Site-Specific, Critical Threshold Barefoot Peak Plantar Pressure Associated with Diabetic Foot Ulcer History: A Novel Approach to Determine DFU Risk in the Clinical Setting.

Background and Objectives: Barefoot peak plantar pressures (PPPs) are elevated in diabetes patients with neuropathic foot ulcer (DFU) history; however, there is limited reported evidence for a causative link between high barefoot PPP and DFU risk. We aimed to determine, using a simple mat-based methodology, the site-specific, barefoot PPP critical threshold that will identify a plantar site with a previous DFU. Materials and Methods: In a cross-sectional study, barefoot, site-specific PPPs were measured with normal gait for patients with DFU history (n = 21) and healthy controls (n = 12), using a validated carbon footprint system. For each participant, PPP was recorded at twelve distinct plantar sites (1st-5th toes, 1st-5th metatarsal heads (MTHs), midfoot and heel), per right and left foot, resulting in the analysis of n = 504 distinct plantar sites in the diabetes group, and n = 288 sites in the control group. Receiver operator characteristic curve analysis determined the optimal critical threshold for sites with DFU history. Results: Median PPPs for the groups were: diabetes sites with DFU history (n = 32) = 5.0 (3.25-7.5) kg/cm2, diabetes sites without DFU history (n = 472) = 3.25 (2.0-5.0) kg/cm2, control sites (n = 288) = 2.0 (2.0-3.25) kg/cm2; (p < 0.0001). Diabetes sites with elevated PPP (>6 kg/cm2) were six times more likely to have had DFU than diabetes sites with PPP ≤ 6 kg/cm2 (OR = 6.4 (2.8-14.6, 95% CI), p < 0.0001). PPP > 4.1 kg/cm2 was determined as the optimal critical threshold for identifying DFU at a specific plantar site, with sensitivity/specificity = 100%/79% at midfoot; 80%/65% at 5th metatarsal head; 73%/62% at combined midfoot/metatarsal head areas. Conclusions: We have demonstrated, for the first time, a strong, site-specific relationship between elevated barefoot PPP and previous DFU. We have determined a critical, highly-sensitive, barefoot PPP threshold value of >4.1 kg/cm2, which may be easily used to identify sites of previous DFU occurrence and, therefore, increased risk of re-ulceration. This site-specific approach may have implications for how high PPPs should be investigated in future trials.

An intelligent insole system with personalised digital feedback reduces foot pressures during daily life: An 18-month randomised controlled trial.

AIMS: High plantar pressure is a major risk factor in the development of diabetic foot ulcers (DFUs) and recent evidence shows plantar pressure feedback reduces DFU recurrence. This study investigated whether continued use of an intelligent insole system by patients at high-risk of DFUs causes a reduction in plantar pressures. METHODS: Forty-six patients with diabetic peripheral neuropathy and previous DFU were randomised to intervention (IG) or control groups (CG). Patients received an intelligent insole system, consisting of pressure-sensing insoles and digital watch. Patients wore the device during all daily activity for 18-months or until ulceration, and integrated pressure was recorded continuously. The device provided high-pressure feedback to IG only via audio-visual-vibrational alerts. High-pressure parameters at the whole foot, forefoot and rearfoot were compared between groups, with multilevel binary logistic regression analysis. RESULTS: CG experienced more high-pressure bouts over time than IG across all areas of the foot (P < 0.05). Differences between groups became apparent >16 weeks of wearing the device. CONCLUSIONS: Continuous plantar pressure feedback via an intelligent insole system reduces number of bouts of high-pressure in patients at high-risk of DFU. These findings suggest that patients were learning which activities generated high-pressure, and pre-emptively offloading to avoid further alerts.

The role of foot pressure measurement in the prediction and prevention of diabetic foot ulceration-A comprehensive review.

The predominant risk factor of diabetic foot ulcers (DFU), peripheral neuropathy, results in loss of protective sensation and is associated with abnormally high plantar pressures. DFU prevention strategies strive to reduce these high plantar pressures. Nevertheless, several constraints should be acknowledged regarding the research supporting the link between plantar pressure and DFUs, which may explain the low prediction ability reported in prospective studies. The majority of studies assess vertical, rather than shear, barefoot plantar pressure in laboratory-based environments, rather than during daily activity. Few studies investigated previous DFU location-specific pressure. Previous studies focus predominantly on walking, although studies monitoring activity suggest that more time is spent on other weight-bearing activities, where a lower "peak" plantar pressure might be applied over a longer duration. Although further research is needed, this may indicate that an expression of cumulative pressure applied over time could be a more relevant parameter than peak pressure. Studies indicated that providing pressure feedback might reduce plantar pressures, with an emerging potential use of smart technology, however, further research is required. Further pressure analyses, across all weight-bearing activities, referring to location-specific pressures are required to improve our understanding of pressures resulting in DFUs and improve effectiveness of interventions.

Innovative intelligent insole system reduces diabetic foot ulcer recurrence at plantar sites: a prospective, randomised, proof-of-concept study.

BACKGROUND: Prevention of diabetic foot ulcer recurrence in high risk patients, using current standard of care methods, remains a challenge. We hypothesised that an innovative intelligent insole system would be effective in reducing diabetic foot ulcer recurrence in such patients. METHODS: In this prospective, randomised, proof-of-concept study, patients with diabetes, and with peripheral neuropathy and a recent history of plantar foot ulceration were recruited from two multidisciplinary outpatient diabetic foot clinics in the UK, and were randomly assigned to either intervention or control. All patients received an insole system, which measured plantar pressure continuously during daily life. The intervention group received audiovisual alerts via a smartwatch linked to the insole system and offloading instructions when aberrant pressures were detected; the control group did not receive any alerts. The primary outcome was plantar foot ulcer occurrence within 18 months. This trial is registered with ISRCTN, ISRCTN05585501, and is closed to accrual and complete. FINDINGS: Between March 18, 2014, and Dec 20, 2016, 90 patients were recruited and consented to the study, and 58 completed the study. At follow-up, ten ulcers from 8638 person-days were recorded in the control group and four ulcers from 11 835 person-days in the intervention group: a 71% reduction in ulcer incidence in the intervention group compared with the control group (incidence rate ratio 0·29, 95% CI, 0·09-0·93; p=0·037). The number of patients who ulcerated was similar between groups (six of 26 [control group] vs four of 32 [intervention group]; p=0·29); however, individual plantar sites ulcerated more often in the control group (ten of 416) than in the intervention group (four of 512; p=0·047). In an exploratory analysis of good compliers (n=40), ulcer incidence was reduced by 86% in the intervention group versus control group (incidence rate ratio 0·14, 95% CI 0·03-0·63; p=0·011). In the exploratory analysis, plantar callus severity (change from baseline to 6 months) was greater in re-ulcerating patients (6·5, IQR 4·0-8·3) than non-re-ulcerating patients (2·0, 0·0-4·8; p=0·040). INTERPRETATION: To our knowledge, this study is the first to show that continuous plantar pressure monitoring and dynamic offloading guidance, provided by an innovative intelligent insole system, can lead to a reduction in diabetic foot ulcer site recurrence. FUNDING: Diabetes UK and Orpyx Medical Technologies.

A Foreign Body Through the Shoe of a Person With Diabetic Peripheral Neuropathy Alters Contralateral Biomechanics: Captured Through Innovative Plantar Pressure Technology.

High plantar pressure as a result of diabetic peripheral neuropathy is often reported as a major risk factor for ulceration. However, previous studies are confined to laboratories with equipment limited by cables, reducing the validity of measurements to daily life. The participant concerned in this case report was wearing an innovative plantar pressure feedback system as part of a wider study. The system allows for continuous plantar pressure monitoring and provides feedback throughout all activities of daily living. The participant concerned was a 59-year-old male with type 2 diabetes who presented with severe peripheral neuropathy. In addition, the right ankle had previously undergone fusion. Between monthly study appointments, the participant unknowingly had a screw embedded in his right shoe, while pressure was being recorded. Although no significant differences in pressure were present for the right foot with the embedded screw, the contralateral foot showed significantly higher pressure when the screw was embedded, compared with pre and post time periods. The increase in pressure on the contralateral foot is expected to result from the protrusion of the screw in the right shoe, causing a perturbation to balance and a shift in the center of pressure toward the contralateral side. This compensatory effect is likely to have been magnified by the limited mobility of the fused right ankle. These findings highlight the importance of checking both feet for ulcer risk, in the event of receiving high-pressure feedback. This innovative technology may improve our understanding of diabetic plantar foot ulcer development.

Explanations for less small fibre neuropathy in South Asian versus European subjects with type 2 diabetes in the UK.

BACKGROUND: Low foot ulcer risk in South Asian, compared with European, people with type 2 diabetes in the UK has been attributed to their lower levels of neuropathy. We have undertaken a detailed study of corneal nerve morphology and neuropathy risk factors, to establish the basis of preserved small nerve fibre function in South Asians versus Europeans. METHODS: In a cross-sectional, population-based study, age- and sex-matched South Asians (n = 77) and Europeans (n = 78) with type 2 diabetes underwent neuropathy assessment using corneal confocal microscopy, symptoms, signs, quantitative sensory testing, electrophysiology and autonomic function testing. Multivariable linear regression analyses determined factors accounting for ethnic differences in small fibre damage. RESULTS: Corneal nerve fibre length (22.0 ± 7.9 vs. 19.3 ± 6.3 mm/mm2 ; P = 0.037), corneal nerve branch density (geometric mean (range): 60.0 (4.7-246.2) vs. 46.0 (3.1-129.2) no./mm2 ; P = 0.021) and heart rate variability (geometric mean (range): 7.9 (1.4-27.7) vs. 6.5 (1.5-22.0); P = 0.044), were significantly higher in South Asians vs. Europeans. All other neuropathy measures did not differ, except for better sural nerve amplitude in South Asians (geometric mean (range): 10.0 (1.3-43.0) vs. 7.2 (1.0-30.0); P = 0.006). Variables with the greatest impact on attenuating the P value for age- and HbA1C -adjusted ethnic difference in corneal nerve fibre length (P = 0.032) were pack-years smoked (P = 0.13), BMI (P = 0.062) and triglyceride levels (P = 0.062). CONCLUSIONS: South Asians have better preserved small nerve fibre integrity than equivalent Europeans; furthermore, classic, modifiable risk factors for coronary heart disease are the main contributors to these ethnic differences. We suggest that improved autonomic neurogenic control of cutaneous blood flow in Asians may contribute to their protection against foot ulcers.

A New Mobile Application for Standardizing Diabetic Foot Images.

BACKGROUND: We describe the development of a new mobile app called "FootSnap," to standardize photographs of diabetic feet and test its reliability on different occasions and between different operators. METHODS: FootSnap was developed by a multidisciplinary team for use with the iPad. The plantar surface of 30 diabetic feet and 30 nondiabetic control feet were imaged using FootSnap on two separate occasions by two different operators. Reproducibility of foot images was determined using the Jaccard similarity index (JSI). RESULTS: High intra- and interoperator reliability was demonstrated with JSI values of 0.89-0.91 for diabetic feet and 0.93-0.94 for control feet. CONCLUSIONS: Similarly high reliability between groups indicates FootSnap is appropriate for longitudinal follow-ups in diabetic feet, with potential for monitoring pathology.

Protocol for a systematic review and individual patient data meta-analysis of prognostic factors of foot ulceration in people with diabetes: the international research collaboration for the prediction of diabetic foot ulcerations (PODUS).

BACKGROUND: Diabetes-related lower limb amputations are associated with considerable morbidity and mortality and are usually preceded by foot ulceration. The available systematic reviews of aggregate data are compromised because the primary studies report both adjusted and unadjusted estimates. As adjusted meta-analyses of aggregate data can be challenging, the best way to standardise the analytical approach is to conduct a meta-analysis based on individual patient data (IPD).There are however many challenges and fundamental methodological omissions are common; protocols are rare and the assessment of the risk of bias arising from the conduct of individual studies is frequently not performed, largely because of the absence of widely agreed criteria for assessing the risk of bias in this type of review. In this protocol we propose key methodological approaches to underpin our IPD systematic review of prognostic factors of foot ulceration in diabetes.Review questions;1. What are the most highly prognostic factors for foot ulceration (i.e. symptoms, signs, diagnostic tests) in people with diabetes?2. Can the data from each study be adjusted for a consistent set of adjustment factors?3. Does the model accuracy change when patient populations are stratified according to demographic and/or clinical characteristics? METHODS: MEDLINE and EMBASE databases from their inception until early 2012 were searched and the corresponding authors of all eligible primary studies invited to contribute their raw data. We developed relevant quality assurance items likely to identify occasions when study validity may have been compromised from several sources. A confidentiality agreement, arrangements for communication and reporting as well as ethical and governance considerations are explained.We have agreement from the corresponding authors of all studies which meet the eligibility criteria and they collectively possess data from more than 17000 patients. We propose, as a provisional analysis plan, to use a multi-level mixed model, using "study" as one of the levels. Such a model can also allow for the within-patient clustering that occurs if a patient contributes data from both feet, although to aid interpretation, we prefer to use patients rather than feet as the unit of analysis. We intend to only attempt this analysis if the results of the investigation of heterogeneity do not rule it out and the model diagnostics are acceptable. DISCUSSION: This review is central to the development of a global evidence-based strategy for the risk assessment of the foot in patients with diabetes, ensuring future recommendations are valid and can reliably inform international clinical guidelines.

Prevalence and characteristics of painful diabetic neuropathy in a large community-based diabetic population in the U.K.

OBJECTIVE: To assess, in the general diabetic population, 1) the prevalence of painful neuropathic symptoms; 2) the relationship between symptoms and clinical severity of neuropathy; and 3) the role of diabetes type, sex, and ethnicity in painful neuropathy. RESEARCH DESIGN AND METHODS: Observational study of a large cohort of diabetic patients receiving community-based health care in northwest England (n = 15,692). Painful diabetic neuropathy (PDN) was assessed using neuropathy symptom score (NSS) and neuropathy disability score (NDS). RESULTS: Prevalence of painful symptoms (NSS ≥5) and PDN (NSS ≥5 and NDS ≥3) was 34 and 21%, respectively. Painful symptoms occurred in 26% of patients without neuropathy (NDS ≤2) and 60% of patients with severe neuropathy (NDS >8). Adjusted risk of painful neuropathic symptoms in type 2 diabetes was double that of type 1 diabetes (odds ratio [OR] = 2.1 [95% CI 1.7-2.4], P < 0.001) and not affected by severity of neuropathy, insulin use, foot deformities, smoking, or alcohol. Women had 50% increased adjusted risk of painful symptoms compared with men (OR = 1.5 [1.4-1.6], P < 0.0001). Despite less neuropathy in South Asians (14%) than Europeans (22%) and African Caribbeans (21%) (P < 0.0001), painful symptoms were greater in South Asians (38 vs. 34 vs. 32%, P < 0.0001). South Asians without neuropathy maintained a 50% increased risk of painful neuropathy symptoms compared with other ethnic groups (P < 0.0001). CONCLUSIONS: One-third of all community-based diabetic patients have painful neuropathy symptoms, regardless of their neuropathic deficit. PDN was more prevalent in patients with type 2 diabetes, women, and people of South Asian origin. This highlights a significant morbidity due to painful neuropathy and identifies key groups who warrant screening for PDN.

Explanations for the lower rates of diabetic neuropathy in Indian Asians versus Europeans.

OBJECTIVE: Risks of diabetes and cardiovascular disease are elevated worldwide in Indian Asians. However, risks of other diabetes-related complications, i.e., foot ulceration and amputation, also with a vascular basis, are substantially lower in Asians than in white Europeans in the U.K., possibly due to less neuropathy. We therefore compared signs, symptoms, and objective quantitative measures of diabetic neuropathy and their risk factors in Indian Asians and Europeans. RESEARCH DESIGN AND METHODS: This was a cross-sectional study of a population-based sample of age- and sex-matched adults with type 2 diabetes of European (95 male and 85 female) and Asian (96 male and 84 female) descent in the U.K. Patients were assessed for neuropathic symptoms, signs, nerve conduction, autonomic function, and quantitative sensory testing. Peripheral vascular function and other potential risk factors for neuropathy were measured. RESULTS Mean nerve conduction velocity Z scores were better in Asians (mean +/- SD 0.07 +/- 0.62) than in Europeans (-0.11 +/- 0.60; P = 0.007) and were explained by the shorter height, fewer pack-years smoked, and higher transcutaneous oxygen levels (TCpO(2)) in Indian Asians (P value for ethnic comparison attenuated to 0.2). Small fiber neuropathy was less prevalent in Indian Asians compared with Europeans (odds ratio 0.58 [95% CI 0.37-0.93]; P = 0.02) and was primarily accounted for by better TCpO(2) (0.70 [0.40-1.21]; P = 0.2). CONCLUSIONS: Asians with diabetes have substantially less large and small fiber neuropathy than Europeans, despite comparable traditional risk factors. Independent from smoking, the lower risk of neuropathy in Asians is due to better skin microvascularization and may help explain the substantially reduced Asian foot ulcer risk.

Effects of early mobilization on unhealed dysvascular transtibial amputation stumps: a clinical trial.

OBJECTIVE: To observe the effects of early mobilization on unhealed transtibial (TT) amputation stump wounds of dysvascular etiology. An "unhealed" stump was defined as having a wound greater than 1cm x 1cm at least 3 weeks after surgery. DESIGN: An observational cohort study. SETTING: This center receives about 250 new lower-limb amputees a year from over 50 surgeons working in 16 hospitals. Over 35% are unhealed. PARTICIPANTS: Sixty-six consecutive new TT amputees (age 62.8+/-10.8y) of dysvascular etiology (diabetes 50%) with unhealed stumps were recruited. Sixty-one percent were current or past smokers. The mean +/- SD stump wound size was 7.7+/-2.7cm x 3.2+/-2.0cm. INTERVENTIONS: The wound size was measured, and stump transcutaneous oxygen (TcpO(2)) and transcutaneous carbon dioxide (TcpCO(2)) were measured. Wounds were debrided and dressed by using a standard protocol. Mobilization using a Pneumatic Post-Amputation Mobility (PPAM) Aid for approximately 3 weeks was followed by provision of a TT prosthesis. A standard physiotherapy walking training program was performed. MAIN OUTCOME MEASURES: Stump wound healing, time to achieve healing, and resting transcutaneous oxygen pressure pre- and posttherapy. RESULTS: Of the 66 amputees, 4 did not start. Sixty-two started; 6 withdrew, and 56 completed the trial. Complete wound healing was achieved in 74% (46/62) over a mean of 141 (87-270) days. The mean +/- SD stump TcpO(2) at baseline was 41.3+/-19.8mmHg and increased significantly to 50.6+/-21.9mmHg (P<.02) after 97 (34-185) days of mobilization. Nine of 46 required revision plastic surgery. Five subjects, whose wounds were healing, became unwell, dropped out, and later deceased. Five subjects, all current smokers, did not heal and underwent higher amputation. CONCLUSIONS: Patients with large unhealed TT stump wounds can simultaneously undergo walking training by using a prosthesis and can achieve wound healing. Seventy-four percent of subjects achieved full wound healing. The small minority of patients who did not heal were current smokers whose TcpO(2) levels did not improve throughout the trial. Rising levels of stump TcpO(2)were associated with wound healing.

Foot ulcer risk is lower in South-Asian and african-Caribbean compared with European diabetic patients in the U.K.: the North-West diabetes foot care study.

OBJECTIVE: To determine 1) foot ulcer rates for European, South-Asian, and African-Caribbean diabetic patients in the U.K and 2) the contribution of neuropathy and peripheral arterial disease (PAD) differences to altered ulcer risk between the groups. RESEARCH DESIGN AND METHODS: In this U.K. population-based study, we screened 15,692 type 1 and type 2 diabetic patients in the community health care setting for foot ulcers, foot deformities, neuropathy, and PAD plus other characteristics. In total, 13,409 were European (85.5%), 1,866 were South Asian (11.9%), and 371 were African Caribbean (2.4%). RESULTS: The age-adjusted prevalence of diabetic foot ulcers (past or present) for Europeans, South Asians, and African Caribbeans was 5.5, 1.8, and 2.7%, respectively (P < 0.0001). Asians and African Caribbeans had less neuropathy, PAD, and foot deformities than Europeans (P = 0.003). The unadjusted risk of ulcer (odds ratio [OR]) for Asians versus Europeans was 0.29 (95% CI 0.20-0.41) (P < 0.0001). PAD, neuropathy, foot deformities, and insulin use attenuated the age-adjusted OR from 0.32 to 0.52 (0.35-0.76) (P < 0.0001). African-Caribbean versus European ulcer risk in males was attenuated from 0.60 to 0.71 by vibration sensation. CONCLUSIONS: South Asians with diabetes in the U.K. have about one-third the risk of foot ulcers of Europeans. The lower levels of PAD, neuropathy, insulin usage, and foot deformities of the Asians account for approximately half of this reduced foot ulcer risk. Lower neuropathy is the main contributor to the reduced African-Caribbean ulcer rate, particularly in men. The reasons for these ethnic differences warrant further investigation.

Can motor nerve conduction velocity predict foot problems in diabetic subjects over a 6-year outcome period?

OBJECTIVE: This study examined motor nerve conduction velocity (MNCV) and other peripheral nerve and vascular tests as predictors for foot ulceration, amputation, and mortality in diabetes over a 6-year follow-up period. RESEARCH DESIGN AND METHODS: We recruited 169 diabetic subjects (without significant peripheral vascular disease with an ankle brachial pressure index [ABPI] >/=0.75) for the study and separated them into groups (to ensure diversity of nerve function). The control group consisted of 22 nondiabetic people. At baseline, all subjects underwent assessment of MNCV; vibration, pressure, and temperature perception thresholds; peripheral vascular function; and other diabetes assessments. RESULTS: Over the 6-year outcome period, 37.3% of the diabetic subjects developed at least one new ulcer, 11.2% had a lower-limb amputation (LLA) (minor or major), and 18.3% died. Using multivariate Cox's regression analysis (RR [95% CI] and removing previous ulcers as a confounding variable, MNCV was found to be the best predictor of new ulceration (0.90 [0.84-0.96], P = 0.001) and the best predictors of amputation were pressure perception threshold (PPT) (5.18 [1.96-13.68], P = 0.001) and medial arterial calcification (2.88 [1.13-7.35], P = 0.027). Creatinine (1.01 [1.00-1.01], P < 0.001), MNCV (0.84 [0.73-0.97], P = 0.016), and skin oxygen levels (14.32 [3.04-67.52], P = 0.001) were the best predictors of mortality. CONCLUSIONS: This study shows that MNCV, which is often assessed in clinical trials of neuropathy, can predict foot ulceration and death in diabetes. In addition, tests of PPT and medial arterial calcification can be used in the clinic to predict LLA in diabetic subjects.