Acute Effects of Vibrating Insoles on Dynamic Balance and Gait Quality in Individuals With Diabetic Peripheral Neuropathy: A Randomized Crossover Study.

OBJECTIVE: This study investigated the effects of vibrating insoles on dynamic balance and gait quality during level and stair walking and explored the influence of vibration type and frequency in individuals with diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS: Twenty-two men with DPN were assessed for gait quality and postural and dynamic balance during walking and stair negotiation using a motion capture system and force plates across seven vibratory insole conditions (Vcs) versus a control (Ctrl) condition (insole without vibration). Vibration was applied during standing and walking tasks, and 15-min rest-stop periods without vibration were interposed between conditions. Repeated measures test conditions were randomized. The primary outcomes were gait speed and dynamic balance. RESULTS: Gait speed during walking significantly improved in all Vcs compared with Ctrl (P < 0.005), with Vc2, Vc4, and Vc6 identified as the most effective. Gait speed increased (reflecting faster walking) during stair ascent and descent in Vc2 (Ctrl vs. Vc2 for ascent 0.447 ± 0.180 vs. 0.517 ± 0.127 m/s; P = 0.037 and descent 0.394 ± 0.170 vs. 0.487 ± 0.125 m/s; P = 0.016), Vc4 (Ctrl vs. Vc4 for ascent 0.447 ± 0.180 vs. 0.482 ± 0.197 m/s; P = 0.047 and descent 0.394 ± 0.170 vs. 0.438 ± 0.181 m/s; P = 0.017), and Vc6 (Ctrl vs. Vc6 for ascent 0.447 ± 0.180 vs. 0.506 ± 0.179 m/s; P = 0.043 and descent 0.394 ± 0.170 vs. 0.463 ± 0.159 m/s; P = 0.026). Postural balance improved during quiet standing with eyes closed in Vc2, Vc4, Vc6, and Vc7 (P < 0.005). CONCLUSIONS: Vibrating insoles are an effective acute strategy for improving postural balance and gait quality during level walking and stair descent in individuals with DPN. These benefits are particularly evident when the entire plantar foot surface is stimulated.

Psychosocial Care for People With Diabetic Neuropathy: Time for Action.

Psychological factors and psychosocial care for individuals with diabetic neuropathy (DN), a common and burdensome complication of diabetes, are important but overlooked areas. In this article we focus on common clinical manifestations of DN, unremitting neuropathic pain, postural instability, and foot complications, and their psychosocial impact, including depression, anxiety, poor sleep quality, and specific problems such as fear of falling and fear of amputation. We also summarize the evidence regarding the negative impact of psychological factors such as depression on DN, self-care tasks, and future health outcomes. The clinical problem of underdetection and undertreatment of psychological problems is described, together with the value of using brief assessments of these in clinical care. We conclude by discussing trial evidence regarding the effectiveness of current pharmacological and nonpharmacological approaches and also future directions for developing and testing new psychological treatments for DN and its clinical manifestations.

Diabetic Foot Ulcers: A Review.

Importance: Approximately 18.6 million people worldwide are affected by a diabetic foot ulcer each year, including 1.6 million people in the United States. These ulcers precede 80% of lower extremity amputations among people diagnosed with diabetes and are associated with an increased risk of death. Observations: Neurological, vascular, and biomechanical factors contribute to diabetic foot ulceration. Approximately 50% to 60% of ulcers become infected, and about 20% of moderate to severe infections lead to lower extremity amputations. The 5-year mortality rate for individuals with a diabetic foot ulcer is approximately 30%, exceeding 70% for those with a major amputation. The mortality rate for people with diabetic foot ulcers is 231 deaths per 1000 person-years, compared with 182 deaths per 1000 person-years in people with diabetes without foot ulcers. People who are Black, Hispanic, or Native American and people with low socioeconomic status have higher rates of diabetic foot ulcer and subsequent amputation compared with White people. Classifying ulcers based on the degree of tissue loss, ischemia, and infection can help identify risk of limb-threatening disease. Several interventions reduce risk of ulcers compared with usual care, such as pressure-relieving footwear (13.3% vs 25.4%; relative risk, 0.49; 95% CI, 0.28-0.84), foot skin measurements with off-loading when hot spots (ie, greater than 2 °C difference between the affected foot and the unaffected foot) are found (18.7% vs 30.8%; relative risk, 0.51; 95% CI, 0.31-0.84), and treatment of preulcer signs. Surgical debridement, reducing pressure from weight bearing on the ulcer, and treating lower extremity ischemia and foot infection are first-line therapies for diabetic foot ulcers. Randomized clinical trials support treatments to accelerate wound healing and culture-directed oral antibiotics for localized osteomyelitis. Multidisciplinary care, typically consisting of podiatrists, infectious disease specialists, and vascular surgeons, in close collaboration with primary care clinicians, is associated with lower major amputation rates relative to usual care (3.2% vs 4.4%; odds ratio, 0.40; 95% CI, 0.32-0.51). Approximately 30% to 40% of diabetic foot ulcers heal at 12 weeks, and recurrence after healing is estimated to be 42% at 1 year and 65% at 5 years. Conclusions and Relevance: Diabetic foot ulcers affect approximately 18.6 million people worldwide each year and are associated with increased rates of amputation and death. Surgical debridement, reducing pressure from weight bearing, treating lower extremity ischemia and foot infection, and early referral for multidisciplinary care are first-line therapies for diabetic foot ulcers.

Etiology, Epidemiology, and Disparities in the Burden of Diabetic Foot Ulcers.

Diabetic foot ulcers (DFU) are a major source of preventable morbidity in adults with diabetes. Consequences of foot ulcers include decline in functional status, infection, hospitalization, lower-extremity amputation, and death. The lifetime risk of foot ulcer is 19% to 34%, and this number is rising with increased longevity and medical complexity of people with diabetes. Morbidity following incident ulceration is high, with recurrence rates of 65% at 3-5 years, lifetime lower-extremity amputation incidence of 20%, and 5-year mortality of 50-70%. New data suggest overall amputation incidence has increased by as much as 50% in some regions over the past several years after a long period of decline, especially in young and racial and ethnic minority populations. DFU are a common and highly morbid complication of diabetes. The pathway to ulceration, involving loss of sensation, ischemia, and minor trauma, is well established. Amputation and mortality after DFU represent late-stage complications and are strongly linked to poor diabetes management. Current efforts to improve care of patients with DFU have not resulted in consistently lower amputation rates, with evidence of widening disparities and implications for equity in diabetes care. Prevention and early detection of DFU through guideline-directed multidisciplinary care is critical to decrease the morbidity and disparities associated with DFU. This review describes the epidemiology, presentation, and sequelae of DFU, summarizes current evidence-based recommendations for screening and prevention, and highlights disparities in care and outcomes.

A brief overview of the diabetic neuropathies.

The diabetic neuropathies represent the commonest long-term complications of diabetes, and may be the presenting feature of Type 2 diabetes. In clinical practice, distal symmetrical polyneuropathy (DSPN) and the autonomic neuropathies are the most frequently seen forms of diabetic neuropathy. The 2017 American Diabetes Association classification system for the neuropathies of diabetes are in general use. Treatment challenges remain and the need for revised recommendations and further discussion of management of severely painful DSPN that does not fully respond to conventional medical management is clear, especially in light of the recent opioid crisis in the USA.

Implementation of corneal confocal microscopy for screening and early detection of diabetic neuropathy in primary care alongside retinopathy screening: Results from a feasibility study.

Objective: Screening for diabetic peripheral neuropathy (DPN) is essential for early detection and timely intervention. Quantitative assessment of small nerve fiber damage is key to the early diagnosis and assessment of its progression. Corneal confocal microscopy (CCM) is a non-invasive, in-vivo diagnostic technique that provides an accurate surrogate biomarker for small-fiber neuropathy. In this novel study for the first time, we introduced CCM to primary care as a screening tool for DPN alongside retinopathy screening to assess the level of neuropathy in this novel cohort. Research design and methods: 450 consecutive subjects with type 1 or type 2 diabetes attending for annual eye screening in primary care optometry settings underwent assessment with CCM to establish the prevalence of sub-clinical diabetic peripheral neuropathy. Subjects underwent assessment for neurological and ocular symptoms of diabetes and a history of diabetic foot disease, neuropathy and diabetic retinopathy (DR). Results: CCM examination was completed successfully in 427 (94.9%) subjects, 22% of whom had neuropathy according to Diabetic Neuropathy Symptom (DNS) score. The prevalence of sub-clinical neuropathy as defined by abnormal corneal nerve fiber length (CNFL) was 12.9%. In the subjects with a short duration of type 2 diabetes, 9.2% had abnormal CNFL. CCM showed significant abnormalities in corneal nerve parameters in this cohort of subjects with reduction of corneal nerve fiber density (CNFD, p<0.001), CNFL (p<0.001) and corneal nerve branch density (CNBD, p<0.001) compared to healthy subjects. In subjects who had no evidence of DR (67% of all subjects), 12.0% had abnormal CNFL. Conclusions: CCM may be a sensitive biomarker for early detection and screening of DPN in primary care alongside retinopathy screening.

Corneal Confocal Microscopy Identifies People with Type 1 Diabetes with More Rapid Corneal Nerve Fibre Loss and Progression of Neuropathy.

There is a need to accurately identify patients with diabetes at higher risk of developing and progressing diabetic peripheral neuropathy (DPN). Fifty subjects with Type 1 Diabetes Mellitus (T1DM) and sixteen age matched healthy controls underwent detailed neuropathy assessments including symptoms, signs, quantitative sensory testing (QST), nerve conduction studies (NCS), intra epidermal nerve fiber density (IENFD) and corneal confocal microscopy (CCM) at baseline and after 2 years of follow-up. Overall, people with type 1 diabetes mellitus showed no significant change in HbA1c, blood pressure, lipids or neuropathic symptoms, signs, QST, neurophysiology, IENFD and CCM over 2 years. However, a sub-group (n = 11, 22%) referred to as progressors, demonstrated rapid corneal nerve fiber loss (RCNFL) with a reduction in corneal nerve fiber density (CNFD) (p = 0.0006), branch density (CNBD) (p = 0.0002), fiber length (CNFL) (p = 0.0002) and sural (p = 0.04) and peroneal (p = 0.05) nerve conduction velocities, which was not related to a change in HbA1c or cardiovascular risk factors. The majority of people with T1DM and good risk factor control do not show worsening of neuropathy over 2 years. However, CCM identifies a sub-group of people with T1DM who show a more rapid decline in corneal nerve fibers and nerve conduction velocity.

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.

Corneal nerve loss is related to the severity of painful diabetic neuropathy.

BACKGROUND AND PURPOSE: Previously it has been shown that patients with painful diabetic neuropathy (PDN) have greater corneal nerve loss compared to patients with painless diabetic neuropathy. This study investigated if the severity of corneal nerve loss was related to the severity of PDN. METHODS: Participants with diabetic neuropathy (n = 118) and healthy controls (n = 38) underwent clinical and neurological evaluation, quantitative sensory testing, nerve conduction testing and corneal confocal microscopy and were categorized into those with no (n = 43), mild (n = 34) and moderate-to-severe (n = 41) neuropathic pain. RESULTS: Corneal nerve fibre density (p = 0.003), corneal nerve fibre length (p < 0.0001) and cold perception threshold (p < 0.0001) were lower and warm perception threshold was higher (p = 0.002) in patients with more severe pain, but there was no significant difference in the neuropathy disability score (p = 0.5), vibration perception threshold (p = 0.5), sural nerve conduction velocity (p = 0.3) and amplitude (p = 0.7), corneal nerve branch density (p = 0.06) and deep breathing heart rate variability (p = 0.08) between patients with differing severity of PDN. The visual analogue scale correlated significantly with corneal nerve fibre density (r = -0.3, p = 0.0002), corneal nerve branch density (r = -0.3, p = 0.001) and corneal nerve fibre length (r = -0.4, p < 0.0001). Receiver operating curve analysis showed that corneal nerve fibre density had an area under the curve of 0.78 with a sensitivity of 0.73 and specificity of 0.72 for the diagnosis of PDN. CONCLUSIONS: Corneal confocal microscopy reveals increasing corneal nerve fibre loss with increasing severity of neuropathic pain and a good diagnostic outcome for identifying patients with PDN.

A spatial causal network approach for multi-stressor risk analysis and mapping for environmental impact assessments.

Environmental impact assessment (EIA) relies on rigorous scientific assessment of all potential causal pathways by which large-scale developments may impact on valued assets in a region. Despite their importance to informed decision-making, many EIAs are flawed by incomplete analysis of causal pathways, limited spatial assessment and a lack of transparency about how risks have been evaluated across the region. To address these, we describe an EIA methodology based on network analysis of potential causal pathways in a given region. This network approach is coupled with a systematic evaluation of the likelihood, consequence and mitigation options for each causal pathway from one or more human activities to multiple valued assets. The method includes analysis of the confidence in these evaluations, recognizing where knowledge gaps constrain assessments of risks to particular assets. The causal network approach is complemented by a spatially explicit analysis of the region that allows residual risk (i.e. risk remaining after all feasible mitigations) to be mapped for all valued assets. This identifies which activities could lead to potential impacts of varying concern (rated from 'very low' to 'very high'), their likely pathways, which valued assets are at risk and where these residual risks are greatest. The output maps reveal 'risk hotspots' where more detailed local-scale assessments and monitoring should focus. The method is demonstrated by application to potential impacts on 8 valued assets (aquifers, ecosystems and protected species) due to unconventional gas resource development in the Cooper Basin, central Australia. Results show which activities and causal pathways are of potential concern to different valued assets and where residual risk is greatest for particular species and ecosystems. This spatial causal network provides a systematic, consistent and transparent assessment of potential impacts, improving the quality of decision-making about planned developments and their environmental risks.

Neuromuscular dysfunction and exercise training in people with diabetic peripheral neuropathy: A narrative review.

Diabetic peripheral neuropathy (DPN) is a common condition that is associated with neuromuscular dysfunction and peripheral sensory impairment. These deficits predispose patients to sensory and motor system limitations, foot ulcers and a high risk of falls. Exercise training has been proposed as an effective tool to alleviate neural deficits and improve whole-body function. Here we review the effects of DPN on neuromuscular function, the mechanisms underlying this impairment, and the neural and muscular adaptations to exercise training. Muscle dysfunction is an early hallmark of DPN. Deficits in muscle strength, power, mass and a greater fatigability are particularly severe in the lower extremity muscles. Non-enzymatic glycation of motor proteins, impaired excitation-contraction coupling and loss of motor units have been indicated as the main factors underlying muscular dysfunction. Among the exercise-based solutions, aerobic training improves neural structure and function and ameliorates neuropathic signs and symptoms. Resistance training induces marked improvement of muscle performance and may alleviate neuropathic pain. A combination of aerobic and resistance training (i.e., combined training) restores small sensory nerve damage, reduces symptoms, and improves muscle function. The evidence so far suggests that exercise training is highly beneficial and should be included in the standard care for DPN patients.

Diabetic foot ulcer disease in African continent: 'From clinical care to implementation' - Review of diabetic foot in last 60 years - 1960 to 2020.

The prevalence of diabetes mellitus is increasing globally and the greatest potential increases in diabetes will occur in Africa. Data suggest that these increases is associated with rapid demographic, sociocultural and economic transitions. There will be a parallel increase in the complications of diabetes and among the various complications those related to diabetic foot disease are associated with the highest morbidity and mortality. Diabetic Peripheral neuropathy (DPN) is the most common cause of diabetic foot complications in African countries; however, peripheral arterial disease (PAD) appears to increase, possibly a result of rising urbanization. Search done for the past six decades (1960 to 2020) on all foot complications. Rates of complications of diabetic foot in last six decades varied by country as follow: DPN: 4-90%; PAD: 0-77%; foot ulcers: 4-61%; amputation rates: 3-61% and high mortality rates reaching to 55%, patients who presented late with infection and gangrene. Educational and prevention programmes are required to curb the growing complications of diabetic foot ulcers in Africa among patients and health care workers. Secondly, it is imperative that governments across the African continent recognise the clinical and public health implications of diabetic foot disease in persons with diabetes.

Preventing the Next Pandemic: The Case for Investing in Circulatory Health - A Global Coalition for Circulatory Health Position Paper.

The Coronavirus Disease 2019 (COVID-19) has had a continuous and robust impact on world health. The resulting COVID-19 pandemic has had a devastating physical, mental and fiscal impact on the millions of people living with noncommunicable diseases (NCDs). In addition to older age, people living with CVD, stroke, obesity, diabetes, kidney disease, and hypertension are at a particularly greater risk for severe forms of COVID-19 and its consequences. Meta-analysis indicates that hypertension, diabetes, chronic kidney disease, and thrombotic complications have been observed as both the most prevalent and most dangerous co-morbidities in COVID-19 patients. And despite the nearly incalculable physical, mental, emotional, and economic toll of this pandemic, forthcoming public health figures continue to place cardiovascular disease as the number one cause of death across the globe in the year 2020. The world simply cannot wait for the next pandemic to invest in NCDs. Social determinants of health cannot be addressed only through the healthcare system, but a more holistic multisectoral approach with at its basis the Sustainable Development Goals (SDGs) is needed to truly address social and economic inequalities and build more resilient systems. Yet there is reason for hope: the 2019 UN Political Declaration on UHC provides a strong framework for building more resilient health systems, with explicit calls for investment in NCDs and references to fiscal policies that put such investment firmly within reach. By further cementing the importance of addressing circulatory health in a future Framework Convention on Emergency Preparedness, WHO Member States can take concrete steps towards a pandemic-free future. As the chief representatives of the global circulatory health community and patients, the Global Coalition for Circulatory Health calls for increased support for the healthcare workforce, global vaccine equity, embracing new models of care and digital health solutions, as well as fiscal policies on unhealthy commodities to support these investments.

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.

Corneal Confocal Microscopy Predicts the Development of Diabetic Neuropathy: A Longitudinal Diagnostic Multinational Consortium Study.

OBJECTIVE: Corneal nerve fiber length (CNFL) has been shown in research studies to identify diabetic peripheral neuropathy (DPN). In this longitudinal diagnostic study, we assessed the ability of CNFL to predict the development of DPN. RESEARCH DESIGN AND METHODS: From a multinational cohort of 998 participants with type 1 and type 2 diabetes, we studied the subset of 261 participants who were free of DPN at baseline and completed at least 4 years of follow-up for incident DPN. The predictive validity of CNFL for the development of DPN was determined using time-dependent receiver operating characteristic (ROC) curves. RESULTS: A total of 203 participants had type 1 and 58 had type 2 diabetes. Mean follow-up time was 5.8 years (interquartile range 4.2-7.0). New-onset DPN occurred in 60 participants (23%; 4.29 events per 100 person-years). Participants who developed DPN were older and had a higher prevalence of type 2 diabetes, higher BMI, and longer duration of diabetes. The baseline electrophysiology and corneal confocal microscopy parameters were in the normal range but were all significantly lower in participants who developed DPN. The time-dependent area under the ROC curve for CNFL ranged between 0.61 and 0.69 for years 1-5 and was 0.80 at year 6. The optimal diagnostic threshold for a baseline CNFL of 14.1 mm/mm2 was associated with 67% sensitivity, 71% specificity, and a hazard ratio of 2.95 (95% CI 1.70-5.11; P < 0.001) for new-onset DPN. CONCLUSIONS: CNFL showed good predictive validity for identifying patients at higher risk of developing DPN ∼6 years in the future.

No evidence of improvement in neuropathy after renal transplantation in patients with end stage kidney disease.

To assess the impact of renal transplantation on peripheral nerve damage in patients with chronic kidney disease (CKD). Fifteen patients with CKD (eGFR <15 mL/min/1.73 m2 ) underwent longitudinal assessment after renal transplantation (age: 56.88 ± 2.53 years, eGFR: 46.82 ± 4.86) and were compared with 15 age-matched controls (age: 58.25 ± 2.18 years, eGFR: 86.0 ± 2.0). The neuropathy symptom profile (NSP), neuropathy disability score (NDS), vibration perception threshold (VPT), cold and warm sensation threshold (CST and WST), cold and heat induced pain (CIP and HIP), deep breathing heart rate variability (DB-HRV), nerve conduction studies and corneal confocal microscopy (CCM) to quantify small nerve fibre pathology, were undertaken within 1-month of renal transplantation (baseline) and at 6, 12 and 24 months of follow up. There was no significant difference in NSP (P = .1), NDS (P = .3), VPT (P = .6), CST (P = .2), CIP (P = .08), HIP (P = .1), DB-HRV (P = .9) and sural (P = .4) and peroneal (P = .1) nerve amplitude between patients with CKD and controls at baseline. However, sural (P = .04), peroneal (P = .002) and tibial (P = .007) nerve conduction velocity and tibial nerve amplitude (P = .03) were significantly lower, WST (P = .02) was significantly higher and corneal nerve fibre density (P = .004) was significantly lower in patients with CKD compared with controls. There was no significant change in NSP, NDS, quantitative sensory testing, DB-HRV, nerve conduction or CCM parameters 24 months after renal transplantation. There is evidence of small and large fibre neuropathy in patients with CKD, but no change up to 24 months after successful renal transplantation.