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Effects of Resistance Training on Adiposity and Metabolism after Spinal Cord Injury

GORGEY, ASHRAF S.1,2,3; MATHER, KIEREN J.4; CUPP, HEATHER R.5; GATER, DAVID R.1,3

Medicine & Science in Sports & Exercise: January 2012 - Volume 44 - Issue 1 - p 165–174
doi: 10.1249/MSS.0b013e31822672aa
APPLIED SCIENCES

Purpose This pilot work was conducted to evaluate the effects of neuromuscular electrical stimulation resistance training (RT) of the paralyzed knee extensor muscle groups on skeletal muscle and intramuscular fat (IMF) cross-sectional areas, trunk visceral adipose tissue (VAT), carbohydrate, and lipid profiles in men with spinal cord injury.

Methods Nine individuals with motor complete spinal cord injury were randomly assigned to an RT + diet group (n = 5) or a diet group (n = 4). The RT + diet underwent 12 wk of progressive RT, twice weekly, to the knee extensor muscle groups using neuromuscular electrical stimulation and ankle weights. Weekly feedback was provided to both groups to maintain a standard diet. Magnetic resonance imaging and a whole-body dual-energy x-ray absorptiometric images were obtained before and 1 wk after interventions. Participants underwent a metabolic study after a 12-h overnight fast to measure fasting and postchallenge plasma glucose, insulin, and lipid profiles.

Results Skeletal muscle hypertrophy was detected in the whole thigh, knee extensors, and flexors in the RT + diet group compared with the diet group. VAT cross-sectional area, VAT/subcutaneous adipose tissue ratio at L5–S3, and percent IMF decreased significantly in the RT + diet group. Plasma insulin area under the curve decreased in the RT + diet group but not in the diet group. Fasting triglycerides and cholesterol/HDL decreased in the RT + diet group.

Conclusions Twice-weekly evoked RT to the paralyzed lower extremities resulted in significant skeletal muscle hypertrophy that was associated with reduction in VAT, VAT/subcutaneous adipose tissue ratio, and percent IMF. Significant improvements in insulin profile and lipid metabolism were noted in the RT + diet when compared with diet alone.

1Spinal Cord Injury and Disorders Center, Hunter Holmes McGuire Veterans Affair Medical Center, Richmond, VA; 2Department of Physical Therapy, Indiana University, Indianapolis, IN; 3Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University, Richmond, VA; 4Division of Endocrinology, Indiana University, Indianapolis, IN; and 5Clinical Research Center, Indiana University Hospital, Indianapolis, IN

Address for correspondence: Ashraf S. Gorgey, M.P.T., Ph.D., FACSM, Department of Veterans Affairs, Hunter Holmes McGuire Medical Center, Spinal Cord Injury & Disorders Service, 1201 Broad Rock Boulevard, Richmond, VA 23249; E-mail: ashraf.gorgey@va.gov.

Submitted for publication February 2011.

Accepted for publication May 2011.

Lower extremity skeletal muscle atrophy, decline in fat-free mass (FFM), and increase in fat mass (FM) are natural pathological adaptations after spinal cord injury (SCI) as a result of immobilization and disuse (2,8,12,15,43). These changes in body composition are associated with CHO and lipid disorders (2,4,5). Impaired glucose tolerance, insulin resistance, and type 2 diabetes mellitus (DM) are three times more prevalent in individuals with SCI than in the able-bodied (AB) population (4,5). A person with SCI has a high risk of developing dyslipidemia characterized by depressed HDL-C, elevation of cholesterol, triglycerides (TG), and LDL-C (5,14,34,35). The aforementioned phenotype predisposes to cardiovascular disease, impairs the quality of life, and increases the mortality rate (5,14,27).

The American College of Sports Medicine (ACSM) encourages participation in physical activity to positively affect lipid and CHO metabolism (3). After SCI, exercise opportunities are limited to a small muscle mass above the level of injury (7,14,25), which renders exercise as an ineffective method to attenuate the deterioration in body composition and metabolic profile. Meanwhile, there is insufficient support for the hypothesis that exercise could improve CHO and lipid disorders after SCI (7). Resistance training (RT) has been identified as an attractive rehabilitation tool that mechanically loads skeletal muscle to increase lean mass and decrease FM in different clinical populations as well as after SCI (21,23,30). Enhancing development of metabolically active lean muscle mass could enhance glucose homeostasis and improve lipid profile (3,30,44,45). RT at least twice weekly in the general population provides a safe and effective method for improving muscular strength, inducing skeletal muscle hypertrophy (3,28), reducing visceral adipose tissue (VAT), and accumulating intramuscular fat (IMF) (18,24,40,41).

The principle of loading the paralyzed muscles to evoke exercise-induced RT using neuromuscular electrical stimulation (NMES) was previously applied (11,12,18,30). Forty-eight weeks after injury, a combined NMES and RT protocol for 8 wk resulted in regaining 75% of the muscle size at 6 wk after injury (12). A recent report using NMES RT showed hypertrophy of the major muscle groups, with decrease in IMF, providing credence to the effects of RT on ectopic adipose tissue (18). Short-term bouts of NMES RT have been shown to increase the messenger RNA level of insulin growth factor (IGF-1) (6), a potent anabolic hormone that is inversely associated with hypertrophy and reduction in ectopic adipose tissues (1,36,39).

Previous trials did not consider controlling for caloric intake to match the concomitant decrease in FFM; this could affect energy balance and result in excess body FM (10,14). Moreover, individuals with SCI have a tendency to consume a high-fat diet, which is known to disrupt the metabolic profile (20). Twelve weeks of a weight maintenance program resulted in a decline in FM without changes in lean mass in chronic SCI (10). Therefore, it is equally important to adjust for caloric intake to optimize the effects of RT and to avoid obesity-related secondary complications. The primary purpose of the present study was to investigate the effects of 12 wk of evoked RT with a diet maintenance program (RT + diet) versus a diet program (diet) on the thigh skeletal muscle, subcutaneous adipose tissue (SAT) cross-sectional areas (CSA), IMF, central adiposity (VAT and SAT), and body composition in men with chronic complete SCI. We also measured the effects of the interventions on CHO, lipid profiles, and plasma IGF-1. We hypothesized that skeletal muscle hypertrophy in the RT + diet group would positively affect body composition, ectopic adiposity, and metabolic profiles. It is also hypothesized that plasma IGF-1 would be inversely associated with ectopic adipose tissue accumulation (29,39) and would change with interventions.

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METHODS

Study Design and Participants

Nine healthy males with chronic traumatic motor complete SCI (C5–T11; mean ± SD age = 35 ± 9 yr, body mass index (BMI) = 22 ± 4 kg·m−2) participated in the study. Only men were studied to ensure homogeneity of our sample and to reduce possible effects of gender on body composition, VAT, and metabolic profile (38,46). Participants were required to be at least 1 yr after injury, between 18 and 50 yr old, BMI ≤30 kg·m−2, wheelchair reliant, with traumatic motor complete C5–L1 level of injury, and American Spinal Injury Association Impairment Scale (AIS) A or B; that is, motor deficit below the level of injury. We chose to study motor complete SCI because the magnitude of body composition and metabolic adaptations may vary between complete and incomplete SCI (4,5,43). The BMI criteria used in healthy controls underestimates the %FM in individuals with SCI (14,43); therefore, a person with BMI ≤30 kg·m−2 may have a 30%–40% FM, which would be sufficient to determine whether the RT has a meaningful effect or not. Participants reported that their weight was stable and that they did not participate in routine physical activity for the last 6 months before the study. Participants with preexisting medical conditions were excluded (cardiovascular diseases, type 2 DM, pressure sores stage 2 or 3). Participants were recruited from the community venues of Indianapolis and Indiana University hospitals. All participants signed an informed consent statement that was approved by the local ethics committee at Indiana University, and they were compensated for participation.

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Screening and study design

Potential participants were screened to determine the response of the knee extensor muscle groups to surface NMES. Two surface electrodes were placed on each knee extensor muscle group, and parameters were set at 30 Hz and 450-µs pulse duration and contraction/relaxation time of 5 s on/5 s off (12,18,30). The current (mA) was increased until a visible contraction was noted or the leg started to move. Failure to evoke contraction resulted in exclusion from the study. Afterward, each participant was assigned an ID code and randomly assigned to either 12 wk of RT + diet or a diet control group by drawing the code out of a bag. An orientation session was then completed with a dietitian for each participant to recommend the type and the quantity of the food required to adhere to a standard diet protocol during the study (see next paragraphs). Study measurements included physical examination, ECG, dual-energy x-ray absorptiometry (DXA), magnetic resonance imaging (MRI), and an oral glucose tolerance test (OGTT). Study measurements were performed a week before intervention and were repeated in the same order a week after termination of the intervention in both groups.

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Admission and physical examination

Participants were admitted to the General Clinical Research Center at Indiana University for body composition assessments. All participants were instructed to abstain from exercise, as well as alcohol and caffeine consumption, 24 h preceding the examination. On arrival, participants were asked to void their bladder and then underwent a general physical examination that included vital sign measures and a resting 12-lead ECG performed to rule out any preexisting cardiac problems. Body weight was measured while wearing light clothes in a supine position using a hospital bed scale calibrated to 0.1 kg. Height was measured from the same position to the nearest 0.1 cm. BMI was calculated as weight in kilograms divided by height in square meters (kg·m−2).

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Dietary protocol

After an overnight 12-h fast, at 8:00 a.m., RMR was measured by an indirect calorimetry unit (V max metabolic cart; SensorMedics Vmax, Yorba Linda, CA). Participants were asked to lie in a dark room for 20–30 min to attain a resting state. After this rest period, RMR was measured using a canopy-ventilated system for 20 min. Only the last 15 min of data were used in the calculations. During the measurement period, participants remained supine and were instructed not to talk or sleep. All participants were asked to follow a standard diet (45% CHO, 30% fat, and 25% protein) protocol during the study (9). Food diaries were recorded daily for the duration of 12-wk study and were analyzed weekly using the Nutrition Data System Software for Research Program (http://www.ncc.umn.edu) by a dietitian to assess the caloric intake. The software is designed to determine the caloric intake and the relative contribution of CHO, protein, and fat intakes. Foods consumed were self-selected, and no supplements were provided. To ensure adherence to the standard diet program, weekly feedback was provided by a dietitian through interview, telephone calls, or e-mails. Participants were then randomly assigned to RT + diet (n = 5) or diet control groups (n = 4) for 12 wk. This design was chosen to ensure that daily caloric intake would not affect the measured variables between groups.

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RT protocol via surface NMES

RT was performed at the Clinical Research Laboratory located at the Department of Physical Therapy at Indiana University. The training protocol was implemented twice a week for 12 wk performing leg extensions using surface NMES and ankle weights (12,18,30). The weights were progressively increased by 2 lb on a weekly basis after achieving 40 repetitions of full knee extension in a session. Failure to attain full knee extension of four sets × 10 repetitions resulted in maintaining the same load until the desired repetitions were achieved. Legs were alternated after 10 repetitions and training sets were separated by a 2-min rest interval to minimize muscle fatigue. For the first 2 wk, no ankle weights were used to ensure achievement of full knee extension against gravity and to protect against skeletal muscle damage. The training involved concentric/eccentric paradigms of the knee extensor muscle group from a seated position. When the current increased, knee extensors contracted and dynamically moved the leg and the weights against gravity. After maintaining the position for 3 s, the current was slowly decreased and the leg returned to the starting position. A Theratouch NMES unit (Richmar, Inola, OK) was used in the training with large conductive adhesive gel electrodes (8 × 10 cm) that were replaced every 3 wk. The edge of one electrode was placed on the skin 2–3 cm above the superior aspect of the patella over the vastus medialis muscle, and the other lateral to and 30 cm above the patella over the vastus lateralis muscle. Parameters were set at 30 Hz and 450-μs pulse duration, and contraction/relaxation time of 5 s on/5 s off. The operation of the NMES unit and all training sessions were performed under full supervision.

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DXA and MRI

DXA (Hologic QDR-2000 scanner, Bedford, MA) was used to quantify whole body FFM and FM (kg). Percent FM and FFM were calculated after excluding bone tissue. Regional body composition was also determined by calculating the ratio of trunk FM/leg FM to adjust for relative distribution of FM, trunk FFM/leg FFM, trunk FFM, and leg FFM (16,32). The coefficient of variability of two repeated scans was <3%.

MR images were obtained with a General Electric Signa 1.5-T magnet (Waukesha, WI; repetition time = 550 ms, echo time = 14 ms, field of view (FOV) = 20 cm, matrix size = 256 × 256). Whole thigh, knee extensors, and flexors skeletal muscle CSAs were measured before and after training (1 wk after the last training session). Transaxial images, 10 mm thick and 5 mm apart, were obtained from the hip joint to the knee joint using the whole body coil (12,13). The location of the scan was specifically identified by placing a mark 6 inches proximal to the patella and matched for the follow-up scan after 3 months for a similar position in the magnet (12,18). Before starting the scan, both legs were strapped together to avoid involuntary spasm movements, and participants were provided with earplugs to minimize the magnet noise. This was followed by a noncontrast abdominal MRI to measure trunk VAT and SAT (17). T1-weighted imaging was performed using a fast spin-echo sequence with the following parameters: (axial in-phase/out-phase with a repetition time of 140 ms and echo time of 4.2 and 1.8 ms for the in-phase and the out-phase, respectively; a 46-cm FOV, matrix size of 256 × 256 or 320 × 320; one NEX; and acquisition time of 4–5 min). Transverse slices (0.8‐cm thickness) were acquired every 0.4-cm gap from the xyphoid process to the femoral heads. Images were acquired in series of two stacks, with L4–L5 used as a separating point. After acquisition of a localizer sequence, the intervertebral space between the fourth and fifth lumbar vertebrae was identified. To ensure a short breath holding duration, two sets of nine slices were captured. The first set extended superiorly from L4–L5 to the xyphoid process and the second set distally from L4–L5 to the femoral heads. During scanning, participants were asked to take a deep breath in and hold their breath for 10–15 s. The breath holding technique was applied to reduce the respiratory–motion artifact normally associated with acquisition of MR image in the abdominal region. One of the five participants in the RT + diet was unable to obtain a medical clearance to conduct MRI owing to the lack of documentation about the type of the spinal fusion implants and its MRI compatibility; however, all other inclusion criteria were met to perform the rest of the measurements except for MRI.

Images were downloaded and analyzed using Win Vessels program (Ronald Meyer, Michigan State University, East Lansing, MI) as has been previously described (13,15). For skeletal muscle and IMF CSAs, the outer perimeter of the thigh muscle groups was traced, and the pixel signal intensity within this region was automatically determined. Afterward, a bimodal histogram of two peaks was plotted to distinguish between muscle and IMF pixels. For VAT and SAT, 13 transverse axial slices were analyzed, which covered the region from L1–L2 to S2–S3. For the purpose of statistical analysis, mean CSA of the slices from L1–L2 to L2–L3 intervertebral space (four slices), L3–L4 to L4–L5 intervertebral space (four slices), and L5–S1 to S2–S3 (five slices) were calculated. These cutoffs were chosen because of the nonuniform distribution of VAT in individuals with SCI (17). The images were automatically separated into fat (high-intensity), muscle (midintensity), and background/bone (low-intensity) regions (17). The CSA was computed automatically by summing the tissues’ pixels and multiplying by pixel surface area. Pixel surface area is multiplied by (FOV/matrix size)2. Selection of images was based on visual distinction of VAT and SAT regions within a single slice.

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Metabolic study before and after interventions

After an overnight fast for 10–12 h, participants were admitted to the General Clinical Research Center at Indiana University Hospital. A Teflon catheter was inserted into an antecubital vein of one arm for blood sampling, and 4 mL per subject was sent for analysis of total cholesterol, TG, HDL-C, and LDL-C. After allowing the blood sample to clot, the blood was centrifuged, and the serum was stored (−80°C) for future analysis. In addition, three samples were collected at 15-min intervals under fasting conditions for assessment of total plasma IGF-1 area under the curve (AUC). A standard 75-g OGTT was then administered, and blood was drawn at 0 min before and at 30, 60, 90, and 120 min after glucose administration. A 4-mL sample of blood was drawn at each time point to measure plasma glucose and insulin concentrations. All blood samples were sent to the Clarian Hospital Laboratory for analysis. The plasma concentrations of TG, cholesterol, LDL-C, HDL-C, glucose, and free fatty acid (FFA) concentrations were determined using commercially available colorimetric assays (Sigma, Wako, and Thermo DMA, respectively). The ratio of cholesterol/HDL-C was calculated to follow the guidelines (35). The plasma insulin concentration was measured using a commercially available radioimmunoassay kit (Linco Research, St. Charles, MO). Insulin sensitivity was determined using the homeostasis model assessment of insulin resistance index (HOMA-IR). The HOMA-IR was calculated as the product of the fasting plasma insulin level (μU·mL−1) and the fasting plasma glucose level (mmol·L−1) divided by 22.5. The values of plasma insulin and HOMA-IR were log-transformed to normalize for parametric analyses. The AUCs for plasma IGF-1, plasma glucose, and insulin were computed by integrating with the trapezoidal rule. All metabolic measurements were performed 1 wk before and after interventions.

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Statistical Analysis

One-way ANOVA was used to determine the difference in physical characteristics and dietary records between both groups. Because of possible confounding effects of the level of injury on the primary dependent variables, ANCOVA was used to control for variance that may result from the physical characteristics of the participants. All premeasurement values (body composition and metabolic variables) were used as covariates, and interactions were considered. Partial η 2 was used to determine the effect size of the intervention on the studied variables. Mixed-model ANOVA was used to determine the effects of interventions on insulin per-unit glucose disposal rate as an outcome of OGTT. When appropriate, a Bonferroni post hoc adjustment for multiple comparisons was performed. Pearson correlation coefficients were used to examine for associations between body composition variables and plasma IGF-1. Statistical analyses were performed using SPSS version 17.0 (SPSS, Chicago, IL), and all values are presented as mean ± SD.

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RESULTS

The groups were not significantly different with respect to age or time since injury (Table 1). Participants in the RT + diet group adhered to 12 wk of progressive RT, and both groups completed dietary intake records that were submitted as required. After intervention, the RT + diet group participants were able to lift 10 ± 7 and 12 ± 8 lb on right and left legs, respectively. Analysis of the dietary records indicated that the mean caloric intake was 1781 ± 228 and 1731 ± 127 kcal·d−1 for the RT + diet and diet groups, respectively (P > 0.05). The RT + diet versus diet groups consumed 1745 ± 438 versus 1798 ± 230 kcal (P = 0.1), 1817 ± 268 versus 1839 ± 166 kcal (P = 0.8), and 1779 ± 190 versus 1512 ± 200 kcal (P = 0.08) in the 4th, 8th, and 12th weeks of the study. Contribution of percentage fat (35% ± 3% vs 34% ± 5%), CHO (46% ± 5% vs 47% ± 3%), and protein (18% ± 2%, 1.1 ± 0.29 g·kg−1·d−1 vs 19% ± 4%, 1.09 ± 0.24 g·kg−1·d−1) intakes was not different between groups in the RT + diet versus diet group, respectively.

TABLE 1

TABLE 1

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Effects of interventions on skeletal muscle CSA and body composition

Body weight and BMI were not significantly different between groups before or after interventions (Table 2). For the RT + diet group, skeletal muscle CSA of the whole thigh (28%), knee extensor (35%), and flexor (16%) muscle groups increased significantly (Fig. 1). ANCOVA revealed a significant difference in the skeletal muscle CSA between groups (P < 0.0001; Table 2).

TABLE 2

TABLE 2

FIGURE 1

FIGURE 1

There were no main effects of the treatments on whole body composition variables (FM and FFM). After the 12 wk of intervention, there was a difference in the ratio of leg FFM to whole body FFM in the RT + diet group compared with the diet group (0.15 ± 0.01 vs 0.12 ± 0.02, P = 0.043), associated with a significant interaction effect (P = 0.01, partial η 2 = 0.74). Significant interactions were observed as a result of increases in trunk FFM by 1 kg in the RT + diet group (P = 0.0001) and reduction in trunk %FM by 2% in the diet group (P = 0.0003). Leg FFM increased significantly in the RT + diet group and was accompanied with a reduction in leg %FM compared with the diet group (Table 2).

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Effects of interventions on adipose tissue

The mean CSA of VAT was nominally decreased in both RT + diet (30%) and diet groups (13%) but did not attain statistical significance (Table 2). In the RT + diet group, a significant reduction in the VAT CSA at the region of L5–S1 to S2–S3 was detected (25%; P = 0.028; Table 2). Both groups showed a trend (P = 0.084) toward reduction in VAT/SAT ratio at the region of L1–L2 to L2–L3 space (0.85 ± 0.56 to 0.78 ± 06 vs 0.75 ± 0.54 to 0.56 ± 0.35 for the RT + diet vs diet, respectively). A significant reduction (P = 0.041) in the VAT/SAT ratio was noted at the region of L5–S1 to S2–S3 (0.75 ± 0.27 to 0.52 ± 0.16 vs 0.72 ± 0.58 to 0.58 ± 0.36 for the RT + diet vs diet groups, respectively). The diet group had a baseline nonsignificant larger trunk SAT CSA compared with the RT + diet group (P > 0.1). Neither intervention resulted in significant changes in the trunk SAT CSA (Table 2). There were no between-group differences in VAT, SAT, or VAT/SAT ratio (P > 0.5).

Figure 1C demonstrates the changes observed in %IMF before and after 12 wk of interventions. ANCOVA revealed differences in the %IMF between the RT + diet group versus the diet group after 12 wk (15% ± 8% vs 31% ± 24%, P = 0.009). Paired t-tests showed trends toward reduction (18% ± 10% vs 15% ± 8%, P = 0.06) in the RT + diet group and increase (28% ± 25% vs 31% ± 24%, P = 0.08) in the diet group in %IMF before versus after intervention.

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Effects of RT + diet versus diet on CHO metabolism

Before interventions, fasting plasma glucose was nonsignificantly higher in the RT + diet group compared with the diet group (95 ± 9 vs 88 ± 4 mg·dL−1, P = 0.08), and fasting plasma insulin was not different between groups (14 ± 9 vs 11 ± 5 mmol·L−1, P = 0.5). After 12 wk of intervention, glucose AUC had decreased in both the RT + diet group (883 ± 120 to 824 ± 135 mg·dL−1·min−1; −6.5%) and the diet group (683 ± 182 to 624 ± 103 mg·dL−1·min−1; −8.5%) without attaining statistical significance (P > 0.05). Glucose AUC adjusted to muscle mass was higher before intervention (P = 0.05) and showed a significant reduction (679 ± 195 to 458 ± 95 mg·dL−1·min−1, P = 0.032) in the RT + diet group with no changes in the diet group (362 ± 84 to 368 ± 76 mg·dL−1·min−1). Plasma insulin AUC was higher before intervention (P = 0.05) and nonsignificantly decreased in the RT + diet group (531 ± 140 to 351 ± 110 mmol·L−1·min−1, P = 0.1) but not in the diet group (327 ± 74 to 399 ± 105 mmol·L−1·min−1). The ratio of plasma insulin to plasma glucose concentrations decreased in the RT + diet group compared with the diet group (P = 0.04) and compared with the pretraining values (P = 0.07; Fig. 2). Log10 HOMA-IR did not change in response to RT + diet (0.44 ± 0.27 to 0.41 ± 0.12, P = 0.5) or diet (0.33 ± 0.17 to 0.39 ± 0.09, P = 0.3) from before to after interventions.

FIGURE 2

FIGURE 2

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Effects of RT + diet versus diet on lipid metabolism

Table 3 presents the changes in lipid profile and FFA concentration in response to training. After 12 wk of intervention, there was a significant reduction in TG (P = 0.028) and cholesterol/HDL-C (P = 0.017) in the RT + diet group but not in the diet group. A trend toward improvement (10%) in HDL-C was noted in the RT + diet group compared with the diet group. The plasma FFA concentration showed a trend of significant reduction in both groups.

TABLE 3

TABLE 3

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IGF-1 and relationship with body composition variables

After 12 wk of intervention, plasma IGF-1 AUC increased significantly in the RT + diet group (779 ± 330 to 973 ± 402 ng·mL−1·min−1 (25%), P < 0.01) but not in the diet group (827 ± 237 to 938 ± 274 ng·mL−1·min−1). A linear positive relationship was noted between IGF-1 and knee extensor muscle CSA (r = 0.53, P = 0.037; Fig. 3A). Furthermore, inverse correlations were identified between IGF-1 AUC and VAT CSA L5–S1 to S2–S3 (r = −0.56, P = 0.023; Fig. 3B) and IGF-1 and %IMF (r = −0.44, P = 0.08).

FIGURE 3

FIGURE 3

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DISCUSSION

This is the first study that addressed the effects of evoked RT of the paralyzed skeletal muscles on body composition variables, ectopic adipose tissue, and metabolic profile in men with SCI. Exercise training using functional electrical stimulation (FES) is beneficial in maintaining muscle mass, lean body mass, and improving the metabolic profile (12,19,30). However, the outcomes of these trials are limited relative to the extent of muscle atrophy and changes in body composition after SCI. Ten weeks of FES cycling in individuals with SCI resulted in about 4% increase in lean mass with no changes in adipose tissue (19). In a recent case report, evoked RT resulted in a meaningful muscle hypertrophy to several skeletal muscle groups (18). The current study showed an increase in whole thigh, knee extensor, and flexor muscle CSA by 28%, 35%, and 16%, respectively. Therefore, the addition of an RT program is able to achieve metabolic adaptations, which are linked to muscle hypertrophy and reduction in ectopic adipose tissue. A standard healthy diet, which accounts for the tendency to consume high-fat diet and low-protein intake, is not sufficient to induce metabolic improvement after SCI (20).

Prevalence of obesity, type 2 DM, dyslipidemia, and cardiovascular diseases in men with SCI have been alarming compared with the general population (5,14,27). Adaptations in body composition factors are primarily responsible for disrupted metabolic profile in men with SCI (16,17,32). An association was previously noted between whole body insulin-mediated glucose uptake and skeletal muscle mass in tetraplegics (2). Regional adipose tissue distribution has also been shown to affect the metabolic profile (16,32). A negative relationship was previously observed between trunk FM and insulin sensitivity (32). Leg FM was associated with detrimental metabolic effect on glucose and lipid profile in men with SCI (16). The findings documented that 12 wk of RT resulted in a significant increase in leg lean mass (10%) and reduction in leg %FM (−6%). These favorable regional body composition adaptations may explain the metabolic improvements noted in the RT + diet group.

The role of exercise on ectopic adipose tissue after SCI is appealing considering the association with metabolic profile (13,17). Ectopic adipose tissues are primarily responsible for glucose intolerance, hyperinsulinemia, and dyslipidemia (13,17). Twice-weekly progressive RT for 8 wk resulted in 10% and 11% reduction in VAT and SAT volumes in AB men, respectively; accompanied by 15% increase in energy intake (24). Others observed reduction in VAT and SAT in response to energy restriction and either aerobic or RT (40,41). A greater reduction was observed in VAT, SAT, and IMF after 16 wk of reducing energy intake by 1000 kcal·d−1 or adding a diet restriction program to either aerobic or RT programs in obese postmenopausal women (40). Knee extensors hypertrophy was accompanied with decrease in IMF in an individual with complete SCI (18). We have observed a reduction in VAT as well as VAT/SAT ratio in the RT + diet group. The nonuniform adaptations in VAT could be explained by the close proximity of the L5–S1 to S2–S3 region to the activated knee extensor muscle groups. Furthermore, the RT + diet group showed superior effects on %IMF, suggesting that skeletal muscle hypertrophy could potentially negate the deleterious metabolic effects of the ectopic adipose tissue.

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Effects of RT + diet versus diet on CHO metabolism

The effects of the level of injury on body composition, metabolic profile, and energy expenditure have been attributed to differences in autonomic nervous system sparing after SCI (4,5). Individuals with cervical SCI are characterized by decreased lean mass, low physical activity profile, reduced resting energy expenditure, and high risk to cardiovascular diseases. As a consequence of the cervical SCI (2,4), the RT + diet group has significantly higher glucose and insulin concentrations compared with the diet group before trial; skeletal muscle hypertrophy and reduction in ectopic adipose tissue have altered this phenotype, leading to a meaningful decrease in the concentration. Griffin et al. observed improvement in both plasma glucose and insulin after 10 wk of electrical stimulation cycling in individuals with SCI (19). A similar RT protocol for 12 wk showed a trend toward improvement in plasma glucose in men with SCI (31). We did not observe changes in the absolute glucose concentration; a possible explanation is that FES may increase capillary density or GLUT-4 concentration and facilitate diffusion of glucose in a manner not achieved with RT (19).

A significant reduction in the circulating insulin per unit glucose in the RT + diet group was noted compared with the diet only. The findings are in agreement with others who noted that adding RT or endurance training program to calorie-restricted diet augments improvements in insulin sensitivity (37,42). A high concentration of circulating FFA is commonly linked to impaired insulin sensitivity (22). We also documented that interventions were successful in reduction of the circulating FFA. Schenk et al. (42) noted that mobilization of FFA improved insulin sensitivity after either weight loss or weight loss and exercise in abdominally obese premenopausal women. However, their findings suggested that insulin sensitivity improved regardless of adding exercise or not (42). We only observed improvement in insulin profile in the RT + diet group, which may be associated with reduction in VAT (37). Therefore, other mechanisms may be responsible for such improvement and have yet to be elucidated similar to inflammatory biomarkers or regional adiposity (16,31).

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Effects of RT + diet versus diet on lipid metabolism

Unlike CHO metabolism, the effects of electrical stimulation exercise on lipid metabolism are controversial and not well established. Griffin et al. (19) did not observe any improvement in plasma cholesterol levels or TG as well as reduction in HDL-C. However, we observed significant improvement in fasting TG and cholesterol/HDL profiles, with a trend toward an increase in HDL-C in the RT + diet group. Circulating FFA is an important fuel source during exercise (22,26). However, individuals with SCI experience diminished lipolysis as well as lower circulating FFA during FES compared with AB controls because of disruption in the sympathetic nervous system (26). It is possible that TG has compensated for low FFA by providing a source of energy to the exercising muscles through enhancing the activity of lipoprotein lipase enzyme. In the general population, the effects of RT on lipid profile are inconsistent and inconclusive; a summary of 23 studies suggested that the main effects of RT are reduction in LDL-C and cholesterol profile (45). There were no changes in LDL-C, which may be explained by the tendency of individuals with SCI to consume a high-fat diet as presented or failure to significantly decrease total FM (20).

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IGF-1 and relationships between body composition variables

The results clearly documented that the RT + diet intervention has positively affected the IGF-1 profile after 12 wk of training. In rat and human models, a reduction in IGF-1 is associated with skeletal muscle atrophy and increase in FM (1). In our study, the increase in circulating IGF-1 was associated with the hypertrophy of the knee extensor muscle group and reduction in both VAT and %IMF. A prior study showed that skeletal muscle IGF-1 messenger RNA increased significantly after two bouts of NMES in the knee extensors of individuals with SCI (6). Previously, IGF-1 was inversely associated with VAT as well as fat distribution before and during moderate energy restriction in men and women (29,39). However, there is contradictory evidence suggesting that the increase in IGF-1 is not necessarily accompanied by an increase in protein synthetic rate (47). Our data support further exploration of possible connections of IGF-1 with the metabolic benefits of RT in SCI.

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Limitations

A limitation to the current study is the sample size; the study was primarily powered based on the effect size of RT intervention on skeletal muscle CSA as previously published (12,18,30). Because there were no published data on central adiposity or IMF, this report will allow accurate calculations of the sample size. Another limitation is the uneven distribution of the sample between both groups. We adopted a randomization strategy that resulted in the RT + diet group having more individuals with cervical SCI and the diet group having more individuals with thoracic SCI. Patients with complete cervical SCI have more extreme metabolic disorders compared to those with complete thoracic or incomplete SCI. We have statistically adjusted for this difference by using ANCOVA. Future studies should consider the effects of RT on those with spared versus lacking sympathetic nervous systems to address variability that may result in the metabolic profile because of the level of injury or may consider even randomization. Failure to measure total daily energy expenditure may have limited accurate estimation of the caloric intake; however, RMR represents >83% of total daily energy expenditure and is the best predictor of changes in lean body mass in this population (33). It is also unclear if the training volume, twice weekly, may have affected the outcomes of glucose or LDL-C. However, we have adopted the criteria of ACSM that twice weekly RT could affect body composition and metabolic adaptations (3).

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CONCLUSIONS

The current study demonstrated the efficacy of 12 wk of progressive RT that evoked skeletal muscle hypertrophy and improved regional body composition, central adiposity, and IMF in men with SCI. The RT program is accompanied with improvement in indices of CHO, insulin resistance, and lipid profiles in men with SCI. Furthermore, RT seems to improve the IGF-1 profile and is associated with meaningful reduction in ectopic adipose tissues that have been previously noted to induce metabolic disorders after SCI. Monitoring caloric intake is a feasible strategy to optimize the outcomes of training programs after SCI; however, maintaining a standard healthy diet regimen is not enough to evoke body composition or metabolic adaptations after SCI. These promising results may provide hope to this population as they have limited access to aerobic training, particularly, since the protocol can be simply adopted and conducted at home without direct supervision after initial setup.

This work was supported by Research Support Funds Grant Program from Indiana University and General Clinical Research Center (M01 RR00750 and RR025761).

The authors declare no conflicts of interest.

The authors thank Hunter Poarch and Ashley Bruce for assistance with MRI analysis.

The authors also thank feedback provided by Drs. Jeffery Horowitz and David Dolbow and the technical assistance of Laurie Trevino, Ronald McClintock, and Cindy McClintock.

Finally, the authors thank all the participants who enthusiastically joined the study.

The results of the present study do not constitute endorsement by the ACSM.

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Keywords:

SPINAL CORD INJURY; RESISTANCE TRAINING; NEUROMUSCULAR ELECTRICAL STIMULATION; ECTOPIC ADIPOSE TISSUE; CHO METABOLISM; LIPID METABOLISM

©2012The American College of Sports Medicine