Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY)
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PROVIDER: PRJNA734382 | ENA |
REPOSITORIES: ENA
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Project description:Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY)
| PRJNA734383 | ENA
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
Project description:Lifestyle intervention can improve insulin sensitivity in obese youth yet few studies have examined the biological mechanisms underlying improvements. Therefore, the purpose of this study was to explore biological pathways associated with intervention-induced improvements in insulin sensitivity. Fifteen (7M/8F) overweight/obese (BMI percentile=96.3M-BM-11.1) Latino adolescents (15.0M-BM-10.9 years) completed a 12-week lifestyle intervention that included weekly nutrition education and 180 minutes of moderate-vigorous exercise per week. Insulin sensitivity, estimated by an oral glucose tolerance test and the Matsuda Index, increased 29.2% post intervention (2.4M-BM-10.3 to 3.1M-BM-10.3, p=0.01). Global microarray analysis profiling from whole blood was performed to examine changes in gene expression and to explore biological pathways that were significantly changed in response to the intervention. A total of 1,459 probes corresponding to mRNA transcripts (717 up, 742 down) were differentially expressed with a fold changeM-bM-^IM-%1.2 and P<0.05. Among the genes identified were hexokinase 3 (HK3), ATPase, H+ transporting V0 subunit e2 (ATPV0E), and sterol regulatory element binding transcription factor 1 (SREBF1), and endothelial cell adhesion molecule (ESAM). There were 8 pathways identified that met the criteria for significance, including insulin signaling, type 1 diabetes, and glycerophospholipid metabolism. Participants that increased insulin sensitivity exhibited five times the number of significant genes altered compared to non-responders (1,144 vs. 230). These findings offer insight into the molecular mechanisms underlying health improvements among high-risk Latino youth. Lifestyle interventions may contribute to improved insulin sensitivity through pathways related to insulin signaling and immune response. Further, genetic factors may mediate response to lifestyle intervention. Fifteen (7M/8F) overweight/obese Latino Youth Whole blood RNA samples evaluated pre and post intervention.
2013-11-04 | E-GEOD-50800 | biostudies-arrayexpress
Project description:Context:Little is known about reproductive function in girls with youth-onset type 2 diabetes. Objectives:To characterize girls with irregular menses and effects of glycemic treatments on menses and sex steroids in the Treatment Options for Type 2 Diabetes in Youth (TODAY) study. Design:Differences in demographic, metabolic, and hormonal characteristics between regular- vs irregular-menses groups were tested; treatment group (metformin with or without rosiglitazone, metformin plus lifestyle) effect on menses and sex steroids over time in the study was assessed. This is a secondary analysis of TODAY data. Setting:Multicenter study in an academic setting. Patients:TODAY girls not receiving hormonal contraception and those at least 1-year postmenarche were included. Irregular menses was defined as three or fewer periods in the prior 6 months. Results:Of eligible participants with serum measurement of sex steroids (n = 190; mean age, 14 years), 21% had irregular menses. Those with irregular vs regular menses had higher body mass index (BMI) (P = 0.001), aspartate aminotransferase (AST) (P = 0.001), free androgen index (P = 0.0003), and total testosterone (P = 0.01) and lower sex hormone-binding globulin (SHBG) (P = 0.004) and estradiol (P = 0.01). Differences remained after adjustment for BMI. There was no treatment group effect on menses or sex steroids at 12 or 24 months, and no association of sex steroids was seen with measures of insulin sensitivity or secretion. Conclusions:Menstrual dysfunction is common in girls with recently diagnosed type 2 diabetes and associated with alterations in sex steroids, SHBG, and AST but not with alteration in insulin sensitivity or β-cell function and did not improve with 2 years of antihyperglycemic treatment.
| S-EPMC6276678 | biostudies-literature
Project description:SEARCH for Diabetes in Youth Study - Genetic Risk Score
| PRJNA782027 | ENA
Project description:SEARCH for Diabetes in Youth Study - Genetic Risk Score
| PRJNA782026 | ENA
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
Project description:To evaluate functional consequences of insulin-deficient diabetes mellitus for the liver, we used a genetically engineered pig model of mutant INS gene induced diabetes of youth (MIDY). Liver 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.
2019-11-12 | PXD011536 | Pride
Project description:Fifty-six children and adolescents with type 1 diabetes at least one year after diagnosis, aged 6-17 years old and fifty-six healthy age- and sex-matched subjects were enrolled in this cross-sectional study. Tear samples were collected using Schirmer strips placed on the lower eyelid. The proteomic analysis was based on a detergent-assisted protein extraction and their digestion from the tears, analysis of the tryptic peptides with LC-MS/ enabling the identification, and quantification of the Shirmer strip protein content via DIA-NN, and subsequently the statistical and bioinformatic analysis using the R and Metascape enrichment analysis tool.
2024-10-17 | PXD052994 | Pride
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