Edward B. Jude

High prevalence of ischaemia, infection and serious comorbidity in patients with diabetic foot disease in Europe. Baseline results from the Eurodiale study

Aims/hypothesisLarge clinical studies describing the typical clinical presentation of diabetic foot ulcers are limited and most studies were performed in single centres with the possibility of selection of specific subgroups. The aim of this study was to investigate the characteristics of diabetic patients with a foot ulcer in 14 European hospitals in ten countries.MethodsThe study population included 1,229 consecutive patients presenting with a new foot ulcer between 1 September 2003 and 1 October 2004. Standardised data on patient characteristics, as well as foot and ulcer characteristics, were obtained. Foot disease was categorised into four stages according to the presence or absence of peripheral arterial disease (PAD) and infection: A: PAD −, infection −; B: PAD −, infection +; C: PAD +, infection −; D: PAD +, infection +.ResultsPAD was diagnosed in 49% of the subjects, infection in 58%. The majority of ulcers (52%) were located on the non-plantar surface of the foot. With regard to severity, 24% had stage A, 27% had stage B, 18% had stage C and 31% had stage D foot disease. Patients in the latter group had a distinct profile: they were older, had more non-plantar ulcers, greater tissue loss and more serious comorbidity.Conclusions/interpretationAccording to our results in this European cohort, the severity of diabetic foot ulcers at presentation is greater than previously reported, as one-third had both PAD and infection. Non-plantar foot ulcers were more common than plantar ulcers, especially in patients with severe disease, and serious comorbidity increased significantly with increasing severity of foot disease. Further research is needed to obtain insight into the clinical outcome of these patients.

The Role of Matrix Metalloproteinases in Wound Healing

The structure, classification, function, and regulation of matrix metalloproteinases in normal and abnormal wound healing is discussed. Results from key studies suggest that neutrophil-derived matrix metalloproteinase 8 (MMP-8) is the predominant collagenase present in normal healing wounds, and that overexpression and activation of this collagenase may be involved in the pathogenesis of nonhealing chronic leg ulcers. Excessive collagenolytic activity in these chronic wounds is possible because of the reduced levels of tissue inhibitor metalloproteinase 1 (TIMP-1). However, until recently, there have been no studies evaluating levels of matrix metalloproteinase or tissue inhibitors of metalloproteinase activity in chronic diabetic foot wounds. Improving basic knowledge and pharmaceutical intervention in this area ultimately may help clinicians identify and proactively intervene in an effort to prevent normal wounds from becoming chronic. This may prevent the high prevalence of morbidity associated with this significant health problem.

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

Aims  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.

A role for mitogen-activated protein kinases in the etiology of diabetic neuropathy

The onset of diabetic neuropathy, a complication of diabetes mellitus, has been linked to poor glycemic control. We tested the hypothesis that the mitogen‐activated protein kinases (MAPK) form transducers for the damaging effects of high glucose. In cultures of adult rat sensory neurons, high glucose activated JNK and p38 MAPK but did not result in cell damage. However, oxidative stress activated ERK and p38 MAPKs and resulted in cellular damage. In the dorsal root ganglia of streptozotocin‐induced diabetic rats (a model of type I diabetes), ERK and p38 were activated at 8 wk duration, followed by activation of JNK at 12 wk duration. We report activation of JNK and increases in total levels of p38 and JNK in sural nerve of type I and II diabetic patients. These data implicate MAPKs in the etiology of diabetic neuropathy both via direct effects of glucose and via glucose‐induced oxi‐dative stress.—Purves, T., Middlemas, A., Agthong, S., Jude, E. B., Boulton, A. J. M., Fernyhough, P., Tomlinson, D. R. A role for mitogen‐activated protein kinases in the etiology of diabetic neuropathy. FASEB J. 15, 2508–2514 (2001)

The Charcot Foot in Diabetes

The diabetic Charcot foot syndrome is a serious and potentially limb-threatening lower-extremity complication of diabetes. First described in 1883, this enigmatic condition continues to challenge even the most experienced practitioners. Now considered an inflammatory syndrome, the diabetic Charcot foot is characterized by varying degrees of bone and joint disorganization secondary to underlying neuropathy, trauma, and perturbations of bone metabolism. An international task force of experts was convened by the American Diabetes Association and the American Podiatric Medical Association in January 2011 to summarize available evidence on the pathophysiology, natural history, presentations, and treatment recommendations for this entity.

The effects of ulcer size and site, patient's age, sex and type and duration of diabetes on the outcome of diabetic foot ulcers

SUMMARY

Bisphosphonates in the treatment of Charcot neuroarthropathy: a double-blind randomised controlled trial

Abstract.Aims/hypothesis: The management of charcot neuroarthropathy, a severe disabling condition in diabetic patients with peripheral neuropathy, is currently inadequate with no specific pharmacological treatment available. We undertook a double-blind randomised controlled trial to study the effect of pamidronate, a bisphosphonate, in the management of acute diabetic Charcot neuroarthropathy. Methods: Altogether 39 diabetic patients with active Charcot neuroarthropathy from four centres in England were randomised in a double-blind placebo-controlled trial. Patients received a single infusion of 90 mg of pamidronate or placebo (saline). Foot temperatures, symptoms and markers of bone turnover (bone specific alkaline phosphatase and deoxypyridinoline crosslinks) were measured over the 12 months, in 10 visits. All patients also had standard treatment of the Charcot foot. Results: Mean age of the study group (59 % Type II (non-insulin-dependent) diabetes mellitus) was 56.3 ± 10.2 years. The mean temperature difference between active and control groups was 3.6 ± 1.7 °C and 3.3 ± 1.4 °C, respectively. There was a fall in temperature of the affected foot in both groups after 2 weeks with a further reduction in temperature in the active group at 4 weeks (active and placebo vs baseline; p = 0.001; p = 0.01, respectively), but no difference was seen between groups. An improvement in symptoms was seen in the active group compared with the placebo group (p < 0.001). Reduction in bone turnover (means ± SEM) was greater in the active than in the control group. Urinary deoxypyridinoline in the pamidronate treated group fell to 4.4 ± 0.4 nmol/mmol creatinine at 4 weeks compared with 7.1 ± 1.0 in the placebo group (p = 0.01) and bone-specific alkaline phosphatase fell to 14.1 ± 1.2 u/l compared with 18.6 ± 1.6 u/l after 4 weeks, respectively (p = 0.03). Conclusion/interpretation: The bisphosphonate, pamidronate, given as a single dose leads to a reduction in bone turnover, symptoms and disease activity in diabetic patients with active Charcot neuroarthropathy. [Diabetologia (2001) 44: 2032–2037]

Methicillin-resistant Staphylococcus aureus: an increasing problem in a diabetic foot clinic

Aim To study the prevalence of pathogenic organisms and the prevalence and outcome of methicillin‐resistant Staphylococcus aureus (MRSA) infection in foot ulcers in diabetic patients.

Peripheral arterial disease in diabetes—a review

Diabet. Med. 27, 4–14 (2010)

Resource utilisation and costs associated with the treatment of diabetic foot ulcers. Prospective data from the Eurodiale Study

Aims/hypothesisThe aim of the present study was to investigate resource utilisation and associated costs in patients with diabetic foot ulcers and to analyse differences in resource utilisation between individuals with or without peripheral arterial disease (PAD) and/or infection.MethodsData on resource utilisation were collected prospectively in a European multicentre study. Data on 1,088 patients were available for the analysis of resource use, and data on 821 patients were included in the costing analysis. Costs were calculated for each patient by multiplying the country-specific direct and indirect unit costs by the number of resources used from inclusion into the study up to a defined endpoint. Country-specific costs were converted into purchasing power standards.ResultsResource use and costs varied between outcome groups and between disease severity groups. The highest costs per patient were for hospitalisation, antibiotics, amputations and other surgery. All types of resource utilisation and costs increased with the severity of disease. The total cost per patient was more than four times higher for patients with infection and PAD at inclusion than for patients in the least severe group, who had neither.Conclusions/interpretationImportant differences in resource use and costs were found between different patient groups. The costs are highest for individuals with both peripheral arterial disease and infection, and these are mainly related to substantial costs for hospitalisation. In view of the magnitude of the costs associated with in-hospital stay, reducing the number and duration of hospital admissions seems an attractive option to decrease costs in diabetic foot disease.