{"id":4563,"date":"2020-02-13T09:06:28","date_gmt":"2020-02-13T09:06:28","guid":{"rendered":"http:\/\/www.mymedicplus.com\/news\/?p=4563"},"modified":"2020-02-13T09:06:28","modified_gmt":"2020-02-13T09:06:28","slug":"metabolic-alterations-in-immune-cells-associate-with-progression-to-type-1-diabetes","status":"publish","type":"post","link":"https:\/\/www.mymedicplus.com\/blog\/metabolic-alterations-in-immune-cells-associate-with-progression-to-type-1-diabetes\/","title":{"rendered":"Metabolic alterations in immune cells associate with progression to type 1 diabetes"},"content":{"rendered":"\n<p>Source: link.springer.com<\/p>\n<section lang=\"en\" aria-labelledby=\"Abs1\">\n<div id=\"Abs1-section\" class=\"c-article-section\">\n<div id=\"ez-toc-container\" class=\"ez-toc-v2_0_81 counter-hierarchy ez-toc-counter ez-toc-grey ez-toc-container-direction\">\n<div class=\"ez-toc-title-container\">\n<p class=\"ez-toc-title\" style=\"cursor:inherit\">Table of Contents<\/p>\n<span class=\"ez-toc-title-toggle\"><a href=\"#\" class=\"ez-toc-pull-right ez-toc-btn ez-toc-btn-xs ez-toc-btn-default ez-toc-toggle\" aria-label=\"Toggle Table of Content\"><span class=\"ez-toc-js-icon-con\"><span class=\"\"><span class=\"eztoc-hide\" style=\"display:none;\">Toggle<\/span><span class=\"ez-toc-icon-toggle-span\"><svg style=\"fill: #999;color:#999\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" class=\"list-377408\" width=\"20px\" height=\"20px\" viewBox=\"0 0 24 24\" fill=\"none\"><path d=\"M6 6H4v2h2V6zm14 0H8v2h12V6zM4 11h2v2H4v-2zm16 0H8v2h12v-2zM4 16h2v2H4v-2zm16 0H8v2h12v-2z\" fill=\"currentColor\"><\/path><\/svg><svg style=\"fill: #999;color:#999\" class=\"arrow-unsorted-368013\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" width=\"10px\" height=\"10px\" viewBox=\"0 0 24 24\" version=\"1.2\" baseProfile=\"tiny\"><path d=\"M18.2 9.3l-6.2-6.3-6.2 6.3c-.2.2-.3.4-.3.7s.1.5.3.7c.2.2.4.3.7.3h11c.3 0 .5-.1.7-.3.2-.2.3-.5.3-.7s-.1-.5-.3-.7zM5.8 14.7l6.2 6.3 6.2-6.3c.2-.2.3-.5.3-.7s-.1-.5-.3-.7c-.2-.2-.4-.3-.7-.3h-11c-.3 0-.5.1-.7.3-.2.2-.3.5-.3.7s.1.5.3.7z\"\/><\/svg><\/span><\/span><\/span><\/a><\/span><\/div>\n<nav><ul class='ez-toc-list ez-toc-list-level-1 ' ><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-1\" href=\"https:\/\/www.mymedicplus.com\/blog\/metabolic-alterations-in-immune-cells-associate-with-progression-to-type-1-diabetes\/#Abstract\" >Abstract<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-2\" href=\"https:\/\/www.mymedicplus.com\/blog\/metabolic-alterations-in-immune-cells-associate-with-progression-to-type-1-diabetes\/#Aimshypothesis\" >Aims\/hypothesis<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-3\" href=\"https:\/\/www.mymedicplus.com\/blog\/metabolic-alterations-in-immune-cells-associate-with-progression-to-type-1-diabetes\/#Methods\" >Methods<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-4\" href=\"https:\/\/www.mymedicplus.com\/blog\/metabolic-alterations-in-immune-cells-associate-with-progression-to-type-1-diabetes\/#Results\" >Results<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-5\" href=\"https:\/\/www.mymedicplus.com\/blog\/metabolic-alterations-in-immune-cells-associate-with-progression-to-type-1-diabetes\/#Conclusionsinterpretation\" >Conclusions\/interpretation<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-6\" href=\"https:\/\/www.mymedicplus.com\/blog\/metabolic-alterations-in-immune-cells-associate-with-progression-to-type-1-diabetes\/#Data_availability\" >Data availability<\/a><\/li><\/ul><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-7\" href=\"https:\/\/www.mymedicplus.com\/blog\/metabolic-alterations-in-immune-cells-associate-with-progression-to-type-1-diabetes\/#Introduction\" >Introduction<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-8\" href=\"https:\/\/www.mymedicplus.com\/blog\/metabolic-alterations-in-immune-cells-associate-with-progression-to-type-1-diabetes\/#Methods-2\" >Methods<\/a><ul class='ez-toc-list-level-3' ><li class='ez-toc-heading-level-3'><a class=\"ez-toc-link ez-toc-heading-9\" href=\"https:\/\/www.mymedicplus.com\/blog\/metabolic-alterations-in-immune-cells-associate-with-progression-to-type-1-diabetes\/#Study_design_and_protocol\" >Study design and protocol<\/a><\/li><\/ul><\/li><\/ul><\/nav><\/div>\n<h2 id=\"Abs1\" class=\"c-article-section__title u-h2 js-section-title js-c-reading-companion-sections-item\"><span class=\"ez-toc-section\" id=\"Abstract\"><\/span>Abstract<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<div id=\"Abs1-content\" class=\"c-article-section__content\">\n<h3 class=\"c-article__sub-heading u-h3\" data-test=\"abstract-sub-heading\"><span class=\"ez-toc-section\" id=\"Aimshypothesis\"><\/span>Aims\/hypothesis<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>Previous metabolomics studies suggest that type 1 diabetes is preceded by specific metabolic disturbances. The aim of this study was to investigate whether distinct metabolic patterns occur in peripheral blood mononuclear cells (PBMCs) of children who later develop pancreatic beta cell autoimmunity or overt type 1 diabetes.<\/p>\n<h3 class=\"c-article__sub-heading u-h3\" data-test=\"abstract-sub-heading\"><span class=\"ez-toc-section\" id=\"Methods\"><\/span>Methods<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>In a longitudinal cohort setting, PBMC metabolomic analysis was applied in children who (1) progressed to type 1 diabetes (PT1D,\u00a0<i>n<\/i>\u2009=\u200934), (2) seroconverted to \u22651 islet autoantibody without progressing to type 1 diabetes (P1Ab,\u00a0<i>n<\/i>\u2009=\u200927) or (3) remained autoantibody negative during follow-up (CTRL,\u00a0<i>n<\/i>\u2009=\u200910).<\/p>\n<h3 class=\"c-article__sub-heading u-h3\" data-test=\"abstract-sub-heading\"><span class=\"ez-toc-section\" id=\"Results\"><\/span>Results<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>During the first year of life, levels of most lipids and polar metabolites were lower in the PT1D and P1Ab groups compared with the CTRL group. Pathway over-representation analysis suggested alanine, aspartate, glutamate, glycerophospholipid and sphingolipid metabolism were over-represented in PT1D. Genome-scale metabolic models of PBMCs during type 1 diabetes progression were developed by using publicly available transcriptomics data and constrained with metabolomics data from our study. Metabolic modelling confirmed altered ceramide pathways, known to play an important role in immune regulation, as specifically associated with type 1 diabetes progression.<\/p>\n<h3 class=\"c-article__sub-heading u-h3\" data-test=\"abstract-sub-heading\"><span class=\"ez-toc-section\" id=\"Conclusionsinterpretation\"><\/span>Conclusions\/interpretation<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>Our data suggest that systemic dysregulation of lipid metabolism, as observed in plasma, may impact the metabolism and function of immune cells during progression to overt type 1 diabetes.<\/p>\n<h3 class=\"c-article__sub-heading u-h3\" data-test=\"abstract-sub-heading\"><span class=\"ez-toc-section\" id=\"Data_availability\"><\/span>Data availability<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>The GEMs for PBMCs have been submitted to BioModels (www.ebi.ac.uk\/biomodels\/), under accession number MODEL1905270001. The metabolomics datasets and the clinical metadata generated in this study were submitted to MetaboLights (https:\/\/www.ebi.ac.uk\/metabolights\/), under accession number MTBLS1015.<\/p>\n<\/div>\n<\/div>\n<\/section>\n<section aria-labelledby=\"Sec1\">\n<div id=\"Sec1-section\" class=\"c-article-section\">\n<h2 id=\"Sec1\" class=\"c-article-section__title u-h2 js-section-title js-c-reading-companion-sections-item\"><span class=\"ez-toc-section\" id=\"Introduction\"><\/span>Introduction<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<div id=\"Sec1-content\" class=\"c-article-section__content\">\n<p>The incidence of type 1 diabetes in most Western countries has been increasing over the past few decades, particularly among children below 5\u00a0years of age [1]. About 70% of children with type 1 diabetes carry increased risk-associated genotypes in HLA loci, whereas only 3\u20137% of the population with the same risk alleles develop type 1 diabetes [2].<\/p>\n<p>The appearance of autoantibodies against insulin (IAA), a 65\u00a0kDa isoform of GAD (GADA), insulinoma-associated antigen-2 (IA-2A), and\/or zinc transporter 8 (ZnT8A) in the plasma is an early sign of emerging islet autoimmunity and clinical type 1 diabetes [3]. It is known that children with multiple islet autoantibodies in particular have an increased risk of type 1 diabetes [4]. In addition to genetic predisposition, other exogenous environmental factors affect risk, such as intestinal dysbiosis, reduced gut microbial diversity [5], level of hygiene [6] and infant-feeding regimen [7,\u00a08] are implicated in the initiation of beta cell autoimmunity. Our recent data also suggest that prenatal exposure to environmental chemicals modulates lipid metabolism in newborn infants and increases their subsequent risk of type 1 diabetes [9]. However, the early pathogenesis of type 1 diabetes is still poorly understood and of the molecular signatures and related pathways predictive of progression to overt type 1 diabetes have yet to be identified.<\/p>\n<p>Alterations in immune cell metabolism may affect the host immune system [10]. In fact, external perturbation of key metabolic processes, such as glycolysis and amino acid metabolism, have already been shown to impair T cell activation, differentiation and cytokine production [11]. Human peripheral blood mononuclear cells (PBMCs), including T cells (~70%), B cells (~15%), monocytes (~5%), dendritic cells (~1%) and natural killer (NK) cells (~10%) obtained from healthy donors and progressors to type 1 diabetes are already being investigated in order to better understand this phenomenon [12]. Such efforts seek to elucidate how immune cell metabolic processes are altered in seroconversion and progression to overt type 1 diabetes; currently a largely unknown area.<\/p>\n<p>Metabolomics is the study of small (&lt;1500\u00a0Da) molecules and their functions in cells, tissues and body fluids [13]. The metabolome, which can be seen partly as a phenotypic readout of the genome, is sensitive to changes in immune system status, diet and the gut microbiota [14]. Through metabolomic analyses, we have previously shown that decreased levels of plasma sphingomyelins (SMs) and phosphatidylcholines (PCs) are associated with progression to type 1 diabetes [15,16,17].<\/p>\n<p>In this study, we applied metabolomics to determine levels of molecular lipids and polar metabolites in PBMCs isolated from prospective samples collected in the Type 1 Diabetes Prediction and Prevention (DIPP) study, with the aim of elucidating the events preceding the onset of islet autoimmunity and overt type 1 diabetes. We sought to address whether distinct metabolic patterns can be discerned during infancy among three study groups of children: (1) those who developed clinical type 1 diabetes, (2) those who seroconverted to at least one islet autoantibody but were not diagnosed with type 1 diabetes during follow-up and (3) a control group, i.e. children who remained autoantibody negative during follow-up.<\/p>\n<\/div>\n<\/div>\n<\/section>\n<section aria-labelledby=\"Sec2\">\n<div id=\"Sec2-section\" class=\"c-article-section\">\n<h2 id=\"Sec2\" class=\"c-article-section__title u-h2 js-section-title js-c-reading-companion-sections-item\"><span class=\"ez-toc-section\" id=\"Methods-2\"><\/span>Methods<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<div id=\"Sec2-content\" class=\"c-article-section__content\">\n<h3 class=\"c-article__sub-heading u-h3\"><span class=\"ez-toc-section\" id=\"Study_design_and_protocol\"><\/span>Study design and protocol<span class=\"ez-toc-section-end\"><\/span><\/h3>\n<p>In this study, the samples were obtained from the Finnish DIPP study [18]. The DIPP study has screened more than 230,000 newborn infants for HLA-conferred susceptibility to type 1 diabetes in three university hospitals: those at Turku, Tampere and Oulu in Finland [19]. The children involved in the current study were chosen from the subset of DIPP children which were from the city of Tampere, Finland. The study protocol was approved by the ethics and research committee of University of Tampere and Tampere University Hospital. The study was conducted according to the guidelines of the Declaration of Helsinki. Written informed consent was provided by the parents at the beginning of the study for the children to participate in the study. Here, longitudinal samples for each child were collected between 1998 and 2012. For each child, longitudinal samples for PBMC metabolomic analysis were obtained at 12, 24 and 36\u00a0months of age.<\/p>\n<p>This study comprises samples (<i>n<\/i>\u2009=\u2009137 for lipidomics and\u00a0<i>n<\/i>\u2009=\u2009134 for polar metabolites) from 71 children, divided into three groups:: (1) 27 children who seroconverted to at least one islet autoantibody but were not diagnosed with type 1 diabetes during the follow-up period (P1Ab), (2) 34 children who seroconverted to more than one islet autoantibody and subsequently developed type 1 diabetes (PT1D), and (3) ten control children (CTRL), i.e. children who remained islet autoantibody negative during follow-up. The three study groups were similar in terms of HLA-associated risk for type 1 diabetes, sex and age. Selected characteristics of the participants involved in this study are listed in (Table\u00a01<b>)<\/b>.<\/p>\n<\/div>\n<\/div>\n<\/section>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":1,"featured_media":4564,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[32],"tags":[3032,3033,458,3031,2955],"class_list":["post-4563","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-diabetes","tag-alterations","tag-cells-associate","tag-immune","tag-metabolic","tag-type-1-diabetes"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.0 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Metabolic alterations in immune cells associate with progression to type 1 diabetes - MyMedicPlus<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.mymedicplus.com\/blog\/metabolic-alterations-in-immune-cells-associate-with-progression-to-type-1-diabetes\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Metabolic alterations in immune cells associate with progression to type 1 diabetes - 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