Andrew J.M. Boulton

The global burden of diabetic foot disease

Diabetic foot problems are common throughout the world, resulting in major economic consequences for the patients, their families, and society. Foot ulcers are more likely to be of neuropathic origin, and therefore eminently preventable, in developing countries, which will experience the greatest rise in the prevalence of type 2 diabetes in the next 20 years. People at greatest risk of ulceration can easily be identified by careful clinical examination of the feet: education and frequent follow-up is indicated for these patients. When assessing the economic effects of diabetic foot disease, it is important to remember that rates of recurrence of foot ulcers are very high, being greater than 50% after 3 years. Costing should therefore include not only the immediate ulcer episode, but also social services, home care, and subsequent ulcer episodes. A broader view of total resource use should include some estimate of quality of life and the final outcome. An integrated care approach with regular screening and education of patients at risk requires low expenditure and has the potential to reduce the cost of health care.

Diabetic neuropathies: Update on definitions, diagnostic criteria, estimation of severity, and treatments

Preceding the joint meeting of the 19th annual Diabetic Neuropathy Study Group of the European Association for the Study of Diabetes (NEURODIAB) and the 8th International Symposium on Diabetic Neuropathy in Toronto, Canada, 13–18 October 2009, expert panels were convened to provide updates on classification, definitions, diagnostic criteria, and treatments of diabetic peripheral neuropathies (DPNs), autonomic neuropathy, painful DPNs, and structural alterations in DPNs.

The North‐West Diabetes Foot Care Study: incidence of, and risk factors for, new diabetic foot ulceration in a community‐based patient cohort

Aims To determine the incidence of, and clinically relevant risk factors for, new foot ulceration in a large cohort of diabetic patients in the community healthcare setting.

The risk of foot ulceration in diabetic patients with high foot pressure: a prospective study

SummaryFoot ulceration results in substantial morbidity amongst diabetic patients. We have studied prospectively the relationship between high foot pressures and foot ulceration using an optical pedobarograph. A series of 86 diabetic patients, mean age 53.3 (range 17–77) years, mean duration of diabetes 17.1 (range 1–36) years, were followed-up for a mean period of 30 (range 15–34) months. Clinical neuropathy was present in 58 (67%) patients at baseline examination. Mean peak foot pressure was higher at the follow-up compared to baseline (13.5 kg·cm−2±7.1 SD vs 11.2±5.4, p<0.001) with abnormally high foot pressures (>12.3) being present in 55 patients at follow-up and 43 at the baseline visit (p=NS). Plantar foot ulcers developed in 21 feet of 15 patients (17%), all of whom had abnormally high pressures at baseline; neuropathy was present in 14 patients at baseline. Non-plantar ulcers occurred in 8 (9%) patients. Thus, plantar ulceration occurred in 35% of diabetic patients with high foot pressures but in none of those with normal pressures. We have shown for the first time in a prospective study that high plantar foot pressures in diabetic patients are strongly predictive of subsequent plantar ulceration, especially in the presence of neuropathy.

The Prediction of Diabetic Neuropathic Foot Ulceration Using Vibration Perception Thresholds: A prospective study

OBJECTIVE To assess the ability of vibration perception threshold (VPT) to predict the development of diabetic foot ulceration. RESEARCH DESIGN AND METHODS A prospective follow-up study of consecutive patients with vibration perception measured by biothesiometry from April 1988 to March 1989. Patients were stratified in various risk groups. RESULTS Patients with a VPT <15 V had a cumulative incidence of foot ulceration of 2.9% compared with 19.8% in patients with a VPT >25 V, odds ratio (OR) 7.99 (3.65–17.5, 95% confidence intervals), P < 0.01. The incidence of ulceration increased with duration of diabetes, but even with this effect removed, the excess of ulceration persisted, OR 6.82 (2.75–16.92), P < 0.01. CONCLUSIONS VPT is an effective predictor of the risk of foot ulceration in diabetes and therefore could be used to target foot-care education to those patients most likely to benefit and, thereby, possibly improve its effectiveness.

Serum paraoxonase activity, concentration, and phenotype distribution in diabetes mellitus and its relationship to serum lipids and lipoproteins.

Human serum paraoxonase is physically associated with HDL and has been implicated in the detoxification of organophosphates and possibly in the prevention of LDL lipid peroxidation. We investigated the serum activity and concentration of paraoxonase in 78 patients with type 1 diabetes mellitus, 92 with type 2 diabetes, and 82 nondiabetic control subjects. Paraoxonase activity was generally lower in diabetics than in control subjects. This decrease was unrelated to differences in paraoxonase phenotype distribution or its serum concentration. Rather, the difference in paraoxonase activity was explained by its specific activity, which was lower in diabetics, indicating either the presence of a circulating inhibitor or disturbance of the interaction of paraoxonase with HDL affecting its activity. Paraoxonase specific activity was lowest in patients with peripheral neuropathy, suggesting an association of paraoxonase with neuropathy. In control subjects but not patients with diabetes, paraoxonase correlated with HDL cholesterol and apolipoprotein A-1. Our results indicate that the low paraoxonase activity in diabetes is due to decreased specific activity. In other studies low serum paraoxonase activity has been associated with increased susceptibility to atherosclerosis, and the present results also suggest an association with peripheral neuropathy, which could be due to reduced capacity to detoxify lipid peroxides in diabetes.

Dynamic Foot Pressure and Other Studies as Diagnostic and Management Aids in Diabetic Neuropathy

The pressures and loads under the feet during walking have been compared in three groups of 41 patients each, using a microprocessor-controlled optical system. Group A consisted of patients with diabetic neuropathy, group B of non-neuropathic diabetic patients, and group C of nondiabetic controls. Thirteen patients in group A had a history of neuropathic foot ulceration. Other investigations in the diabetic patients included motor conduction velocity (MCV) in the median and peroneal nerves, vibration perception threshold (VPT) in the great toes, the valsalva response (VR), skin resistance (SR), and the ankle pressure index (API). Fifty-one percent of neuropathic feet had abnormally high pressures underneath the metatarsal heads compared with 17% of the diabetic controls and 7% of nondiabetic subjects. All those feet with previous ulceration had abnormally high pressures at the ulcer sites. Of the other investigations, the VPT correlated most significantly with the presence of foot ulceration. In addition, a low median and peroneal nerve MCV, an abnormal VR, a high API, and the absence of sweating all correlated with the presence of foot ulceration. We therefore conclude that simple bedside investigations, such as measurement of the VPT alone, may be useful in identifying those patients at risk of foot ulceration. Foot pressure studies may then be used in such patients as a predictive and management aid by determining specific areas under the foot that are prone to ulceration.

Comprehensive Foot Examination and Risk Assessment A report of the Task Force of the Foot Care Interest Group of the American Diabetes Association, with endorsement by the American Association of Clinical Endocrinologists

It is now 10 years since the last technical review on preventative foot care was published (1), which was followed by an American Diabetes Association (ADA) position statement on preventive foot care in diabetes (2). Many studies have been published proposing a range of tests that might usefully identify patients at risk of foot ulceration, creating confusion among practitioners as to which screening tests should be adopted in clinical practice. A task force was therefore assembled by the ADA to address and concisely summarize recent literature in this area and then recommend what should be included in the comprehensive foot exam for adult patients with diabetes. The committee was cochaired by the immediate past and current chairs of the ADA Foot Care Interest Group (A.J.M.B. and D.G.A.), with other panel members representing primary care, orthopedic and vascular surgery, physical therapy, podiatric medicine and surgery, and the American Association of Clinical Endocrinologists. The lifetime risk of a person with diabetes developing a foot ulcer may be as high as 25%, whereas the annual incidence of foot ulcers is ∼2% (3–7). Up to 50% of older patients with type 2 diabetes have one or more risk factors for foot ulceration (3,6). A number of component causes, most importantly peripheral neuropathy, interact to complete the causal pathway to foot ulceration (1,3–5). A list of the principal contributory factors that might result in foot ulcer development is provided in Table 1. View this table: Table 1— Risk factors for foot ulcers The most common triad of causes that interact and ultimately result in ulceration has been identified as neuropathy, deformity, and trauma (5). As identification of those patients at risk of foot problems is the first step in preventing such complications, this report will focus on key components of the …

Surrogate Markers of Small Fiber Damage in Human Diabetic Neuropathy

Surrogate markers of diabetic neuropathy are being actively sought to facilitate the diagnosis, measure the progression, and assess the benefits of therapeutic intervention in patients with diabetic neuropathy. We have quantified small nerve fiber pathological changes using the technique of intraepidermal nerve fiber (IENF) assessment and the novel in vivo technique of corneal confocal microscopy (CCM). Fifty-four diabetic patients stratified for neuropathy, using neurological evaluation, neurophysiology, and quantitative sensory testing, and 15 control subjects were studied. They underwent a punch skin biopsy to quantify IENFs and CCM to quantify corneal nerve fibers. IENF density (IENFD), branch density, and branch length showed a progressive reduction with increasing severity of neuropathy, which was significant in patients with mild, moderate, and severe neuropathy. CCM also showed a progressive reduction in corneal nerve fiber density (CNFD) and branch density, but the latter was significantly reduced even in diabetic patients without neuropathy. Both IENFD and CNFD correlated significantly with cold detection and heat as pain thresholds. Intraepidermal and corneal nerve fiber lengths were reduced in patients with painful compared with painless diabetic neuropathy. Both IENF and CCM assessment accurately quantify small nerve fiber damage in diabetic patients. However, CCM quantifies small fiber damage rapidly and noninvasively and detects earlier stages of nerve damage compared with IENF pathology. This may make it an ideal technique to accurately diagnose and assess progression of human diabetic neuropathy.

Multicenter Study of the Incidence of and Predictive Risk Factors for Diabetic Neuropathic Foot Ulceration

OBJECTIVE To investigate longitudinally prognostic factors for foot ulceration in a large population of diabetic patients with established neuropathy. RESEARCH DESIGN AND METHODS A double-blind multicenter study of a potential new agent for diabetic neuropathy provided the opportunity for this 1-year investigation since intervention demonstrated no efficacy in the condition. A total of 1,035 patients with N1DDM and IDDM were included. Inclusion criteria were vibration perception threshold (VPT) at the great toe ≥25 V in at least one foot and ≤50 V in both feet, normal peripheral circulation, and no previous foot ulceration. VPT and clinical components of the Michigan diabetic polyneuropathy (DPN) score were assessed at baseline and subsequent visits. RESULTS After 1 year, the incidence of first foot ulcers for the total population was 7.2%. Neuropathy parameters were the same between the treatment and placebo groups at baseline and were unchanged at 1 year; therefore, baseline data were combined for multiple regression analysis. VPT, age, and Michigan DPN scores for muscle strength and reflexes were significant independent predictors for first foot ulceration (P < 0.01). For each 1-U increase in VPT values at baseline, the hazard of the first foot ulcer increased by 5.6%. Similarly, for each 1-U increase in muscle strength and reflex components of the Michigan DPN scores, the hazard of the first foot ulcer increased by 5.0%. CONCLUSIONS Tests of VPT and Michigan DPN scores for muscle strength and reflexes are useful clinical predictors for foot ulceration in diabetic patients with established neuropathy. The rate of subsequent ulceration in the following year was alarmingly high, however, despite standardized foot care education at baseline and regular follow-up visits.