Chronic hyperglycemia and cardiovascular dysfunction: an in-depth exploration of metabolic and cellular pathways in type 2 diabetes mellitus.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic pathways and therapeutic targets without original clinical data or systematic review methodology.
PubMed 41382274 · doi:10.1186/s40842-025-00247-3
What was done
This narrative review synthesized classical and emerging literature on the biochemical, cellular, and epigenetic mechanisms by which chronic hyperglycemia leads to cardiovascular dysfunction in type 2 diabetes mellitus (T2DM). It evaluated pathways including the polyol pathway, advanced glycation end-products (AGEs), protein kinase C (PKC) activation, oxidative stress, the hexosamine biosynthetic pathway, and epigenetic mechanisms underpinning metabolic memory, alongside potential targeted interventions.
What was found
The abstract reports no empirical data, effect estimates, or quantitative results. It describes how persistent hyperglycemia triggers oxidative damage, endothelial dysfunction, inflammation, adverse cardiac remodeling, and sustained vascular injury through epigenetic modifications (DNA methylation, histone modifications, non-coding RNAs) that persist despite subsequent glycemic control. It identifies experimental therapeutic strategies targeting these specific pathways, including reactive oxygen species inhibitors, mitochondrial modulators, PKC regulators, glycation blockers, and epidrugs.
Why it matters
It provides a comprehensive conceptual framework illustrating why glucose lowering alone often fails to eliminate cardiovascular risk in diabetes, highlighting pathway-specific targets to overcome metabolic memory.
Limits
The abstract describes a narrative review rather than a systematic review or meta-analysis. No inclusion criteria, search strategy, sample sizes, or quantitative outcome measures are reported. Clinical efficacy and safety of the proposed targeted interventions were not evaluated with primary trial data in the abstract.
Cited by
- supports Having excess glucose or insulin circulating for too long causes inflammation, which is related to sarcopenia, and all of these lead to cardiovascular disease.