Diabetes and Covid-19: Diabetes research funding and support during the pandemic.

AIMS: Between late 2020 and early 2022, EURADIA undertook a survey of organisations and individuals supporting or working in the field of diabetes research with the aim of understanding better the impact of the Covid-19 pandemic on funding for diabetes research in Europe. METHODS: Information was collected via online survey augmented in some cases by face-to-face interviews. RESULTS: Findings were mixed but the majority of those responding suggested a moderate impact of the pandemic on diabetes research activity. Many respondents reported a reduction in funding during the pandemic and many of those involved in clinical research experienced a reduction in research clinicians' availability for diabetes research as they were redeployed to Covid-19 patient care. It was frequently reported that the impact might not be fully appreciated until several years after the end of the pandemic. CONCLUSIONS: This preliminary survey suggests there may be a significant impact of the pandemic on all aspects of diabetes research and that a more detailed follow-up on the impact of the pandemic on funding of diabetes research should be carried out in the future.

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.

Altered accelerator pedal control in a driving simulator in people with diabetic peripheral neuropathy.

AIM: To investigate whether the sensory-motor impairment attributable to diabetic peripheral neuropathy would affect control of the accelerator pedal during a driving simulator task. METHODS: A total of 32 active drivers, 11 with diabetic peripheral neuropathy (mean ± sd age 67±5.0 years), 10 with diabetes but no neuropathy (diabetes group; mean ± sd age 62±10 years), and 11 healthy individuals without diabetes (healthy group; mean ± sd age 60±11 years), undertook a test on a dynamometer to assess ankle plantar flexor muscle strength and ankle joint proprioception function of the right leg, in addition to a driving simulator task. The following variables were measured: maximal ankle plantar flexor muscle strength; speed of strength generation (Nm/s); and ankle joint proprioception (ankle repositioning error, degrees). In the driving simulator task, driving speed (mph), accelerator pedal signal (degrees) and the duration of specific 'loss-of-control events' (s) were measured during two drives (Drive 1, Drive 2). RESULTS: Participants with diabetic peripheral neuropathy had a lower speed of strength generation (P<0.001), lower maximal ankle plantar flexor muscle strength (P<0.001) and impaired ankle proprioception (P=0.034) compared to healthy participants. The diabetic peripheral neuropathy group drove more slowly compared with the healthy group (Drive 1 P=0.048; Drive 2 P=0.042) and showed marked differences in the use of the accelerator pedal compared to both the diabetes group (P=0.010) and the healthy group (P=0.002). Participants with diabetic peripheral neuropathy had the longest duration of loss-of-control events, but after one drive, this was greatly reduced (P=0.023). CONCLUSIONS: Muscle function, ankle proprioception and accelerator pedal control are all affected in people with diabetic peripheral neuropathy, adversely influencing driving performance, but potential for improvement with targeted practice remains possible.

'When the dog bites': What can we learn about health geography from newspaper coverage in a 'model city' for dog-bite prevention?

Despite calls for the adoption of 'One-Health' approaches, dog-bite injuries remain neglected in healthcare and public health, and our study may help to understand why. Media coverage can influence policy directions, including policies that address dogs. We collected articles (n = 65) published in two local newspapers, 2012-2017, then carried out an ethnographically-informed discourse analysis of the dog-bite reports. The newspapers portrayed dog-bites mainly as matters of public disorder, as opposed to priorities for healthcare and public health. Even as our study took place in a city that has shown dog-bite reductions without recourse to 'breed bans' or restrictions (i.e., breed-specific legislation), journalists still tended to emphasize dog breed as a narrative element in explaining dog-bite incidents. Nonetheless, the news coverage did not reproduce a 'nature versus nurture' dichotomy. Rather, the journalists presented dog breed, and presumably associated aggressive behaviour, as entanglements with social, economic, and cultural contexts. Meanwhile, the news stories reduced contextual complexity to geographic locations, as codes for community reputation, in attributing causality and morality.

Vertical displacement of the centre of mass during walking in people with diabetes and diabetic neuropathy does not explain their higher metabolic cost of walking.

People with diabetes display biomechanical gait alterations compared to controls and have a higher metabolic cost of walking (CoW), but it remains unknown whether differences in the vertical displacement of the body centre of mass (CoM) may play a role in this higher CoW. The aim of this study was to investigate vertical CoM displacement (and step length as a potential underpinning factor) as an explanatory factor in the previously observed increased CoW with diabetes. Thirty-one non-diabetic controls (Ctrl); 22 diabetic patients without peripheral neuropathy (DM) and 14 patients with moderate/severe Diabetic Peripheral Neuropathy (DPN), underwent gait analysis using a motion analysis system and force plates while walking at a range of matched speeds between 0.6 and 1.6 m/s. Vertical displacement of the CoM was measured over the gait cycle, and was not different in either diabetes patients with or without diabetic peripheral neuropathy compared to controls across the range of matched walking speeds examined (at 1 m/s: Ctrl: 5.59 (SD: 1.6), DM: 5.41 (1.63), DPN: 4.91 (1.66) cm; p > 0.05). The DPN group displayed significantly shorter steps (at 1 m/s: Ctrl: 69, DM: 67, DPN: 64 cm; p > 0.05) and higher cadence (at 1 m/s: Ctrl: 117 (SD1.12), DM: 119 (1.08), DPN: 122 (1.25) steps per minute; p > 0.05) across all walking speeds compared to controls. The vertical CoM displacement is therefore unlikely to be a factor in itself that contributes towards the higher CoW observed recently in people with diabetic neuropathy. The higher CoW in patients with diabetes may not be explained by the CoM displacement, but rather may be more related to shorter step lengths, increased cadence and the associated increased internal work and higher muscle forces developed by walking with more flexed joints.

Latent autoimmune diabetes of adulthood (LADA) is associated with small fibre neuropathy.

AIM: To assess if latent autoimmune diabetes of adulthood (LADA) is associated with small fibre neuropathy. METHODS: Participants with LADA (n=31), Type 2 diabetes (n=31) and healthy control participants without diabetes (n=31) underwent a detailed assessment of neurologic deficits, quantitative sensory testing, electrophysiology, skin biopsy and corneal confocal microscopy. RESULTS: The groups were matched for age (healthy control without diabetes: 53.5±9.1 vs. Type 2 diabetes: 58.0±6.5 vs. LADA: 53.2±11.6 years), duration of diabetes (Type 2 diabetes: 10.0±8.3 vs. LADA: 11.0±9.1 years) and blood pressure. However, BMI (P=0.01) and triglycerides (P=0.0008) were lower and HbA1c (P=0.0005), total cholesterol (P=0.01) and HDL (P=0.002) were higher in participants with LADA compared with Type 2 diabetes. Peroneal motor nerve conduction velocity (P=0.04) and sural sensory nerve conduction velocity (P=0.008) were lower in participants with latent autoimmune diabetes in adults compared with Type 2 diabetes. Intra-epidermal nerve fibre density (P=0.008), corneal nerve fibre density (P=0.003) and corneal nerve branch density (P=0.006) were significantly lower in participants with LADA compared with Type 2 diabetes. There were no significant differences in the other neuropathy parameters. CONCLUSIONS: Despite comparable age and duration of diabetes, participants with LADA demonstrate more severe neuropathy and particularly small fibre neuropathy, compared with participants with Type 2 diabetes.

Developing a foot ulcer risk model: what is needed to do this in a real-world primary care setting?

AIM: To determine how routinely collected data can inform a risk model to predict de novo foot ulcer presentation in the primary care setting. METHODS: Data were available on 15 727 individuals without foot ulcers and 1125 individuals with new foot ulcers over a 12-year follow-up in UK primary care. We examined known risk factors and added putative risk factors in our logistic model. RESULTS: People with foot ulcers were 4.2 years older (95% CI 3.1-5.2) than those without, and had higher HbA1c % (mean 7.9 ± 1.9 vs 7.5 ± 1.7) / HbA1c mmol/mol (63 ± 21 vs 59 ± 19) (p<0.0001) concentration [+0.45 (95% CI 0.33-0.56), creatinine level [+6.9 µmol/L (95% CI 4.1-9.8)] and Townsend score [+0.055 (95% CI 0.033-0.077)]. Absence of monofilament sensation was more common in people with foot ulcers (28% vs 21%; P<0.0001), as was absence of foot pulses (6.4% vs 4.8%; P=0.017). There was no difference between people with or without foot ulcers in smoking status, gender, history of stroke or foot deformity, although foot deformity was extremely rare (0.4% in people with foot ulcers, 0.6% in people without foot ulcers). Combining risk factors in a single logistic regression model gave modest predictive power, with an area under the receiver-operating characteristic curve of 0.65 (95% CI 0.62-0.67). The prevalence of ulceration in the bottom decile of risk was 1.8% and in the top decile it was 13.4% (compared with an overall prevalence of 6.5%); thus, the presence of all six risk factors gave a relative risk of 7.4 for development of a foot ulcer over 12 years. CONCLUSION: We have made some progress towards defining a variable set that can be used to create a foot ulcer prediction model. More accurate determination of foot deformity/pedal circulation in primary care may improve the predictive value of such a future risk model, as will identification of additional risk variables.

Altered Achilles tendon function during walking in people with diabetic neuropathy: implications for metabolic energy saving.

The Achilles tendon (AT) has the capacity to store and release elastic energy during walking, contributing to metabolic energy savings. In diabetes patients, it is hypothesized that a stiffer Achilles tendon may reduce the capacity for energy saving through this mechanism, thereby contributing to an increased metabolic cost of walking (CoW). The aim of this study was to investigate the effects of diabetes and diabetic peripheral neuropathy (DPN) on the Achilles tendon and plantarflexor muscle-tendon unit behavior during walking. Twenty-three nondiabetic controls (Ctrl); 20 diabetic patients without peripheral neuropathy (DM), and 13 patients with moderate/severe DPN underwent gait analysis using a motion analysis system, force plates, and ultrasound measurements of the gastrocnemius muscle, using a muscle model to determine Achilles tendon and muscle-tendon length changes. During walking, the DM and particularly the DPN group displayed significantly less Achilles tendon elongation (Ctrl: 1.81; DM: 1.66; and DPN: 1.54 cm), higher tendon stiffness (Ctrl: 210; DM: 231; and DPN: 240 N/mm), and higher tendon hysteresis (Ctrl: 18; DM: 21; and DPN: 24%) compared with controls. The muscle fascicles of the gastrocnemius underwent very small length changes in all groups during walking (~0.43 cm), with the smallest length changes in the DPN group. Achilles tendon forces were significantly lower in the diabetes groups compared with controls (Ctrl: 2666; DM: 2609; and DPN: 2150 N). The results strongly point toward the reduced energy saving capacity of the Achilles tendon during walking in diabetes patients as an important factor contributing to the increased metabolic CoW in these patients. NEW & NOTEWORTHY From measurements taken during walking we observed that the Achilles tendon in people with diabetes and particularly people with diabetic peripheral neuropathy was stiffer, was less elongated, and was subject to lower forces compared with controls without diabetes. These altered properties of the Achilles tendon in people with diabetes reduce the tendon's energy saving capacity and contribute toward the higher metabolic energy cost of walking in these patients.

An empirical analysis of the cost of rearing dairy heifers from birth to first calving and the time taken to repay these costs.

Rearing quality dairy heifers is essential to maintain herds by replacing culled cows. Information on the key factors influencing the cost of rearing under different management systems is, however, limited and many farmers are unaware of their true costs. This study determined the cost of rearing heifers from birth to first calving in Great Britain including the cost of mortality, investigated the main factors influencing these costs across differing farming systems and estimated how long it took heifers to repay the cost of rearing on individual farms. Primary data on heifer management from birth to calving was collected through a survey of 101 dairy farms during 2013. Univariate followed by multivariable linear regression was used to analyse the influence of farm factors and key rearing events on costs. An Excel spreadsheet model was developed to determine the time it took for heifers to repay the rearing cost. The mean±SD ages at weaning, conception and calving were 62±13, 509±60 and 784±60 days. The mean total cost of rearing was £1819±387/heifer with a mean daily cost of £2.31±0.41. This included the opportunity cost of the heifer and the mean cost of mortality, which ranged from £103.49 to £146.19/surviving heifer. The multivariable model predicted an increase in mean cost of rearing of £2.87 for each extra day of age at first calving and a decrease in mean cost of £6.06 for each percentile increase in time spent at grass. The model also predicted a decrease in the mean cost of rearing in autumn and spring calving herds of £273.20 and £288.56, respectively, compared with that in all-year-round calving herds. Farms with herd sizes⩾100 had lower mean costs of between £301.75 and £407.83 compared with farms with <100 milking cows. The mean gross margin per heifer was £441.66±304.56 (range £367.63 to £1120.08), with 11 farms experiencing negative gross margins. Most farms repaid the cost of heifer rearing in the first two lactations (range 1 to 6 lactations) with a mean time from first calving until breaking even of 530±293 days. The results of the economic analysis suggest that management decisions on key reproduction events and grazing policy significantly influence the cost of rearing and the time it takes for heifers to start making a profit for the farm.

Altered walking strategy and increased unsteadiness in participants with impaired glucose tolerance and Type 2 diabetes relates to small-fibre neuropathy but not vitamin D deficiency.

AIMS: To investigate alterations in walking strategy and dynamic sway (unsteadiness) in people with impaired glucose tolerance and people with Type 2 diabetes in relation to severity of neuropathy and vitamin D levels. METHODS: A total of 20 people with Type 2 diabetes, 20 people with impaired glucose tolerance and 20 people without either Type 2 diabetes or impaired glucose tolerance (control group) underwent gait analysis using a motion analysis system and force platforms, and detailed assessment of neuropathy and serum 25 hydroxy-vitamin D levels. RESULTS: Ankle strength (P = 0.01) and power (P = 0.003) during walking and walking speed (P = 0.008) were preserved in participants with impaired glucose tolerance but significantly lower in participants with Type 2 diabetes compared with control participants; however, step width (P = 0.005) and dynamic medio-lateral sway (P = 0.007) were significantly higher and posterior maximal movement (P = 0.000) was lower in participants with impaired glucose tolerance, but preserved in those with Type 2 diabetes compared with the control group. Dynamic medio-lateral sway correlated with corneal nerve fibre length (P = 0.001) and corneal nerve branch density (P = 0.001), but not with vibration perception threshold (P = 0.19). Serum 25 hydroxy-vitamin D levels did not differ significantly among the groups (P = 0.10) and did not correlate with any walking variables or measures of dynamic sway. CONCLUSIONS: Early abnormalities in walking strategy and dynamic sway were evident in participants with impaired glucose tolerance, whilst there was a reduction in ankle strength, power and walking speed in participants with Type 2 diabetes. Unsteadiness correlated with small-, but not large-fibre neuropathy and there was no relationship between vitamin D levels and walking variables.

Distal lower limb strength is reduced in subjects with impaired glucose tolerance and is related to elevated intramuscular fat level and vitamin D deficiency.

AIM: To quantify muscle strength and size in subjects with impaired glucose tolerance (IGT) in relation to intramuscular non-contractile tissue, the severity of neuropathy and vitamin D level. METHODS: A total of 20 subjects with impaired glucose tolerance and 20 control subjects underwent assessment of strength and size of knee extensor, flexor and ankle plantar and dorsi-flexor muscles, as well as quantification of intramuscular non-contractile tissue and detailed assessment of neuropathy and serum 25-hydroxy vitamin D levels. RESULTS: In subjects with impaired glucose tolerance, proximal knee extensor strength (P = 0.17) and volume (P = 0.77), and knee flexor volume (P = 0.97) did not differ from those in control subjects. Ankle plantar flexor strength was significantly lower (P = 0.04) in the subjects with impaired glucose tolerance, with no difference in ankle plantar flexor (P = 0.62) or dorsiflexor volume (P = 0.06) between groups. Intramuscular non-contractile tissue level was significantly higher in the ankle plantar flexors and dorsiflexors (P = 0.03) of subjects with impaired glucose tolerance compared with control subjects, and it correlated with the severity of neuropathy. Ankle plantar flexor muscle strength correlated significantly with corneal nerve fibre density (r = 0.53; P = 0.01), a sensitive measure of small fibre neuropathy, and was significantly lower in subjects with vitamin D deficiency (P = 0.02). CONCLUSIONS: People with impaired glucose tolerance have a significant reduction in distal but not proximal leg muscle strength, which is not associated with muscle atrophy, but with increased distal intramuscular non-contractile tissue, small fibre neuropathy and vitamin D deficiency.

A study of extracellular vesicle concentration in active diabetic Charcot neuroarthropathy.

It was the aim of this work to determine whether the plasma concentration of extracellular vesicles (EVs) in active diabetic Charcot neuroarthropathy (CN) is connected to the inflammatory markers, temperature elevation in the affected foot and concentration of soluble receptor for advanced glycation end products (RAGE). EVs were isolated from peripheral blood of 35 patients with active CN. EVs were counted after repetitive centrifugation and washing of samples, by flow cytometry. Foot temperature was measured by infrared thermometer. Concentration of soluble receptor for advanced glycation end products (RAGE) was determined by enzyme-linked immunosorbent assay (ELISA). We found statistically significant correlations of EV concentration (but not soluble RAGE concentration) with C-Reactive Protein (CRP) and with temperature difference between the affected and the contralateral foot (r=0.40, p=0.032; r=0.89, p<10-8, respectively). We provide evidence that the concentration of EVs is related to elevation of markers of inflammation (CRP and foot temperature difference) in acute Diabetic CN. EV-based markers could be considered as a potential aid in early diagnosis of CN.

MAPK/ERK2 phosphorylates ERG at serine 283 in leukemic cells and promotes stem cell signatures and cell proliferation.

Aberrant ERG (v-ets avian erythroblastosis virus E26 oncogene homolog) expression drives leukemic transformation in mice and high expression is associated with poor patient outcomes in acute myeloid leukemia (AML) and T-acute lymphoblastic leukemia (T-ALL). Protein phosphorylation regulates the activity of many ETS factors but little is known about ERG in leukemic cells. To characterize ERG phosphorylation in leukemic cells, we applied liquid chromatography coupled tandem mass spectrometry and identified five phosphorylated serines on endogenous ERG in T-ALL and AML cells. S283 was distinct as it was abundantly phosphorylated in leukemic cells but not in healthy hematopoietic stem and progenitor cells (HSPCs). Overexpression of a phosphoactive mutant (S283D) increased expansion and clonogenicity of primary HSPCs over and above wild-type ERG. Using a custom antibody, we screened a panel of primary leukemic xenografts and showed that ERG S283 phosphorylation was mediated by mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling and in turn regulated expression of components of this pathway. S283 phosphorylation facilitates ERG enrichment and transactivation at the ERG +85 HSPC enhancer that is active in AML and T-ALL with poor prognosis. Taken together, we have identified a specific post-translational modification in leukemic cells that promotes progenitor proliferation and is a potential target to modulate ERG-driven transcriptional programs in leukemia.

Is the metabolic cost of walking higher in people with diabetes?

People with diabetes walk slower and display biomechanical gait alterations compared with controls, but it remains unknown whether the metabolic cost of walking (CoW) is elevated. The aim of this study was to investigate the CoW and the lower limb concentric joint work as a major determinant of the CoW, in patients with diabetes and diabetic peripheral neuropathy (DPN). Thirty-one nondiabetic controls (Ctrl), 22 diabetic patients without peripheral neuropathy (DM), and 14 patients with moderate/severe DPN underwent gait analysis using a motion analysis system and force plates and treadmill walking using a gas analyzer to measure oxygen uptake. The CoW was significantly higher particularly in the DPN group compared with controls and also in the DM group (at selected speeds only) compared with controls, across a range of matched walking speeds. Despite the higher CoW in patients with diabetes, concentric lower limb joint work was significantly lower in DM and DPN groups compared with controls. The higher CoW is likely due to energetic inefficiencies associated with diabetes and DPN reflecting physiological and biomechanical characteristics. The lower concentric joint work in patients with diabetes might be a consequence of kinematic gait alterations and may represent a natural strategy aimed at minimizing the CoW.

The diabetic foot in 2015: an overview.

In 2015, it can be said that the diabetic foot is no longer the Cinderella of diabetic complications. Thirty years ago there was little evidence-based research taking place on the diabetic foot, and there were no international meetings addressing this topic. Since then, the biennial Malvern Diabetic Foot meetings started in 1986, the American Diabetes Association founded their Foot Council in 1987, and the European Association for the Study of Diabetes established a Foot Study Group in 1998. The first International Symposium on the Diabetic Foot in The Netherlands was convened in 1991, and this was soon followed by the establishment of the International Working Group on the Diabetic Foot that has produced useful guidelines in several areas of investigation and the management of diabetic foot problems. There has been an exponential rise in publications on diabetic foot problems in high impact factor journals, and a comprehensive evidence-base now exists for many areas of treatment. Despite the extensive evidence available, it, unfortunately, remains difficult to demonstrate that most types of education are efficient in reducing the incidence of foot ulcers. However, there is evidence that education as part of a multi-disciplinary approach to diabetic foot ulceration plays a pivotal role in incidence reduction. With respect to treatment, strong evidence exists that offloading is the best modality for healing plantar neuropathic foot ulcers, and there is also evidence from two randomized controlled trials to support the use of negative-pressure wound therapy in complex post-surgical diabetic foot wounds. Hyperbaric oxygen therapy exhibits the same evidence level and strength of recommendation. International guidelines exist on the management of infection in the diabetic foot. Many randomized trials have been performed, and these have shown that the agents studied generally produced comparable results, with the exception of one study in which tigecycline was shown to be clinically inferior to ertapenem ± vancomycin. Similarly, there are numerous types of wound dressings that might be used in treatment and which have shown efficacy, but no single type (or brand) has shown superiority over others. Peripheral artery disease is another major contributory factor in the development of ulceration, and its presence is a strong predictor of non-healing and amputation. Despite the proliferation of endovascular procedures in addition to open revascularization, many patients continue to suffer from severely impaired perfusion and exhaust all treatment options. Finally, the question of the true aetiopathogenesis of Charcot neuroarthropathy remains enigmatic, although much work is currently being undertaken in this area. In this area, it is most important to remember that a clinically uninfected, warm, insensate foot in a diabetic patient should be considered as a Charcot foot until proven otherwise, and, as such, treated with offloading, preferably in a cast.

People with diabetic peripheral neuropathy display a decreased stepping accuracy during walking: potential implications for risk of tripping.

AIM: To examine the stepping accuracy of people with diabetes and diabetic peripheral neuropathy. METHODS: Fourteen patients with diabetic peripheral neuropathy (DPN), 12 patients with diabetes but no neuropathy (D) and 10 healthy non-diabetic control participants (C). Accuracy of stepping was measured whilst the participants walked along a walkway consisting of 18 stepping targets. Preliminary data on visual gaze characteristics were also captured in a subset of participants (diabetic peripheral neuropathy group: n = 4; diabetes-alone group: n = 4; and control group: n = 4) during the same task. RESULTS: Patients in the diabetic peripheral neuropathy group, and patients in the diabetes-alone group were significantly less accurate at stepping on targets than were control subjects (P < 0.05). Preliminary visual gaze analysis identified that patients diabetic peripheral neuropathy were slower to look between targets, resulting in less time being spent looking at a target before foot-target contact. CONCLUSIONS: Impaired motor control is theorized to be a major factor underlying the changes in stepping accuracy, and potentially altered visual gaze behaviour may also play a role. Reduced stepping accuracy may indicate a decreased ability to control the placement of the lower limbs, leading to patients with neuropathy potentially being less able to avoid observed obstacles during walking.

Resistance exercise training increases lower limb speed of strength generation during stair ascent and descent in people with diabetic peripheral neuropathy.

AIM: To examine the effects of a 16-week resistance exercise training intervention on the speed of ankle and knee strength generation during stair ascent and descent, in people with neuropathy. METHODS: A total of 43 people: nine with diabetic peripheral neuropathy, 13 with diabetes but no neuropathy and 21 healthy control subjects ascended and descended a custom-built staircase. The speed at which ankle and knee strength were generated, and muscle activation patterns of the ankle and knee extensor muscles were analysed before and after a 16-week intervention period. RESULTS: Ankle and knee strength generation during both stair ascent and descent were significantly higher after the intervention than before the intervention in the people with diabetes who undertook the resistance exercise intervention (P < 0.05). Although muscle activations were altered by the intervention, there were no observable patterns that underpinned the observed changes. CONCLUSIONS: The increased speed of ankle and knee strength generation observed after the intervention would be expected to improve stability during the crucial weight acceptance phase of stair ascent and descent, and ultimately contribute towards reducing the risk of falling. Improvements in muscle strength as a result of the resistance exercise training intervention are likely to be the most influential factor for increasing the speed of strength generation. It is recommended that these exercises could be incorporated into a multi-faceted exercise programme to improve safety in people with diabetes and neuropathy.

Responding to health inequities: Indigenous health system innovations.

Over the past decades, Indigenous communities around the world have become more vocal and mobilized to address the health inequities they experience. Many Indigenous communities we work with in Canada, Australia, Latin America, the USA, New Zealand and to a lesser extent Scandinavia have developed their own culturally-informed services, focusing on the needs of their own community members. This paper discusses Indigenous healthcare innovations from an international perspective, and showcases Indigenous health system innovations that emerged in Canada (the First Nation Health Authority) and Colombia (Anas Wayúu). These case studies serve as examples of Indigenous-led innovations that might serve as models to other communities. The analysis we present suggests that when opportunities arise, Indigenous communities can and will mobilize to develop Indigenous-led primary healthcare services that are well managed and effective at addressing health inequities. Sustainable funding and supportive policy frameworks that are harmonized across international, national and local levels are required for these organizations to achieve their full potential. In conclusion, this paper demonstrates the value of supporting Indigenous health system innovations.

Deep wound cultures correlate well with bone biopsy culture in diabetic foot osteomyelitis.

BACKGROUND: Osteomyelitis is a major complication in patients with diabetic foot ulceration. Accurate pathogenic identification of organisms can aid the clinician to a specific antibiotic therapy thereby preventing the need for amputation. METHODS: All diabetic patients with bone biopsy-confirmed osteomyelitis were included into the study: biopsies were performed either during surgical removal of infected bone or percutaneously under guided fluoroscopy through non-infected tissue. The depth and extent of the ulcer was assessed using a sterile blunt metal probe. Deep wound cultures were taken from the wound base after sharp debridement. RESULTS: Of 66 cases of suspected osteomyelitis in 102 joints, 34 patients had both bone biopsies and deep wound cultures over the study period. Thirty two of 34 (94%), had a history of preceding foot ulceration, and in 25 of the cases a positive probe to bone test was recorded. In a high proportion of patients, at least one similar organism was isolated from both the deep wound culture and bone biopsy procedures (25 of 34 cases, 73.5%, p<0.001). When organisms were isolated from both wound cultures and bone biopsies, the identical strain was identified in both procedures in a significant proportion of cases (16 of 25 cases, 64%, p<0.001, total sample analysis in 16 of 34 cases, 47%). CONCLUSIONS: Deep wound cultures correlate well with osseous cultures and provide a sensitive method in assessing and targeting likely pathogens that cause osseous infections. This will help aid the clinician in guiding antibiotic therapy in centers where bone biopsies may not be readily available.