Biochemical pathways for microvascular complications of diabetes mellitus

To review the current biochemical theories on how diabetes contributes to microvascular disease.

MEDLINE search (1980-June 2003) and bibliographies of articles obtained on this topic.

Articles identified from the data sources were evaluated and those deemed relevant to this review were incorporated.

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.

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.