Pathogenesis of chronic hyperglycemia: from reductive stress to oxidative stress.
Level 5 - mechanism / opinion, no new human data
Narrative review of biochemical mechanisms without original human clinical data
PubMed 25019091 · doi:10.1155/2014/137919
What was done
This narrative review describes the mechanistic progression from nutrient overload to oxidative damage, synthesizing biochemical literature on mitochondrial electron transport, NADH dynamics, and downstream glucose metabolic shunts.
What was found
No quantitative findings, sample sizes, or statistical estimates are reported in the abstract. Mechanistically, elevated NADH flux through mitochondrial complex I leads to increased electron leakage and reactive oxygen species (ROS) formation. The resulting excess of NADH and ROS inhibits glyceraldehyde 3-phosphate dehydrogenase (GAPDH), halting glycolysis, causing upstream metabolite accumulation (such as glycerol 3-phosphate), and shunting excess glucose into the polyol and advanced glycation pathways, which further amplify oxidative stress.
Why it matters
The paper presents a unifying mechanistic framework placing reductive stress upstream of oxidative stress and diabetic metabolic complications.
Limits
This is a narrative framework with no original experimental or clinical data presented in the abstract. No quantitative effect sizes, clinical endpoints, or systematic search methodology are provided.
Cited by
- supports Overconsuming calories increases blood glucose and blood lipids, leading to increased reactive oxygen species and molecular damage.