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SEARCH for Diabetes in Youth Study - Genetic Risk Score

ABSTRACT: SEARCH for Diabetes in Youth Study - Genetic Risk Score

PROVIDER: PRJNA782026 | ENA |

REPOSITORIES: ENA

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SEARCH for Diabetes in Youth Study - Genetic Risk Score

Project description:SEARCH for Diabetes in Youth Study - Genetic Risk Score

| PRJNA782027 | ENA

D-score - D-score: a search engine independent MD-score

Project description:Processing of the dataset of synthetic phosphopeptides by Savitzki et al. (MCP, 2011) using multiple search engines. Establishment of the D-score: a search engine independent MD-score.

2013-01-23 | PXD000021 | Pride

Metabolic surgery mitigates early kidney injury in obese youth with diabetes by suppressing mTORC1/JAK–STAT signaling

Project description:Background Youth with type 2 diabetes (T2D) and severe obesity face high risk of diabetic kidney disease, which metabolic bariatric surgery (MBS) can mitigate. This study explores structural and molecular changes in kidneys after vertical sleeve gastrectomy (VSG), a form of MBS. Methods Paired analyses, including metabolic profiling, kidney volume assessment, histological evaluation, and single-cell RNA sequencing (scRNAseq) on kidney biopsies from five youth with T2D and obesity pre- and 12 months post-VSG in the IMPROVE-T2D (Impact of Metabolic surgery on Pancreatic, Renal and cardiOVascular hEalth in youth with T2D) cohort. Circulating proteomics with kidney transcriptomics, were linked using data from an independent cohort of youth with obesity, with or without T2D, undergoing MBS in Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS, n=64). Results Post-VSG, participants lost weight and had improvements in insulin sensitivity and metabolic parameters. Kidney changes included reduced renal hyperfiltration, total kidney volume, mesangial matrix area, and microalbuminuria. scRNAseq in proximal tubule (PT) and thick ascending limb cells indicated repression of glycolysis, gluconeogenesis, and tricarboxylic acid cycle genes, with upregulation of AMP-activated protein kinase (AMPK) and Forkhead box O3 (FOXO3). Decreased metabolic signaling aligned with reduced ribosomal phosphorylated S6K (pS6K), suggesting attenuated mTORC1 activity. JAK-STAT pathway activation in PT was diminished, correlating with lower circulating ligands from Teen-LABS proteomic data. Conclusion MBS/VSG prompts kidney molecular adaptations, providing potential targets for non-surgical interventions against obesity- and diabetes-associated kidney disease.

2026-01-09 | GSE315877 | GEO

SGLT2 inhibitors mitigate kidney tubular metabolic and mTORC1 perturbations in youth onset type 2 diabetes

Project description:Single cell RNA-sequencing analysis allows for a more complete cell-by-cell analysis of the effects of SGLT2 inhibitors on the kidneys of patients with youth onset type 2 diabetes.

2023-01-19 | GSE220939 | GEO

Platelet Reactivity ExpreSsion Score Predicts Cardiovascular Risk

Project description:Platelet Reactivity ExpreSsion Score Predicts Cardiovascular Risk

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Predictive computational obesity risk framework through integration of gene expression profiles and genetic risk score.

Project description:We aimed to predict obesity risk with genetic data, specifically, obesity-associated gene expression profiles. Genetic risk score was computed. The genetic risk score was significantly correlated with BMI when an optimization algorithm was used. Linear regression and built support vector machine models predicted obesity risk using gene expression profiles and the genetic risk score with a new mathematical method.

2018-01-25 | GSE109597 | GEO

Serum Protein Risk Stratification Score for Diagnostic Evaluation of Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Project description:Reliable non-invasive tools to diagnose at risk metabolic dysfunction-associated steatohepatitis (MASH) are urgently needed to improve management. We developed a risk stratification score incorporating proteomics-derived serum markers with clinical variables to identify high risk MASH patients (NAFLD Activity Score (NAS) >4 and fibrosis score >2). In this three-phase proteomic study of biopsy-proven metabolic dysfunction-associated steatotic fatty liver disease (MASLD), we first developed a multi-protein predictor for discriminating NAS>4 based on SOMAscan proteomics quantifying 1,305 serum proteins from 57 US patients. Four key predictor proteins were verified by ELISA in the expanded US cohort (N=168), and enhanced by adding clinical variables to create the 9-feature MASH Dx Score which predicted MASH and also high risk MASH (F2+). The MASH Dx Score was validated in two independent, external cohorts from Germany (N=139) and Brazil (N=177). The discovery phase identified a 6-protein classifier that achieved an AUC of 0.93 for identifying MASH. Significant elevation of four proteins (THBS2, GDF15, SELE, IGFBP7) was verified by ELISA in the expanded discovery and independently in the two external cohorts. MASH Dx Score incorporated these proteins with established MASH risk factors (age, BMI, ALT, diabetes, hypertension) to achieve good discrimination between MASH and MASLD without MASH (AUC:0.87- discovery; 0.83- pooled external validation cohorts), with similar performance when evaluating high risk MASH F2-4 (vs. MASH F0-1 and MASLD without MASH). The MASH Dx Score offers the first reliable non-invasive approach combining novel, biologically plausible ELISA-based fibrosis markers and clinical parameters to detect high risk MASH in patient cohorts from the US, Brasil and Europe.

2023-12-22 | GSE251855 | GEO

Proteomic analysis of liver tissue from a pig model of mutant INS gene induced diabetes of youth (MIDY)

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2019-11-12 | PXD011536 | Pride

Proteomic analysis of adipose tissue from a pig model of mutant INS gene induced diabetes of youth (MIDY)

Project description:To evaluate functional consequences of insulin-deficient diabetes mellitus for adipose tissue, we used a genetically engineered pig model of mutant INS gene induced diabetes of youth (MIDY). Adipose tissue samples of MIDY pigs and wild-type (WT) littermate controls were analyzed by label-free proteomics to reveal pathways and key drivers significantly affected by chronic insulin deficiency and hyperglycemia.

2022-02-17 | PXD026910 | Pride

Cardiovascular risk in patients with type 2 diabetes is associated with alteration of blood monocyte phenotype and plasma metabolome

Project description:To gain insight into the relationship between circulating monocytes and cardiovascular risk (CV) progression in patients with type 2 diabetes (T2D), we collected blood monocytes (CD14 positive selection) from 92 people with type 2 diabetes and coronary artery calcium score (CAC-score). Gene expression profiles of circulating monocytes were assessed by RNA sequencing.

2024-01-08 | GSE201087 | GEO

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