Project description:While insulin replacement therapy restores the health and prevents the onset of diabetic complications (DC) for many decades, some T1D patients have elevated hemoglobin A1c values suggesting poor glycemic control, a risk factor of DC. We surveyed the stool microbiome and urinary proteome of a cohort of 220 adolescents and children, half of which had lived with T1D for an average of 7 years and half of which were healthy siblings. Phylogenetic analysis of the 16S rRNA gene did not reveal significant differences in gut microbial alpha-diversity comparing the two cohorts. The urinary proteome of T1D patients revealed increased abundances of several lysosomal proteins that correlated with elevated HbA1c values. In silico protein network analysis linked such proteins to extracellular matrix components and the glycoprotein LRG1. LRG1 is a prominent inflammation and neovascularization biomarker. We hypothesize that these changes implicate aberrant glycation of macromolecules that alter lysosomal function and metabolism in renal tubular epithelial cells, cells that line part of the upper urinary tract.
Project description:The “nonclassic” apparent mineralocorticoid excess (NC-AME) has been identified in approximately 7% of general population. Our aim was to identify miRNAs within urinary exosomes associated to the NC-AME phenotype. A total of 18 urine samples (9 control and 9 NC-AME) derived from adult and children subjects were analyzed using small RNA sequencing.
Project description:To unravel genes and molecular pathways involved in the pathogenesis of type 1 diabetes (T1D), we performed genome-wide gene expression profiling of prospective venous blood samples from children developing T1D-associated autoantibodies or progressing towards clinical diagnosis. 247 peripheral blood RNA samples from 18 prediabetic children and their matched controls were analyzed with Illumina Human HT-12 Expression BeadChips version 3 arrays, in order to study the gene expression changes occuring during the pathogenesis of Type 1 diabetes (T1D). Each case child (with T1D-specific autoantibodies) was matched with a persistently autoantibody-negative control child, with the same HLA-DQB1 risk category, gender, and place and date of birth. Two control children were selected for T1D cases 3, 5, 13 and 17. Seroconversion is determined as the first detection of T1D-specific autoantibody/autoantibodies (ICA titre >4 JDFU, IAA >3.47 RU, GADA >5.4 RU, IA-2A >0.43 RU, ZnT8A >0.61 RU).
Project description:To unravel genes and molecular pathways involved in the pathogenesis of type 1 diabetes (T1D), we performed genome-wide gene expression profiling of prospective venous blood samples from children developing T1D-associated autoantibodies or progressing towards clinical diagnosis. 357 peripheral blood RNA samples from 10 autoantibody-positive children (Case) and their matched controls (Control) or alternatively 18 prediabetic children (T1DCase) and their matched controls (T1DControl) were analyzed with Affymetrix U219 gene array, in order to study the gene expression changes occuring during the pathogenesis of Type 1 diabetes (T1D). Each case child (positive for T1D-specific autoantibodies) was matched with a persistently autoantibody-negative control child, with the same HLA-DQB1 risk category, gender, and place and date of birth. Seroconversion is determined as the first detection of T1D-specific autoantibody/autoantibodies (ICA titre >4 JDFU, IAA >3.47 RU, GADA >5.4 RU, IA-2A >0.43 RU, ZnT8A >0.61 RU). Two control children were selected for T1D cases 3, 5, 13 and 17. Case5 & T1DCase15 and Case7 & T1DCase3 share the same matched control. Sample T1DControl7_4 was excluded from the final analysis as an outlier, resulting in 356 total Samples listed below.
Project description:Type 1 diabetes (T1D) is one of the most prevalent autoimmune diseases among children in Western countries. Earlier metabolomics studies suggest that T1D is preceded by dysregulation of lipid metabolism. Here we used a lipidomics approach to analyze molecular lipids in a prospective series of 428 plasma samples from 40 children who progressed to T1D (PT1D), 40 children who developed at least a single islet autoantibody but did not progress to T1D during the follow-up (P1Ab) and 40 matched controls (CTR). Sphingomyelins were found to be persistently downregulated in PT1D when compared to the P1Ab and CTR groups. Triacylglycerols and phosphatidylcholines were mainly downregulated in PT1D as compared to P1Ab at the age of 3 months. Our study suggests that children who progressed to islet autoimmunity or overt T1D are characterized by distinct lipidomic signatures, which may be helpful in the identification of at-risk children before the initiation of autoimmunity.