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Background: Limited ankle dorsiflexion has been implicated as a contributing factor to plantar ulceration of the forefoot in diabetes mellitus. The purpose of this study was to compare outcomes for patients with diabetes mellitus and a neuropathic plantar ulcer treated with a total-contact cast with and without an Achilles tendon lengthening. Our primary hypothesis was that the Achilles tendon lengthening would lead to a lower rate of ulcer recurrence.Methods: Sixty-four subjects were randomized into two treatment groups, immobilization in a total-contact cast alone or combined with percutaneous Achilles tendon lengthening, with measurements made before and after treatment, at the seven-month follow-up examination, and at the final follow-up evaluation (a mean [and standard deviation] of 2.1 +/- 0.7 years after initial healing). There were thirty-three subjects in the total-contact cast group and thirty-one subjects in the Achilles tendon lengthening group. There were no significant differences in age, body-mass index, or duration of diabetes between the groups. Outcome measures were time to healing of the ulcer, ulcer recurrence rate, range of dorsiflexion of the ankle, peak torque (strength) of the plantar flexor muscles, and peak plantar pressures on the forefoot.Results: Twenty-nine (88%) of thirty-three ulcers in the total-contact cast group and all thirty ulcers (100%) in the Achilles tendon lengthening group healed after a mean duration (and standard deviation) of 41 +/- 28 days and 58 +/- 47 days, respectively (p > 0.05). (One patient in the Achilles tendon lengthening group died before treatment was completed.) In the first seven months of follow-up, sixteen (59%) of the twenty-seven patients in the total-contact cast group who were available for follow-up and four (15%) of the twenty-seven patients in the Achilles tendon lengthening group who were available for follow-up had an ulcer recurrence (p = 0.001). At the time of the two-year follow-up, twenty-one (81%) of the twenty-six patients in the total-contact cast group and ten (38%) of the twenty-six patients in the Achilles tendon lengthening group had ulcer recurrence (p = 0.002). Compared with the group treated with the total-contact cast, the group treated with Achilles tendon lengthening had increased dorsiflexion and it remained increased at seven months (p < 0.001). Plantar flexor peak torque also decreased after Achilles tendon lengthening (p < 0.004), but it returned to baseline after seven months. Peak plantar pressures on the forefoot during barefoot walking were reduced (p < 0.0002) following Achilles tendon lengthening yet returned to baseline values within seven months after treatment.Conclusions: All ulcers healed in the Achilles tendon lengthening group, and the risk for ulcer recurrence was 75% less at seven months and 52% less at two years than that in the total-contact cast group. Achilles tendon lengthening should be considered an effective strategy to reduce recurrence of neuropathic ulceration of the plantar aspect of the forefoot in patients with diabetes mellitus and limited ankle dorsiflexion (

Background: Decreased muscle volume and increased muscle-associated adipose tissue (MAAT, sum of intra and inter-muscular adipose tissue) of the foot intrinsic muscle compartment are associated with deformity, decreased function, and increased risk of ulceration and amputation in those with diabetic peripheral neuropathy (DPN)., Research Question: What is the muscle quality (normal, abnormal muscle, and adipose volumes) of the DPN foot intrinsic compartment, how does it change over time, and is muscle quality related to gait and foot function?, Methods: Computed tomography was performed on the intrinsic foot muscle compartment of 45 subjects with DPN (mean age: 67.2 ± 6.4 years) at baseline and 3.6 years. Images were processed to obtain volumes of MAAT, highly abnormal, mildly abnormal, and normal muscle. For each category, annual rates of change were calculated. Paired t-tests compared baseline and follow-up. Foot function during gait was assessed using 3D motion analysis and the Foot and Ankle Ability Measure. Correlations between muscle compartment and foot function during gait were analyzed using Pearson's correlations., Results: Total muscle volume decreased, driven by a loss of normal muscle and mildly abnormal muscle (p<0.05). MAAT and the adipose-muscle ratio increased. At baseline, 51.5% of the compartment was abnormal muscle or MAAT, increasing to 55.0% at follow-up. Decreased total muscle volume correlated with greater midfoot collapse during gait (r = -0.40, p = 0.02). Greater volumes of highly abnormal muscle correlated with a lower FAAM score (r = -0.33, p = 0.03)., Significance: Muscle volume loss may progress in parallel with MAAT accumulation, impacting contractile performance in individuals with DPN. Only 48.5% of the DPN intrinsic foot muscle compartment consists of normal muscle and greater abnormal muscle is associated with worse foot function. These changes identify an important target for rehabilitative intervention to slow or prevent muscle deterioration and poor foot outcomes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Type 2 diabetes mellitus (T2DM) is linked to impaired mitochondrial function. Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is a gadolinium-contrast-free 1 H method to assess mitochondrial function by measuring low-concentration metabolites. A CEST MRI-based technique may serve as a non-invasive proxy for assessing mitochondrial health., Hypothesis: A 1 H CEST MRI technique may detect significant differences in in vivo skeletal muscle phosphocreatine (SMPCr) kinetics between healthy volunteers and T2DM patients undergoing standardized isometric exercise., Study Type: Cross-sectional study., Subjects: Seven subjects without T2DM (T2DM-) and seven age, sex, and BMI-matched subjects with T2DM (T2DM+)., Field Strength/sequence: Single-shot rapid acquisition with refocusing echoes (RARE) and single-shot gradient-echo sequences, 3 T., Assessment: Subjects underwent a rest-exercise-recovery imaging protocol to dynamically acquire SMPCr maps in calf musculature. Medial gastrocnemius (MG) and soleus SMPCr concentrations were plotted over time, and SMPCr recovery time, τ , was determined. Mitochondrial function index was calculated as the ratio of resting SMPCr to τ . Participants underwent a second exercise protocol for imaging of skeletal muscle blood flow (SMBF), and its association with SMPCr was assessed., Statistical Tests: Unpaired t-tests and Pearson correlation coefficient. A P value <0.05 was considered statistically significant., Results: SMPCr concentrations in MG and soleus displayed expected declines during exercise and returns to baseline during recovery. τ was significantly longer in the T2DM+ cohort (MG 83.5 ± 25.8 vs. 54.0 ± 21.1, soleus 90.5 ± 18.9 vs. 51.2 ± 14.5). The mitochondrial function index in the soleus was significantly lower in the T2DM+ cohort (0.33 ± 0.08 vs. 0.66 ± 0.19). SMBF was moderately correlated with the SMPCr in T2DM-; this correlation was not significant in T2DM+ (r = -0.23, P = 0.269)., Conclusion: The CEST MRI method is feasible for quantifying SMPCr in peripheral muscle tissue. T2DM+ individuals had significantly lower oxidative capacities than T2DM- individuals. In T2DM, skeletal muscle metabolism appeared to be decoupled from perfusion., Level of Evidence: 1 TECHNICAL EFFICACY: Stage 1., (© 2023 International Society for Magnetic Resonance in Medicine.)

Quantitative MRI (qMRI) measures are useful in assessing musculoskeletal tissues, but application to tendon has been limited. The purposes of this study were to optimize, identify sources of variability, and establish reproducibility of qMRI to assess Achilles tendon. Additionally, preliminarily estimates of effect of tendon pathology on qMRI metrics and structure-function relationships between qMRI measures and ankle performance were examined. T1, T1ρ, T2, and T2* maps of the Achilles tendon were obtained using a 3T MRI scanner. In participants with asymptomatic tendons (n = 21), MRI procedures were repeated twice, and region of interest selection was performed by three raters. Variance decomposition and reproducibility statistics were completed. To estimate the effect of pathology, qMRI measures from individuals with asymptomatic tendons were compared to qMRI measures from a pilot group of individuals with Achilles tendinopathy (n = 7). Relationships between qMRI and ankle performance measures were assessed. Between-participant variation accounted for the majority of variability (46.7%-64.0%) in all qMRI measures except T2*. ICCs met or exceeded 0.7 for all qMRI measures when averaged across raters or scans. Relaxation times were significantly longer in tendinopathic tendons (mean (SD) T1: 977.8 (208.6) ms, T1ρ: 35.4 (7.1) ms, T2: 42.8 (7.9) ms, T2*: 14.1 (7.6) ms, n = 7) compared to asymptomatic control tendons (T1: 691.7 (32.4) ms, T1ρ: 24.0 (3.6) ms, T2: 24.4 (7.5) ms, T2*: 9.5 (3.4) ms, n = 21) (p < 0.011 for all comparisons). T1 related to functional performance measures in symptomatic and asymptomatic groups. Study findings suggest that qMRI is reliable to assess the Achilles tendon. qMRI quantitatively assesses the presence of tendon pathology and relates to functional performance outcomes, supporting the utility of incorporating qMRI in research and clinic., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Quantitative magnetic resonance imaging (qMRI) measures have provided insights into the composition, quality, and structure-function of musculoskeletal tissues. Low signal-to-noise ratio has limited application to tendon. Advances in scanning sequences and sample positioning have improved signal from tendon allowing for evaluation of structure and function. The purpose of this study was to elucidate relationships between tendon qMRI metrics (T1, T2, T1ρ and diffusion tensor imaging [DTI] metrics) with tendon tissue mechanics, collagen concentration and organization. Sixteen human Achilles tendon specimens were collected, imaged with qMRI, and subjected to mechanical testing with quantitative polarized light imaging. T2 values were related to tendon mechanics [peak stress (r sp  = 0.51, p = 0.044), equilibrium stress (r sp  = 0.54, p = 0.033), percent relaxation (r sp  = -0.55, p = 0.027), hysteresis (r sp  = -0.64, p = 0.007), linear modulus (r sp  = 0.67, p = 0.009)]. T1ρ had a statistically significant relationship with percent relaxation (r = 0.50, p = 0.048). Collagen content was significantly related to DTI measures (range of r = 0.56-0.62). T2 values from a single slice of the midportion of human Achilles tendons were strongest predictors of tendon tensile mechanical metrics. DTI diffusivity indices (mean diffusivity, axial diffusivity, radial diffusivity) were strongly correlated with collagen content. These findings build on a growing body of literature supporting the feasibility of qMRI to characterize tendon tissue and noninvasively measure tendon structure and function. Statement of Clinical Significance: Quantitative MRI can be applied to characterize tendon tissue and is a noninvasive measure that relates to tendon composition and mechanical behavior., (© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Objectives: The purpose of this study was to leverage a magnetic resonance imaging (MRI) approach to characterize foot perfusion distribution in patients with diabetes, with or without foot ulcers, and determine the ability of the regional perfusion measurements to identify ulcer-healing status., Methods: Three groups of participants (n = 15 / group) were recruited: controls (without diabetes), type II diabetes, and type II diabetes with foot ulcers. All participants underwent MRI evaluating foot perfusion in three muscle layers (from plantar to dorsal) at rest and during a standardized toe-flexion exercise. The exercise perfusion and perfusion reserve values were analyzed around and away from ulcers. Participants with foot ulcers were followed up 3 months after the MRI exams to determine the foot healing status., Results: Foot plantar muscle perfusion reserves were progressively lower from controls to diabetes, and to diabetes with foot ulcers (e.g., 2.58 ± 0.67, 1.48 ± 0.71, 1.12 ± 0.35, p < 0.001). In controls, the plantar layer had significantly higher perfusion reserve than the dorsal layer, whereas in either diabetes group, there was no significant difference in perfusion reserve among muscle layers. Using the ratio of total exercise perfusion around ulcers to that away from ulcers, the sensitivity and specificity to differentiate healing from non-healed ulcers were 100% and 86%, respectively., Conclusions: Our study reveals significantly different foot perfusion distribution among controls, diabetes, and diabetes with foot ulcers. The prognostic value of MRI regional perfusion assessments has the potential to monitor interventions to improve ulcer healing outcomes., Key Points: • Contrast-free MRI permits quantitative assessment of regional foot muscle perfusion at rest and during isometric exercise. • Patients with diabetes and foot ulcers, without clinical evidence of peripheral arterial disease, had significantly impaired foot muscle perfusion and perfusion reserve. • Regional foot perfusion distribution may be used to predict the short-term healing status of foot ulcers in diabetes., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Background: In people with diabetes (DM) and peripheral neuropathy (PN), loss of bone mineral density (BMD) in the tarsals and metatarsals contribute to foot complications; however, changes in BMD of the calcaneal bone is most commonly reported. This study reports rate of change in BMD of all the individual bones in the foot, in participants with DM and PN. Our aim was to investigate whether the rate of BMD change is similar across all the bones of the foot., Methods: Participants with DM and PN (n = 60) were included in this longitudinal cohort study. Rate of BMD change of individual bones was monitored using computed tomography at baseline and 6 months, 18 months, and 3-4 years from baseline. Personal factors (age, sex, medication use, step count, sedentary time, and PN severity) were assessed. A random coefficient model estimated rate of change of BMD in all bones and Pearson correlation tested relationships between personal factor variables and rate of BMD change., Results: Mean and calcaneal BMD decreased over the study period (p < 0.05). Individual tarsal and metatarsal bones present a range of rate of BMD change (-0.3 to -0.9%/year) but were not significantly different than calcaneal BMD change. Only age showed significant correlation with BMD and rate of BMD change., Conclusion: The rate of BMD change did not significantly differ across different foot bones at the group level in people with DM and PN without foot deformity. Asymmetric BMD loss between individual bones of the foot and aging may be indicators of pathologic changes and require further investigation., Trial Registration: Metatarsal Phalangeal Joint Deformity Progression-R01. Registered 25 November 2015, https://clinicaltrials.gov/ct2/show/NCT02616263., (© 2023. The Author(s).)

Background: Stay-at-home orders associated with the SARS-CoV-2 (COVID-19) pandemic were particularly important for older adults with type 2 diabetes, at risk for severe COVID-19 complications. In response, research shifted to remote telehealth methodology. Study participant interests, equipment needs, and ability to adapt methods to the remote/telehealth environment were unknown. Study purposes to assess (1) resource needs (internet/devices accessibility), (2) future telehealth interests, and (3) ability to adapt common research and clinical measures of glycemic control, physical function, activity measures, and quality of life outcomes to a telehealth setting., Method: Twenty-one participants with type 2 diabetes and peripheral neuropathy were recruited from a longitudinal study (11 female; age: 66.3 ± 8.3 years; DM: 15.1 ± 8.7 years). Technology needs and future telehealth interests were assessed. A glycemic measure (HbA1c), a five-times chair rise, a one-week activity monitor, and surveys (self-efficacy, depression, and balance) were collected. All aspects of the study were completed remotely over email and video/phone call., Results: Twelve participants used computers; nine used phones for study completion. Participants had the following resource needs: connectivity (n = 3), devices (n = 6), and technical support (n = 12). Twenty people expressed interest in participating in future telehealth studies related to balance, exercise, and diabetes management. Methodological considerations were primarily the need for assistance for participants to complete the home HbA1c test, five-time chair rise, wearable activity monitoring, and surveys., Conclusions: Older adults with type 2 diabetes and peripheral neuropathy would need technological and personal assistance (connection, device, guidance) to complete a long-term telehealth intervention. Despite technology needs, participants were interested in telehealth interventions., Clinical Trial: Parent study, "Metatarsal Phalangeal Joint Deformity Progression-R01 (NCT02616263) is registered at https://clinicaltrials.gov/.

Background: A heel rise task can be used to evaluate midfoot and ankle movement dysfunction in people with diabetes mellitus and peripheral neuropathy. Quantifying movement coordination during heel rise is important to better understand potentially detrimental movement strategies in people with foot pathologies; however, coordination and the impact of limited excursion on coordination is not well-understood in people with diabetes., Methods: Sixty patients with diabetes mellitus and peripheral neuropathy, and 22 older and 25 younger controls performed single-limb heel rise task. Midfoot (forefoot relative to hindfoot) sagittal and ankle (hindfoot relative to shank) sagittal and frontal kinematics were measured and normalized to time (0 to 100%). Cross-correlation coefficients were calculated across individuals in each group. A graphical illustration was used to interpret the relationship of midfoot and ankle excursion and cross-correlation coefficient during heel rise., Findings: People with diabetes mellitus and peripheral neuropathy showed significantly lower midfoot and ankle cross-correlation coefficients during heel rise compared to older controls (p = 0.003-0.007). There was no difference in the midfoot and ankle cross-correlation coefficients during heel rise for the older and younger controls (p = 0.059-0.425). The graphic data illustrated a trend of greater excursion of two joints and a higher cross-correlation coefficient. Some individuals with lower excursion showed a high cross-correlation coefficient., Interpretation: Foot pathologies, but not aging, impairs midfoot and ankle movement coordination during heel rise task. Investigating both movement coordination as well as joint excursion would better inform and characterize the dynamic movements of midfoot and ankle during heel rise task., (Copyright © 2022. Published by Elsevier Ltd.)

Purpose: Midfoot movement dysfunction, as measured by heel rise performance, is associated with midfoot deformity in people with diabetes and peripheral neuropathy. Understanding contributors of midfoot movement dysfunction may help clinicians understand deformity progression. The purpose of this study was to determine the factors associated with midfoot angle at peak heel rise., Methods: The outcomes of fifty-eight participants with type 2 diabetes mellitus and peripheral neuropathy were analyzed. Midfoot (forefoot on hindfoot) sagittal kinematics during unilateral heel rise task were measured using 3-dimensional motion analysis. A multivariate linear regression model was used to predict midfoot sagittal movements at peak heel rise. Independent variables that were entered in the model were (in order of entry): age, body mass index, intrinsic foot muscle volume, and maximum available midfoot plantarflexion range of motion. Intrinsic foot muscle volume was obtained from magnetic resonance imaging and maximum available midfoot motion was measured during non-weightbearing plantarflexion using 3-dimensional motion analysis., Results: Body mass index (R 2 = 30.5%, p < 0.001) and maximum available midfoot plantarflexion range of motion (R 2 = 10.9%, p = 0.001) were significant factors that accounted for 41.4% of variance of midfoot angle at peak heel rise, while age and intrinsic foot muscle volume were not significant predictors., Conclusions: Greater body mass index and less available midfoot plantarflexion range of motion were associated with greater midfoot movement dysfunction. These two significant predictors are potentially modifiable, suggesting possible improvements in midfoot movements with reduction in body weight and increasing midfoot plantarflexion range of motion. Health care professionals should consider patient's weight and joint motion when prescribing foot exercise(s) to prevent excessive midfoot collapse during weightbearing tasks., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Volumetric measures of intrinsic foot muscle and intermuscular adipose tissue (IMAT) infiltration are important in understanding foot injury and disease. We questioned whether measures of muscle and fat derived from computed tomography (CT) and magnetic resonance (MR) would be comparable., Methods: This study determined the correlation and level of agreement between CT and MR measurements of foot muscle and IMAT from 32 subjects with diabetes and peripheral neuropathy. Volumetric CT and DIXON 3T MR scans were obtained. Intermuscular adipose tissue and muscle volumes used to create the IMAT to muscle ratio were obtained by segmenting the forefoot muscle compartment from each modality., Results: Computed tomography IMAT ratios were significantly correlated (r = 0.85, P < 0.0001) with MR IMAT ratios. Computed tomography and MR IMAT ratio mean difference between CT and MR was small (0.044 unit, Bland-Altman plots)., Conclusions: The CT and MR IMAT ratio measurements were highly correlated, indicating both modalities represent tissue quantification similarly.Level of Evidence: 2Technical Efficacy: 1., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Diabetes is associated with impaired tendon homeostasis and subsequent tendon dysfunction, but the mechanisms underlying these associations is unclear. Advanced glycation end-products (AGEs) accumulate with diabetes and have been suggested to alter tendon function. In vivo imaging in humans has suggested collagen disorganization is more frequent in individuals with diabetes, which could also impair tendon mechanical function. The purpose of this study was to examine relationships between tendon tensile mechanics in human Achilles tendon with accumulation of advanced glycation end-products and collagen disorganization. Achilles tendon specimens (n = 16) were collected from individuals undergoing lower extremity amputation or from autopsy. Tendons were tensile tested with simultaneous quantitative polarized light imaging to assess collagen organization, after which AGEs content was assessed using a fluorescence assay. Moderate to strong relationships were observed between measures of collagen organization and tendon tensile mechanics (range of correlation coefficients: 0.570-0.727), whereas no statistically significant relationships were observed between AGEs content and mechanical parameters (range of correlation coefficients: 0.020-0.210). Results suggest that the relationship between AGEs content and tendon tensile mechanics may be masked by multifactorial collagen disorganization at larger length scales (i.e., the fascicle level)., (© 2021. The Author(s).)

Diagnostic imaging modalities, like computed tomography (CT) and magnetic resonance imaging (MRI), can be used to assess in vivo muscle quality. Quantitative assessment using these techniques is time-intensive and costly due in part to extensive post-processing needs. The purpose of this study was to identify whether a subset of slices on CT and MRI would yield comparable results to the full number of slices for a measure of muscle quality (muscle deterioration ratio = fat volume/muscle volume) in the foot intrinsic muscles of people with diabetes and peripheral neuropathy. CT (0.6 mm slice thickness) and MRI (3.5 mm slice thickness) scans were obtained using previously described methods. The total number of slices acquired during the scan was compared to several conditions using a portion of slices. Bland-Altman plots and Lin's concordance correlation coefficient were used to test agreement. Any condition using at least three slices yielded substantial to almost perfect agreement with the total number of slices on both CT and MRI (Range of Lin's concordance correlation coefficient: 0.947-0.999). Using a single slice in the middle of the region of interest demonstrated poor to moderate agreement with the total number of slices. The findings of this study suggest that using a limited number of slices to quantify muscle deterioration ratio on CT or MRI is a viable way to balance the combined need for measurement accuracy with feasibility in research and clinical settings., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Diabetic peripheral neuropathy (DPN) is the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after the exclusion of other causes. It is associated with pain, paresthesia, sensory loss, muscle atrophy with fat infiltration, and muscular dysfunction typically starting distally in the feet and progressing proximally. Muscle deterioration within the leg and foot can lead to muscle dysfunction, reduced mobility, and increases the risk of disability, ulceration, and amputation. Exercise training is an established method for increasing the different components of physical fitness, including enhancing body composition and improving neuromuscular strength. A number of experimental studies have utilized exercise training to treat various impairments associated with DPN, such as nerve conduction velocity, pain tolerance, and balance. However, the broad spectrum of exercise training modalities implemented and differences in target outcome measurements have made it difficult to understand the efficacy of exercise training interventions or provide appropriate exercise prescription recommendations. Therefore, the aims of this review were to (1) briefly describe the pathophysiology of DPN and (2) discuss the effects of exercise training interventions on sensorimotor, metabolic, and physical functions in people with DPN.

Patients with diabetes mellitus (DM) are more likely to have densely calcified lesions in the below-the-knee tibial arteries. However, the relationship between peripheral arterial calcification and local skeletal muscle perfusion has not been explored. Thirty subjects were prospectively recruited into three groups in this pilot study: (1) Non-DM: 10 people without DM; (2) DM, ABI < 1.3: 10 people with DM and normal ankle-brachial index (ABI) (0.9-1.3); and (3) DM, ABI ⩾ 1.3: 10 people with DM and ABI ⩾ 1.3. All subjects underwent calf perfusion measurements at rest and during an isometric plantarflexion contraction exercise within the magnetic resonance imaging (MRI) system. The noncontrast MRI techniques were applied to quantitatively assess skeletal muscle blood flow (SMBF) and oxygen extraction fraction (SMOEF) in medial gastrocnemius and soleus muscles. Both SMBF and SMOEF reserves were calculated as the ratio of the exercise value to the resting value. Exercise SMBF and SMOEF values in the medial gastrocnemius muscle were lower in the two DM groups than in the non-DM group ( p < 0.05). The SMBF reserve in medial gastrocnemius was significantly lower in the DM, ABI ⩾ 1.3 group compared to the DM, ABI < 1.3 group ( p < 0.05). This study demonstrates that people with DM and calcified arteries had lower perfusion in gastrocnemius muscle compared to those without DM and those with DM and a normal ABI.

Objective: To evaluate regional calf muscle microcirculation in people with diabetes mellitus (DM) with and without foot ulcers, compared to healthy control people without DM, using contrast-free magnetic resonance imaging methods., Methods: Three groups of subjects were recruited: non-DM controls, DM, and DM with foot ulcers (DM + ulcer), all with ankle brachial index (ABI) > 0.9. Skeletal muscle blood flow (SMBF) and oxygen extraction fraction (SMOEF) in calf muscle were measured at rest and during a 5-min isometric ankle plantarflexion exercise. Subjects completed the Yale physical activity survey., Results: The exercise SMBF (ml/min/100 g) of the medial gastrocnemius muscle were progressively impaired: 63.7 ± 18.9 for controls, 42.9 ± 6.7 for DM, and 36.2 ± 6.2 for DM + ulcer, p  < 0.001. Corresponding exercise SMOEF was the lowest in DM + ulcers (0.48 ± 0.09). Exercise SMBF in the soleus muscle was correlated moderately with the Yale physical activity survey ( r  = 0.39, p  < 0.01)., Conclusions: Contrast-free MR imaging identified progressively impaired regional microcirculation in medial gastrocnemius muscles of people with DM with and without foot ulcers. Exercise SMBF in the medial gastrocnemius muscle was the most sensitive index and was associated with HbA1c. Lower exercise SMBF in the soleus muscle was associated with lower Yale score.

Objective: The objective of this study was to examine the effects of diabetes mellitus and peripheral neuropathy (DMPN), limited joint mobility, and weight-bearing on foot and ankle sagittal movements and characterize the foot and ankle position during heel rise., Methods: Sixty people with DMPN and 22 controls participated. Primary outcomes were foot (forefoot on hindfoot) and ankle (hindfoot on shank) plantar-flexion/dorsiflexion angle during 3 tasks: unilateral heel rise, bilateral heel rise, and non-weight-bearing ankle plantar flexion. A repeated-measures analysis of variance and Fisher exact test were used., Results: Main effects of task and group were significant, but not the interaction in both foot and ankle plantar flexion. Foot and ankle plantar flexion were less in people with DMPN compared with controls in all tasks. Both DMPN and control groups had significantly less foot and ankle plantar flexion with greater weight-bearing; however, the linear trend across tasks was similar between groups. The DMPN group had a greater percentage of individuals in foot and/or ankle dorsiflexion at peak unilateral heel rise compared with controls, but the foot and ankle position was similar at peak bilateral heel rise between DMPN and control groups., Conclusion: Foot and ankle plantar flexion is less in people with DMPN. Less plantar flexion in non-weight-bearing suggests that people with DMPN have limited joint mobility. However, peak unilateral and bilateral heel rise is less than the available plantar flexion range of motion measured in non-weight-bearing, indicating that limited joint mobility does not limit heel rise performance. A higher frequency of people with DMPN are in foot and ankle dorsiflexion at peak unilateral heel rise compared with controls, but the position improved with lower weight-bearing., Impact: Proper resistance should be considered with physical therapist interventions utilizing heel rise because foot and ankle plantar flexion position could be improved by reducing the amount of weight-bearing., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Diabetes mellitus (DM) with peripheral neuropathy (PN) results in foot deformity increasing ulceration, joint dislocation, and amputation risk. This study describes the frequency and severity of foot and ankle musculoskeletal abnormalities and their relationship to radiographic alignment in people with DMPN with (DMPN + MCD) and without (DMPN - MCD) medial column deformity (MCD) compared to age- and body mass index-matched controls without DMPN or MDC., Methods: DMPN + MCD (n = 11), DMPN - MCD (n = 12), and controls (n = 12) were studied. A radiologist scored foot and ankle magnetic resonance images (MRI) for abnormalities in tendons/fascia, ligaments, muscles, joints, and bones. Higher scores represent greater abnormalities. Foot alignment was measured from lateral weightbearing radiographs. Frequency of abnormalities between groups and relationships between abnormalities and foot alignment in the combined group (n = 35) were examined., Results: DMPN + MCD had higher total muscle, joint, and bone scores compared to controls and higher total joint scores than DMPN - MCD. DMPN - MCD had higher total muscle scores than controls. DMPN + MCD higher bone and joint scores were driven by increased frequency of osteophytes, cartilage damage, focal bone marrow edema, new bone formation, and subchondral cysts. Significant correlations included cuboid height and total bone and joint scores (ρ = -0.37 and ρ = -0.40, respectively) and talar declination angle and total joint score (ρ = 0.38)., Conclusion: High contrast resolution MRI allowed identification of structural lesions of the foot affecting the cartilage surfaces, bone marrow, and soft tissue supports in patients with DMPN + MCD. As expected, the presence of bone and joint lesions on MRI were strongly associated with DMPN + MCD; surprisingly, although the sample is small, lesions of the soft tissue supports were not associated with MCD. While MRI is not done routinely to investigate MCD, opportunistic use of the information from MRI done for the common clinical indications may allow early identification of the structural lesions associated with MCD and facilitate early, aggressive therapy., Level of Evidence: III., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: A toe-extension movement pattern may contribute to metatarsophalangeal joint deformity and ulceration in people with diabetes. We sought to quantify the relationship between toe extension magnitude and variability during three functional tasks (ankle range of motion, sit to stand, walking) with metatarsophalangeal joint deformity, and identify potential mechanisms associated with a toe-extension movement pattern., Methods: Individuals with diabetes and peripheral neuropathy were included (n = 60). Metatarsophalangeal joint deformity was assessed using computed tomography (CT). Toe-extension movement was quantified using 3-dimensional motion capture. Linear regression was used to investigate the role of toe-extension movement pattern on metatarsophalangeal joint deformity. Regression analysis was used to identify mechanisms (neuropathy severity, foot intrinsic muscle deterioration ratio, ankle dorsiflexion range of motion) contributing to toe-extension movement pattern., Findings: Toe extension with each functional task as well as the mean and coefficient of variation across all tasks were significantly related to metatarsophalangeal joint deformity (range of correlation coefficients = (-0.386, 0.692), p ≤ 0.001). Ankle dorsiflexion range of motion was associated with mean toe extension across all tasks (r sp  = -0.282, p = 0.029). Neuropathy severity and foot intrinsic muscle deterioration ratio were associated with toe extension variability (r sp  = -0.373, p = 0.003 and r sp  = -0.266, p = 0.043; respectively)., Interpretation: Greater magnitude and lower variability of a toe-extension movement pattern was found to be associated with metatarsophalangeal joint deformity. These findings may support clinical assessment and treatment of movement across more than one task., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Midfoot and ankle movement dysfunction in people with diabetes mellitus and peripheral neuropathy (DMPN) is associated with midfoot deformity and increased plantar pressures during gait. If midfoot and ankle motion during heel rise and push-off of gait have similar mechanics, heel rise performance could be a clinically feasible way to identify abnormal midfoot and ankle function during gait., Research Question: Is midfoot and ankle joint motion during a heel rise associated with midfoot and ankle motion at push-off during gait in people with DMPN?, Methods: Sixty adults with DMPN completed double-limb heel rise, single-limb heel rise, and walking. A modified Oxford multi-segment foot model (forefoot, hindfoot, shank) was used to analyze midfoot (forefoot on hindfoot) and ankle (hindfoot on shank) sagittal angle during heel rise and gait. Pearson correlation was used to test the relationship between heel rise and gait kinematic variables (n = 60). Additionally, we classified 60 participants into two subgroups based on midfoot and ankle position at peak heel rise: midfoot and ankle dorsiflexed (dorsiflexed; n = 23) and midfoot and ankle plantarflexed (plantarflexed; n = 20). Movement trajectories of midfoot and ankle motion during single-limb heel rise and gait of the subgroups were examined., Results: Peak double-limb heel rise and gait midfoot and ankle angles were significantly correlated (r = 0.49 and r = 0.40, respectively). Peak single-limb heel rise and gait midfoot and ankle angles were significantly correlated (r = 0.63 and r = 0.54, respectively). The dorsiflexed subgroup, identified by heel rise performance showed greater midfoot and ankle dorsiflexion during gait compared to the plantarflexed subgroup (mean difference between subgroups: midfoot 3°, ankle 3°)., Significance: People with DMPN who fail to plantarflex the midfoot and ankle during heel rise have difficulty plantarflexing the midfoot and ankle during gait. Utilizing a heel rise task may help identify midfoot and ankle dysfunction associated with gait in people with DMPN., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Context: The authors hypothesized that in people with hip-related groin pain, less static ankle dorsiflexion could lead to compensatory hip adduction and contralateral pelvic drop during step-down. Ankle dorsiflexion may be a modifiable factor to improve ability in those with hip-related groin pain to decrease hip/pelvic motion during functional tasks and improve function., Objective: To determine whether smaller static ankle dorsiflexion angles were associated with altered ankle, hip, and pelvis kinematics during step-down in people with hip-related groin pain., Design: Cross-sectional Setting: Academic medical center., Patients: A total of 30 people with hip-related groin pain (12 males and 18 females; 28.7 [5.3] y) participated., Intervention: None., Main Outcome Measures: Weight-bearing static ankle dorsiflexion with knee flexed and knee extended were measured via digital inclinometer. Pelvis, hip, and ankle kinematics during forward step-down were measured via 3D motion capture. Static ankle dorsiflexion and kinematics were compared with bivariate correlations., Results: Smaller static ankle dorsiflexion angles were associated with smaller ankle dorsiflexion angles during the step-down for both the knee flexed and knee extended static measures. Among the total sample, smaller static ankle dorsiflexion angle with knee flexed was associated with greater anterior pelvic tilt and greater contralateral pelvic drop during the step-down. Among only those who did not require a lowered step for safety, smaller static ankle dorsiflexion angles with knee flexed and knee extended were associated with greater anterior pelvic tilt, greater contralateral pelvic drop, and greater hip flexion., Conclusions: Among those with hip-related groin pain, smaller static ankle dorsiflexion angles are associated with less ankle dorsiflexion motion and altered pelvis and hip kinematics during a step-down. Future research is needed to assess the effect of treating restricted ankle dorsiflexion on quality of motion and symptoms in patients with hip-related groin pain.

Introduction: Diabetes mellitus (DM) is associated with systemic musculoskeletal system impairments suggesting concurrent development of lower and upper extremity musculoskeletal problems. This study aims to examine relationships between lower and upper extremity function in people with DM., Methods: Sixty people with type 2 DM and peripheral neuropathy [mean (standard deviation); 67(6) years old, DM duration 14(10) yrs] completed the following measures: 1) Self-reports of function: Foot and Ankle Ability Measure (FAAM; higher = better function) and Shoulder Pain and Disability Index (SPADI; lower = better function), 2) Range of motion (goniometry): ankle dorsiflexion and shoulder flexion, and 3) Strength: unilateral heel rise power (UHR, 3D kinetics) and hand grip dynamometry. Pearson correlations examined associations between lower and upper extremity measures, p < .05., Results: Forty of 60 (67%) reported pain/disability in both the foot/ankle and shoulder and 95% of study participants had some limitation in foot or shoulder function. Significant between extremity correlations: FAAM and SPADI (r = -0.39), ankle dorsiflexion and shoulder flexion range of motion (r = 0.35), and UHR and hand grip strength (r = 0.40). Significant within extremity correlations: FAAM and UHR (r = .47) and SPADI with shoulder flexion (r = -0.44)., Conclusion: Upper and lower extremity inter- and intra-relationships indicate systemic musculoskeletal impairments in people with DM. Healthcare practitioners should consider the potential for concurrent and disabling musculoskeletal problems in people with DM., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Decreased lean muscle mass in the lower extremity in diabetic peripheral neuropathy (DPN) is thought to contribute to altered joint loading, immobility, and disability. However, the mechanism behind this loss is unknown and could derive from a reduction in size of myofibers (atrophy), destruction of myofibers (degeneration), or both. Degenerative changes require participation of muscle stem (satellite) cells to regenerate lost myofibers and restore lean mass. Determining the degenerative state and residual regenerative capacity of DPN muscle will inform the utility of regeneration-targeted therapeutic strategies., Methods: Biopsies were acquired from 2 muscles in 12 individuals with and without diabetic neuropathy undergoing below-knee amputation surgery. Biopsies were subdivided for histological analysis, transcriptional profiling, and satellite cell isolation and culture., Results: Histological analysis revealed evidence of ongoing degeneration and regeneration in DPN muscles. Transcriptional profiling supports these findings, indicating significant upregulation of regeneration-related pathways. However, regeneration appeared to be limited in samples exhibiting the most severe structural pathology as only extremely small, immature regenerated myofibers were found. Immunostaining for satellite cells revealed a significant decrease in their relative frequency only in the subset with severe pathology. Similarly, a reduction in fusion in cultured satellite cells in this group suggests impairment in regenerative capacity in severe DPN pathology., Conclusion: DPN muscle exhibited features of degeneration with attempted regeneration. In the most severely pathological muscle samples, regeneration appeared to be stymied and our data suggest that this may be partly due to intrinsic dysfunction of the satellite cell pool in addition to extrinsic structural pathology (eg, nerve damage)., Clinical Relevance: Restoration of DPN muscle function for improved mobility and physical activity is a goal of surgical and rehabilitation clinicians. Identifying myofiber degeneration and compromised regeneration as contributors to dysfunction suggests that adjuvant cell-based therapies may improve clinical outcomes.

The underlying factors contributing to metatarsophalangeal joint deformity, a known precursor to skin breakdown in individuals with diabetes mellitus (DM), is likely to involve multiple body systems. The purpose of this cross-sectional study was to identify multi-system factors associated with metatarsophalangeal joint deformity in individuals with type 2 DM and peripheral neuropathy ( n = 60). Metatarsophalangeal joint deformity was quantified with a computed tomography (CT) scan. System biomarkers included the musculoskeletal system (foot intrinsic muscle deterioration, tarsal/metatarsal bone mineral density, ankle dorsiflexion, metatarsophalangeal extension movement during a sit to stand task); the vascular system (ankle-brachial index); and the endocrine/immune systems (high sensitivity C-reactive protein, skin intrinsic fluorescence, and hemoglobin A1C). Muscle deterioration ( r = 0.27), bone density ( r = -0.35), metatarsophalangeal extension movement ( r = 0.50), maximum dorsiflexion ( r = -0.31), and ankle-brachial index ( r = 0.33) were related to metatarsophalangeal joint deformity ( p < 0.05). Bone mineral density and metatarsophalangeal extension movement were retained in a regression model relating to deformity ( R 2 = 0.34). All musculoskeletal system biomarkers and the ankle-brachial index demonstrated weak to moderate relationships to metatarsophalangeal joint deformity. Bone mineral density of the tarsal/metatarsal bones and extending the toes during a sit to stand task were the two strongest factors associated with metatarsophalangeal joint deformity. Evaluation and management of foot bone mineral density and toe extension movement pattern could reduce metatarsophalangeal joint deformity and the risk of skin breakdown and subsequent amputation.

Background: In 2014, the total prevalence of diabetes was estimated to be 422 million people worldwide. Due to the aging population and continued increase in obesity rates, the prevalence is expected to rise to 592 million by 2035. Diabetes can lead to several complications, including cardiovascular disease, stroke, peripheral arterial disease, nephropathy, neuropathy, retinopathy, lower extremity amputation, and musculoskeletal impairments., Clinical Question: Up to 80% of patients referred for outpatient physical therapy have diabetes or are at risk for diabetes, providing an opportunity for physical therapists to intervene. Therefore, we asked, "What is the role of physical therapists in fighting the diabetes epidemic?", Key Results: Physical therapists commonly prescribe physical activity for the treatment of diabetes and other chronic diseases, such as cardiovascular disease and osteoarthritis. Physical therapists may also screen for risk factors for diabetes and diabetes-related complications and modify traditional musculoskeletal exercise prescription accordingly. Physical therapists must advocate for regular physical activity as a key component of the treatment of chronic diseases in all patient interactions., Clinical Application: This commentary (1) describes the diabetes epidemic and the health impact of diabetes and diabetes-related complications, (2) highlights the physical therapist's role as front-line provider, and (3) provides recommendations for physical therapists in screening for diabetes risk factors and diabetes-related complications and considerations for patient management. We focus on type 2 diabetes. J Orthop Sports Phys Ther 2020;50(1):5-16. Epub 28 Nov 2019. doi:10.2519/jospt.2020.9154 .

Background: Impaired foot perfusion is a primary contributor to foot ulcer formation. There is no existing device nor method that can be used to measure local foot perfusion during standardized foot muscle exercise in an MRI environment., Purpose: To develop a new MRI-compatible foot dynamometer and MRI methods to characterize local perfusion in diabetic feet with ulcers., Study Type: Prospective., Population/subjects: Seven participants without diabetes and 10 participants with diabetic foot ulcers., Field Strength/sequence: 3.0T, arterial spin labeling (ASL)., Assessments: Using a new MRI-compatible foot dynamometer, all participants underwent MRI ASL perfusion assessment at rest and during a standardized toe-flexion exercise. The participants without diabetes were scanned twice to assess the reproducibility of perfusion measurements. The absolute perfusion and perfusion reserve values were compared between two groups and between regions near ulcers (peri-ulcer) and away from ulcers (away-ulcer)., Statistical Tests: Bland-Altman methods for the calculation of coefficient of repeatability (CR) and two-sided and unpaired Student's t-test to compare multiple differences., Results: The perfusion reserves measured had the best reproducibility (CR in medial region: 1.6, lateral region: 0.9). The foot perfusion reserve was significantly lower in the participants with diabetes compared with the participants without diabetes (1.34 ± 0.32, 95% confidence interval [CI]: 1.1, 1.58 vs. 1.76 ± 0.31, 95% CI: 1.53, 1.98, P = 0.02). Both peri-ulcer exercise perfusion (8.7 ± 3.9 ml/min/100g) and perfusion reserve (1.07 ± 0.39, 95% CI: 0.78, 1.35) were significantly lower than away-ulcer exercise perfusion (12.7 ± 3.8 ml/min/100g, P = 0.02) and perfusion reserve (1.39 ± 0.37, 95% CI: 1.11, 1.66, P = 0.03), respectively., Data Conclusion: This study demonstrates intravenous contrast-free methods for local perfusion in feet with ulcers by standardized exercise-based MRI. Ischemia regions around foot ulcers can be quantitatively distinguished from normal perfused muscle regions., Level of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:474-480., (© 2018 International Society for Magnetic Resonance in Medicine.)

Background: Diffusion tensor imaging (DTI) has been used to characterize calf skeletal muscle architecture., Purpose: To assess the diffusional properties of the calf muscles of subjects with and without diabetes, at rest and during isometric plantarflexion exercise., Study Type: Prospective., Subjects: Twenty-six subjects in two groups: 13 healthy and 13 subjects with type 2 diabetes (DM); each group consisted of seven females and six males., Field Strength/sequence: 3T/2D single-shot spin echo planar imaging., Assessment: Fractional anisotropy (FA), mean diffusivity (MD), diffusion eigenvalues, and fiber tracking indices were obtained from the medial gastrocnemius (MG), lateral gastrocnemius (LG), and soleus (SOL) muscles of the calf at rest and during isometric plantarflexion exercise., Statistical Tests: We used a combination of nonparametric (Wilcoxon) and parametric (t-test) statistical assessments., Results: The medial gastrocnemius muscle had more indices with significant differences between the two groups (six indices with P < 0.05) than did the lateral gastrocnemius (three indices with P < 0.05) and soleus muscles (only one index with P < 0.05). While the healthy group showed elevated MD values from rest to exercise (MG = 5.83%, LG = 13.45%, and SOL = 11.68%), the diabetic MD showed higher increases (MG = 19.74%, LG = 29.31%, and SOL = 20.84%) that were different between groups (MG: P = 0.009, LG: P = 0.037, and SOL: P = 0.049)., Data Conclusion: Our results indicate considerable diffusional changes between healthy subjects and subjects with diabetes at rest and during isometric plantarflexion exercise in the calf muscles. The medial gastrocnemius muscle displayed the most diffusion sensitivity to diabetes-related microstructural changes., Level of Evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1285-1295., (© 2018 International Society for Magnetic Resonance in Medicine.)

Background: People with diabetes are at high risk for shoulder pain, limited joint mobility, and adhesive capsulitis., Objective: The objective of this study was to evaluate the effects of a shoulder movement intervention (ShoMo) compared to a wellness intervention on the primary outcomes of active shoulder flexion and reported Shoulder Pain and Disability Index (SPADI) measured after intervention and 9 months later., Design: The design was a prospective, randomized, controlled clinical trial., Setting: The setting was a research center at an academic medical center., Participants: Fifty-two participants with type 2 diabetes and shoulder pain or limited motion were randomized to a group receiving ShoMo (N = 27; mean age = 59.3; SD = 7.0) or a group receiving wellness activities (N = 25; mean age = 57.9; SD = 7.7)., Intervention: The ShoMo group received instruction in a progressive, active shoulder movement program. The wellness group received instruction in diabetes management., Measurements: Measurements were made at baseline, after 3 months of intervention, and at 6, 9, and 12 months after baseline., Results: After intervention, the ShoMo group had a 7.2-degree increase in active shoulder flexion compared with the wellness group (95% CI = 0.9-13.5°), but there was no difference at subsequent follow-ups. The ShoMo group showed a 12.7-point improvement in the SPADI score compared to the wellness group after intervention (95% CI = 1.1-24.3), which remained better than the wellness group 9 months later., Limitations: The number of participants and duration of follow-up were inadequate to determine if intervention can help to prevent future severe shoulder problems., Conclusions: A progressive shoulder movement program can have meaningful effects on active motion and symptoms in people with type 2 diabetes and mild-to-moderate shoulder symptoms, with symptom improvement lasting at least 9 months.

Background: Neuropathic foot impairments treated with immobilization and off-loading result in osteolysis. In order to prescribe and optimize rehabilitation programs after immobilization we need to understand the magnitude of pedal osteolysis after immobilization and the time course for recovery., Objective: To determine differences in a) foot skin temperature; b) calcaneal bone mineral density (BMD) after immobilization; c) calcaneal BMD after 33-53weeks of recovery; and d) percent of feet classified as osteopenic or osteoporotic after recovery in participants with neuropathic plantar ulcers (NPU) compared to Charcot neuroarthropathy (CNA)., Methods: Fifty-five participants with peripheral neuropathy were studied. Twenty-eight participants had NPU and 27 participants had CNA. Bilateral foot skin temperature was assessed before immobilization and bilateral calcaneal BMD was assessed before immobilization, after immobilization and after recovery using quantitative ultrasonometry., Results: Before immobilization, skin temperature differences in CNA between their index and contralateral foot were markedly higher than NPU feet (3.0 degree C versus 0.7 degree C, respectively, p<0.01); BMD in NPU immobilized feet averaged 486±136mg/cm 2 , and CNA immobilized feet averaged 456±138mg/cm 2 , p>0.05). After immobilization, index NPU feet lost 27mg/cm 2 ; CNA feet lost 47mg/cm 2 of BMD, p<0.05. After recovery, 61% of NPU index feet and 84% of CNA index feet were classified as osteopenic or osteoporotic., Conclusions: There was a greater osteolysis after immobilization with an attenuated recovery in CNA feet compared to NPU feet. The attenuated recovery of pedal BMD in CNA feet resulted in a greater percentage of feet classified as osteoporotic and osteopenic., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aim: People with type 2 diabetes (T2DM) have a high incidence of musculoskeletal disorders thought to be influenced by high non-enzymatic advanced glycated end-products (AGEs). The goals of this study were to determine differences in shoulder activity level and AGEs in people with T2DM compared to matched controls, and to determine factors associated with shoulder pain and disability., Methods: Eighty-one participants, T2DM (n=52) and controls (n=29), were examined for magnitude and duration of shoulder activity (measured using accelerometers), skin intrinsic florescence (SIF) as a surrogate measure of AGE level, and the Shoulder Pain and Disability Index (SPADI) as a self-report of shoulder pain and disability., Results: Compared with controls, T2DM participants had 23% less shoulder activity (p=0.01), greater SIF level (3.6±1.7 vs 2.7±0.6AU, p=0.01), less shoulder strength (p<0.05), and the duration of their shoulder activity was moderately associated (r=0.40; p<0.01) with reported shoulder pain and disability. Shoulder pain and disability were not related to SIF level., Conclusions: Persons with T2DM have higher SIF levels and shoulder symptoms and disability indices than controls. Research is needed to determine if a shoulder mobility intervention to increase strength and mobility can help decrease shoulder pain and disability., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aims: To determine local and systemic markers of inflammation and bone mineral density (BMD) in the foot and central sites in participants with diabetes mellitus and peripheral neuropathy (DMPN) with and without acute Charcot neuropathic osteoarthropathy (CN)., Methods: Eighteen participants with DMPN and CN and 19 participants without CN had foot temperature assessments, serum markers of inflammation [C-reactive protein, (CRP) and erythrocyte sedimentation rate, (ESR)] and BMD of the foot, hip and lumbar spine at baseline and 1year follow-up., Results: CN foot temperature difference was higher compared to DMPN controls at baseline (4.2±1.9°F vs. 1.2±0.9°F, P<0.01) and after 1year (2.9±3.2°F vs. 0.9±1.1°F, P<0.01). Serum inflammatory markers in the CN group were greater at baseline and remained elevated 1year later compared to DMPN controls (CRP, P=0.02, ESR, P=0.03). All pedal bones' BMD decreased an average of 3% in the CN foot with no changes in hip or lumbar spine. DMPN controls' foot, hip and lumbar spine BMD remained unchanged., Conclusions: Local and systemic inflammation persists 1 year after CN with an accompanying pedal osteolysis that may contribute to mid foot deformity which is the hallmark of the chronic Charcot foot., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To develop a noncontrast oximetric angiosome imaging approach to assess skeletal muscle oxygenation in diabetic feet., Materials and Methods: In four healthy and five subjects with diabetes, the feasibility of foot oximetry was examined using a 3T clinical magnetic resonance imaging (MRI) scanner. The subjects' feet were scanned at rest and during a toe-flexion isometric exercise. The oxygen extraction fraction of skeletal muscle was measured using a susceptibility-based MRI method. Our newly developed MR foot oximetric angiosome model was compared with the traditional angiosome model in the assessment of the distribution of oxygen extraction fraction., Results: Using the traditional angiosome during the toe-flexion exercise, the oxygen extraction fraction in the medial foot of healthy subjects increased (4.9 ± 3%) and decreased (-2.7 ± 4.4%) in subjects with diabetes (difference = 7.6%; 95% confidence interval = -13.7 ± 1.4; P = 0.02). Using the oximetric angiosome, the percent difference in the areas of oxygen extraction fraction within the 0.7-1.0 range (expected oxygen extraction fraction during exercise) between rest and exercise was higher in healthy subjects (8 ± 4%) than in subjects with diabetes (4 ± 4%; P = 0.02)., Conclusion: This study demonstrates the feasibility of measuring skeletal muscle oxygen extraction fraction in the foot muscle during a toe-flexion isometric exercise. Instead of assessing oxygen extraction fraction in a foot muscle region linked to a supplying artery (traditional angiosome), the foot oximetric angiosome model assesses oxygen extraction fraction by its different levels in all foot muscle regions and thus may be more appropriate for assessing local ischemia in ulcerated diabetic feet. J. Magn. Reson. Imaging 2016. J. MAGN. RESON. IMAGING 2016;44:940-946., (© 2016 International Society for Magnetic Resonance in Medicine.)

Background: Metatarsophalangeal joint (MTPJ) hyperextension deformity is common in people with diabetic neuropathy and a known risk factor for ulceration and amputation. An MTPJ hyperextension movement pattern may contribute to the development of this acquired deformity., Objective: The purpose of this study was to determine, in people with diabetes mellitus and peripheral neuropathy (DM+PN), the ankle and MTPJ ranges of motion that characterize an MTPJ hyperextension movement pattern and its relationship to MTPJ deformity severity. It was hypothesized that severity of MTPJ deformity would be related to limitations in maximum ankle dorsiflexion and increased MTPJ extension during active ankle dorsiflexion movement tasks., Design: A cross-sectional study design was used that included 34 people with DM+PN (mean age=59 years, SD=9)., Methods: Computed tomography and 3-dimensional motion capture analysis were used to measure resting MTPJ angle and intersegmental foot motion during the tasks of ankle dorsiflexion and plantar flexion with the knee extended and flexed to 90 degrees, walking, and sit-to/from-stand., Results: The MTPJ extension movement pattern during all tasks was directly correlated with severity of MTPJ deformity: maximum ankle dorsiflexion with knee extended (r=.35; 95% confidence interval [CI]=.02, .62), with knee flexed (r=.35; 95% CI=0.01, 0.61), during the swing phase of gait (r=.47; 95% CI=0.16, 0.70), during standing up (r=.48; 95% CI=0.17, 0.71), and during sitting down (r=.38; 95% CI=0.05, 0.64). All correlations were statistically significant., Limitations: This study was cross-sectional, and causal relationships cannot be made., Conclusions: A hyperextension MTPJ movement pattern associated with limited ankle dorsiflexion has been characterized in people with diabetic neuropathy. Increased MTPJ extension during movement and functional tasks was correlated with severity of resting MTPJ alignment. Repetition of this movement pattern could be an important factor in the etiology of MTPJ deformity and future risk of ulceration., (© 2016 American Physical Therapy Association.)

Background: Diabetic forefoot joint deformities are a known risk factor for skin breakdown and amputation, but the causes of deformity are not well understood. The purposes of this study were to determine the effects of intrinsic foot muscle deterioration and limited ankle joint mobility on the severity of metatarsophalangeal joint (MTPJ) deformity, and determine the relationships between these potential contributing factors and indicators of diabetic complications (peripheral neuropathy and advanced glycation end products)., Methods: A total of 34 participants with diabetic neuropathy (average age, 59 years; range 41-73) were studied. MTPJ angle and intrinsic foot muscle deterioration were measured with computed tomography and magnetic resonance imaging, respectively. Maximum ankle dorsiflexion was measured using kinematics. Skin intrinsic fluorescence served as a proxy measure for advanced glycation end product accumulation., Results: Total forefoot lean muscle volume (r = -0.52, P < .01) and maximum ankle dorsiflexion (r = -0.42, P < .05) were correlated with severity of MTPJ deformity. Together they explained 35% of the variance of MTPJ angle. Neuropathy was correlated with forefoot muscle deterioration (ρ = 0.53, P < .01). Skin intrinsic fluorescence was correlated to severity of neuropathy (r = 0.50, P < .01) but not maximum ankle dorsiflexion, or forefoot deterioration when controlling for neuropathy., Conclusion: These results suggest that the interplay of intrinsic foot muscle deterioration and limited ankle mobility may be the primary contributor to the development of MTPJ deformity. Identifying these muscle and ankle motion impairments as risk factors for MTPJ deformity supports the need for targeted interventions early in the disease process to slow, or possibly stop the progression of deformity over time and reduce the risk of amputation., Level of Evidence: Level IV, case series., (© The Author(s) 2015.)

Background: Diabetes mellitus related medial column foot deformity is a major contributor to ulceration and amputation. However, little is known about the relationship between medial column alignment and function and the integrity of the soft tissues that support and move the medial column. The purposes of this study were to determine the predictors of medial column alignment and function in people with diabetes and peripheral neuropathy., Methods: 23 participants with diabetes and neuropathy had radiographs, heel rise kinematics, magnetic resonance imaging and isokinetic muscle testing to measure: 1) medial column alignment (Meary's angle--the angle between the 1st metatarsal longitudinal axis and the talar head and neck), 2) medial column function (forefoot relative to hindfoot plantarflexion during heel rise), 3) intrinsic foot muscle and fat volume, ratio of posterior tibialis to flexor digitorum tendon volume, 4) plantar fascia function (Meary's angle change from toes flat to extended) and 5) plantarflexor peak torque. Predictors of medial column alignment and function were determined using simultaneous entry multiple regression., Findings: Posterior tibialis to flexor digitorum tendon volume ratio and intrinsic foot muscle volume were significant predictors of medial column alignment (P<.05), accounting for 44% of the variance. Intrinsic foot fat volume and plantarflexor peak torque were significant predictors of medial column function (P<.05), accounting for 37% of the variance., Interpretation: Deterioration of medial column supporting structures predicted alignment and function. Prospective research is required to monitor alignment, structure, and function over time to inform early intervention strategies to prevent deformity, ulceration, and amputation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Foot progression angle (FPA) is a predictor of elevated regional plantar stresses and loads, which are indicators of dermal injury risk in individuals with diabetes mellitus and peripheral neuropathy (DMPN). FPA accounts for 15-45% of the variance in plantar stresses and loads in adults with DMPN. However, the biomechanical factors underlying an "out-toeing" gait pattern in this clinical population have not been examined. The primary purpose of this study was to identify static and dynamic predictors of foot progression angle magnitude in adults with and without DMPN., Methods: Thirty-three adults with and 12 adults without diabetes mellitus participated. Hip rotation, ankle dorsiflexion, and resting calcaneal stance position were measured using a standard goniometer. Kinematic and kinetic data were collected during walking., Results and Discussion: Static predictor variables did not significantly predict foot progression angle magnitude using multiple regression analysis. Of the dynamic predictor variables, thigh and shank lateral rotation accounted for 37% of foot progression angle variance (p<.01)., Conclusions: Our results show that dynamic measures of external rotation of proximal segments (thigh, shank) during gait are strong predictors of foot progression angle. Static measures of limited joint mobility and joint position do not predict foot progression angle. These findings suggest that targeting the thigh and shank rotation using verbal or tactile cueing may be a potential strategy when trying to alter walking movement patterns towards decreasing external (lateral) FPA to minimize risk of elevated regional plantar stresses in adults with DMPN at risk for ulceration.

Aims: To determine if participants can reduce foot progression angle (FPA), and if FPA reduction decreases regional plantar stresses and forces in individuals with diabetes., Methods: Design: Three-group cross-sectional design with repeated measures. subjects: twenty-eight participants either with diabetes mellitus (DM), diabetes and peripheral neuropathy with (DMPN+NPU) or without a prior history of ulceration (DMPN-NPU) were studied. Intervention: Participants were first instructed to walk over a 3.6 m walkway at their preferred FPA, and then to walk with their foot aligned parallel with the line of gait progression at their self-selected speed. Dynamic plantar kinetics in six masked regions were collected using an EMED-st-P-2 pedobarograph. Main measures: Primary outcome measures were FPA, peak plantar pressure (PPP), and force-time integral (FTI). A repeated measures ANOVA was conducted to determine group differences in FPA for both walking conditions. Regional differences in PPPs and FTIs between preferred and corrected walking conditions were analyzed using repeated measures ANCOVA., Results: Participants showed a reduction in FPA magnitude on the 'Involved' foot between the preferred and corrected walking conditions ( p <0.01). There were no differences in PPPs or FTIs in any mask between walking conditions ( p >0.05)., Conclusion: Results from this investigation offer important evidence that people with diabetes can modify their FPA with a simple intervention of visual and verbal cueing. Future research should examine if gait retraining strategies in regular footwear more effectively offload areas of elevated regional plantar stresses and forces in adults with diabetes mellitus and peripheral neuropathy., Competing Interests: Authors declare no conflict of interest.

Background: The purpose of this study was to determine the clinical outcomes and objective measures of function that can be expected for patients following the Bridle procedure (modification of the posterior tibial tendon transfer) for the treatment of foot drop., Methods: Nineteen patients treated with a Bridle procedure and 10 matched controls were evaluated. The Bridle group had preoperative and 2-year postoperative radiographic foot alignment measurements and completion of the Foot and Ankle Ability Measure. At follow-up, both groups were tested for standing balance (star excursion test) and for ankle plantarflexion and dorsiflexion isokinetic strength, and the American Orthopaedic Foot & Ankle Society and Stanmore outcome measures were collected only on the Bridle patients., Results: There was no change in radiographic foot alignment from pre- to postoperative measurement. Foot and Ankle Ability Measure subscales of activities of daily living and sport, American Orthopaedic Foot & Ankle Society, and Stanmore scores were all reduced in Bridle patients as compared with controls. Single-limb standing-balance reaching distance in the anterolateral and posterolateral directions were reduced in Bridle participants as compared with controls (P < .03). Isokinetic ankle dorsiflexion and plantarflexion strength was lower in Bridle participants (2 ± 4 ft·lb, 44 ± 16 ft·lb) as compared with controls (18 ± 13 ft·lb, 65 ± 27 ft·lb, P < .02, respectively). All Bridle participants reported excellent to good outcomes and would repeat the operation. No patient wore an ankle-foot orthosis for everyday activities., Conclusion: The Bridle procedure was a successful surgery that did not restore normal strength and balance to the foot and ankle but allowed individuals with foot drop and a functional tibialis posterior muscle to have significantly improved outcomes and discontinue the use of an ankle-foot orthosis. In addition, there was no indication that loss of the normal function of the tibialis posterior muscle resulted in change in foot alignment 2 years after surgery., Level of Evidence: Level III, retrospective comparative series., (© The Author(s) 2015.)

Aims: To determine leg intermuscular (IMAT) and subcutaneous (SQAT) adipose tissue and their relationships with muscle performance and function in obese adults with and without type 2 diabetes and peripheral neuropathy (T2DMPN)., Methods: Seventy-nine age-matched obese adults were studied, 13 T2DM, 54 T2DMPN, and 24 obese controls. Leg fat (%IMAT, %SQAT) volumes were quantified using MRI. Ankle plantar flexion (PF) torque and power were assessed with isokinetic dynamometry. Physical function was assessed with 9-item Physical Performance Test (PPT), 6-minute walk distance, single-limb balance, and time to ascend 10 stairs. One-way ANOVAs determined group differences, and multiple regression predicted PPT score from disease status, % IMAT, and PF power., Results: T2DMPN participants had 37% greater IMAT volumes and 15% lower SQAT volumes than controls (p =. 01). T2DMPN and T2DM showed reduced PF torque and power compared to controls. T2DMPN participants had lower PPT score, 6-minute walk, single-limb balance, and stair climbing than controls (all p<.05). %IMAT volume correlated inversely, and %SQAT correlated directly, with PPT. Leg %IMAT and disease status predicted 49% of PPT score., Conclusions: T2DMPN may represent a shift in adipose tissue accumulation from SQAT to IMAT depots, which is inversely associated with muscle performance and physical function., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study is to develop a non-contrast magnetic resonance imaging (MRI) approach to evaluate skeletal muscle perfusion in the diabetic foot based on the concept of angiosomes of the foot., Methods: Five healthy volunteers and five participants with diabetes (HbA1c = 7.2 ± 1.8%) without a history of peripheral artery disease were examined. The non-contrast perfusion measurements were performed during a toe flexion challenge. Absolute perfusion maps were created and two regions (medial and lateral) on the maps were segmented based on angiosomes., Result: Regional difference in the perfusion of foot muscle was readily visualized in the MRI perfusion angiosomes during the challenge. In the participants with diabetes, the perfusion during toe flexion challenge was significantly lower than in healthy volunteers (P < 0.01). The average perfusion for the medial plantar region of the right foot was lower in subjects with diabetes (38 ± 9 ml/min/100 g) than in healthy subjects (93 ± 33 ml/min/100 g)., Conclusions: Non-contrast MRI perfusion angiosome maps demonstrate the feasibility of determining regional perfusion in foot muscles during toe challenge and may facilitate evaluation of muscle perfusion in diabetic feet., Key Points: • Non-contrast MRI perfusion angiosome maps measure regional perfusion in foot muscles non-invasively. • Foot perfusion response to challenge is reduced in persons with diabetes. • MRI perfusion angiosome maps may help evaluation of regional foot muscle perfusion.

Background: Diabetes-related medial column foot deformities contribute to high plantar pressure, joint instability, ulceration and amputation. Impaired foot function may be an early indicator of foot structural incompetence and contribute to deformity progression. This study examines the ability of single-limb heel rise multi-segmental kinematics and kinetics to identify midfoot and hindfoot dysfunction in those with diabetes-related medial column foot deformity., Methods: Single-limb heel rise foot kinematics and kinetics were examined in adults with diabetes mellitus and peripheral neuropathy with and without medial column foot deformity and age-, weight-matched controls., Findings: Hindfoot relative to shank plantarflexion, peak and excursion, were reduced in both diabetes groups compared to controls (P<0.017). Controls' initial forefoot relative to hindfoot position was plantarflexed 31° and plantarflexed an additional 13° during heel rise. The initial forefoot relative to hindfoot position for the diabetes group without deformity was similarly plantarflexed as controls (34°) while the diabetes deformity group was less plantarflexed (lower arch position: 23°, P<0.017). During the heel rise task both diabetes groups demonstrated less ability to plantarflex the forefoot relative to the hindfoot compared to controls (2 and 5° respectively, P<0.017). Ankle plantarflexion power was reduced in the diabetes deformity group compared to controls (P<0.017)., Interpretation: The single-limb heel rise task identified movement dysfunction in those with diabetes mellitus and peripheral neuropathy. Failure to plantarflex the forefoot relative to hindfoot may compromise midfoot joint stability and increase the risk of injury and arch collapse., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: The windlass mechanism, acting through the plantar fascia, stabilizes the arches of the foot during stance phase of gait. The purpose of this study was to compare changes in radiographic measurements of the medial longitudinal arch (MLA) between toe-flat and -extended positions in participants with and without diabetes mellitus (DM), peripheral neuropathy (PN), and a low MLA., Methods: Twelve participants with DMPN and low MLA and 12 controls received weightbearing radiographs in a toe-flat and toe-extended position. DMPN participants were subcategorized from radiographs into DMPN severe, evidence of severe joint changes, and DMPN low, absence of joint changes. Primary measurements of MLA were determined in each position and included Meary's angle, talar declination angle, first metatarsal declination angle, and navicular height., Results: The DMPN severe group had no difference between toe-flat and -extended positions for Meary's, talar declination, and first metatarsal declination angles (P > .35) while navicular height elevated (P < .05). The DMPN low group had no difference between toe-flat and -extended positions for talar declination angle (P = .38), while Meary's angle, first metatarsal declination angle, and navicular height elevated (P < .05). All measurements in the control group changed, consistent with arch height elevation, when toes were extended (P < .05)., Conclusion: The DMPN severe and low groups showed impaired ability to raise the arch from the toe-flat to -extended position. Further research is needed to examine the contribution of specific windlass mechanism components (ie, plantar fascia, ligament, foot joint integrity, and mobility) as they relate to progressive foot deformity in adults with DMPN., Level of Evidence: Level III, comparative series., (© The Author(s) 2014.)

Diabetic foot deformity onset and progression maybe associated with abnormal foot and ankle motion. The modified Oxford multi-segmental foot model allows kinematic assessment of inter-segmental foot motion. However, there are insufficient anatomical landmarks to accurately representation the alignment of the hindfoot and forefoot segments during model construction. This is most notable for the sagittal plane which is referenced parallel to the floor, allowing comparison of inter-segmental excursion but not capturing important sagittal hind-to-forefoot deformity associated with diabetic foot disease and can potentially underestimate true kinematic differences. The purpose of the study was to compare walking kinematics using local coordinate systems derived from the modified Oxford model and the radiographic directed model which incorporated individual calcaneal and 1st metatarsal declination pitch angles for the hindfoot and forefoot. We studied twelve participants in each of the following groups: (1) diabetes mellitus, peripheral neuropathy and medial column foot deformity (DMPN+), (2) DMPN without medial column deformity (DMPN-) and (3) age- and weight-match controls. The modified Oxford model coordinate system did not identify differences between groups in the initial, peak, final, or excursion hindfoot relative to shank or forefoot relative to hindfoot dorsiflexion/plantarflexion during walking. The radiographic coordinate system identified the DMPN+ group to have an initial, peak and final position of the forefoot relative to hindfoot that was more dorsiflexed (lower arch phenotype) than the DMPN- group (p<.05). Use of radiographic alignment in kinematic modeling of those with foot deformity reveals segmental motion occurring upon alignment indicative of a lower arch., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Carbon fiber (CF) ankle-foot orthoses (AFOs) can improve gait by increasing ankle plantar-flexor power and improving plantar-flexor ankle joint moment and energy efficiency compared with posterior leaf spring AFOs made of thermoplastic. However, fabricating a CF AFO to optimize the performance of the individual user may require multiple AFOs and expensive fabrication costs. Finite element analysis (FEA) models were developed to predict the mechanical behavior of AFOs in this study. Three AFOs, two made of CF composite material and one made of thermoplastic material, were fabricated and then mechanically tested to produce force-displacement data. The FEA models were validated by comparing model predictions with mechanical testing data performed under the same loading and boundary conditions. The actual mechanical testing demonstrated that CF performs better than thermoplastic. The simulation results showed that FEA models produced accurate predictions for both types of orthoses. The relative error of the energy return ratio predicted by the CF AFO FEA model developed in this study is less than 3%. We conclude that highly accurate FEA models will allow orthotists to improve CF AFO fabrication without wasting resources (time and money) on trial and error fabrications that are expensive and do not consistently improve AFO and user performance.

Background: Metatarsophalangeal joint deformity is associated with skin breakdown and amputation. The aims of this study were to compare intrinsic foot muscle deterioration ratios (ratio of adipose to muscle volume), and physical performance in subjects with diabetic neuropathy to controls, and determine their associations with 1) metatarsophalangeal joint angle and 2) history of foot ulcer., Methods: 23 diabetic, neuropathic subjects [59 (SD 10) years] and 12 age-matched controls [57 (SD 14) years] were studied. Radiographs and MRI were used to measure metatarsophalangeal joint angle and intrinsic foot muscle deterioration through tissue segmentation by image signal intensity. The Foot and Ankle Ability Measure evaluated physical performance., Findings: The diabetic, neuropathic group had a higher muscle deterioration ratio [1.6 (SD 1.2) vs. 0.3 (SD 0.2), P<0.001], and lower Foot and Ankle Ability Measure scores [65.1 (SD 24.4) vs. 98.3 (SD 3.3) %, P<0.01]. The correlation between muscle deterioration ratio and metatarsophalangeal joint angle was r=-0.51 (P=0.01) for all diabetic, neuropathic subjects, but increased to r=-0.81 (P<0.01) when only subjects with muscle deterioration ratios >1.0 were included. Muscle deterioration ratios in individuals with diabetic neuropathy were higher for those with a history of ulcers., Interpretation: Individuals with diabetic neuropathy had increased intrinsic foot muscle deterioration, which was associated with second metatarsophalangeal joint angle and history of ulceration. Additional research is required to understand how foot muscle deterioration interacts with other impairments leading to forefoot deformity and skin breakdown., (© 2013.)