Shared and distinct metabolomics profiles associated with microvascular complications in the Diabetes Prevention Program Outcomes Study
Authors' conclusion
The existence of distinct metabolite profiles associated with single microvascular complications highlights the importance of characterising pathophysiological mechanisms specific to each complication, in addition to studying shared mechanisms across multiple complications.
Study context
- Population
- Participants in the Diabetes Prevention Program Outcomes Study, the long-term follow-up of the Diabetes Prevention Program (DPP)
- Participants
- 1,947 participants
- Outcome
- Metabolite profiles prospectively associated with nephropathy, retinopathy and neuropathy
- Follow-up
- 15 years'
Methodological detailsmetabolomics analysis of the Diabetes Prevention Program Outcomes Study, bootstrapped LASSO, 353 annotated metabolites, multivariable models, pooled or within treatment group
- Metabolomics analysis of the Diabetes Prevention Program Outcomes Study
- Bootstrapped LASSO
- 353 annotated metabolites
- Multivariable models, pooled or within treatment group
Main finding
As reported in the abstract
Metabolites prospectively associated with microvascular complications
- Participants with ≥1 complication
- 572
- Nephropathy
- 277
- Retinopathy
- 194
- Neuropathy
- 212
- Metabolites predicting any complication
- 105
- Metabolites predicting one complication
- 74
- Metabolites predicting two complications
- 27
- Metabolites predicting all three complications
- four
- Pooled (69 metabolites without treatment arm interaction): histidine, nephropathy, OR
- 0.75 (0.69, 0.88) (95% CI)
- Pooled: serine, nephropathy, OR
- 0.69 (0.58, 0.82) (95% CI)
- Pooled: serine, neuropathy, OR
- 0.68 (0.56, 0.84) (95% CI)
- Metformin arm (36 metabolites interacting with arm): higher N-carbamoyl-β-alanine, nephropathy, OR
- 1.99 (1.38, 2.99) (95% CI)
- Metformin arm: C22:0-sphingomyelin, neuropathy, OR
- 0.54 (0.37, 0.77) (95% CI)
- Lifestyle intervention arm: quinolinic acid, neuropathy, OR
- 1.64 (1.24, 2.19) (95% CI)
Observational data: associations, not effects.
Original publication
Shared and distinct metabolomics profiles associated with microvascular complications in the Diabetes Prevention Program Outcomes Study. Diabetologia. Published 11 October 2025. doi:10.
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