EMOTIONAL STRESS AND WOUND HEALING IN DIABETES
all patients satisfying the inclusion criteria will undergo the procedures listed below, with the exception of ulcer biopsies which will only be performed on neuropathic non-infected foot ulcers without ischaemia (aBPi[Greater Than]0.8). The baseline visit will occur in the morning with patients arriving between 8.30-9.00 am. after giving informed consent, baseline blood tests including cortisol, oxytocin and gender hormones will be taken (see table). Following 15 minutes relaxation, patients will complete the baseline psychological measures which will be followed by foot ulcer treatment using a standardized foot ulcer management protocol (see appendix 1). Foot ulcer treatment procedures will be provided by a member of the research team and will include regular, sharp surgical wound debridement, dressings and off-loading of ulcers on weight-bearing areas, using the DH removable cast walker (Royce Medical, Camarillo, Ca) (41). Locally-infected ulcers (evidenced by surrounding erythema, local heat and/or purulent discharge) will be treated as per standard protocols. Thus, a deep swab will be taken and sent for microbiological analysis: treatment with a broad-spectrum antibiotic, normally amoxycillin-clavulanate, until the swab results are available: treatment thereafter will be according to sensitivities. as active infection might alter the cellular profile of the wound, infected ulcers will not be biopsied. However, if the infection has been treated at 6 weeks as judged by the clinical appearance of the wound, the biopsy will be taken and the protocol followed as per the table below. The baseline biopsy in clinically non-infected ulcers will be taken by a clinical research fellow after the initial ulcer debridement. at the end of the visit at 12 noon, a second blood sample for cortisol will be taken.
* Age range - 18-80 years.
* Type 2 diabetes. Type 1diabetic patients will not be included as they would comprise <8% of any sample. There are also suggestions that the pathogenesis of complications in the two major types of diabetes may differ in several respects.
* Male or post-menopausal female.
* New foot ulcer episode (defined as a full skin thickness breakdown at a pressure-bearing area of the foot requiring offloading).
* Foot ulcers will be classified according to the University of Texas, UT, scheme (101). Ulcer grades 1A/B/C/D and 2A/B/C/D by UT system, i.e., neuroischaemic ulcers without severe ischemia and with or without local infection, will be eligible for inclusion in the study.
* Neuropathy Disability Score (NDS) >= 3. The NDS determines the severity of neuropathy. This is derived from abnormalities of pain sensation using a NeurotipTM, vibration sensation using a 128 Hz tuning fork, dorsal temperature sensation using warm and cool rods, and Achilles reflex using a tendon hammer. The maximum score is 10 (including both feet) with a score >= 3 indicating the presence of neuropathy (102).
* Vibration Perception threshold (VPT) using the biothesiometer (Arnold Horwell, Nottingham, UK) of >25 volts. The mean of three readings over the apex of each hallux will be taken, and the final result calculated as the mean of the two feet. VPT > 25 is strongly associated with neuropathic foot ulcer risk (19, 33).
* No evidence of severe ischaemia as defined by i) an ankle brachial pressure index (ABPI) >= 0.5, assessed using a doppler ultrasound stethoscope, and ii) transcutaneous partial pressure of oxygen (TCPO2) >= 30 mmHg.
* Agreement to participate in this study.