A. J. M. Boulton

Methicillin‐resistant Staphylococcus aureus in the diabetic foot clinic: a worsening problem

Aimsu2003 To determine if there has been a change in the prevalence of pathogenic organisms in foot ulcers in diabetic patients in 2001 compared with our previous study in 1998.

The relationship between blood glucose excursions and painful diabetic peripheral neuropathy: a pilot study

Aims Peripheral neuropathy affects 30% of Type 1 diabetic patients. Unfortunately, 10–20% of affected patients have disabling symptoms. The aim of this study was to examine the relationship between blood glucose excursions and pain in patients with symptomatic diabetic neuropathy.

A comparative study of the Podotrack, a simple semiquantitative plantar pressure measuring device, and the optical pedobarograph in the assessment of pressures under the diabetic foot.

Aims To test the Podotrack, a simple inexpensive semiquantitative footprint mat, for potential use as a screening tool for high plantar pressures, against the optical pedobarograph (a computerized device).

Electrical stimulation therapy through stocking electrodes for painful diabetic neuropathy: a double blind, controlled crossover study

Aimsu2003 Peripheral neuropathy affects more than a third of diabetic patients, of whom a significant minority will have disabling symptoms. The aim of this study was to assess the efficacy of pulsed‐dose electrical stimulation (through stocking electrodes) in the treatment of painful diabetic neuropathy.

Charcot neuroarthropathy triggered by osteomyelitis and/or surgery

Introductionu2003 Charcot neuroarthropathy (CN) is a rare but devastating complication of diabetic neuropathy. Osteomyelitis is also a complication of the diabetic foot and it may be difficult to differentiate from CN.

The hazards of the holiday foot: persons at high risk for diabetic foot ulceration may be more active on holiday.

The pathway to neuropathic diabetic foot ulceration may be generally expressed as a consistent formula. This formula can be described as pressure (otherwise known as deformity or high plantar pressure) multiplied by cycles of repetitive stress (steps taken each day) equals failure of skin [1]. While most treatments have logically focused on pressure reduction [2–4], the other aspect of the equation, namely activity, has been largely ignored. It could be hypothesized that mitigation or perhaps modulation of activity might play a significant role in the pathogenesis and prevention of diabetic foot ulceration. It is increasingly recognized that holiday is associated with the development of diabetic foot ulcer. The term diabetic holiday foot syndrome (DHFS) [5] was first coined by Stanway and Gill. They reported six cases of foot ulceration in patients with diabetes on holiday. The main causes of ulceration were direct trauma from walking barefoot or from poorly fitting sandals. It has been further suggested by Morbach et al . [6] that unaccustomed exercise may also play a pivotal role in the development of DHFS. Experiences from our foot clinics in Manchester, UK and Tucson, Arizona, USA have revealed that despite good foot care education and advice regarding the use of correct footwear during holidays, we have anecdotally noted a marked tendency for high-risk patients to develop foot ulceration while on holiday. Our group has recently begun using novel continuous computerized activity monitors which allow us to identify not only magnitude of activity, but also the specific time when that activity occurred. This device is quite innocuous and is worn on the waistband of clothing. In a recent study of male United States military veterans at high risk for diabetic foot ulceration, we found, surprisingly, that patients were as active inside of their home as they were in the community. Unfortunately, only 15% of these subjects indicated that they wore their physician-approved shoes while in the home [7]. We have postulated that these patients might similarly be more active and therefore are at potentially higher risk of developing foot ulceration while on holiday than when they are at home. In this population of 20 men, aged 64.6 ± 1.8 (mean ± SEM ) years with peripheral neuropathy and a mean 13.4 ± 1.3 year history of diabetes mellitus, a total of 25% had taken at least 3 days’ holiday out of town during the period of continuous activity monitoring. These patients were an average 29% more active (as measured by steps taken per day) during their holiday than when they were home (3603.0 ± 663.8 vs. 2796 ± 489.1, P = 0.04). This trend toward increased activity was encountered in all patients evaluated in this study. These data are graphically illustrated in Fig. 1. The results from this brief analysis suggest that there may be increased activity in patients at risk of developing foot ulceration while on holiday. The implication, particularly if emulated by larger trials, is that patients should be given specific advice regarding foot care for holidays to minimize their risk of developing foot ulcers. Patients should be made aware of the potential problems. Good practice of foot care should be maintained while on holiday, including the use of protective footwear and the avoidance of unsuitable beach footwear or the temptation to walk barefoot. Increased surveillance of the feet is needed with at least daily inspection and urgent medical advice should be sought when required. It should be possible to plan daily itinerary to avoid prolonged periods of continuous activity or to spread activities more evenly throughout the holiday. We would suggest that patients at high risk of foot ulceration plan their holiday with care with the consultation of their physician.

Effect of L-arginine on the microcirculation in the neuropathic diabetic foot in Type 2 diabetes mellitus: a double-blind, placebo-controlled study.

Diabet. Med.

The Diabetic Foot 1998.

The seventh national diabetic foot conference, held in the newly refurbished Malvern Winter Gardens complex, was inaugurated by Grace Warren (Australia) whose superbly compiled lecture `The Diabetic Foot ± Lessons from Leprosy gave a comprehensive review of her experience in leprosy patients with neuropathic foot problems. Dr Warren compared the similarities between diabetes and leprosy causing foot pathology. Her global experience of the anaesthetic foot has many lessons for the management of diabetic foot problems, including the `painless Charcot foot. She emphasized the importance of `pain, as a protective sensation and the need for regular foot care. She also stressed the fact that neuropathic ulcers heal, whatever the aetiology ± be it leprosy or diabetes, and that amputation need not be inevitable. She described well-tried methods of foot care including soaking the feet daily and, for the occasional patients, self-chiropody using pumice. The most important treatment, namely pressure relief, was highlighted by the observation that it was not so much what is put on to an ulcer that matters, but rather what is taken off. Psychological issues surrounding patients at `high risk of neuropathic foot ulceration were addressed by Loretta Vileikyte (UK) who discussed the complex interaction between physical and behavioural factors in such a patient population. When diagnosed as `high risk by health care professionals, patients do not change the behaviour, in contrast, they exhibit strong defensive biases (e.g. personal vulnerability beliefs) in response to health threatening messages. It is the development of an ulcer that leads to a behavioural change. She hypothesized that ulceration alters personal vulnerability beliefs giving rise to fear of amputation that subsequently leads to a behavioural change. Cognitive/ emotional processes involved in this behavioural change need to be explored using an appropriate illness focused theoretical model. Max Spraul (Germany) attempted to answer the question `can education of patients prevent amputation?. He discussed his study of elderly insulin-treated diabetic patients which showed that education improved metabolic control but did not prevent amputations (personal communication). This study showed that educating not only the high-risk patient, but also the high-risk doctor and orthotist, is critical if reduction in amputation rate is to be met world-wide. He also cited various studies done in the UK, Germany and America which showed a reduction in amputation by 60±78% as a consequence of a multidisciplinary team approach. Rhys Williams (UK) gave an enlightening lecture on evidence based medicine in diabetic foot management. He criticised the paucity of good randomized clinical trials (RCTs) in diabetic foot care and management. There have been 6661 publications about trials in diabetes and only 69 of these are about the diabetic foot. The number of RCTs regarding prevention of diabetic foot ulcers is as low as four. The potential importance of negative trials and the statistical problems of an underpowered trial were discussed. He concluded by saying that if we wait for evidence from all new interventions and RCTs we will be in danger of `evidencebased paralysis rather than `evidence-based practice. The second session related to different aspects of providing a diabetic foot service. Mollie Donohue (UK) presented the Exeter Integrated Footcare Project which looked at the impact of integration between Primary and Secondary Care (personal communication). Emphasis was placed on teaching the Primary Care Team to identify the high risk patient and on the criteria for referral to a specialist foot clinic. This resulted in more appropriate use of specialist resources. Mary Burden (UK) discussed various barriers to implementing services and ways to overcome these. She suggested that, whilst most elements needed to provide an integrated service already exist, there needs to be agreement from the different parties about the structure and policies, with common documentation and structured team training. The requirements of establishing a podiatry service were addressed by David Clements (UK) who explained that an ef®cient service was dependent on agreed assessment tools and referral criteria, clear objectives and communication with the rest of the team. The perspective of the `patient experience should also be considered. The session was completed by a very amusing account of screening as viewed by a busy general practitioner. Colin Kenny (N. Ireland) reviewed the requirements of any screening programme and then discussed the process and role of screening in general practice. In the next session, Bob Frykberg (USA) gave a comprehensive account of the historical aspects of Charcot neuroarthropathy and of the progress made over the last 20 years. He also discussed the aetiological theories into the causation of the Charcot foot; namely, neurovascular, neurotraumatic and L

Diabetic thoracic polyradiculoneuropathy (DTP) following normalization of blood glucose post‐pancreatic transplantation

Diabetic thoracic polyradiculoneuropathy (DTP) is a complication of poorly controlled diabetes [1], but this condition has not been reported following normalization of blood glucose. We present a case of DTP following pancreatic transplantation. A 31-year-old female with Type 1 diabetes for 28 years with poor glycaemic control and end-stage renal disease had simultaneous kidney–pancreas transplants 5 years ago. Whilst the kidney survived, the pancreas failed immediately. She had a transplant pancreatectomy and recommenced multiple insulin injection until she had a second pancreas transplant. This survived rejection, stabilized her blood glucose control and she became insulin independent. Anti-rejection therapy included tacrolimus. Two months after the second pancreas transplant, she presented with hyperaesthesiae and severe pain on the left upper quadrant and left flank, with nocturnal exacerbations. She was apyrexial with a soft abdomen and normal bowel sounds. There was tenderness on the left flank but no guarding or rigidity. On neurologic assessment, abdominal reflexes were absent on the upper part of the left side, with diminished vibration sense and light touch on the left dermatomes T8-T12. There was loss of tactile sensation on both feet and ankle reflexes were absent bilaterally. Her glycated haemoglobin had dropped from 10.3% before pancreas transplant to 5.4%, 3 months after. An abdominal computerized tomography (CT) scan showed good pancreatic enhancement, making allograft pancreatic rejection unlikely. Pleuritic chest pain was ruled out after a negative ventilation ⁄ perfusion lung scan (V ⁄ Q scan). Pelvic ultrasound scan and multiple X-rays were non-diagnostic. Virology screens for cytomegalovirus and Ebstein–Barr virus were negative. Electromyography (EMG) showed evidence of generalized sensory motor polyneuropathy, predominantly axonal in nature, but no evidence of chronic inflammatory demyelinating polyneuropathy. The finding of denervation in the thoracic paraspinal muscles along with denervation followed by re-innervation in both paraspinals and rectus abdominus lent support to a diagnosis of left-sided thoracic polyradiculoneuropathy. She was started on pregabalin and, subsequently, amitriptyline was added. She became pain free several weeks later without any further similar complaints after 16 months’ follow-up. It should be highlighted that this woman’s symptoms only began after the second transplant, which resulted in rapid blood glucose control (and not the first failed transplant), thus suggesting that rapid normalization of blood glucose (and not merely the pancreas transplant per se) was the likely cause. In addition, the fact that she had tacrolimus in both the first and second transplants argues against tacrolimus neurotoxicity as the likely cause of her symptoms. DTP is characterized by sensory deficit in the distribution of thoracic intercostals nerves, which is asymmetrical and can involve multiple thoracic dermatomes. Its association with autonomic neuropathy has been documented. It is easily differentiated from thoracic disc protrusion by the absence of signs ⁄ symptoms of cord compression. DTP frequently presents as abdominal pain and ⁄ or swelling [1], hence patients are frequently referred to surgeons and ⁄ or gastroenterologist, potentially leading to a delay in the diagnosis and ⁄ or treatment. Another consequence of this, as it was indeed in this case, is the extensive use of laboratory and imaging investigations which ineffectively consumes resources. In our case, DTP was not considered in the initial differential diagnosis until the patient was eventually reviewed by the diabetes team. When suspected, the diagnosis of DTP is easily ascertained by EMG showing paraspinal muscle denervation. Painful symptoms generally respond to conventional agents used in diabetic neuropathic pain, as highlighted by this case. This is the first report of DTP following pancreas transplant or normalization of blood glucose. Currently available evidence indicating new onset or worsening of neuropathy after rapid normalization of blood glucose is focused on distal sensory neuropathyandvarious formsofautonomicneuropathy,withno mention of DTP [2]. The suggested mechanism of neuropathy following sudden blood glucose normalization includes epineural arteriovenous shunting with decreased nerve blood flow [3]. DTP was first recognized as a complication of diabetes in the 1980s and since then there has been a plethora of case reports of DTP in poorly controlled diabetes, but none has been on patients who have had a pancreas transplant. It is important to suspect and actively rule out DTP in the differential diagnosis of diabetic patients with abdominal pain or swelling, especially in those with recent normalization of blood glucose, including post-pancreas transplant. The patient has given written consent to publication of this report.

BAS/BSCR4 The role of receptor activator of nuclear factor κ-B ligand and its decoy receptor, osteoprotegerin in vascular calcification

Charcot neuroarthropathy (CN) is characterised by pathological foot fractures and osteopenia in patients with diabetes, often resulting in debilitating deformity. Paradoxically, these patients show evidence of medial vascular calcification. Recently, accentuated signalling of the receptor activator of nuclear factor κ-B ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG) have been implicated in the development of diabetic CN. This study aims to investigate the role of RANKL and OPG signalling in vascular calcification in patients with diabetes and CN, compared with healthy controls. RANKL and OPG serum levels were measured using ELISA in 12 patients with CN, 10 diabetic patients and five healthy controls. Serum RANKL and OPG levels were elevated in acute CN and in diabetic patients compared with healthy controls (p<0.05). Immunohistochemistry identifies upregulation of RANKL in calcified tibial arterial sections versus non-calcified controls. Human vascular smooth muscle cells (hVSMC) were grown in osteogenic conditions, as our in vitro model of calcification. When hVSMCs were treated with serum from patients with diabetes and CN, we demonstrated (i) accelerated mineralisation of hVSMC, confirmed by Alizarin red staining, and elevated alkaline phosphatase activity compared with control cells and (ii) reduced mineralisation when co-incubated with OPG. These findings demonstrate that RANKL/OPG signalling is modulated in diabetic and CN patients. Furthermore, serum from these patients accelerates vascular calcification in vitro, an effect attenuated by OPG treatment. These are the first human data implicating RANKL/OPG in diabetic vascular calcification and suggest that OPG/anti-RANKL therapy may be a potential target in combating disease progression.