Elevation of von Willebrand factor in plasma in diabetic patients with neuropathic foot ulceration.

AIMS: The present study examines the relationship between markers of endothelial dysfunction and diabetic neuropathy or consequent neuropathic foot ulceration in patients with Type 2 diabetes mellitus. METHODS: We studied 65 Type 2 diabetic patients including 25 diabetic patients without neuropathy, 27 with neuropathy but no history of foot ulceration, and 13 with neuropathic ulceration. Plasma concentrations of von Willebrand factor (vWF) and soluble thrombomodulin (TM), measures of endothelial dysfunction, were determined by enzyme immunoassays. We performed various tests quantifying aspects of diabetic neuropathy including vibration perception threshold (VPT; for sensory neuropathy), coefficient of variation of R-R intervals (CVR-R; for cardiac autonomic neuropathy), and cold-induced vasodilation in the great toe for peripheral sympathetic neuropathy. RESULTS: CVR-R and cold-induced vasodilation were significantly diminished in patients with neuropathic foot ulceration compared with patients with neuropathy but no history of foot ulceration. Plasma vWF concentrations were positively correlated with VPT and cold-induced vasodilation test, and were inversely correlated with CVR-R. Multivariate analysis disclosed that VPT and percentage vasodilation were independent factors for plasma vWF. Plasma vWF was significantly elevated in patients with foot ulceration compared with patients without neuropathy or those with neuropathy but not foot ulceration. However, plasma TM concentrations did not differ between the three groups. CONCLUSIONS: Diabetic patients with neuropathic foot ulceration had severe impairment of cardiac autonomic and peripheral sympathetic nerves. Elevation of vWF in plasma was associated with neuropathic foot ulceration, linking endothelial dysfunction to foot ulceration.     

Frequency of risk factors for foot ulceration in individuals with chronic kidney disease

Background: Although chronic kidney disease (CKD) has been associated with foot ulceration, the pathological pathway involved remains unclear. This pilot study was designed to investigate the risk factors for foot ulceration in individuals with CKD who do not have diabetes. The aims of this study were to establish the risk status for foot ulceration in individuals with CKD and to identify the particular foot ulcer risk factors most prevalent in this group. Methods: One hundred outpatients were recruited from a metropolitan hospital and allocated into one of four groups: (i) control: neither diabetes nor CKD, (ii) diabetes alone, (iii) coexisting CKD and diabetes and (iv) CKD alone. All participants were assessed for past/current foot ulcers, peripheral neuropathy, vascular insufficiency, structural deformity and skin pathology. Comparisons were made between the groups regarding the prevalence of these factors. Results: Participants with CKD who did not have diabetes displayed no significant differences in risk factor presentation from those with diabetes alone. Of the participants with CKD and no diabetes, 36% had peripheral neuropathy, 20% had vascular insufficiency and 24% had the copresentation of peripheral neuropathy and structural deformity. Overall, participants with both CKD and diabetes had the highest presentation of past/current foot ulcers, peripheral neuropathy and vascular insufficiency, all significantly more frequent in this group than in controls (P < 0.05). Eight of the total 10 participants found to have a past/current foot ulcer were in end‐stage kidney failure. Conclusion: Individuals with CKD frequently display risk factors for foot ulceration. Risk factors are more prevalent in individuals who also have diabetes and foot ulcers become more frequent with progression to end‐stage kidney failure. Risk assessment and patient awareness strategies should therefore be extended to include all patients with CKD so as to reduce future foot ulcer development.     

Magnitude of foot problems in diabetes in the developing world: a study of 1044 patients

Aim To gain insight into the prevalence of peripheral neuropathy, foot care practices, foot at risk and foot ulcers in patients with diabetes mellitus at a tertiary care centre. Methods A prospective case study involving 1044 patients with diabetes mellitus attending the diabetes clinic of a tertiary care centre in north India from January 2007 to May 2008. All subjects underwent a detailed clinical assessment including vibration perception threshold (VPT) and ankle brachial pressure index (ABI), along with metabolic parameters, and were categorized into ulcer, foot at risk and patients with no risk factors. Foot care practices were assessed with a questionnaire. Peripheral neuropathy was defined as VPT score ≥ 25 V. Peripheral vascular disease (PVD) was defined as ABI < 0.9. One hundred and forty‐nine patients with foot at risk were followed up for 9.0 ± 2.3 months (range 5–13 months). Results The prevalence of peripheral neuropathy was 34.9% and of PVD 12.6%. Two thirds of the patients were at risk for foot ulceration; 9% had an ulcer and 20.2% of them required amputation. Correct foot care practices were followed by 214 (20.5%) subjects of the whole study population and by only 135 (19.3%) of the patients with foot at risk. Improvement in glycaemic control in the patients on follow‐up was associated with improvement or stabilization of VPT score. Five (3.4%) patients developed new ulcers on follow‐up. Conclusion The high prevalence of neuropathy and PVD, coexisting with poor adherence to foot care practices predisposes to foot problems in people with diabetes in our study population.     

The Prevalence of Foot Ulceration and its Correlates in Type 2 Diabetic Patients: a Population-based Study

The prevalence of peripheral neuropathy, peripheral vascular disease, and foot ulceration in Type 2 diabetic patients in the community were determined in a community-based study. Eight hundred and eleven subjects (404 male, 407 female, mean age 65.4 (range 34–90) years, diabetes duration 7.4 (0–50) years) from 37 general practices in three UK cities were studied. Neuropathy was diagnosed clinically using modified neuropathy disability scores which were ascertained using structured interviews and clinical examinations by one observer in each city. Peripheral vascular disease was diagnosed if a history of revascularization was present or ≥ 2 foot pulses were absent. History of current or previous foot ulceration was recorded. The prevalence of neuropathy was 41.6% (95% confidence limits 38.3–44.9%) and the prevalence of PVD, 11% (9.1–13.7%). Forty-eight percent of neuropathic patients reported significant neuropathic symptoms. Forty-three patients (5.3% (3.8-6.8%)) had current or past foot ulcers; 20 of these were pure neuropathic ulcers, 13 neuroischaemic, 5 pure vascular, and 5 were unclassified. Multiple logistic regression showed history of amputation, neuropathy disability score, and peripheral vascular disease to be significantly associated with foot ulceration after adjusting for age and diabetes duration. A substantial proportion of Type 2 diabetic patients, often elderly patients who do not attend hospitals, suffered from peripheral neuropathy and peripheral vascular disease. These patients are at risk of foot ulceration and may benefit from preventive footcare.     

糖尿病患者530例足部状况的临床评估

目的对糖尿病患者足部状况及足溃疡发生相关因素进行临床评估.方法对530例糖尿病患者以自行设计的调查评价表对患者的一般临床资料、各项检查、化验指标、足部状况等与足溃疡相关内容进行评估.结果糖尿病患者的足部皮肤状况不良,糖尿病患者合并足溃疡发生率为14.34%,40%以上的糖尿病患者下肢大血管供血状况不良,有25%的糖尿病患者足部感觉异常,近50%的糖尿病患者处于足溃疡中度危险状态之中.结论糖尿病足发生的危险性与其神经病变、血管病变等并发症、足部不良状况、病程长、代谢紊乱等多种因素有密切的关系.     

The distribution of diabetic neuropathy in a British clinic population

A survey of over 1,000 diabetic patients attending a routine hospital clinic clinic in a British city revealed 104 with neuropathic symptoms or foot ulceration. Patients could be assigned to one of four clinical neuropathy groups: chronic sensorimotor, predominantly sensory, proximal motor and mononeuropathy. Only duration of diabetes differed significantly between the groups, with the longest duration in the chronic sensorimotor group. Objective measures of neuropathy did not correlate with symptom scores indicating that careful clinical assessment must augment neurophysiological studies. Patients with neuropathic foot ulceration had significantly higher vibration and thermal thresholds compared with neuropathic patients without ulceration, whereas there was no difference in autonomic function between the two groups.     

Screening diabetic patients at risk for foot ulceration. A multi-centre hospital-based study in France

BACKGROUND: To determine the prevalence of risk factors for diabetic foot ulceration in diabetic patients free of active pedal ulceration in a hospital setting. METHODS: In sixteen French diabetology centres, a survey was conducted on a given day in all diabetic people attending the units, both as in- or out-patients. RESULTS: 664 patients were evaluated: 105 had an active foot ulcer and were excluded from the analysis as were four other patients due to lack of reliable data. From the 555 assessable patients, 40 (7.2%) had a history of foot ulcer or lower-limb amputation. Sensory neuropathy with loss of protective sensation, as measured by the 5.07 (10 g) Semmes-Weinstein monofilament testing, was present in 27.1% of patients, whereas 17% had a peripheral arterial disease mainly based on the clinical examination. On addition, foot deformities were found in 117 patients (21.1%). According to the classification system of the International Working Group on the Diabetic Foot, 72.8% of patients were at low-risk for pedal ulceration (grade 0) and 17,5% were in the higher-risk groups (grade 2 & 3). If patients with isolated peripheral arterial disease were considered as a separate risk group (as was those with isolated neuropathy), percentage of low-risk patients decreased to 65.6%. There was a clear trend between the increasing severity of the staging and age, duration of diabetes, prevalence of nephropathy and retinopathy. CONCLUSIONS: Prevalence of risk factors for foot ulceration is rather high in a hospital-based diabetic population, emphasising the need for implementing screening and preventive strategies to decrease the burden of diabetic foot problems and to improve the quality of life for people with diabetes.     

Identification of patients at risk for diabetic foot: a comparison of standardized noninvasive testing with routine practice at community diabetes clinics

The aim of the study was the comparison of a simple standardized noninvasive examination of neuropathy and angiopathy with routine diagnostic practice in community diabetes clinics for the identification of patients at risk of foot ulceration. Consecutive patients (n=322), aged 30 years and more, with a diabetes duration of more than 5 years, were examined by trained podiatric nurses in six diabetes clinics over a 1-year period; 44 of these patients had active or previous foot ulcerations. We evaluated the differences between the routine diagnostic practice (based on the patient's medical history and a physical examination) and noninvasive testing of peripheral neuropathy [vibration perception threshold (VPT) and the Semmes-Weinstein 10-g monofilament wire system] and angiopathy [Doppler ankle/brachial index (ABI)]. Using receiver operating characteristic (ROC) analysis, we evaluated the sensitivity and specificity of noninvasive testing methods for identifying patients at risk and selecting the optimal diagnostic cutoff points. Patients with severe neuropathy, as determined by noninvasive testing (VPT > or =30 V and/or insensitivity to 10 g monofilament), had been diagnosed to have neuropathy in diabetes clinics in 54% of cases. Patients with angiopathy at risk of developing diabetic foot ulcers (ABI < or =0.8) had been diagnosed, in diabetes clinics, to have peripheral arterial disease in 50% (they reported claudications in 41%, had femoral artery bruits detected in 29% and nonpalpable peripheral pulsations in 12%). Our findings stress the importance of using standardized simple noninvasive testing methods to increase the accuracy of identifying patients at risk for the diabetic foot at the community level.     

Comparison of Risk Factors for Foot Problems in Diabetic Patients Attending Teaching Hospital Outpatient Clinics in Four Different European States

Although the St Vincent declaration calls for common European action in order to reduce major amputations, the differences in the incidence of foot problems and the prevalence of risk factors has not been fully investigated. We have examined the risk factors for foot ulceration and amputation in 278 consecutive patients (mean age 50.4 years, range 18–79 years) attending outpatient clinics of four teaching hospitals: Athens, Manchester, Rome, and Antwerp. There were no differences in age, weight or sex among the four groups but the percentage of patients with Type 1 diabetes was higher in Rome and Antwerp. Patients in Rome and Antwerp also had a longer duration of diabetes compared to Athens and Manchester. Mean vibration perception threshold was similar in all groups. No differences were found in the number of patients with moderate or severe clinical neuropathy (neuropathy disability score > 5), severe sensory loss (VPT > 25 V), and limited joint mobility. Symptomatic peripheral vascular disease was more frequent in Antwerp (p < 0.05) compared to the other three centres and foot ulceration in Rome compared to Manchester (p < 0.05). The number of smokers or ex-smokers and the average alcohol consumption were similar in all centres. We conclude that, despite a few differences mainly in Type 1 diabetic patients, there are no major differences in the risk factors for foot ulceration and that, therefore, similar strategies for the prevention of foot problems may be equally successful in different European countries.     

Factors Associated with Diabetic Foot Ulceration in Thailand: a Case-control Study

A case-control study was conducted to determine factors involved in foot ulceration in Thai non-insulin-dependent (Type 2) diabetic patients. Fifty-five patients with foot ulcers (42 females and 13 males) and 110 patients without foot ulcers (83 females and 27 males) were evaluated for 26 factors possibly associated with foot ulceration. The results showed that diabetic patients with foot ulcers had significantly lower diabetic knowledge and foot-care practice scores; poorer glycaemic control, renal function, and visual function, and higher prevalence of retinopathy and peripheral neuropathy than diabetic patients without foot ulcers, whereas there were no differences in peripheral vascular status between both groups, each having a low prevalence. Multiple logistic regression analyses indicated that the risk of developing foot ulcers was associated with only three factors which were peripheral nerve status as determined by somatosensory evoked potentials (OR = 1.67; 95% CI 0.31 −8.97), visual acuity (OR = 0.223 per unit decrease in decimal visual acuity; 95 % CI = 0.005, 0.39) and fasting plasma glucose level (OR = 1.01 per mmol l⁻¹ increase; 95 % CI = 1.00, 1.02). We conclude that peripheral neuropathy, visual impairment, and poor glycaemic control, but not peripheral vascular insufficiency, are the major independent risk factors associated with foot ulceration in Thai diabetic patients. © 1997 by John Wiley & Sons, Ltd.     

糖尿病周围神经病变和血管病变对糖尿病足溃疡的相互作用及相关性探讨

目的 探讨糖尿病足溃疡（DFU）发生的危险因素,分析糖尿病周围神经病变（DPN）和糖尿病血管病变（PAD）与DFU的相互作用.方法 选取T2DM患者278例,按其是否合并DFU分成糖尿病足溃疡组（DFU,102例）和糖尿病非足溃疡组（NDFU,176例）,回顾性分析两组生化特征和并发症情况.采用Logistic回归分析DFU发生的危险因素,并通过相对超额危险度比（RERI）,归因比（AP）和相互作用指数（S）评价DPN与PAD的相加相互作用.结果 与NDFU组比较,DFU组HbA1c和纤维蛋白原（FIB）水平,DR、DPN和PAD发生率均升高,血红蛋白（Hb）、血白蛋白（Alb）、TC和LDL-C降低（P＜0.05）.Logistic回归分析显示,DFU相关影响因素有：HbA1 c、DPN、PAD、Hb、Alb和FIB（OR分别为1.41、3.66、3.00、0.98、0.79和2.51）.DPN和PAD对DFU的相加相互作用指标RERI、AP和S分别为3.45（95％CI：1.22～8.56）、0.29（95％CI：0.02～0.58）和1.45（95％CI：1.03～4.96）.结论 血糖控制欠佳、合并DPN和PAD、营养不良及FIB代谢失衡是DFU发生的主要危险因素.DPN和PAD对DFU存在相加相互作用,同时患有DPN和PAD可增加DFU的患病风险.     

Foot complications in Type 2 diabetes: an Australian population-based study.

AIMS: To determine the prevalence and risk factors for neuropathy and peripheral vascular disease (PVD) in the Australian diabetic population and identify those at high risk of foot ulceration. METHODS: The Australian Diabetes Obesity and Lifestyle study included 11 247 adults aged >or= 25 years in 42 randomly selected areas of Australia. Neuropathy and PVD were assessed in participants identified as having diabetes (based on self report and oral glucose tolerance test), impaired fasting glucose, impaired glucose tolerance and in a random sample with normal glucose tolerance (total n = 2436). RESULTS: The prevalence of peripheral neuropathy was 13.1% in those with known diabetes (KDM) and 7.1% in those with newly diagnosed (NDM). The prevalence of PVD was 13.9% in KDM and 6.9% in NDM. Of those with diabetes, 19.6% were at risk of foot ulceration. Independent risk factors for peripheral neuropathy were diabetes duration (odds ratio (95% CI) 1.73 (1.33-2.28) per 10 years), height (1.42 (1.08-1.88) per 10 cm), age (2.57 (1.94-3.40) per 10 years) and uric acid (1.59 (1.21-2.09) per 0.1 mmol/l). Risk factors for PVD were diabetes duration (1.64 (1.25-2.16) per 10 years), age (2.45 (1.86-3.22) per 10 years), smoking (2.07 (1.00-4.28)), uric acid (1.03 (1.00-1.06) per 0.1 mmol/l) and urinary albumin/creatinine ratio (1.11 (1.01-1.21) per 1 mg/mmol). CONCLUSIONS: The prevalence of neuropathy and PVD was lower in this population than has been reported in other populations. This may reflect differences in sampling methods between community and hospital-based populations. Nevertheless, a substantial proportion of the diabetic population had risk factors for foot ulceration.     

Postural Instability in Diabetic Neuropathic Patients at Risk of Foot Ulceration

Diabetic peripheral neuropathy is believed to cause postural instability due to abnormal proprioception. We assessed body sway in four groups, each of 20 subjects, matched for age, sex, and BMI: non-diabetic controls, non-neuropathic diabetic controls, subjects with diabetic neuropathy and no history of foot ulceration, and subjects with diabetic neuropathy and a history of foot ulceration. Postural sway was assessed on a Kistler force plate using the Romberg test, measuring the standard deviation of the centre of pressure in both sagittal (antero-posterior movement) and frontal (side to side movement) planes with eyes open and closed. The Romberg test results were log transformed and then analysed using analysis of variance followed by Newman-Keuls test. There was no significant difference in body sway between the two control groups and the first group of subjects with diabetic neuropathy. However, in patients with a history of ulceration, values were significantly higher (p < 0.05) compared to all other groups in both planes and conditions studied. These results are suggestive of a relationship between impaired body sway control and foot ulceration. Postural instability may have clinical significance and increase the risk of minor trauma and ulceration in patients with diabetic neuropathy. © 1997 by John Wiley & Sons, Ltd.     

Management of the diabetic Charcot foot

The diabetic Charcot foot is a major limb-threatening complication of long-term diabetes mellitus and neuropathy. Although first described over 100 years ago, we are still lacking definitive studies regarding its prevalence in this population, precise etiology, or most effective treatments. Trauma in the presence of peripheral sensory neuropathy and abundant arterial perfusion seem to be the primary causal factors leading to this severe foot deformity. Misdiagnosis or delayed diagnosis of osteoarthropathy allows the destructive phase of this disorder to continue with resultant further destruction of the foot architecture. The authors discuss the natural history of this entity as well as potential treatment options and recommendations. Through a better understanding of the underlying pathogenesis, Charcot arthropathy can be more effectively managed and thereby limit the development of severe deformity, ulceration, infection and limb loss.     

Blood flow in the foot,polyneuropathy and foot ulceration in diabetes mellitus

Summary Comparable groups of diabetic patients asymptomatic of neuropathy (Group A), with chronic painful polyneuropathy (Group B) and painless polyneuropathy causing recurrent foot ulceration (Group C) were studied for differences in pedal blood flow, peripheral somatic and autonomic neuropathy and vascular calcification. Blood flow abnormalities detected by doppler waveform analysis, and consistent with reduced peripheral vascular resistance, were found in all three diabetic patient groups. The abnormalities were of similar severity in Group A and B but generally more marked in Group C. Tests of peripheral somatic nerve function became progressively more abnormal from Group A to Group C. Autonomic neuropathy was equally severe in Groups B and C, although mild abnormalities were recorded in diabetic patients asymptomatic of neuropathy. A similar pattern was seen for vascular calcification in the tarsal and metatarsal arteries: marked in both neuropathic groups (B and C) but mild in Group A. It was concluded that abnormal blood flow consistent with reduced peripheral vascular resistance is very common in the feet of diabetic patients whether or not they are symptomatic of neuropathy, and is most severe in those with chronic painless polyneuropathy and recurrent foot ulceration. No clear relationship was found between autonomic nerve dysfunction and the degree of abnormality of blood flow.     

Venous oxygenation in the diabetic neuropathic foot: Evidence of arteriovenous shunting?

Summary Venous PO₂ was measured in the feet and hands of four subject groups: 14 diabetics with neuropathy and foot ulceration; 12 diabetics with neuropathy but no ulceration; 11 diabetics with no evidence of microvascular complications; and 10 nondiabetic controls. Neither patients nor controls had clinical evidence of peripheral vascular disease. The mean venous PO₂ in the feet of subjects with neuropathy and foot ulceration was significantly higher than in controls or the other two diabetic groups. Venous PO₂ in the feet of the subjects with ulcers was also significantly higher than in their hands or in the hands of the other groups. These results provide further evidence of abnormal blood flow in the diabetic neuropathic foot and are compatible with arteriovenous shunting.     

Diagnosis and assessment of peripheral arterial disease in the diabetic foot

Approximately half of all patients with a diabetic foot ulcer have co‐existing peripheral arterial disease. Identifying peripheral arterial disease among patients with foot ulceration is important, given its association with failure to heal, amputation, cardiovascular events and increased risk of premature mortality. Infection, oedema and neuropathy, often present with ulceration, may adversely affect the performance of diagnostic tests that are reliable in patients without diabetes. Early recognition and expert assessment of peripheral arterial disease allows measures to be taken to reduce the risk of amputation and cardiovascular events, while determining the need for revascularization to promote ulcer healing. When peripheral arterial disease is diagnosed, the extent of perfusion deficit should be measured. Patients with a severe perfusion deficit, likely to affect ulcer healing, will require further imaging to define the anatomy of disease and indicate whether a revascularization procedure is appropriate.     

Gustatory sweating and diabetes

Gustatory sweating as a feature of autonomic neuropathy is an unusual phenomenon in diabetes mellitus. We describe a patient with type 1 diabetes mellitus complicated by retinopathy, nephropathy and neuropathy. This patient presented with bilateral diffuse facial sweating during eating. She was treated with the antimuscarine agent oxybutynine, which provided a striking relief from the gustatory sweating.     

How Effective is Cushioned Therapeutic Footwear in Protecting Diabetic Feet? A Clinical Study

Therapeutic footwear with cushioned insoles was supplied to 50 diabetic patients with severe peripheral neuropathy and/or peripheral vascular disease (age 59(SD 12) years, known duration of diabetes 17(7) years), 36 of whom had a history of foot ulceration. A follow-up examination was carried out 25(14) months later, except in 8 patients who died from conditions unrelated to their foot lesions, and 1 patient who died from sepsis due to upper limb amputation. Among the surviving 41 patients, intercurrent foot lesions during follow-up occurred in significantly fewer (42%) of the 26 who had worn the shoes regularly than of the 15 who had worn the shoes irregularly (87%, p less than 0.01). At follow-up, only 15% of the 41 patients were being treated for foot-lesions, compared with 78% of these 41 patients before cushioned shoes were provided. It is concluded that the availability of therapeutic shoes with cushioned insoles for diabetic patients at risk of foot lesions decreases the morbidity due to the diabetic foot syndrome.     

Impaired vibratory perception and diabetic foot ulceration

We have studied risk factors for diabetic foot ulceration by comparing diabetic patients who had active foot ulcers (n = 86) with diabetic patients who had no history of foot ulcers (n = 49). Whereas there was a strong association of diabetic foot ulceration with abnormal vibratory perception (Odds Ratio = 10.77; p less than 0.001, which increased with worsening vibratory perception), there was little association with abnormality of the ankle-pressure index (Odds Ratio = 2.84, p = n.s.). Although foot ulceration and limited joint mobility were associated (Odds Ratio = 3.57, p less than 0.001), this relation was not significant when allowances for abnormal vibratory perception and diabetes duration were made. These data suggest that sensory neuropathy is of greater aetiological importance than peripheral vascular disease in the development of diabetic foot ulceration. The measurement of the vibratory perception threshold is clinically useful in identifying those diabetic patients at high risk of foot ulceration.