Neurovascular factors in wound healing in the foot skin of type 2 diabetic subjects

Singhan T.M. Krishnan, Cristian Quattrini, Maria Jeziorska, Rayaz Malik, Gerry Rayman

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OBJECTIVE - Delayed wound healing in diabetic patients without large-vessel disease has been attributed to microvascular dysfunction, neuropathy, and abnormal cellular and inflammatory responses. The role of these abnormalities has mainly been examined in animal models. Few studies have been undertaken in diabetic patients, and those that have are limited due to analysis in wounds from chronic ulcers. In this study, we quantified the rate of wound healing in relation to skin neurovascular function and structure following a dorsal foot skin biopsy in type 2 diabetes. RESEARCH DESIGN AND METHODS - Twelve healthy control subjects and 12 type 2 diabetic subjects with neuropathy but without macrovascular disease were studied. We quantified rate of wound healing and related it to skin microvascular function (laser Doppler imager [LDI] max), blood vessel density, small nerve fiber function (LDI flare) and nerve fiber density, vascular endothelial growth factor (VEGF) and its receptor (FLK1), and hypoxia-inducible factor (HIF)-1α expression. RESULTS - The rate of wound closure was identical between control subjects and diabetic patients despite a significant reduction in maximum hyperemia (LDImax), epidermal and dermal VEGF-A, and epidermal and dermal blood vessel VEGFR-2 expression as well as the neurogenic flare response (LDIflare) and dermal nerve fiber density. There was no significant difference in HIF-1α and dermal blood vessel density between control subjects and diabetic patients. CONCLUSIONS - In conclusion, the results of this study suggest that wound closure in subjects with type 2 diabetes is not delayed despite significant alterations in neurovascular function and structure.

Original languageEnglish
Pages (from-to)3058-3062
Number of pages5
JournalDiabetes Care
Issue number12
Publication statusPublished - Dec 2007
Externally publishedYes


ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialised Nursing

Cite this

Krishnan, S. T. M., Quattrini, C., Jeziorska, M., Malik, R., & Rayman, G. (2007). Neurovascular factors in wound healing in the foot skin of type 2 diabetic subjects. Diabetes Care, 30(12), 3058-3062.