Use of computed tomography to identify muscle quality subgroups, spatial mapping, and preliminary relationships to function in those with diabetic peripheral neuropathy.

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.

Achilles tendon assessment on quantitative MRI: Sources of variability and relationships to tendinopathy.

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.

Guidelines on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes mellitus (IWGDF 2023).

The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the prevention and management of diabetic foot disease since 1999. This is the first guideline on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes published by the IWGDF. We followed the GRADE Methodology to devise clinical questions in the PACO (Population, Assessment, Comparison, Outcome) and PICO (Population, Intervention, Comparison, Outcome) format, conducted a systematic review of the medical literature, and developed recommendations with the rationale. The recommendations are based on the evidence from our systematic review, expert opinion when evidence was not available, and also taking into account weighing of the benefits and harms, patient preferences, feasibility and applicability, and costs related to an intervention. We here present the 2023 Guidelines on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes mellitus and also suggest key future topics of research.

Diagnosis and treatment of active charcot neuro-osteoarthropathy in persons with diabetes mellitus: A systematic review.

BACKGROUND: There are uncertainties regarding the diagnostic criteria, optimal treatment methods, interventions, monitoring and determination of remission of Charcot neuro-osteoarthropathy (CNO) of the foot and ankle in people with diabetes mellitus (DM). The aims of this systematic review are to investigate the evidence for the diagnosis and subsequent treatment, to clarify the objective methods for determining remission and to evaluate the evidence for the prevention of re-activation in people with CNO, DM and intact skin. METHODS: We performed a systematic review based on clinical questions in the following categories: Diagnosis, Treatment, Identification of Remission and Prevention of Re-Activation in people with CNO, DM and intact skin. Included controlled studies were assessed for methodological quality and key data from all studies were extracted. RESULTS: We identified 37 studies for inclusion in this systematic review. Fourteen retrospective and observational studies relevant to the diagnosis of active CNO with respect to clinical examination, imaging and blood laboratory tests in patients with DM and intact skin were included. We identified 18 studies relevant to the treatment of active CNO. These studies included those focused on offloading (total contact cast, removable/non-removable knee high devices), medical treatment and surgical treatment in the setting of active CNO. Five observational studies were identified regarding the identification of remission in patients who had been treated for active CNO. We did not identify any studies that met our inclusion criteria for the prevention of re-activation in patients with DM and intact skin who had been previously treated for active CNO and were in remission. CONCLUSIONS: There is a paucity of high-quality data on the diagnosis, treatment, and prognosis of active CNO in people with DM and intact skin. Further research is warranted to address the issues surrounding this complex disease.

Quantitative Assessment of Peripheral Oxidative Metabolism With a New Dynamic 1 H MRI Technique: A Pilot Study in People With and Without Diabetes Mellitus.

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 $$ \tau $$ , was determined. Mitochondrial function index was calculated as the ratio of resting SMPCr to τ $$ \tau $$ . 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 $$ \tau $$ 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.

Rate of tarsal and metatarsal bone mineral density change in adults with diabetes mellitus and peripheral neuropathy: a longitudinal study.

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.

Regional skeletal muscle perfusion distribution in diabetic feet may differentiate short-term healed foot ulcers from non-healed ulcers.

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.

Remote Research: Resources, Intervention Needs, and Methods in People with Diabetes and Peripheral Neuropathy.

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/.

Quantative MRI predicts tendon mechanical behavior, collagen composition, and organization.

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 (rsp = 0.51, p = 0.044), equilibrium stress (rsp = 0.54, p = 0.033), percent relaxation (rsp = -0.55, p = 0.027), hysteresis (rsp = -0.64, p = 0.007), linear modulus (rsp = 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.

Midfoot and ankle movement coordination during heel rise is disrupted in people with diabetes and peripheral neuropathy.

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.

Body mass index and maximum available midfoot motion are associated with midfoot angle at peak heel rise in people with type 2 diabetes mellitus and peripheral neuropathy.

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 (R2 = 30.5%, p < 0.001) and maximum available midfoot plantarflexion range of motion (R2 = 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.

Computed Tomography and Magnetic Resonance Correlation and Agreement for Foot Muscle and Adipose Tissue Measurements.

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.

Human Achilles tendon mechanical behavior is more strongly related to collagen disorganization than advanced glycation end-products content.

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).

The Application of Exercise Training for Diabetic Peripheral Neuropathy.

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.

A limited number of slices yields comparable results to all slices in foot intrinsic muscle deterioration ratio on computed tomography and magnetic resonance imaging.

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.

Deteriorated regional calf microcirculation measured by contrast-free MRI in patients with diabetes mellitus and relation with physical activity.

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.

Qualitative study of musculoskeletal tissues and their radiographic correlates in diabetic neuropathic foot deformity.

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.

Association of toe-extension movement pattern magnitude and variability during three functional tasks with diabetic foot complications.

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 (rsp = -0.282, p = 0.029). Neuropathy severity and foot intrinsic muscle deterioration ratio were associated with toe extension variability (rsp = -0.373, p = 0.003 and rsp = -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.

Pilot study of contrast-free MRI reveals significantly impaired calf skeletal muscle perfusion in diabetes with incompressible peripheral arteries.

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.