Omics · study · 2026
SGLT2 inhibition reverses metabolic and inflammatory kidney signatures in youth with type 1 diabetes
Listed in NCBI GEO
Sodium-glucose cotransporter-2 (SGLT2) inhibitors slow progression of diabetic kidney disease, but their intrarenal mechanisms remain unclear, particularly in patients with type 1 diabetes (T1D).
Description
In a prespecified ancillary study within the placebo-controlled ATTEMPT trial of dapagliflozin in youth with T1D and well-preserved kidney function (N=98), we integrated sequential kidney biopsies, multiparametric kidney MRI, and proteomics.
Single-cell RNA-seq of N=16 baseline and N=11 16-week follow-up biopsies (N=27; 214,415 cells) revealed a coordinated network of metabolic, fibrotic, and inflammatory transcriptional changes across nephron, vascular, and immune compartments. These gene shifts paralleled attenuation of hyperfiltration and improvement in glycemic control (HbA1c and time-in-range), implicating 594 transcripts. MRI indicated a reversal of the medullary hyperoxia characteristic of T1D with dapagliflozin.
Read the rest (1 more)
Urine proteomic profiles echoed the transcriptomic patterns. Together, these multimodal data point to metabolic reprogramming, reduced inflammation, and improved oxygen handling as convergent mechanisms of SGLT2-mediated kidney protection. ClinicalTrials.gov: NCT04333823.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE316nnn/GSE316742 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE316742 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1404116 ncbi.nlm.nih.gov/bioproject/PRJNA1404116 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Disease 75% · Magnetic resonance imaging 65% · Mass spectrometry 65% · RNA sequencing 65% · Single-cell RNA sequencing 65%
Provenance · 1 source records, 12 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE316742 | 11 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:mass-spectrometry | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[modality].local:modality:mri | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[modality].local:modality:single-cell-rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |