Where does spinal cord stimulation fit into the international guidelines for refractory painful diabetic neuropathy? a consensus statement.

BACKGROUND: Although pharmacotherapy with anticonvulsants and/or antidepressants can be effective for many people with painful diabetic neuropathy (PDN), albeit with frequent side-effects, a critical juncture occurs when neuropathic pain no longer responds to standard first- and second-step mono- and dual therapy and becomes refractory. Subsequent to these pharmacotherapeutic approaches, third-line treatment options for PDN may include opioids (short-term), capsaicin 8% patches, and spinal cord stimulation (SCS). AIM: This document summarizes consensus recommendations regarding appropriate treatment for refractory peripheral diabetic neuropathy (PDN), based on outcomes from an expert panel convened on December 10, 2022, as part of the Worldwide Initiative for Diabetes Education Virtual Global Summit, "Advances in the Management of Painful Diabetic Neuropathy." PARTICIPANTS: Nine attendees, eminent physicians and academics, comprising six diabetes specialists, two pain specialists, and one health services expert. EVIDENCE: For individuals with refractory PDN, opioids are a high-risk option that do not provide a long-term solution and should not be used. For appropriately selected individuals, SCS is an effective, safe, and durable treatment option. In particular, high-frequency (HF) SCS (10 kHz) shows strong efficacy and improves quality of life. To ensure treatment success, strict screening criteria should be used to prioritize candidates for SCS. CONSENSUS PROCESS: Each participant voiced their opinion after reviewing available data, and a verbal consensus was reached during the meeting. CONCLUSION: Globally, the use of opioids should rarely be recommended for refractory, severe PDN. Based on increasing clinical evidence, SCS, especially HF-SCS, should be considered as a treatment for PDN that is not responsive to first- or second-line monotherapy/dual therapy.

Correlates of self-rated health in people with diabetic peripheral neuropathy: a longitudinal study.

AIM: Self-rated health, a measure of self-reported general health, is a robust predictor of morbidity and mortality in various populations, including persons with diabetes. This study examines correlates of self-rated health in adults with diabetic peripheral neuropathy (DPN). METHODS: Participants recruited from the UK and USA (n = 295; mean (± sd) age: 61.5 ± 10.7 years; 69% male; 71% type 2 diabetes) rated their health at baseline and 18 months. DPN severity was assessed using the neuropathy disability score and the vibration perception threshold. Validated self-report measures assessed neuroticism, DPN-symptoms of pain, unsteadiness and reduced sensation in feet, DPN-related limitations in daily activities, DPN-specific emotional distress and symptoms of depression. RESULTS: In the fully adjusted baseline model, younger age, presence of cardiovascular disease and higher depression symptom scores showed likely clinically meaningful independent associations with worse health ratings. Being at the UK study site and presence of nephropathy indicated potentially meaningful independent associations with lower baseline health ratings. These predictors were largely consistent in their association with health ratings at 18 months. CONCLUSION: Results identify independent correlates of health ratings among adults with DPN. Future research should investigate the clinical implications of associations and examine changes in these variables over time and potential effects on changes in health perceptions. If these associations reflect causal pathways, our results may guide interventions to target issues that are likely to have an impact on subjectively experienced health as an important patient-reported outcome in DPN care.

Painful diabetic peripheral neuropathy: consensus recommendations on diagnosis, assessment and management.

Painful diabetic peripheral neuropathy (DPN) is common, is associated with significant reduction in quality of life and poses major treatment challenges to the practising physician. Although poor glucose control and cardiovascular risk factors have been proven to contribute to the aetiology of DPN, risk factors specific for painful DPN remain unknown. A number of instruments have been tested to assess the character, intensity and impact of painful DPN on quality of life, activities of daily living and mood. Management of the patient with DPN must be tailored to individual requirements, taking into consideration the co-morbidities and other factors. Pharmacological agents with proven efficacy for painful DPN include tricyclic anti-depressants, the selective serotonin and noradrenaline re-uptake inhibitors, anti-convulsants, opiates, membrane stabilizers, the anti-oxidant alpha-lipoic acid and topical agents including capsaicin. Current first-line therapies for painful DPN include tricyclic anti-depressants, the serotonin and noradrenaline re-uptake inhibitor duloxetine and the anti-convulsants pregabalin and gabapentin. When prescribing any of these agents, other co-morbidities and costs must be taken into account. Second-line approaches include the use of opiates such as synthetic opioid tramadol, morphine and oxycodone-controlled release. There is a limited literature with regard to combination treatment. In extreme cases of painful DPN unresponsive to pharmacotherapy, occasional use of electrical spinal cord stimulation might be indicated. There are a number of unmet needs in the therapeutic management of painful DPN. These include the need for randomized controlled trials with active comparators and data on the long-term efficacy of agents used, as most trials have lasted for less than 6 months. Finally, there is a need for appropriately designed studies to investigate non-pharmacological approaches.

Foot care education in patients with diabetes at low risk of complications: a consensus statement.

AIMS: To define and agree a practical educational framework for delivery by all healthcare professionals managing patients with diabetes, particularly those at low risk of developing foot complications. METHODS: A consensus meeting of a multidisciplinary expert panel. Prior to the meeting, relevant clinical papers were disseminated to the panel for review. The consensus was largely based upon the experts' clinical experience and judgement. RESULTS: Four main health behaviours were identified for those at low risk of developing foot complications, namely: control of blood glucose levels; attendance at annual foot screening examination; reporting of any changes in foot health immediately; and the engagement in a simple daily foot care routine. CONCLUSION: There is currently little evidence-based literature to support specific foot care practices. Patients with diabetes at low risk of developing complications should be encouraged to undertake a basic foot care regimen to reduce their likelihood of developing complications.

Depression predicts first but not recurrent diabetic foot ulcers.

AIMS/HYPOTHESIS: This study examined the relationship between symptoms of depression and the development of diabetic foot ulcers. METHODS: Participants were 333 patients (71% male; mean age 62 years; 73% with type 2 diabetes) with diabetic peripheral neuropathy (DPN), but without peripheral vascular disease (PVD). Severity of DPN and the presence of PVD were assessed by clinical examination. Depression, other diabetes complications and foot self-care were assessed by self-report. Cox regression tested whether depression was an independent predictor of foot ulceration over 18 months, whether this relationship was moderated by foot ulcer history, and whether foot self-care mediated this relationship. RESULTS: During follow-up, 63 patients developed a foot ulcer. Those with prior foot ulcers had more than four-fold greater risk of subsequent foot ulceration compared with those without a history of foot ulcer. A significant interaction effect showed that depression was significantly related to the development of first but not recurrent foot ulcers. This relationship was independent of biological risk factors. In the final model, each standard deviation increase in depression symptoms was significantly associated with increased risk of developing first foot ulcers (HR 1.68, 95% CI 1.20-2.35), while foot self-care was associated with lower risk (HR 0.61, 95% CI 0.40-0.94). Foot self-care did not mediate the relationship between depression and foot ulceration. CONCLUSIONS/INTERPRETATION: These data suggest that depression is associated with increased risk of first foot ulcers in DPN patients and that this relationship is independent of biological risk factors and foot self-care. Interventions that target depression and foot self-care before the development of foot ulcers may maximise the likelihood of successful prevention of foot ulceration.

Predictors of depressive symptoms in persons with diabetic peripheral neuropathy: a longitudinal study.

AIMS/HYPOTHESIS: The aim of the study was to determine whether diabetic peripheral neuropathy (DPN) is a risk factor for depressive symptoms and examine the potential mechanisms for this relationship. METHODS: This longitudinal study (9 and 18 month follow-up) of 338 DPN patients (mean age 61 years; 71% male; 73% type 2 diabetes) examined the temporal relationships between DPN severity (mean +/- SD; neuropathy disability score [NDS], 7.4 +/- 2.2; mean vibration perception threshold, 41.5 +/- 9.5 V), DPN somatic experiences (symptoms and foot ulceration), DPN psychosocial consequences (restrictions in activities of daily living [ADL] and social self-perception) and the Hospital Anxiety and Depression subscale measuring depressive symptoms (HADS-D; mean 4.9 +/- 3.7). RESULTS: Controlling for baseline HADS-D and demographic/disease variables, NDS at baseline significantly predicted increased HADS-D over 18 months. This association was mediated by baseline unsteadiness, which was significantly associated with increased HADS-D. Baseline ADL restrictions significantly predicted increased HADS-D and partly mediated the association between baseline unsteadiness and change in HADS-D. Increased pain, unsteadiness and ADL restrictions from baseline to 9 months each significantly predicted increased HADS-D over 18 months. Change in social self-perception from baseline to 9 months significantly predicted increased HADS-D and partly mediated the relationships of change in unsteadiness and ADL restrictions with change in HADS-D. CONCLUSIONS/INTERPRETATION: These results confirm that neuropathy is a risk factor for depressive symptoms because it generates pain and unsteadiness. Unsteadiness is the symptom with the strongest association with depression, and is linked to depressive symptoms by perceptions of diminished self-worth as a result of inability to perform social roles.

Diabetic foot ulcers: a quality of life issue.

Foot ulcers are a serious complication of diabetes mellitus that are associated with adverse sequelae and high costs. In addition, such foot ulcers have a significant impact on quality of life (QoL). For example, the loss of mobility associated with foot ulcers affects patients' ability to perform simple, everyday tasks and to participate in leisure activities. These and other consequences of foot ulcers often lead to depression and poor QoL. Notably, several studies have shown that patients with diabetes mellitus and foot ulcers were more depressed and had poorer QoL than those who had no diabetic complications. Given the detrimental effect foot ulcers have on patients, it is essential that these foot ulcers are prevented or treated more effectively than at present. Evidence suggests that many foot ulcers can be prevented by using intensive interventions and adopting a multidisciplinary approach to treatment. In addition, preventative strategies may become more effective if new research into how patients with diabetes experience and interpret their health threats (e.g. diagnosis "loss of sensation" or a foot ulcer episode) is taken into account. With regard to treatment, new options should enable ulcers to heal more quickly than with standard therapies. One area of interest is the use of growth factors. For example, recombinant platelet-derived growth factor, in addition to good ulcer care, has been shown to improve the number of ulcers that heal and healing times significantly compared with good ulcer care alone. Other potential new treatments include the use of skin substitutes. In summary, improved preventative measures and wound treatment should reduce the potential for patients with diabetes mellitus to experience impaired QoL caused by foot ulcers.

Efficacy of injected liquid silicone in the diabetic foot to reduce risk factors for ulceration: a randomized double-blind placebo-controlled trial.

OBJECTIVE: To investigate the effectiveness of injecting liquid silicone in the diabetic foot to reduce risk factors for ulceration in a randomized double-blind placebo-controlled trial. RESEARCH DESIGN AND METHODS: A total of 28 diabetic neuropathic patients without peripheral vascular disease were randomized to active treatment with 6 injections of 0.2 ml liquid silicone in the plantar surface of the foot or to treatment with an equal volume of saline (placebo). No significant differences were evident regarding age or neuropathy status between the 2 groups. All injections were under the metatarsal heads at sites of calluses or high pressures. Barefoot plantar pressures (pedobarography) and plantar tissue thickness under the metatarsal heads (Planscan ultrasound device) were measured at baseline and at 3, 6, and 12 months after the first injection. Injection sites were photographed at all stages, and callus formation was scored as a change from baseline. Throughout the study, patients were treated by the same podiatrist for all podiatry treatment. RESULTS: Patients who received silicone treatment had significantly increased plantar tissue thickness at injection sites compared with the placebo group (1.8 vs. 0.1 mm) (P < 0.0001) and correspondingly significantly decreased plantar pressures (-232 vs. -25 kPa) (P < 0.05) at 3 months, with similar results at 6 and 12 months. A trend was noted toward a reduction of callus formation in the silicone-treated group compared with no change in the placebo group. CONCLUSIONS: The results confirm the efficacy of plantar silicone injections in reducing recognized risk factors associated with diabetic foot ulceration.

Benefits of a multidisciplinary approach in the management of recurrent diabetic foot ulceration in Lithuania: a prospective study.

OBJECTIVE: To assess the ability of a multidisciplinary approach to diabetic foot care to reduce the incidence of recurrent ulceration and amputations compared with standard care in a 2-year prospective study. RESEARCH DESIGN AND METHODS: A total of 145 patients with a past history of neuropathic foot ulcers but no evidence of peripheral vascular disease entered the study. Subjects were screened for their neuropathic and vascular status at baseline, and all received identical foot care education. The intervention group (n = 56) was followed by the multidisciplinary team of physicians, nurses, and podiatrists with regular podiatry and reeducation every 3 months and the provision of specialty footwear as required. The standard treatment group was followed in local clinics on a trimonthly basis and received identical screening and education at baseline. RESULTS: There were no significant differences at baseline in age (intervention 59.2+/-13.4, standard treatment 58.5+/-11.5 years), duration of diabetes (14.0+/-7.1 vs. 15.6+/-7.8 years), or neuropathic status (vibration perception threshold [VPT]: 31.1+/-12.1 vs. 33.9+/-11.3 V, neuropathy disability score [NDS]: 8.1+/-1.4 vs. 7.9+/-1.7). All patients had an ankle brachial pressure index (ABPI) of >0.9 and at least one palpable foot pulse. Significantly fewer recurrent ulcers were seen in the intervention group than in the standard treatment group during the 2-year period (30.4 vs. 58.4%, P < 0.001). CONCLUSIONS: This prospective study has demonstrated the effectiveness of a multidisciplinary approach to diabetic foot care together with the provision of specialty footwear in the long-term management of high-risk patients with a history of neuropathic foot ulcers.

A comparative study of the Podotrack, a simple semiquantitative plantar pressure measuring device, and the optical pedobarograph in the assessment of pressures under the diabetic foot.

AIMS: To test the Podotrack, a simple inexpensive semiquantitative footprint mat, for potential use as a screening tool for high plantar pressures, against the optical pedobarograph (a computerized device). METHODS: The Podotrack was superimposed on the pedobarograph for simultaneous measurement of pressures from both systems. Three independent observers quantified the pressures of Podotrack footprints from healthy controls and diabetic patients, both before (n=164) and after (n=183) training. The sensitivity of the Podotrack to identify high pressure areas measured by the pedobarograph (> 12.3 kg/cm2) was 78.7%, 45.8% and 44.3% (observer A, B and C) before training, but improved to 96.2%, 92.4% and 91.1% after training (P<0.01). Specificity for all three observers was more than 90% before and after training. Inter-observer agreement improved significantly after training (P<0.001). CONCLUSION: After a simple training of the observers, the Podotrack identified approximately all high pressure areas, suggesting that the Podotrack could be a useful screening tool to identify areas at risk of ulceration in diabetic patients. We recommend a standard training package for new Podotrack users, to optimize identification of diabetic patients at risk of foot ulceration.

Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings.

OBJECTIVE: To determine the frequency and constellations of anatomic, pathophysiologic, and environmental factors involved in the development of incident diabetic foot ulcers in patients with diabetes and no history of foot ulcers from Manchester, U.K., and Seattle, Washington, research settings. RESEARCH DESIGN AND METHODS: The Rothman model of causation was applied to the diabetic foot ulcer condition. The presence of structural deformities, peripheral neuropathy, ischemia, infection, edema, and callus formation was determined for diabetic individuals with incident foot ulcers in Manchester and Seattle. Demographic, health, diabetes, and ulcer data were ascertained for each patient. A multidisciplinary group of foot specialists blinded to patient identity independently reviewed detailed abstracts to determine component and sufficient causes present and contributing to the development of each patient's foot ulcer. A modified Delphi process assisted the group in reaching consensus on component causes for each patient. Estimates of the proportion of ulcers that could be ascribed to each component cause were computed. RESULTS: From among 92 study patients from Manchester and 56 from Seattle, 32 unique causal pathways were identified. A critical triad (neuropathy, minor foot trauma, foot deformity) was present in > 63% of patient's causal pathways to foot ulcers. The components edema and ischemia contributed to the development of 37 and 35% of foot ulcers, respectively. Callus formation was associated with ulcer development in 30% of the pathways. Two unitary causes of ulcer were identified, with trauma and edema accounting for 6 and < 1% of ulcers, respectively. The majority of the lesions were on the plantar toes, forefoot, and midfoot. CONCLUSIONS: The most frequent component causes for lower-extremity ulcers were trauma, neuropathy, and deformity, which were present in a majority of patients. Clinicians are encouraged to use proven strategies to prevent and decrease the impact of modifiable conditions leading to foot ulcers in patients with diabetes.

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 NIDDM and IDDM were included. Inclusion criteria were vibration perception threshold (VPT) at the great toe > or = 25 V in at least one foot and < or = 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.

Gait abnormalities in diabetic neuropathy.

OBJECTIVE: To investigate the effect of peripheral neuropathy on gait in diabetic patients. RESEARCH DESIGN AND METHODS: Gait analysis was performed in the following groups matched for age, sex, and BMI: 20 normal healthy control subjects (NC), 20 non-neuropathic diabetic control subjects (DC), 20 neuropathic diabetic subjects (DN), and 20 neuropathic diabetic subjects with a history of foot ulceration (DNU). All subjects with orthopedic foot problems were excluded from the study. The following gait parameters were investigated: 1) walking speed; 2) stance phase duration; 3) joint angles and moment arms for the ankle, knee, and hip joints in both sagittal and frontal planes; 4) the components of the ground reaction force (GRF) vector; and 5) the ankle, knee, and hip joint moments originating from the GRF vector in both planes. RESULTS: There were no statistical differences in any of the parameters studied between the NC and DC groups. Walking speed was significantly slower in the DNU group compared with the two control groups (P < 0.02). The maximum knee joint angle was smaller in the sagittal plane for the DNU group compared with the DC group values (P < 0.05). The maximum value of the vertical component of GRF was found to be higher (P < 0.03) in the two control groups compared with the DNU group. The maximum value of the anteroposterior forces was also found to be higher (P < 0.001) in the DC group compared with the DNU group. The maximum frontal plane ankle joint moment was significantly higher (P < 0.05) in the DN compared with the NC group. CONCLUSIONS: Diabetic subjects with peripheral neuropathy demonstrate alterations in some gait parameters during walking. These alterations could facilitate foot injuries, thus contributing to frequent 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.

The tactile circumferential discriminator. A new, simple screening device to identify diabetic patients at risk of foot ulceration.

OBJECTIVE: To evaluate the tactile circumferential discriminator (TCD) (Tacticon Medical Enterprises, West Chester, PA), a new, simple, handheld quantitative sensory testing device, in the identification of patients at potential risk of neuropathic ulceration. RESEARCH DESIGN AND METHODS: Patients with diabetes (n = 133) attending the Manchester Diabetes Centre or diabetic foot clinic seen within a 5-week period were assessed using the TCD, monofilaments, and vibration perception threshold (VPT) measured over the hallux. The sensitivity and specificity of each method in the identification of "high-risk" patients were compared. RESULTS: The TCD was easy to use, and there was a highly significant correlation between the results obtained compared with both filaments and VPT (P < 0.0001). Similarly, in the identification of patients at risk of ulceration, the TCD agreed with VPT in 75.2% of cases and with the monofilaments in 78.9%. In the identification of the 37 foot ulcer patients, TCD was highly sensitive (100%) but less specific (58.3%) than VPT (86.5%; 79.2%) and the monofilaments (91.9%; 76.0%). CONCLUSIONS: These data suggest that the TCD is a simple and reliable new technique for population screening for neuropathy and foot ulcer risk.