A07: Metabolic Pathways of Hyperglycaemic Tissue Damage

Diabetes damages the lower limb in many ways at once: a numb foot, a wound that will not close, an infection that spreads fast, an artery so calcified that the usual perfusion tests mislead. These failures concentrate in tissues such as nerve and endothelium because their glucose entry does not depend on insulin. They cannot refuse the glucose that arrives.

The module explains the flux-diversion principle: when glycolysis is saturated, surplus glucose is forced down four accessory pathways. It works through the polyol pathway, the NADPH tug-of-war with glutathione defence, advanced glycation end-products and RAGE signalling, protein kinase C and the hexosamine pathway, then appraises the unifying mitochondrial superoxide hypothesis. The payoff is clinical: each pathway is mapped to neuropathy, impaired healing, immune impairment and medial arterial calcification, with hyperglycaemic memory explaining why good glucose control reduces risk without erasing it.

Content is tiered at Foundation, Core and Advanced level, with two reasoning maps and case vignettes. You receive the Teaching Document, the Evidence Base, the slide deck, a narrated video and an audio overview.