ArticleClinical science (London, England : 1979)2020
Metabolomics reveals the impact of Type 2 diabetes on local muscle and vascular responses to ischemic stress.
Article in Clinical science (London, England : 1979), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Genetic Architecture of Plasma Alpha-Aminoadipic Acid Reveals a Relationship With High-Density Lipoprotein Cholesterol.Journal of the American Heart Association · 2022Pooled it
- Comparative effects of weight loss and incretin-based therapies on vascular endothelial function, fibrinolysis and inflammation in individuals with obesity and prediabetes: A randomized controlled trial.Diabetes, obesity & metabolism · 2023Trial
- Regional and systemic adipose mass and peripheral conduit artery function.Diabetes research and clinical practice · 2025Article
- A synthesis and quantification method for endogenous metabolites dimethylguanidino valeric acid.Scientific reports · 2025Article
- Symmetric dimethylguanidino valeric acid, a novel single biomarker of hepatic steatosis.iScience · 2024Article
- Promising Strategies for Preserving Adult Endothelium Health and Reversing Its Dysfunction: From Liquid Biopsy to New Omics Technologies and Noninvasive Circulating Biomarkers.International journal of molecular sciences · 2022Review
- Exercise improves choroid plexus epithelial cells metabolism to prevent glial cell-associated neurodegeneration.Frontiers in pharmacology · 2022Article
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8 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveType 2 diabetes mellitus (T2DM) reduces exercise capacity, but the mechanisms are incompletely understood. We probed the impact of ischemic stress on skeletal muscle metabolite signatures and T2DM-related vascular dysfunction.
methodswe recruited 38 subjects (18 healthy, 20 T2DM), placed an antecubital intravenous catheter, and performed ipsilateral brachial artery reactivity testing. Blood samples for plasma metabolite profiling were obtained at baseline and immediately upon cuff release after 5 min of ischemia. Brachial artery diameter was measured at baseline and 1 min after cuff release.
resultsas expected, flow-mediated vasodilation was attenuated in subjects with T2DM (P<0.01). We confirmed known T2DM-associated baseline differences in plasma metabolites, including homocysteine, dimethylguanidino valeric acid and β-alanine (all P<0.05). Ischemia-induced metabolite changes that differed between groups included 5-hydroxyindoleacetic acid (healthy: -27%; DM +14%), orotic acid (healthy: +5%; DM -7%), trimethylamine-N-oxide (healthy: -51%; DM +0.2%), and glyoxylic acid (healthy: +19%; DM -6%) (all P<0.05). Levels of serine, betaine, β-aminoisobutyric acid and anthranilic acid were associated with vessel diameter at baseline, but only in T2DM (all P<0.05). Metabolite responses to ischemia were significantly associated with vasodilation extent, but primarily observed in T2DM, and included enrichment in phospholipid metabolism (P<0.05).
conclusionsour study highlights impairments in muscle and vascular signaling at rest and during ischemic stress in T2DM. While metabolites change in both healthy and T2DM subjects in response to ischemia, the relationship between muscle metabolism and vascular function is modified in T2DM, suggesting that dysregulated muscle metabolism in T2DM may have direct effects on vascular function.
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