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PROVIDER: PRJNA1068989 | ENA |
REPOSITORIES: ENA
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Project description:OBJECTIVE: Novel biomarkers of disease progression after type 1 diabetes onset are needed. RESEARCH DESIGN AND METHODS: We profiled peripheral blood (PB) monocyte gene expression in 6 healthy subjects and 16 children with type 1 diabetes diagnosed ~3 months previously, and analyzed clinical features from diagnosis to 1 year. RESULTS: Monocyte expression profiles clustered into two distinct subgroups, representing mild and severe deviation from healthy controls, along the same continuum. Patients with strongly divergent monocyte gene expression had significantly higher insulin dose-adjusted HbA1c levels during the first year, compared to patients with mild deviation. The diabetes-associated expression signature identified multiple perturbations in pathways controlling cellular metabolism and survival, including endoplasmic reticulum and oxidative stress (e.g. induction of HIF1A, DDIT3, DDIT4 and GRP78). qPCR quantitation of a 9-gene panel correlated with glycaemic control in 12 additional recent-onset patients. The qPCR signature was also detected in PB from healthy first-degree relatives. CONCLUSIONS: A PB gene expression signature correlates with glycaemic control in the first year after diabetes diagnosis, and is present in at-risk subjects. These findings implicate monocyte phenotype as a candidate biomarker for disease progression pre- and post-onset, and systemic stresses as contributors to innate immune function in type 1 diabetes. CD14+ monocytes from a total of 16 children with recent-onset type 1 diabetes and 6 adult healthy controls were profiled in 2 independent microarrays.
2012-05-31 | E-GEOD-33440 | biostudies-arrayexpress
Project description:Type 1 diabetes (T1D) is an autoimmune disease caused by selective destruction of insulin producing pancreatic beta-cells in the islets of the Langerhans. The progression to clinical diabetes is characterized by the appearance of autoantibodies against islet cells (ICA) and beta-cell-specific antigens (IAA, IA-2 and GADA), which are considered the first markers signifying onset of autoimmunity. The mechanisms initiating or enhancing the autoimmune process remain poorly understood. Transcriptomic profiling on whole blood samples provides an approach for monitoring T1D disease process. In these investigations of pathways that are changed during the disease process, we have analyzed RNA from longitudinal peripheral blood samples of children who have developed T1D associated autoantibodies and eventually clinical type 1 diabetes . All study subjects were participants of the Type 1 Diabetes Prediction and Prevention (DIPP) study in Finland (38). Whole-blood RNA samples were collected during periodic clinic visits, typically at 3 to 12 month intervals. 2.5 ml venous blood was drawn into PAXgene Blood RNA tubes (Becton-Dickinson) and stored at -70°C. T1D-associated autoantibodies were measured from blood samples taken at each visit. Prospective samples from 3 children who developed T1D (subjects T1D_1 - T1D_3) and 2 children who developed ICA (subjects ICA_1 and ICA_2) during the DIPP follow-up were selected to the present study. Control children for the T1D cases (subjects T1D_C1 - T1D_C2) were matched for age, gender, birth place and HLA-genotype, from families who have no first-degree relatives with T1D. All samples (n=60) were processed and hybridized on Affymetrix Human Genome U133 Plus 2.0 arrays.
2010-03-31 | E-TABM-666 | biostudies-arrayexpress
Project description:<h4><strong>AIMS/HYPOTHESIS: </strong>Metabolic 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.</h4><h4><strong>METHODS: </strong>We 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.</h4><h4><strong>RESULTS: </strong>In 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.</h4><h4><strong>CONCLUSIONS/INTERPRETATION: </strong>Our 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.</h4>
2022-01-19 | MTBLS802 | MetaboLights
Project description:Inflammatory pathways in peripheral blood expression profile of recent-onset type 1 diabetes
| PRJNA656519 | ENA
Project description:The gastrointestinal ecosystem is a highly complex environment with a profound influence on human health. Inflammation in the gut, linked to an altered gut microbiome has been associated with the development of multiple human conditions including type 1 diabetes (T1D). Viruses infecting the gastrointestinal tract, especially enteroviruses, are also thought to play an important role in T1D pathogenesis possibly via overlapping mechanisms. Here, we apply an integrative approach to combine comprehensive faecal virome, microbiome and metaproteome data sampled before and at the onset of islet autoimmunity in 40 children. We show strong age and antibody related effects across the datasets. Mastadenovirus infection was associated with profound functional changes in the faecal metaproteome. Multiomic factor analysis modelling revealed proteins associated with carbohydrate transport from the genus Faecalibacterium were associated with islet autoimmunity. These findings demonstrate functional remodelling of the gut microbiota accompanies both islet autoimmunity and viral infection.
2022-08-22 | PXD032997 | Pride
Project description:Pancreatic cancer is the 3rd most prevalent cause of cancer related deaths in United states alone, with over 55000 patients being diagnosed in 2019 alone and nearly as many succumbing to it. Late detection, lack of effective therapy and poor understanding of pancreatic cancer systemically contributes to its poor survival statistics. Obesity and high caloric intake linked co-morbidities like type 2 diabetes (T2D) have been attributed as being risk factors for a number of cancers including pancreatic cancer. Studies on gut microbiome has shown that lifestyle factors as well as diet has a huge effect on the microbial flora of the gut. Further, modulation of gut microbiome has been seen to contribute to effects of intensive insulin therapy in mice on high fat diet. In another study, abnormal gut microbiota was reported to contribute to development of diabetes in Db/Db mice. Recent studies indicate that microbiome and microbial dysbiosis plays a role in not only the onset of disease but also in its outcome. In colorectal cancer, Fusobacterium has been reported to promote therapy resistance. Certain intra-tumoral bacteria have also been shown to elicit chemo-resistance by metabolizing anti-cancerous agents. In pancreatic cancer, studies on altered gut microbiome have been relatively recent. Microbial dysbiosis has been observed to be associated with pancreatic tumor progression. Modulation of microbiome has been shown to affect response to anti-PD1 therapy in this disease as well. However, most of the studies in pancreatic cancer and microbiome have remained focused om immune modulation. In the current study, we observed that in a T2D mouse model, the microbiome changed significantly as the hyperglycemia developed in these animals. Our results further showed that, tumors implanted in the T2D mice responded poorly to Gemcitabine/Paclitaxel (Gem/Pac) standard of care compared to those in the control group. A metabolomic reconstruction of the WGS of the gut microbiota further revealed that an enrichment of bacterial population involved in drug metabolism in the T2D group.
2020-11-30 | E-MTAB-8739 | biostudies-arrayexpress
Project description:Partial remission (PR) occurs in only half of patients with new-onset type 1 diabetes (T1D) and correspond to a transient period characterized by low daily insulin needs, low glycemic fluctuations and increased endogenous insulin secretion. While identification of newly-onset T1D patients with significant residual beta-cell function may foster patient-specific interventions, reliable predictive biomarkers of PR occurrence currently lack. We analyzed the plasma of children with new-onset T1D to identify biomarkers present at diagnosis that predicted PR at 3 months post-diagnosis. We first performed an extensive shotgun proteomic analysis using Liquid Chromatography-Tandem-Mass-Spectrometry (LCMS/MS) on the plasma of 16 children with new-onset T1D and quantified nearly 1500 unique proteins with 98 significantly correlating with Insulin-Dose Adjusted glycated hemoglobin A1c score (IDAA1C). We next applied a series of both qualitative and statistical filters that yielded to the selection of 26 protein candidates that were associated to pathophysiological mechanisms related to T1D. Finally, we translationally validated several of the candidates using single-shot targeted proteomic (PRM method) on raw plasma. Taken together, we identified plasmatic biomarkers present at diagnosis that may predict the occurrence of PR in a single mass-spectrometry run. We believe that the identification of new predictive biomarkers of PR and β-cell function is key to stratify patients with new-onset T1D for β-cell preservation therapies
2024-04-05 | PXD049795 | Pride
Project description:OBJECTIVE: Novel biomarkers of disease progression after type 1 diabetes onset are needed. RESEARCH DESIGN AND METHODS: We profiled peripheral blood (PB) monocyte gene expression in 6 healthy subjects and 16 children with type 1 diabetes diagnosed ~3 months previously, and analyzed clinical features from diagnosis to 1 year. RESULTS: Monocyte expression profiles clustered into two distinct subgroups, representing mild and severe deviation from healthy controls, along the same continuum. Patients with strongly divergent monocyte gene expression had significantly higher insulin dose-adjusted HbA1c levels during the first year, compared to patients with mild deviation. The diabetes-associated expression signature identified multiple perturbations in pathways controlling cellular metabolism and survival, including endoplasmic reticulum and oxidative stress (e.g. induction of HIF1A, DDIT3, DDIT4 and GRP78). qPCR quantitation of a 9-gene panel correlated with glycaemic control in 12 additional recent-onset patients. The qPCR signature was also detected in PB from healthy first-degree relatives. CONCLUSIONS: A PB gene expression signature correlates with glycaemic control in the first year after diabetes diagnosis, and is present in at-risk subjects. These findings implicate monocyte phenotype as a candidate biomarker for disease progression pre- and post-onset, and systemic stresses as contributors to innate immune function in type 1 diabetes.
2012-06-01 | GSE33440 | GEO
Project description:Peripheral Blood Monocyte Gene Expression in Recent-Onset Type 1 Diabetes
| PRJNA148693 | ENA