Biochemical Pathways for Microvascular Complications of Diabetes Mellitus

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Abstract
OBJECTIVE: To review the current biochemical theories on how diabetes contributes to microvascular disease. DATA SOURCES: MEDLINE search (1980–June 2003) and bibliographies of articles obtained on this topic. STUDY SELECTION AND DATA EXTRACTION: Articles identified from the data sources were evaluated and those deemed relevant to this review were incorporated. DATA SYNTHESIS: The prevailing biochemical theories on how diabetes leads to microvascular disease include increased polyol (sorbitol/aldose reductase) pathway flux, production of advanced glycation end-products, generation of reactive oxygen species, and activation of diacylglycerol and protein kinase C isoforms. These pathways contribute to endothelial damage and dysfunction and may alter gene functioning. CONCLUSIONS: Each pathway, via varied and often overlapping mechanisms, contributes to altered microvascular function that leads to the development of retinopathy, neuropathy, and nephropathy, the major microvascular complications associated with diabetes.