Lori J. Tuttle

Excessive Adipose Tissue Infiltration in Skeletal Muscle in Individuals With Obesity, Diabetes Mellitus, and Peripheral Neuropathy: Association With Performance and Function

Background and Purpose: The primary purpose of this study was to report differences in calf intermuscular adipose tissue (IMAT), muscle strength (peak torque), power, and physical function in individuals with obesity, diabetes mellitus (DM), and peripheral neuropathy (PN) compared with those without these impairments. A secondary purpose was to assess the relationship between IMAT and muscle strength, power, and physical function. Subjects and Methods: Six participants with obesity, DM, and PN (2 women, 4 men; mean age=58 years, SD=10; mean body mass index=36.3, SD=5; mean modified Physical Performance Test [PPT] score=22, SD=3) and 6 age- and sex-matched control subjects without these impairments were assessed and compared in muscle strength, muscle power, physical functioning, and muscle and fat volume, including IMAT in the calf muscles. Muscle, adipose tissue, and IMAT volumes of each calf were quantified by noninvasive magnetic resonance imaging. Muscle strength and power of the plantar-flexor and dorsiflexor muscles were quantified using isokinetic dynamometry. The modified PPT was used to assess physical function. Results: Leg muscle and fat volumes were similar between groups, although IMAT volumes were 2.2-fold higher in the subjects with obesity, DM, and PN (X̄=120 cm3, SD=47) than in the control subjects (X̄=54 cm3, SD=41). Muscle strength, muscle power, ratio of leg muscle power to leg muscle volume, and modified PPT scores were lower in subjects with obesity, DM, and PN compared with the control subjects. Discussion and Conclusion: 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.

Intermuscular adipose tissue is muscle specific and associated with poor functional performance

Purpose. People with obesity, diabetes, and peripheral neuropathy have high levels of intermuscular adipose tissue (IMAT) volume which has been inversely related to physical function. We determined if IMAT is muscle specific, if calf IMAT is different between a healthy obese group (HO), a group with diabetes mellitus (D), and a group with diabetes mellitus and peripheral neuropathy (DN), and if IMAT volume or the ratio of IMAT/muscle volume is related to physical function in these groups. Methods. 10 healthy obese people, 11 with type 2 diabetes, 24 with diabetes and peripheral neuropathy, had assessments of muscle morphology, physical function and muscle performance. Results. The gastrocnemius muscle had a higher ratio of IMAT/muscle volume than any other muscle or compartment. There were no differences between groups in calf muscle or IMAT volumes. Calf IMAT was inversely related to physical performance on the 6-minute walk test (r = −0.47) and physical performance test (r = −0.36). IMAT/muscle volume was inversely related to physical performance (PPT, r = −0.44; 6 MW r = −0.48; stair power, r = −0.30). Conclusions. IMAT accumulation varies in calf muscles, is highest in the gastrocnemius muscle, and is associated with poor physical performance.

Plantar Stresses on the Neuropathic Foot During Barefoot Walking

Background and Purpose: Patients with diabetes mellitus and peripheral neuropathy are at high risk for plantar skin breakdown due to unnoticed plantar stresses during walking. The purpose of this study was to determine differences in stress variables (peak plantar pressure, peak pressure gradient, peak maximal subsurface shear stress, and depth of peak maximal subsurface shear stress) between the forefoot (where most ulcers occur) and the rear foot in subjects with and without diabetes mellitus, peripheral neuropathy, and a plantar ulcer measured during barefoot walking. Subjects: Twenty-four subjects participated: 12 with diabetes mellitus, peripheral neuropathy, and a plantar ulcer (DM+PN group) and 12 with no history of diabetes mellitus or peripheral neuropathy (control group). The subjects (11 men, 13 women) had a mean age (±SD) of 54±8 years. Methods: Plantar pressures were measured during barefoot walking using a pressure platform. Stress variables were estimated at the forefoot and the rear foot for all subjects. Results: All stress variables were higher (127%–871%) in the forefoot than in the rear foot, and the peak pressure gradient showed the greatest difference (538%–871%). All stress variables were higher in the forefoot in the DM+PN group compared with the control group (34%–85%), and the peak pressure gradient showed the greatest difference (85%). The depth (X̄±SD) of peak maximum subsurface shear stress in the forefoot in the DM+PN group was half that in the control group (3.8±2.0 versus 8.0±4.3 mm, respectively). Discussion and Conclusions: These results indicate that stresses are relatively higher and located closer to the skin surface in locations where skin breakdown is most likely to occur. These stress variables may have additional value in predicting skin injury over the traditionally measured peak plantar pressure, but prospective studies using these variables to predict ulcer risk are needed to test this hypothesis.

Lower physical activity is associated with higher intermuscular adipose tissue in people with type 2 diabetes and peripheral neuropathy

Background Increased lipid accumulation in skeletal muscle has been linked to insulin resistance, impaired muscle performance, and impaired physical function. It is unclear whether physical activity is associated with lipid content in skeletal muscle, muscle performance, or overall physical function. Objective The purpose of this study was to characterize physical activity levels (average daily step count) in a sample of people with diabetes and peripheral neuropathy and to determine the relationship among step count, intermuscular adipose tissue volume (IMAT), muscle performance (peak torque, power), and physical function. Design A cross-sectional design was used in this study. Methods Twenty-two people with diabetes and peripheral neuropathy (15 men and 7 women, mean age=64.5 years [SD=12.7], and mean body mass index=33.2 kg/m2 [SD=6.4]) participated. Average daily step count, glycosylated hemoglobin, modified 9-item Physical Performance Test scores, Six-Minute Walk Test distance, calf intermuscular adipose tissue volume (via magnetic resonance imaging), and isokinetic dynamometry of the ankle muscles were recorded. Results Average daily step count was 7,754 (SD=4,678; range=3,088–20,079). Five participants had an average daily step count greater than 10,000. Average IMAT volume was 84 cm3 (SD=88). Greater average daily step count was associated with younger age (r=−.39, P<.05) and with lower IMAT volume in the calf (r=−.44, P<.05). Lower IMAT volume was associated with greater muscle performance (r=−.45) and physical function (r=−.43 to −.48). Limitations The sample in this study may be biased toward people with high levels of activity because participants were recruited for an exercise study. The results should not be generalized to people taking fewer than 3,000 steps/day or to those with a current foot ulcer, peripheral arterial disease, or severe foot deformity or amputation or who weigh more than 136 kg (300 lb). Conclusions Average daily step count was inversely related to IMAT, and IMAT was inversely related to muscle performance and overall physical function. In addition, we found that people with diabetes and peripheral neuropathy and without severe foot deformity appear to be able to take a large number of steps per day.

Weight-bearing versus nonweight-bearing exercise for persons with diabetes and peripheral neuropathy: a randomized controlled trial.

OBJECTIVE To determine the effects of weight-bearing (WB) versus nonweight-bearing (NWB) exercise for persons with diabetes mellitus (DM) and peripheral neuropathy (PN). DESIGN Randomized controlled trial with evaluations at baseline and after intervention. SETTING University-based physical therapy research clinic. PARTICIPANTS Participants with DM and PN (N=29) (mean age ± SD, 64.5±12.5y; mean body mass index [kg/m(2)] ± SD, 35.5±7.3) were randomly assigned to WB (n=15) and NWB (n=14) exercise groups. All participants (100%) completed the intervention and follow-up evaluations. INTERVENTIONS Group-specific progressive balance, flexibility, strengthening, and aerobic exercise conducted sitting or lying (NWB) or standing and walking (WB) occurred 3 times a week for 12 weeks. MAIN OUTCOME MEASURES Measures included the 6-minute walk distance (6MWD) and daily step counts. Secondary outcome measures represented domains across the International Classification of Functioning, Disability and Health. RESULTS The WB group showed greater gains than the NWB group over time on the 6MWD and average daily step count (P<.05). The mean and 95% confidence intervals (CIs) between-group difference over time was 29m (95% CI, 6-51) for the 6MWD and 1178 (95% CI, 150-2205) steps for the average daily step count. The NWB group showed greater improvements than the WB group over time in hemoglobin A1c values (P<.05). CONCLUSIONS The results of this study indicate the ability of this population with chronic disease to increase 6MWD and daily step count with a WB exercise program compared with an NWB exercise program.

Magnetic resonance imaging measurement reproducibility for calf muscle and adipose tissue volume.

To describe a new semiautomated method for segmenting and measuring the volume of the muscle, bone, and adipose (subcutaneous and intermuscular) tissue in calf muscle compartments using magnetic resonance (MR) images and determine the intrarater and interrater reproducibility of the measures.

A Moderate-Intensity Weight-Bearing Exercise Program for a Person With Type 2 Diabetes and Peripheral Neuropathy

Background and Purpose The exercise guidelines for people with diabetes mellitus and peripheral neuropathy (DM+PN) have recently changed to allow moderate-intensity weight-bearing exercise, but there are few reports in the literature describing appropriate weight-bearing exercise for those with DM+PN. This case report describes a successful and safe progressive exercise program for an individual with DM+PN. Case Description The patient was a 76-year-old man with a 30-year history of DM+PN. He participated in a 12-week, moderate-intensity, progressive exercise program (heart rate approximately 75% of maximum heart rate; rate of perceived exertion=11–13; 3 times per week) involving walking on a treadmill, balance exercises, and strengthening exercises for the lower extremities using body weight resistance. Outcomes Measurements were taken before and after the 12 weeks of exercise. The patients Six-Minute Walk Test distance increased from 1,200 to 1,470 ft. His Physical Performance Test score did not change. His Foot and Ankle Ability Measure questionnaire score improved from 89 to 98. Dorsiflexor and plantar-flexor peak torque increased (dorsiflexor peak torque: right side=4.5–4.6 N·m, left side=2.8–3.8 N·m; plantar-flexor peak torque: right side=44.7–62.4 N·m, left side=40.8–56.0 N·m), as did his average daily step count (6,176–8,273 steps/day). Close monitoring of the plantar surface of the feet indicated that the exercise program was well tolerated and there were no adverse events. Discussion and Conclusions This case report describes a moderate-intensity exercise program that was successful in increasing some measures of muscle strength, physical function, and activity without causing injury in an individual with DM+PN.

Adipose tissue content, muscle performance and physical function in obese adults with type 2 diabetes mellitus and peripheral neuropathy

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.

Contribution of denervated muscle to contractures after neonatal brachial plexus injury: not just muscle fibrosis.

Introduction: We investigated the contribution of muscle fibrosis to elbow flexion contractures in a murine model of neonatal brachial plexus injury (NBPI). Methods: Four weeks after NBPI, biceps and brachialis fibrosis were assessed histologically and compared with the timing of contracture development and the relative contribution of each muscle to contractures. Modulus of elasticity and hydroxyproline (collagen) content were measured and correlated with contracture severity. The effect of halofuginone antifibrotic therapy on fibrosis and contractures was investigated. Results: Elbow contractures preceded muscle fibrosis development. The brachialis was less fibrotic than the biceps, yet contributed more to contractures. Modulus and hydroxyproline content increased in both elbow flexors, but neither correlated with contracture severity. Halofuginone reduced biceps fibrosis but did not reduce contracture severity. Conclusions: Contractures after NBPI cannot be explained solely by muscle fibrosis, arguing for investigation of alternate pathophysiologic targets for contracture prevention and treatment. Muscle Nerve 49:398–404, 2014

Reliability and Validity of Measures of Hammer Toe Deformity Angle and Tibial Torsion

BACKGROUND Measures of second-fourth metatarsophalangeal joint (MTPJ) angle (indicator of hammer toe deformity) and clinical measures of tibial torsion have limited evidence for validity and reliability. The purposes of this study are to determine: (1) reliability of using a 3D digitizer (Metrecom) and computed tomography (CT) to measure MTPJ angle for toes 2-4; (2) reliability of goniometer, 3D digitizer, and CT to measure tibial torsion; (3) validity of MTPJ angle measures for toes 2-4 using goniometry and 3D digitizer compared to CT (gold standard) and (4) validity of tibial torsion measures using goniometry and 3D digitizer (Metrecom) compared to CT (gold standard). METHODS Twenty-nine subjects participated in this study. 27 feet with hammer toe deformity and 31 feet without hammer toe deformity were tested using standardized gonimetric, 3D digitizer and CT methods. ICCs (3,1), standard error of the measurement (SEM) values, and difference measures were used to characterize intrarater reliability. Pearson correlation coefficients and an analysis of variance were used to determine associations and differences between the measurement techniques. FINDINGS 3D digitizer and CT measures of MTPJ angle had high test-retest reliability (ICC = 0.95-0.96 and 0.98-0.99, respectively; SEM = 2.64-3.35 degrees and 1.42-1.47 degrees, respectively). Goniometry, 3D digitizer, and CT measures of tibial torsion had good test-retest reliability (ICC = 0.75, 0.85, and 0.98, respectively; SEM = 2.15 degrees, 1.74 degrees, and 0.72 degree, respectively). Both goniometric and 3D digitizer measures of MTPJ angle were highly correlated with CT measures of MTPJ angle (r = 0.84-0.90, r = 0.84-0.88, respectively) and tibial torsion (r = 0.72, r = 0.83). Goniometry, 3D digitizer, and CT measures were all different from each other for measures of hammer toe deformity (p < 0.001). Goniometry measures were different from CT measures and 3D digitizer measures of tibial torsion (p < 0.002). CT measures and 3D digitizer measures of tibial torsion were similar (p = 0.112). INTERPRETATIONS These results suggest that 3D digitizer and CT scan measures of MTPJ angle and goniometric, 3D digitizer, and CT scan measures of tibial torsion are reliable. Goniometer and 3D digitizer measures of MTPJ angle and tibial torsion measures are highly correlated with the gold standard CT method indicating good validity of measures, but the measures are not interchangeable.