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


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)-1alpha expression.


RESULTS
The rate of wound closure was identical between control subjects and diabetic patients despite a significant reduction in maximum hyperemia (LDI(max)), epidermal and dermal VEGF-A, and epidermal and dermal blood vessel VEGFR-2 expression as well as the neurogenic flare response (LDI(flare)) and dermal nerve fiber density. There was no significant difference in HIF-1alpha 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.
Krishnan
Singhan T M
ST
Diabetes Centre, Ipswich Hospital, Ipswich, UK.
Quattrini
Cristian
C
Jeziorska
Maria
M
Malik
Rayaz A
RA
Rayman
Gerry
G
D017668:Age of Onset; D001706:Biopsy; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000473:pathology / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000473:pathology / Q000503:physiopathology*; D018409:Foot Injuries / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008875:Middle Aged; D012016:Reference Values; D012684:Sensory Thresholds; D012867:Skin / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D014732:Vibration; D014945:Wound Healing / Q000502:physiology*
D042461:Vascular Endothelial Growth Factor A