Foot ulceration in persons with diabetes is the most frequent precursor to amputation. In the United States, there are approximately 120,000 nontraumatic lower-extremity amputations performed each year.1 The incidence of amputation ranges from 70 to 150 per 10,000 person-years. It has been estimated that 5% to 15% of persons with diabetes will have a lower-extremity amputation in their lifetime.2,3 In the United States, 45% to 83% of all lower-extremity amputations involve persons with diabetes.2,3 Overall, patients with diabetes are 15 to 46 times more likely to have an amputation than patients without diabetes.4 Several studies have demonstrated a significant decrease in ulceration, reulceration, and amputation when therapeutic footwear, education, and regular diabetic foot care are provided. However, even at specialty diabetic foot centers, 19% to 40% of high-risk patients still had reulceration within a year of healing.2,3
There are only 2 randomized studies that evaluate ulcer prevention using therapeutic shoes and insoles in patients with diabetes.5,6 However, the results are contradictory. A recent systematic review by Patton et al7 demonstrated that insoles may prevent diabetic foot ulceration, but most of the evidence is poor and inconclusive. Their group found and included only 5 studies with high levels of evidence. One study showed a significant benefit, and 1 study showed no difference when therapeutic shoes were used compared with self-selected shoes. The current state of the art in insole design primarily addresses vertical forces with the aim of reducing foot pressures.8–10 There are no insole designs available that specifically reduce both abnormal pressure and shear. Both empiric evidence and a growing body of basic science work support the important role of friction and shear in ulcer development in the neuropathic foot.11–14
The authors hypothesized that an insole that could reduce shear, as well as pressure, would reduce the incidence of foot ulcers better than traditional insoles. In previous work, the authors evaluated a shear-reducing insole (SRI) design in healthy patients without diabetes or sensory neuropathy. This study demonstrated a 2.5-fold reduction in shear forces and an equivalent reduction in pressure compared with traditional insole designs and material combinations with in-shoe pressure studies.15 The aim of this study was to evaluate the effectiveness of a novel SRI to prevent foot ulcerations in high-risk persons with diabetes.
After reading this article, clinicians will be better able to determine if an SRI would help prevent ulcers in their high-risk patients with diabetes.
EXPERIMENT DESIGN AND METHODS
This was a single (physician)–blinded randomized trial. Two hundred ninety-nine patients at high risk for diabetic foot ulceration were randomized from 3 clinics in south Texas into 2 treatment groups (Figure 1). Approval for the study was obtained from the local hospital institutional review board. Informed consent was obtained prior to evaluation and enrollment in the study. Patients were assigned to receive either a standard insole or an SRI.
The standard therapy group (STG) consisted of foot and lower-extremity evaluation by a physician every 10 to 12 weeks, an education program that focused on foot complications and self-care practices, and therapeutic shoes and insoles. The education segment of training was provided by a video that addressed the etiology of diabetic foot ulcers, risk factors, self-care practices, and early warning signs of diabetic foot disease. If study patients identified an area of concern on their feet, they were instructed to contact the study nurse. All patients were provided with the same brand of therapeutic shoes, with one specific model for men and another for women. The insoles were replaced every 4 months, and shoes once a year. These time parameters were based on current guidelines of the Medicare Diabetic Therapeutic Shoe Bill.
Patients in the SRI group received the same therapy as patients in the STG with one exception: SRI patients used an insole design to reduce shear instead of the standard insole. A multilaminar design was used for both experimental and control groups. Insoles were constructed with a 35-durometer ethyl vinyl acetate (EVA), upper pad (3 mm thick), a 45-durometer EVA lower pad (3 mm thick), and a 20-durometer, closed-cell, cross-linked polyethylene foam top cover (1.5 mm). The only difference between the groups was that the SRI also includes elastic binders and 2 thin nonstick sheets. The nonstick sheets were placed between the upper and lower pads of the insole, and the binders held the insole together. Shear and pressure-reduction characteristics of the SRI have previously been published.
Inclusion criteria included diagnosis of diabetes by American Diabetes Association criteria, ability to provide informed consent, 18 to 80 years of age, history of a foot ulceration, or presence of sensory neuropathy with loss of protective sensation and foot deformity. Patients were excluded if there was an open ulcer or open amputation site, Charcot arthropathy, unable or unwilling to use an over-the-counter shoe, severe peripheral vascular disease (ankle brachial index <0.70), transmetatarsal foot amputation or higher, active foot infection, dementia, impaired cognitive function, history of drug or alcohol abuse within 1 year of the study, or other conditions based on the investigator’s clinical judgment.
Neuropathy with loss of protective sensation was defined as vibratory perception threshold testing greater than 25 V or any site missed with the 10-g Semmes Weinstein monofilament. The authors used the techniques described by Young et al16 and Mayfield and Sugarman.17 Range of motion of the ankle, subtalar, and first metatarsophalangeal joint was assessed using standard landmarks and procedures.18 Hallux rigidus was defined as first metatarsophalangeal joint dorsiflexion of 50 degrees or less, and equinus as 10 degrees of dorsiflexion or less. Toe and metatarsophalangeal joint deformities were defined as rigid, nonreducible deformities. The International Working Group on the Diabetic Foot’s Risk Classification (IWGDF) was used.19,20 Enrollment included patients with a history of a foot ulcer (IWGDF group 3) and with neuropathy and structural foot deformity of limited joint motion (IWGDF group 2). The primary clinical outcome was foot ulceration, which was defined as full-thickness loss of epidermis and dermis or involvement of deeper structures. At the conclusion of the study, patients were asked to complete a questionnaire about their compliance with wearing prescribed shoes and insoles (Table 1).
Sample Size Estimation and Statistical Analysis
Sample size was calculated based on the proportion of patients expected to develop foot complications in the 18-month study period. For this study, the statistical model used to examine the 2 treatments was a binomial model in which the proportion of patients who developed foot ulceration in the 2 treatment groups was examined. The outcome is a dichotomous variable (0 or 1), representing whether the patient had an ulceration. If 35% of the STG would have a foot ulcer during the study period, a sample size of 120 patients per group was required to detect a 25% difference between groups with an α of .05 and a power of 80%. Expectations are that 20% of the patients would not be able to complete the study and subsequently drop out. Therefore, we estimated to enroll 150 patients in each treatment arm to get 120 patients to fully complete the study.
The data were evaluated with the “last observation carried forward” intent-to-treat approach. The Fisher exact test was used to compare incident ulcers during the study in patients who used SRI and standard insoles. To determine odds ratio and confidence intervals, the authors used the method described by Woolf as referenced by Schlesselman.21 The Cox proportional hazard model was used to conduct a survival analysis based on the time to ulceration comparing the SRI with a standard insole. Several variables were included in the Cox regression analysis (risk group, treatment group, vibration perception threshold, ankle joint range, metatarsophalangeal joint range of motion, ABI, foot deformity, and race, type of diabetes, age).
No significant differences in patient characteristics (Table 1) were found. The SRI patients had fewer foot ulcers than did patients who received standard prevention therapy; however, this trend was not statistically significant (Fisher exact P = .08). Three ulcers developed in the SRI group, and 10 ulcers in the STG. A trend of fewer amputations in the SRI group was noticed; however, the analysis was not statistically significant. Patients in the STG were about 3.5 times more likely to develop an ulcer during the study period compared with patients treated in the SRI (odds ratio, 3.47; 95% confidence interval, 0.94–12.89). No significant difference was self-reported in frequency of shoe and insole usage in SRI and STG (Table 1).
There are only 2 other randomized clinical trials the authors identified that have evaluated ulcer prevention with therapeutic shoes and traditional custom-molded insoles. Uccioli et al6 demonstrated a significant reduction in the incidence of foot ulcers in persons with a history of diabetic foot ulcers that were treated with custom shoes and insoles compared with a second group that used self-selected shoes. In the therapeutic shoe and insole group, 28% of patients developed ulcers compared with 58% of patients who used their own shoes. On the other hand, Reiber et al5 did not demonstrate any difference in outcomes among patients treated with therapeutic shoes and insoles and self-selected shoes. Reiber et al5 evaluated a cohort of 400 persons with diabetes who were randomized to self-selected shoes, and 2 treatment groups who were provided therapeutic shoes and either a custom-made cork insole or a prefabricated polyurethane insole. Over a 2-year period, there was no difference in foot ulcers in patients who used self-selected shoes (17%), cork insoles (15%), and prefabricated insoles (14%). The yearly ulcer incidence was probably low in this study because the authors enrolled a population with a low risk for ulceration. Only 58% of the study population had sensory neuropathy, 32% had foot deformity, and 1% had peripheral vascular disease. The results of the authors’ study suggest a trend toward fewer foot ulcers, but the results did not meet the requirement for statistical significance.
The main shortcoming of the study was that it was underpowered. In this study, the authors’ group evaluated patients who are characteristically prescribed therapeutic shoes and insoles to prevent foot ulceration. The study population fit the highest-risk groups described in the IWGDF,22–24 patients with neuropathy, a foot deformity, and a history of a foot ulcer. The study demonstrated fewer ulcers than expected in this study. This was due to, at least in part, a large proportion of the study population having a lower risk of ulceration than the authors anticipated. At the time, the study did not have incidence data available for diabetic foot risk groups.24,25 In this study, a minority of study patients had a history of previous foot ulceration (25.3% and 27.5%; Table 1), and a majority of patients in both treatment arms were in IWGDF risk group 2 (neuropathy and foot deformity).24 In patients with sensory neuropathy and structural foot deformity, the incidence of ulceration is only about 3% to 6% a year. In contrast, among patients with a history of a foot ulcer, the incidence of ulceration is 19% to 40% per year.6,26,27 And, without preventive care, the incidence of ulceration increases to 50% to 83% per year.6,26
The etiology of ulcerations in persons with diabetes is commonly associated with the presence of peripheral neuropathy and repetitive trauma due to normal walking activities to areas of the foot exposed to moderate or high pressure and shear forces.28,29 Foot deformities, limited joint mobility, partial-foot amputations, and other structural deformities often predispose persons with diabetes with peripheral neuropathy to abnormal weight bearing, areas of concentrated pressure, and abnormal shear forces that significantly increase their risk of ulceration.30–32 The SRI used in this study has demonstrated a significant reduction in shear in laboratory studies with a similar reduction of pressure compared with standard insole designs in healthy adults.15 Shear is probably a strong component in many patients who develop wounds in the presence of relatively moderate vertical forces. However, at this time, in vivo testing of shear in the gait laboratory or clinic setting is not readily available; thus, very little has been published regarding the contribution of shear to the development of foot ulcers in the neuropathic foot.
The authors’ results may not reflect outcomes observed in the general medical community because foot ulcer prevention is often overlooked. Only a small percentage of patients who are eligible for therapeutic shoes and insoles receive them.33 Patients in this trial received a higher level of preventative care than is generally provided in the general medical community. As part of the study, insoles were replaced every 4 months, and shoes were replaced once a year, per Medicare guidelines. In addition, patients had structured foot care and foot-specific education. These practices are used in many clinic practice guidelines as standards of care, but they are not often implemented in community practices.34,35 In addition, patients could have had better results simply because they were participating in a clinical study that allowed more personal contact and attention to their feet.36,37
The results of this study suggest that an insole that reduces shear at the foot-insole interface can significantly reduce the risk of foot ulcerations in high-risk patients with diabetic neuropathy, deformity, and a history of foot ulcer than traditional insoles. The SRI used in this study worked well with conventional therapeutic shoes. They did not require any modifications, and they were tolerated as well as traditional shoe and insole combinations. More work is needed to understand effective therapies and risk factors for foot ulcers, such as factors that influence compliance and durability of insoles over time.
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