ArticleThe Journal of clinical endocrinology and metabolism2026
Compartment-specific Metabolic Alterations to Insulin Reflect Adiposity-driven Variation and Predict Type 2 Diabetes.
Article in The Journal of clinical endocrinology and metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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Who cites it
4 citing papers in PubMed.
- Metabolic Stress Testing Reveals Persistent Lipid-Handling Dysfunction in Women With Polycystic Ovary Syndrome Despite Exercise Training.Diabetes, obesity & metabolism · 2026Trial
- Compartment-specific Metabolic Alterations to Insulin Reflect Adiposity-driven Variation and Predict Type 2 Diabetes.The Journal of clinical endocrinology and metabolism · 2026Article
- Central adiposity outperforms disordered eating behavior in predicting type 2 diabetes risk in young adults: an explainable machine learning approach.Frontiers in public health · 2026Article
- Dissecting Genetic and Environmental Determinants of Plasma Molecular Signatures and Their Link to Type 2 Diabetes Risk.medRxiv : the preprint server for health sciences · 2025Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
contextThe metabolic mechanisms underlying insulin resistance are not fully understood. Metabolomic profiling can reveal compartment-specific variations and identify individuals at risk for type 2 diabetes (T2D).
objectiveTo characterize insulin-induced metabolomic changes during a hyperinsulinemic-euglycemic clamp and evaluate a derived risk score's predictive value for T2D. DESIGN, SETTING, AND
participantsClamp studies were conducted in 80 adults (38 with T2D, 42 without) to measure plasma and muscle metabolites in fasting and hyperinsulinemic states. An insulin resistance metabolomic score was developed and tested in a prospective case-control study (367 cases, 910 controls) from the Women's Health Initiative (28.5-year follow-up).
main outcome measuresMetabolite changes during hyperinsulinemia and incident T2D.
resultsHyperinsulinemia altered 79.5% of plasma metabolites (notably fatty acids, lactate, and pyruvate) and 15.8% of muscle metabolites (eg, branched-chain and aromatic amino acids). T2D was associated with higher triglycerides and lower tricarboxylic acid intermediates during clamp. Adiposity amplified insulin-induced increases in plasma lipids. The risk score predicted incident T2D (hazard ratio, 1.20 per SD; 95% CI, 1.09-1.32; P = 7.4 × 10-4).
conclusionCompartment-specific metabolic responses to insulin are shaped by adiposity and predict future T2D risk, supporting use of metabolomic signatures for early identification and prevention.
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