity and type 1 diabetes. Venous blood and rectal swabs were collected every 3-6 months after seroconversion for islet autoantibodies (against GAD, insulin, or insulinoma-associated antigen-2 [IA-2]) until diagnosis of diabetes. Enteroviral RNA in serum or rectal swabs was detected using reverse transcriptase PCR with primers specific for the conserved 5' noncoding region, detecting essentially all enterovirus serotypes.Of 140 children who seroconverted to repeated positivity for islet autoantibodies at a median age of 4.0 years, 50 progressed to type 1 diabetes during a median follow-up of 4.2 years. The risk of progression to clinical type 1 diabetes in the sample interval following detection of enteroviral RNA in serum (three diabetes cases diagnosed among 17 intervals) was significantly increased compared with that in intervals following a negative serum enteroviral RNA test (33 cases diagnosed among 1,064 intervals; hazard ratio 7.02 [95% CI 1.95-25.3] after adjusting for number of autoantibodies). Results remained significant after adjustment for ZnT8-autoantibodies and after restriction to various subgroups. Enteroviral RNA in rectal swabs was not predictive of progression to type 1 diabetes. No evidence for viral persistence was found.This novel observation suggests that progression from islet autoimmunity to type 1 diabetes may increase after an enterovirus infection characterized by the presence of viral RNA in blood.
| S-EPMC2992780 | biostudies-literature