Diabetic foot ulcers are common and may lead to amputation: efforts to improve foot ulcer healing would have an impact on the frequency of lower limb amputation in the USA. One hundred and fifty patients with diabetes presenting with a new (first or recurrent) neuropathic foot ulcer to either UK or USA diabetic foot centers will be .assessed to examine the effects and the potential mechanisms by which emotional distress influences the healing of chronic wounds. Both generalized distress, (perceived stress, anxiety and depression) and the foot ulcer-specific emotional responses (fear of consequences;hostility towards practitioners and interpersonal emotional burden) will be measured, and the relationship of each type of distress to the pathways involved in foot ulcer healing will be assessed. Two hypothesized pathways by which distress may affect wound healing will be examined: the physiological stress response (altered hormonal regulation of the inflammatory response) and the behavioral pathway (non-adherence to use of offloading modalities)The levels of circulating cortisol will be measured and histological (degree of inflammation and extracelullar matrix disposition) and immunohistochemical analyses of wound biopsies (the type and quantity of inflammatory cells;distribution of growth factors, cytokines and proteases) will be performed at baseline and at the six-week visit. Adherence to the foot ulcer offloading treatment (removable cast walker) will be assessed with a computerized accelerometer. The primary clinical endpoint will be defined as the percentage reduction in the wound size at the six- week visit compared to that at study entry. The results of this study will improve our understanding of mechanisms that might impair healing and will indicate potential targets for future clinical and psychological- behavioral interventions in order to accelerate the healing of diabetic foot ulcers.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK071066-05
Application #
8028389
Study Section
Behavioral Medicine, Interventions and Outcomes Study Section (BMIO)
Program Officer
Jones, Teresa L Z
Project Start
2007-04-01
Project End
2014-03-31
Budget Start
2011-04-01
Budget End
2014-03-31
Support Year
5
Fiscal Year
2011
Total Cost
$216,211
Indirect Cost
Name
University of Manchester
Department
Type
DUNS #
229894910
City
Manchester
State
Country
United Kingdom
Zip Code
Crews, Ryan T; Shen, Biing-Jiun; Campbell, Laura et al. (2016) Role and Determinants of Adherence to Off-loading in Diabetic Foot Ulcer Healing: A Prospective Investigation. Diabetes Care 39:1371-7
Ndip, Agbor; Lavery, Lawrence A; Lafontaine, Javier et al. (2010) High levels of foot ulceration and amputation risk in a multiracial cohort of diabetic patients on dialysis therapy. Diabetes Care 33:878-80
Ndip, Agbor; Rutter, Martin K; Vileikyte, Loretta et al. (2010) Dialysis treatment is an independent risk factor for foot ulceration in patients with diabetes and stage 4 or 5 chronic kidney disease. Diabetes Care 33:1811-6
Gonzalez, J S; Vileikyte, L; Ulbrecht, J S et al. (2010) Depression predicts first but not recurrent diabetic foot ulcers. Diabetologia 53:2241-8