Compartment-specific Metabolic Alterations to Insulin Reflect Adiposity-driven Variation and Predict Type 2 Diabetes
Authors' conclusion
Compartment-specific metabolic responses to insulin are shaped by adiposity and predict future T2D risk, supporting use of metabolomic signatures for early identification and prevention.
Study context
- Population
- Adults with and without T2D undergoing clamp studies; prospective case-control study from the Women's Health Initiative (28.5-year follow-up)clamp cohort + case-control
- Comparison
- T2D vs no T2D; insulin resistance metabolomic score and incident T2D
- Outcome
- Metabolite changes during hyperinsulinemia and incident T2D
Methodological detailshyperinsulinemic-euglycemic clamp, prospective case-control validation
- Hyperinsulinemic-euglycemic clamp
- Prospective case-control validation
Main finding
As reported in the abstract
Plasma metabolites altered by hyperinsulinemia (notably fatty acids, lactate, pyruvate)
79.5%
Muscle metabolites altered by hyperinsulinemia (eg, branched-chain and aromatic amino acids)
15.8%
Risk score and incident T2D: HR per SD
1.20
95% CI 1.09–1.32P = 7.4 × 10-4
Parts of this Brief are withheld: the automatic checks could not confirm them against the abstract.
Original publication
Compartment-specific Metabolic Alterations to Insulin Reflect Adiposity-driven Variation and Predict Type 2 Diabetes. J Clin Endocrinol Metab. Published 11 August 2025. doi:10.
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