Calcaneal bone mineral density in patients with Charcot neuropathic osteoarthropathy: differences between Type 1 and Type 2 diabetes.

AIMS: To measure bone density and neuropathy in both feet in Type 1 and Type 2 patients with unilateral Charcot osteoarthropathy and controls. METHODS: Calcaneal bone density, temperature and vibration thresholds were compared between 17 Type 1 diabetic patients with osteoarthropathy and 47 Type 1 controls and between 18 Type 2 diabetic patients and 48 Type 2 controls. As well as the Charcot foot, the non-Charcot foot was studied to assess osteopenia at onset of osteoarthropathy. RESULTS: In Type 1 diabetes, bone density was reduced in the non-Charcot foot compared with controls [Z-score: -1.7 ({-1.9}-{-1.4}) vs. -0.2 ({-1.1}-{0.5}), P < 0.0001, median (interquartile range)]; but not in Type 2 diabetes [Z-score: 0.15 ({-0.45}-{0.85}) vs. 0.3 ({-0.5}-{0.9}), P = 0.675]. Bone density in the Charcot foot was lower compared with the non-Charcot foot in both Type 1 [Z-score: -2.0 ({-2.8}-{-1.4}) vs. -1.7 ({-1.9}-{-1.4}), P = 0.018] and Type 2 diabetes [Z-score: -0.2 ({-1.4}-{0.1}) vs. 0.3 ({-0.5}-{0.9}), P = 0.001]. In Type 1 diabetes, bone density of the non-Charcot foot was reduced compared with that in Type 2 (P < 0.0001). Body mass index was lower in Type 1 than in Type 2 Charcot patients (P = 0.007). Type 2 patients had high temperature (P = 0.001) and vibration thresholds (P < 0.0001) in the non-Charcot foot compared with Type 2 controls whereas Type 1 patients had a high temperature threshold (P = 0.01) but not vibration threshold compared with Type 1 controls (P = 0.077). CONCLUSION: Bone density was reduced in the non-Charcot foot in Type 1 but not in Type 2 diabetes. Type 2 patients had high temperature and vibration thresholds in contrast to Type 1 patients who had a high temperature threshold only.

Is there an evidence base for diabetic foot care?

There is a current lack of evidence for most of the treatments that are applied to those patients who have diabetic foot problems. This paper reviews existing evidence and national and international consensus documents. The diabetic foot is an enormous public health problem and it is important that it receives rapid and effective management.

Is neuropathic ulceration the key to understanding increased mortality due to ischaemic heart disease in diabetic foot ulcer patients? A population approach using a proportionate model.

Ischaemic heart disease (IHD) is the commonest cause of death in diabetic foot ulcer patients and non-ulcerated diabetic patients, yet the mortality rate of diabetic foot ulcer patients is over twice that of non-ulcerated patients. As the cause of this increased mortality is not understood, we plotted the ratio of deaths due to ischaemic heart disease (IHDn) to other causes of death (i.e. IHDn:OCDn) against age for 242 diabetic foot ulcer patients and 121 controls (non-ulcerated diabetic patients). The IHDn:OCDn ratio rose above 1.0 from age 40 years onwards for diabetic foot ulcer patients, but from age 70 years onwards for controls, demonstrating differentially increased mortalities due to IHD. A population model involving summation of IHDn:OCDn ratios for neuropathic and neuroischaemic diabetic foot ulcer patients calculated an overall increased mortality rate of 1.8 compared with that of non-ulcerated diabetics. The model predicted that a 25% reduction in neuropathic diabetic foot ulcer patients dying from IHD would eliminate the increased mortality, demonstrating that neuropathic rather than ischaemic ulceration defines the cause of increased mortality among diabetic foot ulcer patients.

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

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 degrees C and 3.3 +/- 1.4 degrees 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.

Infection of foot ulcers with Staphylococcus aureus associated with increased mortality in diabetic patients.

Diabetic patients with foot ulceration have a poorer prognosis than those without ulceration. The reason for this is unclear, but there is considerable interest in the putative links between infection and atherogenesis, and it is notable that diabetic foot ulcers (DFU) are often infected with Staphylococcus aureus and the main cause of death in DFU patients is ischaemic heart disease. We examined the 5 year survival of 71 diabetic patients who presented with foot ulcers that were newly infected (Sa group, n = 56) or not infected at all during the study period (non-Sa group, n = 15) with S. aureus. Twenty-nine patients (52%) infected with S. aureus died compared with three patients (20%) whose foot ulcers were not infected with S. aureus. The patients in the two groups were similar in age and duration of diabetes. The overall five year mortality rate was 10.4% per year for those infected, significantly higher than the average of 4.0% for patients without infection (p = 0.015). None of the patients was bacteraemic or died directly from sepsis. Infection of DFU by S. aureus may increase the risk of death in diabetic patients.

Why do foot ulcers recur in diabetic patients?

AIM: To investigate factors predisposing to recurrent foot ulceration in patients with diabetes mellitus. METHODS: Two groups of patients who had attended a specialist Diabetes Foot Centre were assessed: relapsers (n = 26), whose foot ulceration had recurred at least twice, and nonrelapsers (n = 25), whose initial ulcer had not recurred for at least 2 years. RESULTS: In the relapser group 10/26 patients waited at least 24 h before reporting symptoms compared with only 2/25 in the nonrelapser group (P < 0.05). Vibration perception threshold (volts) was 38 +/- 12 (mean +/- SD) in relapsers compared with 25 +/- 13 in nonrelapsers (P < 0.005). Cold perception threshold (degrees C) was 9.1 +/- 4.6 in relapsers compared with 5.1 +/- 3.5 in nonrelapsers (P<0.005). HbA1c (%) was significantly raised at 8.5 +/- 1.7 in relapsers compared with 7.6 +/- 1.2 in nonrelapsers (P = 0.03). Alcohol intake was 0.5 (median, interquartile range 0-2) units per day in relapsers compared with 0.0 (median, interquartile range 0-0.25) units in nonrelapsers (P = 0.04). Smoking habits, housing conditions, visual acuity, threshold for warm perception and the Doppler pressure index were not significantly different in the two groups. CONCLUSIONS: Patients who develop recurrent foot ulceration delay in reporting symptoms, when compared with diabetic patients whose foot ulceration does not recur. The relapsers also have evidence of poorer glycaemic control, more neuropathy and increased alcohol intake.

Randomised placebo-controlled trial of granulocyte-colony stimulating factor in diabetic foot infection.

BACKGROUND: Diabetic foot infections cause substantial morbidity and mortality. Neutrophil superoxide generation, a crucial part of neutrophil bactericidal activity, is impaired in diabetes. Granulocyte-colony stimulating factor (G-CSF) increases the release of neutrophils from the bone marrow and improves neutrophil function. We assessed G-CSF as adjuvant therapy for the treatment of severe foot infections in diabetic patients. METHODS: 40 diabetic patients with foot infections were enrolled in a double-blind placebo-controlled study. On admission, patients were randomly assigned G-CSF (filgrastim) therapy (n = 20) or placebo (n = 20) for 7 days. Both groups received similar antibiotic and insulin treatment. Neutrophils from the peripheral blood of these participants and from healthy controls were stimulated with opsonised zymosan, and superoxide production was measured by a spectrophotometric assay (reduction of ferricytochrome C). FINDINGS: G-CSF therapy was associated with earlier eradication of pathogens from the infected ulcer (median 4 [range 2-10] vs 8 [2-79] days in the placebo group; p = 0.02), quicker resolution of cellulitis (7 [5-20] vs 12 [5-93] days; p = 0.03), shorter hospital stay (10 [7-31] vs 17.5 [9-100] days; p = 0.02), and a shorter duration of intravenous antibiotic treatment (8.5 [5-30] vs 14.5 [8-63] days; p = 0.02). No G-CSF-treated patient needed surgery, whereas two placebo recipients underwent to amputation and two had extensive debridement under anaesthesia. After 7 days' treatment, neutrophil superoxide production was significantly higher in the G-CSF group than in the placebo group (16.1 [4.2-24.2] vs 7.3 [2.1-11.5] nmol per 10(6) neutrophils in 30 min; p < 0.0001). G-CSF therapy was generally well tolerated. INTERPRETATION: G-CSF treatment was associated with improved clinical outcome of foot infection in diabetic patients. This improvement may be related to an increase in neutrophil superoxide production.

Measurement of markers of osteoclast and osteoblast activity in patients with acute and chronic diabetic Charcot neuroarthropathy.

Excess osteoclast activity is believed to be responsible for the early bone changes associated with Charcot neuroarthropathy in diabetes mellitus. Markers of osteoclast and osteoblast activity were measured in four groups of patients: 16 with an acute Charcot foot, 16 with a chronic Charcot foot, 10 diabetic controls, and 10 non-diabetic controls. Serum carboxyterminal telopeptide of type 1 collagen (1CTP), a marker of osteoclastic bone resorption, was significantly raised in the dorsal venous arch of the acute Charcot foot, 6.1 +/- 1.5 microg l(-1) (mean +/- SD) compared with the chronic Charcot foot 4.1 +/- 1.4, diabetic controls 3.3 +/- 1.4, and non-diabetic controls 2.8 +/- 1.4, p < 0.0001. This local increase in 1CTP was also reflected systemically in a study subgroup of 6 patients with acute Charcot neuroarthropathy, in whom peripheral antecubital vein 1CTP was 9.2 +/- 2.6 compared with 9.0 +/- 3.1 in the foot. In 6 chronic Charcot neuroarthropathy patients, foot (3.8 +/- 1.3) and systemic (4.0 +/- 1.5) 1CTP values were similar. Serum procollagen carboxyterminal propeptide (P1CP), an indicator of osteoblastic bone formation, was not significantly different between the feet of patients with acute Charcot neuroarthropathy 112 +/- 1.5 microg l(-1), patients with chronic Charcot neuroarthropathy 109 +/- 1.5 microg l(-1), diabetic controls 93.5 +/- 2.3 microg l(-1), and non-diabetic controls 90.1 +/- 1.5 microg l(-1). These results suggest that the acute Charcot foot demonstrates excess osteoclastic activity without concomitant increase in osteoblastic function. This may be important in its pathogenesis.

Multidisciplinary Care of the Diabetic Foot.

Patients with diabetes account for about 1-2% of the general population, and will undergo around half of all major leg amputations. Despite this fact, there are no traditional pathways for the referral and treatment of diabetic foot disease. Physicians may view it as a surgical problem, while surgeons may see it as a diabetic complication. All too often, patients are seen as undesirable cases who take up much-needed hospital beds. Until the 1980s, morbidity and mortality associated with diabetic foot problems were unacceptably high and no effective preventive or treatment strategies were known. Health-care professionals managing foot problems in patients with diabetes tended to work in isolation and diabetic foot disease was often neglected or treated inappropriately.

Reduction of gangrene and amputations in diabetic renal transplant patients: the role of a special foot clinic.

This 4-year prospective study investigated the reasons for high levels of gangrene and major amputation in diabetic renal transplant patients and whether regular multidisciplinary foot care could reduce morbidity. All foot lesions were documented and investigated in 50 diabetic patients, mean age 49.2 +/- 11.0 (SD) years, duration of diabetes 25.3 +/- 9.0 years, time since renal transplantation 60.2 +/- 35.1 months, who attended a special foot clinic monthly for education, vascular and neurological assessment, podiatry and footwear. Foot lesions included: neuropathic ulcers, ischaemic ulcers, traumatic lesions, Charcot's arthropathy, pathological fracture. Treatment included antibiotics, podiatry, footwear, and angioplasty or distal bypass where appropriate. Only 13 patients were deemed ischaemic but peripheral neuropathy was a very common finding (mean VPT 24.8 +/- 12.9 V). Gangrene and major amputations showed a decrease on previous years and healing times for lesions were similar to those previously reported in diabetic patients without renal transplants. The majority of foot lesions, both in soft tissue and bone, were related to neuropathy and trauma and responded well to optimal foot care within the renal unit. Gangrene and major amputations were usually preventable.

Letters.

COMPARING DRESSINGS FOR DIABETIC FOOT ULCERS HYDROGEL AND NAPPY RASH ADVANCES IN THE USE OF LASERS IN DERMATOLOGY.

Application of OpSite film: a new and effective treatment of painful diabetic neuropathy.

The aim of the study was to assess the effect of application of OpSite dressings on the pain and quality of life in 33 patients with chronic diabetic neuropathy. The effect of OpSite was compared with no treatment. After a run-in period of 2 weeks, OpSite was applied to one of the painful legs for 4 weeks. This was followed by another period of 4 weeks when OpSite was switched to the opposite leg. Pain was assessed by visual analogue scale and the primary analysis variable was within patient difference in pain between OpSite leg and no treatment leg at week 4 corrected for baseline. Secondary variables were paracetamol pill ingestion and the quality of life dimensions, sleep, mobility, contact discomfort, appetite, and mood. Changes in these variables from baseline to weeks 4 and 8 were analysed. There was a significantly greater reduction in pain in the OpSite treated limbs than the control limbs (p < 0.001). By week 4 paracetamol intake also declined significantly (p = 0.034) and patients experienced a significant improvement in contact discomfort, sleep, mood, appetite, and mobility (p < 0.002 for all 5 variables). OpSite appeared to alleviate the pain associated with diabetic painful neuropathy and thus improved patients' quality of life.

Comparing two dressings in the treatment of diabetic foot ulcers.

A report of a study that compared a polyurethane foam dressing with an alginate dressing for foot ulcers in patients with diabetes.

Abnormal digital pressure measurements in diabetic neuropathic foot ulceration.

The diabetic neuropathic ulcer is typically slow to heal and recurrent. Macrovascular insufficiency is usually excluded as foot pulses are present and ankle:brachial pressure ratios are not decreased. These assessments cannot however exclude more distal vascular disease. Digital pressure measurements enable a reliable assessment of the distal peripheral vascular status to be made. The aim of this study was therefore to use toe pressures to assess the contribution of distal ischaemia in the pathogenesis of the neuropathic ulcer. Sixteen diabetic patients with recurrent neuropathic foot ulceration had their toe pressures compared to 10 neuropathic patients without a history of foot ulceration, 10 diabetic control subjects, and 11 normal subjects. Four non-diabetic patients with neuropathy and foot ulceration were also assessed. All subjects had ankle:brachial pressure indices > or = 1. Toe pressure was assessed using laser Doppler flowmetry to record the return of skin blood flow. The toe:brachial pressure index (TBI) was then calculated. The diabetic patients with a history of recurrent neuropathic ulceration, had the lowest mean TBI, 0.63 +/- 0.14 (SD), compared to the non-ulcerated diabetic neuropathy patients, the diabetic control subjects, and the normal subjects. 0.84 +/- 0.11, 0.82 +/- 0.1, and 0.81 +/- 0.07, p < 0.01, respectively. Three of the four non-diabetic patients with neuropathic foot ulceration also had an abnormally low TBI. Reduced toe pressure measurements are thus found to be associated with neuropathic foot ulceration. The contribution of distal ischaemia in the pathogenesis of the diabetic neuropathic foot ulcer needs to be evaluated.

Selective neuropathy and preserved vascular responses in the diabetic Charcot foot.

Charcot arthropathy is a disabling complication of diabetic neuropathy. It is however, unclear why it occurs in only a small number of neuropathic patients. We have studied 12 diabetic patients (10 insulin-dependent) with an acute Charcot arthropathy, and compared their neuropathy and vascular responsiveness with 12 diabetic patients (10 insulin-dependent) with recurrent neuropathic foot ulceration, 12 diabetic control subjects (9 insulin-dependent) and 10 normal non-diabetic subjects. The Charcot arthropathy patients demonstrated a preservation of warm perception, 6 (5.5) degrees C, but complete loss of peripheral cold perception, 10 (0) degrees C, p less than 0.001 (median (interquartile range)). This contrasted with the ulcerated neuropathy patients, who had equally severe impairement of both warm and cold sensory thresholds, 10(0.5) degrees C vs 10(1) degrees C, respectively, the diabetic control subjects who were able to detect a 2 (1.3) degrees C warm stimulus and 3 (3.5) degrees C cold stimulus and the normal subjects, whose warm threshold was 2 (1) degrees C and cold was 2 (1) degrees C. Light touch perception at the foot was preserved in the Charcot patients 4 (4) g vs 100 (50) g, p less than 0.0002, in the ulcerated neuropathy patients. Vibration perception at the great toe and cardiovascular autonomic function tests (heart rate variability, Valsalva ratio and postural systolic blood pressure fall) were abnormal in both the Charcot patients and ulcerated neuropathy group, with no differences seen between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)