The data indicate that excess fat infiltration in leg skeletal muscles is associated with low calf muscle strength, low calf muscle power, and impaired physical function in individuals who are obese with DM and PN.

Background Elevated plantar loading has been implicated in the etiology of plantar ulceration in individuals with diabetes mellitus and peripheral neuropathy. Total contact casts and cast walker boots are common off-loading strategies to facilitate ulcer healing and prevent re-ulceration. The purpose of this study was to compare off-loading capabilities of these strategies with respect to plantar loading during barefoot walking. Methods Twenty-three individuals with diabetes, peripheral neuropathy, and plantar ulceration were randomly assigned to total contact cast (N=11) or removable cast walker boot (N=12). Each subject underwent plantar loading assessment walking barefoot and wearing the off-loading device. Analysis of covariance was used to compare loading patterns in the off-loading devices for the whole foot, hindfoot, midfoot, and forefoot while accounting for walking speed and barefoot loading. Findings For the foot as a whole, there were no differences in off-loading between the two techniques. Subjects wearing cast walker boots had greater reductions in forefoot peak pressure, pressure-time integral, maximum force, and force-time integral with respect to barefoot walking. Healing times were similar between groups, but a greater proportion of ulcers healed in total contact casting compared to cast walker boots. Interpretation In subjects with diabetes, peripheral neuropathy, and plantar ulceration, cast walker boots provided greater load reduction in the forefoot, the most frequent site of diabetic ulceration, though a greater proportion of subjects wearing total contact casts experienced ulcer healing. Taken together, the less effective ulcer healing in cast walker boots despite superior forefoot off-loading suggests an important role for patient compliance in ulcer healing.

In patients with Charcot neuropathic osteoarthropathy, radiographic alignment measurements demonstrate the presence of foot deformity at the time of the initial clinical presentation and evidence of progressive changes over the first and second years. The six-month data suggest worsening of medial column alignment prior to lateral column worsening. This radiographic evidence of worsening foot alignment over time supports the need for aggressive intervention (conservative bracing or surgical fixation) to attempt to prevent limb-threatening complications.

Inflammation in individuals with DM, PN, and NCA may contribute to or exacerbate a rapid loss of BMD. Inflammatory osteolysis may be a prominent factor responsible for both the spontaneous onset of neuropathic fracture and the insidious and progressive foot deformity that is the hallmark of the chronic Charcot foot.

Barth syndrome (BTHS) is a rare X-linked condition resulting in abnormal mitochondria, cardioskeletal myopathy, and growth delay; however, the effects of BTHS on substrate metabolism regulation and their relationships with tissue function in humans are unknown. We sought to characterize glucose and fat metabolism during rest, submaximal exercise, and postexercise rest in children, adolescents, and young adults with BTHS and unaffected controls and examine their relationships with cardioskeletal energetics and function. Children/adolescents and young adults with BTHS (n = 29) and children/adolescent and young adult control participants (n = 28, total n = 57) underwent an infusion of 6 0 6 0 H2 glucose and U-13 C palmitate and indirect calorimetry during rest, 30-minutes of moderate exercise (50% VO 2peak ), and recovery. Cardiac function, cardioskeletal mitochondrial energetics, and exercise capacity were examined via echocardiography, 31 P magnetic resonance spectroscopy, and peak exercise testing, respectively. The glucose turnover rate was significantly higher in individuals with BTHS during rest (33.2 ± 9.8 vs 27.2 ± 8.1 μmol/kgFFM/min, P < .01) and exercise (34.7 ± 11.2 vs 29.5 ± 8.8 μmol/kgFFM/min, P < .05) and tended to be higher postexercise (33.7 ± 10.2 vs 28.8 ± 8.0 μmol/kgFFM/min, P < .06) compared to controls.Increases in total fat (−3.9 ± 7.5 vs 10.5 ± 8.4 μmol/kgFFM/min, P < .0001) and plasma fatty acid oxidation rates (0.0 ± 1.8 vs 5.1 ± 3.9 μmol/kgFFM/min, P < .0001) from rest to exercise were severely blunted in BTHS compared to controls. Conclusion: An inability to upregulate fat metabolism during moderate intensity exercise appears to be partially compensated by elevations in glucose metabolism. Derangements in fat and glucose metabolism are characteristic of the pathophysiology of BTHS.A severely blunted ability to upregulate fat metabolism during a modest level of physical activity is a defining pathophysiologic characteristic in children, adolescents, and young adults with BTHS.