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AMBULATORY CARE

Biochemical Pathways for Microvascular Complications of Diabetes Mellitus

Assistant Professor, Department of Pharmacotherapy, College of Pharmacy, Washington State University/Elder Services, Spokane, WA

R Keith Campbell, BPharm MBA CDE FASHP FAPhA

Professor, Department of Pharmacotherapy, College of Pharmacy, Washington State University, Pullman, WA

Clifton J Cahoon, PharmD

Clinical Pharmacist, Providence Yakima Medical Center, Yakima, WA

Reprints: Stephen M Setter PharmD DVM, Department of Pharmacotherapy, College of Pharmacy, Washington State University/Elder Services, 5125 N. Market St., Spokane, WA 99217-6131, FAX 509/458-7459, ssetter{at}smhca.org

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.

Key Words: advanced glycosylated end-products, diabetes, microvascular complications, diacylglycerol, polyol pathway, protein kinase C, reactive oxygen species, sorbitol pathway

Published Online, October 29, 2003. www.theannals.com, DOI 10.1345/aph.1D002

THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT
ACPE UNIVERSAL PROGRAM NUMBER: 407-000-03-040-H01

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