T2D Drug Enrichment From Single-Cell Subtypes
Li et al. 2025 used DGIdb drug enrichment on upregulated subtype DEGs to nominate drug hypotheses for T2D immunometabolic subtypes.
Method
- Li et al. 2025 performed differential expression for each subtype.
- Li et al. 2025 used upregulated genes with logFC > 0.5 for drug enrichment.
- Li et al. 2025 used DGIdb as the drug-gene interaction reference.
- Li et al. 2025 considered drugs with adjusted p-values below 0.05 enriched.
Subtype Hits
- Li et al. 2025 nominated suloctidil as the most promising subtype A drug, linked to inflammatory and immune-regulatory genes including NR4A2, IFITM1, PPP1R15A, FOSB, TNFAIP3, FOS, ZFP36, MCL1, DUSP1, NFKBIA, JUN, KLF6, KLF2, and FTH1.
- Li et al. 2025 also nominated suloctidil as the key subtype B drug, linked to stress-response, immune-regulation, and cell-survival genes including NR4A2, FOSB, GADD45B, IFITM1, PPP1R15A, TNFAIP3, DDIT4, IER2, ZFP36, FOS, MCL1, NFKBIA, HSPA5, JUN, CD69, DUSP1, KLF2, and FTH1.
- Li et al. 2025 nominated chlorpropamide for subtype C, associated with genes involved in stress response and metabolic regulation, including GADD45B, PPP1R15A, TNFAIP3, DDIT4, IER2, ZFP36, FOS, HSPA5, JUN, DUSP1, and KLF2.
- Li et al. 2025 also mention fendiline, prenylamine, and perhexiline as subtype B-related cardiovascular drugs with possible indirect diabetes relevance.
Interpretation Constraints
- Drug enrichment is hypothesis-generating and does not demonstrate efficacy, safety, or subtype-specific clinical benefit.
- Chlorpropamide is an established sulfonylurea affecting insulin secretion, but enrichment in subtype C should not be read as a treatment recommendation.
- For manuscript use, this page is more relevant to discussion of personalized immunometabolic hypotheses than to the main ancestry argument.
Links
- li-2025-immunometabolic-alterations-t2d
- t2d-t-cell-immunometabolic-subtypes
- t2d-transcription-factor-activity
- pbmc-immune-changes-in-type-2-diabetes