An early Prediction model of type 2 diabetes in a Chinese cohort
Ontology highlight
ABSTRACT:
INSTRUMENT(S): -
ORGANISM(S): Homo Sapiens
SUBMITTER: Tianjin Medical University
PROVIDER: PRJEB67630 | EVA | 2023-10-19
REPOSITORIES: EVA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| genotypefixed_update.vcf.csi | Other | |||
| genotypefixed_update.vcf.gz | Vcf | |||
| genotypefixed_update.vcf.gz.csi | Vcf |
Items per page: 5 1 - 3 of 3 |
Similar Datasets
Project description:We showed in this present study that HSD feeding could induce type 2 diabetes-like phenotype in fruit flies, resembling the key disease features including hyperglycemia, glucosuria, increased hunger and thirsty, unexplained weight loss, and reduced female fecundity. We also showed that HSD-fed flies shared similar molecular mechanisms underlying type 2 diabetes patients, including both insulin deficiency and insulin resistance. Last but not least, disrupting insulin signaling in fruit flies could mimic the effect of HSD feeding to induce type 2 diabetes-like phenotype, further confirming that these phenotypes were a result of compromised insulin signaling upon HSD feeding. Taken together, we demonstrated that this diet-induced type 2 diabetes model in fruit flies rightly and comprehensively recapitulated the physiological, metabolic, behavioral, and molecular features of human type 2 diabetes, offering a valid and accessible model to study the underlying mechanism of this disease and to validate potential diagnostics and therapeutic tools. Given the highly conserved regulatory framework of physiology and metabolism between flies and human, our work has paved a way to generate novel insights into type 2 diabetes, a common, severe, and yet poorly understood disease in human.
2021-05-17 | GSE150565 | GEO
Project description:Aortic endothelia from mice exposed to dietary model of type II diabetes at 4, 6 and 8 weeks of exposure to Bio-Serv #S3282 diet. Objective: Type II diabetes is associated with endothelial dysfunction, which can contribute to accelerated atherosclerosis and subsequent cardiovascular events. We seek to identify transcripts dysregulated in vivo in response to chronic exposure to high dietary fat that leads to diabetes. Methods: Beginning at 8 weeks of age, male Tie2-GFP mice (transgenically expressing green fluorescent protein exclusively within the endothelia) were fed a 60% fat calorie diet (Bio-Serv #S3282); age-matched mice were fed normal chow. After 4, 6, and 8 weeks on the diet, aortae and skeletal muscles (gastrocnemius, biceps femoris, and plantaris) were excised, minced, and collagenolytically digested. Each tissue digest was then subjected to FACS in order to obtain 10,000 endothelial cells. Transcriptomic analyses were performed with microarrays containing the Operon Murine V4 oligo set, and highly dysregulated genes were confirmed by real-time PCR. Results: By 4 weeks, Tie2-GFP mice receiving a high fat diet exhibited a fasting glucose of 215+17 mg/dL vs. 134+23 mg/dL in controls; by 6 weeks, a high fat diet resulted in lower glucose tolerance vs. control diet. Following 4, 6, and 8 weeks of high-fat regimen, aortic endothelial transcripts up-regulated by greater than 2-fold in biologically replicate experiments included macrophage inflammatory protein 2 (Mip2), chemokine (C-C motif) ligand 9 (CCL9), galectin-3 (Gal-3), and 5-lipoxygenase-activating protein (FLAP). Endothelial transcripts up-regulated in skeletal muscle included Mip2, CCL8 and 9, FLAP, gal-1 and 3, and ferritin light chain 1 (FTL1); transcripts down-regulated in muscle included endothelin-1 (ET-1) and insulin-like growth factor II (IGF II). Discussion: Gal-3 and FTL-1 are known to increase in response to advanced glycation end-products and oxidized LDL, respectively. However, the down-regulation of ET-1 and IGFII was surprising, as the transcription of these genes has previously been thought to exacerbate atherosclerosis. In conclusion, a comprehensive analysis of the endothelial transcript-level response to a dietary model of Type II diabetes has revealed novel regulation of transcripts with roles in inflammation, insulin sensitivity, oxidative stress, and atherosclerosis. Understanding the mechanism of diabetes-associated endothelial dysfunction may lead to improved therapies that lower the risk of cardiovascular complications in diabetic patients.
2009-03-28 | GSE14898 | GEO
Project description:Aortic endothelia from mice exposed to dietary model of type II diabetes at 4, 6 and 8 weeks of exposure to Bio-Serv #S3282 diet. Objective: Type II diabetes is associated with endothelial dysfunction, which can contribute to accelerated atherosclerosis and subsequent cardiovascular events. We seek to identify transcripts dysregulated in vivo in response to chronic exposure to high dietary fat that leads to diabetes. Methods: Beginning at 8 weeks of age, male Tie2-GFP mice (transgenically expressing green fluorescent protein exclusively within the endothelia) were fed a 60% fat calorie diet (Bio-Serv #S3282); age-matched mice were fed normal chow. After 4, 6, and 8 weeks on the diet, aortae and skeletal muscles (gastrocnemius, biceps femoris, and plantaris) were excised, minced, and collagenolytically digested. Each tissue digest was then subjected to FACS in order to obtain 10,000 endothelial cells. Transcriptomic analyses were performed with microarrays containing the Operon Murine V4 oligo set, and highly dysregulated genes were confirmed by real-time PCR. Results: By 4 weeks, Tie2-GFP mice receiving a high fat diet exhibited a fasting glucose of 215+17 mg/dL vs. 134+23 mg/dL in controls; by 6 weeks, a high fat diet resulted in lower glucose tolerance vs. control diet. Following 4, 6, and 8 weeks of high-fat regimen, aortic endothelial transcripts up-regulated by greater than 2-fold in biologically replicate experiments included macrophage inflammatory protein 2 (Mip2), chemokine (C-C motif) ligand 9 (CCL9), galectin-3 (Gal-3), and 5-lipoxygenase-activating protein (FLAP). Endothelial transcripts up-regulated in skeletal muscle included Mip2, CCL8 and 9, FLAP, gal-1 and 3, and ferritin light chain 1 (FTL1); transcripts down-regulated in muscle included endothelin-1 (ET-1) and insulin-like growth factor II (IGF II). Discussion: Gal-3 and FTL-1 are known to increase in response to advanced glycation end-products and oxidized LDL, respectively. However, the down-regulation of ET-1 and IGFII was surprising, as the transcription of these genes has previously been thought to exacerbate atherosclerosis. In conclusion, a comprehensive analysis of the endothelial transcript-level response to a dietary model of Type II diabetes has revealed novel regulation of transcripts with roles in inflammation, insulin sensitivity, oxidative stress, and atherosclerosis. Understanding the mechanism of diabetes-associated endothelial dysfunction may lead to improved therapies that lower the risk of cardiovascular complications in diabetic patients. Each experiment is performed with a technical replicate i.e. dye reversal. there is a biological replicate of the 4 week time point
2009-03-27 | E-GEOD-14898 | biostudies-arrayexpress
Project description:White adipose tissue (WAT) dysfunction along with an aberrant expression of miRNAs are strongly associated with the risk of developing type 2 diabetes (T2D) with limited evidence linking early changes in the WAT-derived miRNAs and T2D. The present study aims to identify early miRNome changes prognostic for T2D in mice and humans. Gonadal (g) WAT of diabetes-resistant and -prone mice were subjected to multi-omics analyses (transcriptome, miRNome, methylome, proteome). Metabolic phenotypes linked with T2D were correlated with adipose tissue miRNA expression and DNA methylation from 14 monozygotic twin pairs discordant for T2D. Plasma miRNA levels from females at high risk of developing T2D (TÜF study) were included. Adipose tissue of the diabetes-susceptible mice was less insulin sensitive with 150 differentially expressed miRNAs compared to diabetes-resistant mice. Integrative analysis of miRNome-transcriptome-proteome identified 61 proteins involved in actin cytoskeleton, amino acid and sphingolipid metabolism. More than 20 miRNAs are located in the imprinted region Dlk1-Gtl2 and miR-335 in Mest and regulated by DNA methylation. Imprinted miRNAs also exhibited similar alteration in monozygotic twin pairs discordant for T2D with miR-335 expression altered only in females. Moreover, plasma levels of miR-335-5p were negatively correlated with fasting blood glucose in female individuals at high risk of developing T2D. Early alterations of WAT-derived miRNAs such as miR-335-5p could contribute to systemic metabolic changes associated with the risk of developing T2D.
2025-12-15 | PXD057291 | Pride
Project description:Chronic hyperglycemia is known to disrupt the proteolytic milieu, initiating compensatory and maladaptive pathways in the diabetic kidney. Such changes in intrarenal proteolysis can be captured in the urinary peptidome. We thus examined the urinary peptidomes of otherwise healthy youths with type 1 diabetes and their non-diabetic peers. This cross-sectional study included two separate cohorts for the discovery (N = 30) and initial validation (N = 30) of differential peptide excretion. Peptide bioactivity was predicted using PeptideRanker and subsequently verified in vitro. Proteasix and the Nephroseq database were used to identify putative proteases responsible for peptide generation and examine their expression in diabetic nephropathy. A total of 6550 urinary peptides were identified in the discovery analysis. Of the 15 differentially excreted peptides (P < 0.05), seven derived from a small region (589SGSVIDQSRVLNLGPITRK607) near the C-terminus of uromodulin. Excretion rates of five uromodulin peptides were validated using parallel reaction monitoring (P < 0.05). One of the validated peptides activated TLR4-dependent NFκB signalling, stimulated cytokine release, and enhanced neutrophil migration in vitro. In silico analyses identified several possible proteases such hepsin, cathepsin B, and meprin A to be responsible for generating these peptides. In summary, uromodulin processing in the kidney produces bioactive peptides, which may be differentially excreted in early diabetes.
2020-01-01 | PXD012389 | panorama
Project description:The RNA-seq analysis continues our work profiling the the gastrointestinal tract of the UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) Rat. Male UCD-T2DM rats (age ~170 days) were included in this study if either recently diagnosed as diabetic (n=6, RD, nonfasting glucose > 300 mg/dl) or 3-month post-onset of diabetes (n=6, D3M). A set of younger non-diabetic UCD-T2DM rats were also studied as a non-diabetic comparison (n=6, ND, age ~70 days).
2022-07-29 | GSE181275 | GEO
Project description:ABIS Cohort Raw Sequencing for Type 1 Diabetes Raw sequence reads
| PRJNA875929 | ENA
Project description:Type 2 diabetes mellitus is mainly affected by genetic and environmental factors, and long noncoding RNAs (lncRNAs) have been shown to be correlated with diabetes.LncRNA is expected to be a target for the treatment and prediction of type 2 diabetes. We used microarrays to detail the lncRNAs and mRNAs expression in type 2 diabetes patients and healthy controls and obtained differentially expressed genes. and then the differentially expressed genes were further studied.
2021-03-23 | GSE168437 | GEO
Project description:Insulin resistance is necessary but not sufficient for the development of type 2 diabetes. Diabetes results when pancreatic beta-cells fail to compensate for insulin resistance by increasing insulin production through an expansion of beta-cell mass or increased insulin secretion. Communication between insulin target tissues and beta-cells may initiate this compensatory response. Correlated changes in gene expression between tissues can provide evidence for such intercellular communication. We profiled gene expression in six tissues of mice from an obesity-induced diabetes-resistant and a diabetes-susceptible strain before and after the onset of diabetes. We studied the correlation structure of mRNA abundance and identified 105 co-expression gene modules. We provide an interactive gene network model showing the correlation structure between the expression modules within and among the six tissues. This resource also provides a searchable database of gene expression profiles for all genes in six tissues in lean and obese diabetes-resistant and diabetes-susceptible mice, at 4 and 10 weeks of age. A cell cycle regulatory module in islets predicts diabetes susceptibility. The module predicts islet replication; we found a strong correlation between ^2 H_2 O incorporation into islet DNA /in vivo/ and the expression pattern of the cell cycle module. This pattern is highly correlated with that of several individual genes in insulin target tissues, including IGF2, which has been shown to promote beta-cell proliferation, suggesting that these genes may provide a link between insulin resistance and beta-cell proliferation. Keywords: time course, mouse strain comparison, effect of obesity, Type 2 diabetes is a disorder that involves an increased demand for insulin brought about by insulin resistance, together with a failure to compensate with sufficient insulin production. Although Insulin resistance occurs in most obese individuals, diabetes is generally forestalled through compensation with increased insulin. This increase in insulin occurs through an expansion of beta-cell mass and/or increased insulin secretion by individual beta-cells. Failure to compensate for insulin resistance leads to type 2 diabetes. One way to understand the pathophysiology of diabetes is to examine the coordinate changes in gene expression that occur in insulin-responsive tissues and pancreatic islets in obese animals that either compensate for insulin resistance or progress to type 2 diabetes. In each case, there are groups of genes that undergo changes in expression in a highly correlated fashion. By identifying groups of correlated transcripts (gene expression modules) during the compensation and development of diabetes, we can gain insight into potential pathways and regulatory networks in obesity-induced diabetes. We study two strains of mice that differ in obesity-induced diabetes susceptibility. In this study, we surveyed gene expression in six tissues of lean and obese C57BL/6 (B6) and BTBR mice aged 4 wks and 10 wks. B6 mice remain essentially non-diabetic at all ages, irrespective of obesity. When obese, BTBR mice become severely diabetic by 10 weeks of age. By analyzing the correlation structure of the genes under three contrast conditions, obesity, strain, and age, we identified gene expression modules associated with the onset of diabetes and provide an interactive co-expression network model of type 2 diabetes. We found a key module that is comprised of cell cycle regulatory genes. In the islet, the expression profile of these transcripts accurately predicts diabetes and is highly correlated with islet cell proliferation.
2008-03-14 | E-GEOD-10785 | biostudies-arrayexpress
Project description:Diabetic kidney disease is the leading cause of end-stage renal disease worldwide. Our understanding of the early kidney response to chronic hyperglycemia remains incomplete. In this study, we aimed to uncover the early, dysregulated pathways in the diabetic kidney before the onset of microalbuminuria by analysing the urinary proteomes of otherwise healthy youths with and without type 1 diabetes. Our study population included two cohorts for the discovery (N = 30) and validation (N = 30) of differentially excreted proteins. Of the 2451 proteins identified, 576 were quantified in all samples from the discovery cohort, and 34 comprised the urinary signature for early type 1 diabetes after Benjamini-Hochberg adjustment (Q < 0.05). The top pathways associated with this signature included lysosome, glycosaminoglycan degradation, and innate immune system (Q < 0.01). Notably, all enzymes involved in keratan sulfate degradation were significantly elevated in urines from youths with type 1 diabetes (fold change > 1.6). Increased urinary excretion of monocyte differentiation antigen CD14, hexosaminidase A, and lumican was also observed in the validation cohort (P < 0.05). Our findings draw attention to novel pathways such as keratan sulfate degradation in the early kidney response to hyperglycemia.
2020-06-01 | PXD017213 | Pride