Intramuscular fat and glucose tolerance after spinal cord injury – a cross-sectional study

Elder, Christopher P.; Apple, David F.; Bickel, C. Scott; Meyer, Ronald A.; Dudley, Gary A.

doi:10.1038/sj.sc.3101652

Cited by 210 publications

(223 citation statements)

References 17 publications

(21 reference statements)

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“…With ageing, muscle strength is lost at a faster rate than lean mass, pointing to additional determinants of impaired contractility in older adults 32. Findings of appreciable increases in IMAT in the thigh of the immobilized limb are in agreement with previous observations in young5, 33 and older adults 34. Interestingly, no changes were apparent in the non‐casted limb.…”

Section: Discussionsupporting

confidence: 89%

Effect of bimagrumab on thigh muscle volume and composition in men with casting‐induced atrophy

Rooks¹,

Laurent

Præstgaard³

et al. 2017

J cachexia sarcopenia muscle

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BackgroundPatients experiencing disuse atrophy report acute loss of skeletal muscle mass which subsequently leads to loss of strength and physical capacity. In such patients, especially the elderly, complete recovery remains a challenge even with improved nutrition and resistance exercise. This study aimed to explore the clinical potential of bimagrumab, a human monoclonal antibody targeting the activin type II receptor, for the recovery of skeletal muscle volume from disuse atrophy using an experimental model of lower extremity immobilization.MethodsIn this double‐blind, placebo‐controlled trial, healthy young men (n = 24; mean age, 24.1 years) were placed in a full‐length cast of one of the lower extremities for 2 weeks to induce disuse atrophy. After cast removal, subjects were randomized to receive a single intravenous (i.v.) dose of either bimagrumab 30 mg/kg (n = 15) or placebo (n = 9) and were followed for 12 weeks. Changes in thigh muscle volume (TMV) and inter‐muscular adipose tissue (IMAT) and subcutaneous adipose tissue (SCAT) of the thigh, maximum voluntary knee extension strength, and safety were assessed throughout the 12 week study.ResultsCasting resulted in an average TMV loss of −4.8% and comparable increases in IMAT and SCAT volumes. Bimagrumab 30 mg/kg i.v. resulted in a rapid increase in TMV at 2 weeks following cast removal and a +5.1% increase above pre‐cast levels at 12 weeks. In comparison, TMV returned to pre‐cast level at 12 weeks (−0.1%) in the placebo group. The increased adiposity of the casted leg was sustained in the placebo group and decreased substantially in the bimagrumab group at Week 12 (IMAT: −6.6%, SCAT: −3.5%). Knee extension strength decreased by ~25% in the casted leg for all subjects and returned to pre‐cast levels within 6 weeks after cast removal in both treatment arms. Bimagrumab was well tolerated with no serious or severe adverse events reported during the study.ConclusionsA single dose of bimagrumab 30 mg/kg i.v. safely accelerated the recovery of TMV and reversal of accumulated IMAT following 2 weeks in a joint‐immobilizing cast.

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Section: Discussionsupporting

confidence: 89%

Effect of bimagrumab on thigh muscle volume and composition in men with casting‐induced atrophy

Rooks¹,

Laurent

Præstgaard³

et al. 2017

J cachexia sarcopenia muscle

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“…Interestingly, we found a marked increase in the intramuscular lipid content of all individuals with SCI compared to controls. This phenomenon of elevated muscle lipid has been reported in a number of clinical populations including individuals with stroke 15 as well as both complete 9 and incomplete SCI. 10 Elder and co-workers demonstrated that persons with complete SCI display an almost fourfold increase in intramuscular fat relative to controls, and that these values correlate with plasma glucose levels during an oral glucose tolerance test (r 2 ¼ 0.52 and 0.71, Po0.001).…”

Section: Discussionmentioning

confidence: 58%

“…Given the higher reported incidence of insulin resistance in persons with incomplete SCI 7 and a purported relatively inactive lifestyle, 8 we hypothesized that individuals with incomplete SCI would demonstrate an elevated IMCL content in skeletal muscle. Although studies have demonstrated elevated lipid depots in the lower extremity muscles of persons with complete and incomplete SCI using magnetic resonance imaging (MRI), 9,10 we are not aware of any study that has specifically investigated alterations in the IMCL content in persons with motor incomplete SCI.…”

Section: Introductionmentioning

confidence: 99%

Non-invasive assessment of lower extremity muscle composition after incomplete spinal cord injury

et al. 2008

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Study Design: Cross-sectional study. Objective: (1) To quantify intramyocellular lipid (IMCL) content of the soleus muscle. (2) To assess the T 2 relaxation rates in the lower extremity skeletal muscles in persons with incomplete spinal cord injury (SCI). Setting: Academic Institution, Florida. Methods: Eight subjects (42 ± 10 years old; 70 ± 12 kg; 176 ± 10 cm) with chronic (17 ± 9 months post injury) motor SCI (C4-T12; ASIA C or D) and eight matched healthy controls were tested. Localized unsuppressed proton spectroscopy (H-MRS) was performed to estimate total lipid content and individual lipid components; IMCL and extramyocellular lipid (EMCL) from the soleus muscle. T 2 -weighted imaging of lower extremity muscles yielded muscle T 2 rates. Results: The IMCL content of the soleus muscle was 3.3 times higher in the patient group as compared to controls (P ¼ 0.002; 0.0401 (0.0234-0.0849) versus 0.0123 (0.0090-0.0175)). Similarly, EMCL measures were 4.5 times higher as compared to the controls (P ¼ 0.002). Significant differences were observed in the T 2 relaxation times of the soleus and gastrocnemius muscles (Po0.05). Conclusion:The increased levels of IMCL might interfere with the glucose uptake in skeletal muscle; potentially predisposing persons with incomplete SCI to the development of peripheral insulin resistance. Marked elevations in the T 2 relaxation times of the locomotor muscles are reflective of an altered muscle composition.

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“…16 Recent evidence suggests that thigh IMAT and subcutaneous fat areas are increased in sedentary SCI individuals and that relative IMAT is a strong predictor of plasma glucose suggesting an increased risk for impaired glucose tolerance and insulin resistance. 18 Although thigh subcutaneous fat was a strong predictor of metabolic outcomes within group, this effect was largely due to the relation to whole body fat mass and notably the relation was in the positive direction (that is, not protective). Our findings regarding thigh IMAT suggest that insulin sensitivity is associated with thigh IMAT in SCI individuals and that high-volume upper-body physical activity can protect against the risk of insulin resistance resulting from thigh IMAT accumulation and loss of muscle in this population.…”

Section: Discussionmentioning

confidence: 95%

“…Images were automatically segmented into fat, skeletal muscle and background bone regions as described previously. [16][17][18] To correct for differences in muscle area and limb size, IMAT areas of a given limb were divided by the muscle area of that limb, providing the relative IMAT for the limb. Similarly, the muscle areas and subcutaneous fat areas of a given limb were divided by the whole area of the respective limb, resulting in the relative muscle and subcutaneous fat areas for the limb.…”

Section: Magnetic Resonance Imagingmentioning

confidence: 99%

The association between regional body composition and metabolic outcomes in athletes with spinal cord injury

et al. 2007

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Study design: Cross-sectional study comparing athletes with spinal cord injury (SCI) and age and body mass index matched able-bodied controls (AB). Objective: To examine the impact of exercise training on the relation between whole body, regional and intermuscular adipose tissue (IMAT) and glucose tolerance, insulin action and lipid profile. Setting: University Research Laboratory, USA. Methods: Fourteen college-aged athletes with SCI (seven men; duration of injury 16.575.7 years, level of injury T5-L5) and 17 sedentary AB (eight men) were assessed for body composition via dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging. Insulin sensitivity index (ISI) was determined via 2-h oral glucose challenge; standard lipid profile was determined from fasting blood samples. Results: Although ISI was 30% higher in SCI, there were no significant differences between groups in glucose and insulin responses or in lipid measures. Adjusting for absolute and relative thigh IMAT area, fasting insulin (13.875.3 mIU, 16.375.6 mIU; Po0.05; SCI vs AB respectively) and ISI (4.071.4, 3.171.3; Po0.05) were significantly better among SCI athletes compared to AB. Measures of adiposity did not correlate with glucose response or most lipid measures. Within SCI and AB, respectively, ISI correlated strongly (all Po0.05) with absolute (r ¼ À0.70, À0.54) and relative IMAT (r ¼ À0.54, À0.50), than with trunk (r ¼ À0.62, À0.64) and whole body fat mass (r ¼ À0.61, À0.64). Conclusion: Habitual physical activity can maintain insulin sensitivity in SCI compared to sedentary AB controls. Total body fat mass, central adiposity and thigh IMAT appear to impact risk for metabolic disease in SCI individuals with IMAT playing a larger role in SCI than AB.

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Intramuscular fat and glucose tolerance after spinal cord injury – a cross-sectional study

Cited by 210 publications

References 17 publications

Effect of bimagrumab on thigh muscle volume and composition in men with casting‐induced atrophy

Effect of bimagrumab on thigh muscle volume and composition in men with casting‐induced atrophy

Non-invasive assessment of lower extremity muscle composition after incomplete spinal cord injury

The association between regional body composition and metabolic outcomes in athletes with spinal cord injury

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