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© 2001 by the American Diabetes Association, Inc.
Reviews/Commentaries/Position Statements |
Dermal Neurovascular Dysfunction in Type 2 Diabetes
Department of Medicine and Pathology/Anatomy/Neurobiology, the Strelitz Diabetes Research Institutes, Eastern Virginia Medical School, Norfolk, Virginia
OBJECTIVE—To review evidence for a relationship between dermal neurovascular dysfunction and other components of the metabolic syndrome of type 2 diabetes.
RESEARCH DESIGN AND METHODS—We review and present data supporting concepts relating dermal neurovascular function to prediabetes and the metabolic syndrome. Skin blood flow can be easily measured by laser Doppler techniques.
RESULTS—Heat and gravity have been shown to have specific neural, nitrergic, and independent mediators to regulate skin blood flow. We describe data showing that this new tool identifies dermal neurovascular dysfunction in the majority of type 2 diabetic patients. The defect in skin vasodilation is detectable before the development of diabetes and is partially correctable with insulin sensitizers. This defect is associated with C-fiber dysfunction (i.e., the dermal neurovascular unit) and coexists with variables of the insulin resistance syndrome. The defect most likely results from an imbalance among the endogenous vasodilator compound nitric oxide, the vasodilator neuropeptides substance P and calcitonin gene-related peptide, and the vasoconstrictors angiotensin II and endothelin. Hypertension per se increases skin vasodilation and does not impair the responses to gravity, which is opposite to that of diabetes, suggesting that the effects of diabetes override and counteract those of hypertension.
CONCLUSIONS—These observations suggest that dermal neurovascular function is largely regulated by peripheral C-fiber neurons and that dysregulation may be a component of the metabolic syndrome associated with type 2 diabetes.
Abbreviations: Ang, angiotensin • CGRP, calcitonin gene-related peptide • eNOS, endothelial NOS • ET, endothelin • iNOS, inducible NOS • IR, insulin resistance • L-NAME, NG-nitro-arginine-methyl ester • NGF, nerve growth factor • nNOS, neuronal NOS • NO, nitric oxide • NOS, nitric oxide synthase • PGP 9.5, protein gene product 9.5 • VIP, vasoactive intestinal polypeptide • VR1, vanilloid receptor 1
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