Abstract
Abnormal body composition in myotonic dystrophy type 1 (DM1) are affected by energy intake above resting energy expenditure (REE). We aim to investigate the characteristics and relationship between body composition, REE, and pulmonary function in patients with DM1, and to examine their changes in 1 year. The study design was a single-center, cross-sectional, and longitudinal study of body composition, REE characteristics, and pulmonary function. Twenty-one male patients with DM1 and 16 healthy volunteers were registered in the study. Body composition was measured using dual-energy X-ray absorptiometry (DEXA). Fat mass (FM) index (kg/m2), fat-FM index (kg/m2), and skeletal mass index (kg/m2) were calculated. The measurements were taken breath by breath with a portable indirect calorimeter. The REE was calculated using the oxygen intake (VO2) and carbon dioxide output (VCO2) in the Weir equation. Basal energy expenditure (BEE) was calculated by substituting height, weight, and age into the Harris–Benedict equation. The study enrolled male patients with DM1 (n = 12) and healthy male volunteers (n = 16). Patients with DM1 (n = 7) and healthy volunteers (n = 14) could be followed in 1 year. The body composition of patients with DM1 was significantly higher in the FM index and significantly lower in the fat-FM index and skeletal mass index. The REE of patients with DM1 was significantly lower and was not associated with body composition. Patients with DM1 had poor metabolism that was not related to body composition. FM was high and lean body mass was low.
Keywords: body composition, metabolism, myotonic dystrophy, pulmonary
1. Introduction
Myotonic dystrophy type 1 (DM1) is an autosomal dominant degenerative neuromuscular disease caused by a nucleotide triplet (CTG) repeat expansion within the 3′ untranslated regions of the dystrophy myotonic protein kinase gene.[1] It is the most common type of muscular dystrophy in adults. DM1 is a multisystemic disease that affects skeletal muscles and the cardiac, digestive, nervous, and endocrine systems. Typical signs and symptoms include myotonia, heart arrhythmias, cataracts, daytime sleepiness, cognitive impairments, apathy, muscle wasting, and muscle weakness.[2] A study showed that in approximately 96% of patients with DM1, 20% had cachexia, 27% had muscle atrophy with normal body weight (BW), 14% had muscle atrophy with overweight, and 35% were over BW with normal muscle mass, with no report of starvation.[3]
Undernutrition and overweight are common in patients with neuromuscular disorders. Thus, clinically, fat mass (FM) is underestimated, whereas resting energy expenditure (REE) is overestimated.[4] However, indirect calorimetry is not always available, making it necessary to estimate REE through equations. BEE according to the Harris–Benedict equation causes nutrient estimates to be excessive.[5] In addition, indicators of BW and body mass index (BMI) in patients with spinal muscular atrophy can lead to incorrect nutritional management.[6] Therefore, the method of calculating REE from oxygen intake (VO2) and carbon dioxide output (VCO2) using indirect calorimetry is useful in nutrition management.[7–10]
DEXA is a method developed originally for the measurement of bone density and mass. DEXA can also be used to measure soft tissue composition. DEXA can measure total and regional FM, lean body mass (LBM), and bone mineral. The method is based on the attenuation characteristics of tissues exposed to X-rays at 2 peak energies.
Body composition using DEXA correlates with motor strength and is an important biomarker.[11] DEXA in patients with neurological and muscular disorders reflects nutritional imbalance and energy intake in body composition.
By measuring the partial LBM, the progress of the disease can be managed. The measurements are available for safe, noninvasive, and clinical trial outcomes.[12–24]
There is no previous study on the metabolism of patients with severe DM1, which is less well understood. The association between body composition and respiratory function is clinically important and may be 1 of the outcomes.[25] The respiratory disorders associated with DM1 are restricted ventilation disorders and central alveolar hypoventilation.[26] Predictors of respiratory failure are related to the severity of myopathy, overweight, and BMI.[3,27,28]
When patients with DM1 are unable to walk and have reduced physical activity, excessive energy intake accelerates abnormal body composition, increases the burden on cardiopulmonary function, and worsens metabolism and body composition. The REE of obese Duchenne muscular dystrophy is low, and a decrease in the amount of physical activity reduces the REE, resulting in more energy intake than necessary.[29] Fat infiltration and FM in trunk muscles of patients with DM1 are each associated with decreased forced vital capacity (FVC).[25] Therefore, it is important to identify factors and associations in body composition, REE, and respiratory function of patients with DM1.
The REE of patients with DM1 was reported to be lower than that of healthy subjects, and the REE and LBM exhibit significant positive correlations.[30] However, that analysis was not based on a FFMI or FM index (FMI) obtained by dividing the LBM and FM by the square height. Moreover, in the muscular disability rating scale classification[31] (1 = no clinical dysfunction, 2 = small symptoms of dysfunction, 3 = distal muscle weakness, 4 = moderate proximal muscle weakness, 5 = non-walkable), 3 to 5 were subjects of the study. Additionally, men and women were mixed; therefore, gender may have affected the results. In other previous studies, men have severe myotonia, breathing challenges, and muscle weakness, whereas women have cataracts, gastrointestinal dysfunction, and obesity.[32] Therefore, it is reported that gender differences should be considered in medical management and clinical study designs.[32] Moreover, the REE/BW of patients with DM1 is significantly lower than that of healthy subjects, and there is no significant difference in REE/LBM.[33] Previous studies on body composition and REE have also reported several types of Duchenne muscular dystrophy[4,29,34–36] and Becker muscular dystrophy[37,38] but fewer myotonic dystrophy types.
The relationship between body composition, REE, and pulmonary function in limited numbers of patients with DM1 (unable to walk, male) is unclear. Furthermore, very few studies that are similar to this longitudinal study exist.
The hypothesis of the study was that DM1 patients had more fat, less lean mass, and whether there was a relationship between body composition and REE, and how much they decreased in 1 year. This study aims to investigate the relationship between body composition, REE, and pulmonary function characteristics in patients with DM1. In addition, it seeks to examine changes in body composition, REE, and pulmonary function over a 1-year period.
2. Subjects and methods
This single-center, cross-sectional, and short-term longitudinal study included 21 male patients with DM1 who were unable to walk and were admitted to the Akita National Hospital and 16 healthy volunteers. The study was conducted from September 2017 to December 2018. The follow-up method was to collect clinical information obtained from the medical records of patients within the follow-up period.
Inclusion criteria were male patients diagnosed with DM1 with muscular disability rating scale = 5 in male over 20 years of age, as confirmed by the expansion of CTG repeats on genomic DNA extracted from peripheral blood leukocytes using Southern blot analysis. Patients with DM1 who understood the content and method of this study and were able to give consent were included. Previous studies had varying gender ratios and degrees of severity; therefore, this study was limited to male patients with DM1 who were unable to walk.
Exclusion criteria were tracheostomy, ventilator requirement for resting in the supine position, acute exacerbation, and the inability to consent. Patients being treated by a neurologist for worsening general condition.
This study was approved by the ethics committee of the National Hospital Organization, Akita Hospital (IRB No. 30/16).
2.1. Measurement of the body composition
Body composition analysis was performed using DEXA on a Hologic machine (Discovery A, USA). DEXA is a noninvasive technique that allows for the regional assessment of the proportion of fat and nonfat tissue. It is a gold standard method for the diagnosis of sarcopenia and is also used to measure body composition in patients with muscular dystrophy.[39]
With the patient in the supine position, the midline of the body was aligned with the centerline on the bed. The body was positioned within the limits of the scan such that the upper limbs were not touching the body. In addition, standardized Lunar Prodigy software (GE Healthcare), based on a 3-compartment body composition model, namely, FM, LBM, and bone mineral content, was used for positioning the patient.
FMI (kg/m2), FFMI (kg/m2), and skeletal mass index (SMI, kg/m2) were calculated by dividing FM and LBM, both normalized to the square height, by the square height for the following regions: bilateral upper limbs (ULs), trunk, bilateral lower limbs (LLs), and whole body.
2.2. Measurement of metabolism and analysis of expired gas
Measurements were carried out in the rehabilitation room at a temperature of 20°C to 25°C based on previous research.[34] Measurements were performed 2 hours after meals and with a 15-minute rest interval. After confirming that the vital signs of the subjects were normal, the subjects wore face masks, ensuring that there was no air leak, and a heart rate (HR) sensor (Polar Electro Japan, POLAR T31) and were instructed to breathe naturally during the procedure. The exhaled gas and HR were measured by the breath-by-breath method using a portable metabolic monitoring device (MetaMax3B; Cortex, Germany) and the HR sensor. Before the measurement, the gas sensor, volume transducer, and atmospheric pressure sensor were calibrated. To reduce the burden on the subjects, the MetaMax3B equipment was not worn on the body.
The receiver was linked to a personal computer, and the MetaSoft program (Cortex) was used for data analysis. Oxygen uptake (VO2), VCO2, HR, tidal volume (TV), respiratory rate, minute ventilation (VE), and O2 pulse (VO2/HR) were obtained via expired gas measurement.
2.3. Measurement of pulmonary function
An electronic diagnostic spirometer (AS507; MINATO, Japan) was used while patients were sitting in wheelchairs. The vital capacity (VC), FVC, forced expiratory volume in 1 second (FEV1), and cough peak flow (CPF) were measured. The percentage VC and %FEV1 were calculated from the ratio of measured VC and predicted VC and FEV1 and FVC, respectively, and the maximum value was adopted.
2.4. Measurement of activities of daily living
Regarding the activities of daily living, a functional independence measure was used to calculate the total exercise and cognitive scores.[40]
2.5. Calculation of REE and BEE
REE was calculated by substituting VO2 and VCO2 into the equation of Weir,[41] and BEE was calculated by substituting height, weight, and age into the Harris–Benedict equation.[42] The estimation equations are shown below:
REE (kcal/day) = [3.94 × VO2 (mL/min) + 1.11 × VCO2 (mL/min)] × 1.44;
BEE (kcal/day) = [66.47 + (13.75 × Weight) + (5.0 × Height) − (6.76 × Age)].
2.6. Nutritional assessment
The controlling nutritional status (CONUT) method was used for evaluating the nutrition status.[43] CONUT scores were obtained from the levels of serum albumin, total cholesterol, and peripheral blood lymphocytes, which reflect protein metabolism, lipid metabolism, and immunity; thus, CONUT is a comprehensive and multifaceted method of assessing nutritional status.
2.7. Statistical analysis
The Wilcoxon signed-rank test was used for REE and BEE comparison within groups, whereas covariance analysis (confounding variable: BW) and effect size (r) were used for the comparison between the groups.[44] The Wilcoxon signed-rank test was used for the 1-year fluctuations, and the effect size (r) was calculated for the degree of difference.[44] Spearman rank correlation coefficient and partial correlation coefficient (confounding variable: BW) were used in relation to body composition, REE, analysis of expired gas index, and pulmonary function. Statistical analysis was performed using SPSS version 21 (IBM Corporation, Armonk, NY). A P value of <.05 was considered significant.
3. Results
Of the 21 patients with DM1, 9 were excluded according to the inclusion/exclusion criteria. The excluded patient criteria were congenital myotonic dystrophy plus severe intellectual disability, tracheostomy, worsening general condition, and refusal to participate in the study. All 16 healthy volunteers participated and underwent measurements in the study (Table 1, Fig. 1). It was possible for all DM1 patients to maintain a sitting position without with support. The sternocleidomastoid (head up at supine position) and rectus abdominal muscles (flexion of the trunk) were evaluated by Daniels and Worthingham muscle manual testing (MMT). Only 2 DM1 patients were able to resist gravity for head up in the supine position. The swallowing function could not be investigated. Seven patients with DM1 and 14 healthy volunteers were followed up. The reasons for failure to follow up were death, tracheostomy, acute exacerbation, general condition deterioration, and refusal. Also, 2 healthy volunteers changed work locations (Table 2, Fig. 1).
Table 1.
Characteristics of the DM1 and control groups.
| DM1 group (n = 12) | Control group (n = 16) | |
|---|---|---|
| Age, yr | 51 (70, 43) | 50 (62, 42) |
| Gender, n | Male: 12 | Male: 16 |
| Onset Age, yr | 35 (45, 14) | – |
| Height, cm | 167 (183, 150) | 169 (178, 152) |
| Weight, kg | 57 (79, 42)** | 71 (83, 55) |
| BMI, kg/m2 | 20 (24, 16)** | 25 (28, 20) |
| CTG repeat length | 1425 (3550, 200) | – |
| MIRS | 5 | – |
| Able to sit without assistance | 12 | |
| MMT | ||
| Sternocleidomastoid m., n | Good: 2, Poor: 10 | |
| Rectus abdominis m, n | Poor: 2, Trace: 10 | |
| %VC, % | 51 (73, 25)** | 112 (142, 57) |
| %FEV1, % | 83 (100, 66) | 80 (90, 70) |
| CPF, L/min | 177 (522, 37)** | 442 (580, 184) |
| FIM, total score | 76 (118, 44)** | 126 |
| FIM, motor score | 44 (83, 20)** | 91 |
| FIM, cognitive score | 29 (35, 16)** | 35 |
| Amount of transfer assistance (wheelchair and bed) | Total assistance | |
| Albumin, g/dL | 3.5 (4.2, 2.9) | – |
| Total cholesterol, mg/dL | 188 (270, 140) | – |
| Total lymphocyte, μL | 1589 (2870, 903) | – |
| CONUT, score | ||
| Normal, n | 5 | – |
| Mild, n | 6 | – |
| Moderate, n | 1 | – |
| Severe, n | 0 | – |
| Swallowing function | – | |
| Ordinary, n | 2 | 16 |
| Dysphagic food, n | 7 | – |
| Tube feeding, n | 3 | – |
| Intake energy, kcal/d | 1275 (1814, 900) | – |
| NPPV at night, n | 12 | – |
Median (maximum, minimum).
BMI = body mass index, CPF = cough peak flow, CONUT = controlling nutritional status, CTG = cytosine-thymine-guanine, DM1 = myotonic dystrophy type 1, FEV1 = forced expiratory volume in 1 second, FIM = functional independence measure, MIRS = muscular disability rating scale, MMT = muscle manual testing, NPPV = non-invasive positive pressure ventilation, VC = vital capacity.
P < .01.
Figure 1.
Inclusion flowchart of patients with DM1 and control in the study.
Table 2.
Comparison of baseline parameters between follow-up and non-follow-up groups.
| Follow-up group (n = 7) | Non-follow-up group (n = 4) | d | |
|---|---|---|---|
| Age, yr | 50.0 (70.0, 43.0) | 49.0 (62.0, 43.0) | 0.18 |
| Onset-age, yr | 34.0 (45.0, 14.0) | 35.0 (42.0, 14.0) | 0.06 |
| Height, cm | 164.0 (174.0, 150.0) | 169.0 (183.0, 160.0) | 0.77 |
| Weight, kg | 54.5 (67.9, 43.0) | 51.6 (79.0, 42.2) | 0.00 |
| BMI, kg/m2 | 20.3 (22.4, 18.7) | 18.5 (23.6, 15.5) | 0.75 |
| CTG repeat length | 1425 (1900.0, 633.0) | 1162 (3550.0, 200.0) | 0.08 |
| %VC, % | 55.0 (72.7, 42.3) | 34.9 (45.8, 25.1)** | 2.45 |
| FEV1, % | 79.9 (97.9, 65.8) | 98.7 (100.0, 83.2)* | 1.73 |
| CPF, L/min | 141.0 (522.0, 37.1) | 168.6 (249.6, 88.2) | 0.34 |
| HR, bpm | 67.3 (96.0, 53.0) | 74.6 (91.8, 67.0) | 0.63 |
| FIM, total score | 88.0 (118.0, 46.0) | 57.0 (86.0, 44.0) | 0.85 |
| FIM, motor score | 56.0 (83.0, 22.0) | 33.5 (52.0, 20.0) | 0.88 |
| FIM, cognitive score | 30.0 (35.0, 16.0) | 24.0 (34.0, 19.0) | 0.58 |
| %REE, % | 78.3 (122.6, 68.3) | 84.8 (95.6, 55.7) | 0.31 |
| Bone density, g/cm2 | 1.3 (1.3, 0.9) | 1.1 (1.3, 1.0) | 0.06 |
| REE, kcal/d | 1059.7 (1438.7, 818.6) | 979.5 (1349.8, 896.0) | 0.26 |
| REE/kg, kcal/kg/d | 17.9 (27.2, 16.1) | 21.4 (24.7, 12.1) | 0.02 |
| UL FMI, kg/m2 | 0.9 (1.2, 0.7) | 0.9 (0.9, 0.6) | 0.42 |
| Trunk FMI, kg/m2 | 6.1 (9.7, 4.6) | 7.0 (8.8, 4.6) | 0.00 |
| LL FMI, kg/m2 | 2.2 (2.9, 1.3) | 2.3 (2.8, 1.4) | 0.12 |
| Whole FMI, kg/m2 | 7.0 (9.7, 6.1) | 7.7 (8.7, 5.2) | 0.14 |
| UL FFMI, kg/m2 | 1.0 (1.3, 0.8) | 0.8 (1.3, 0.7) | 0.59 |
| Trunk FFMI, kg/m2 | 11.8 (13.1, 9.4) | 9.3 (13.2, 8.4) | 0.76 |
| LL FFMI, kg/m2 | 3.1 (3.8, 2.3) | 2.7 (3.9, 2.2) | 0.16 |
| Whole FFMI, kg/m2 | 12.7 (15.8, 11.6) | 10.8 (14.9, 10.1) | 0.94 |
| SMI, kg/m2 | 4.0 (5.1, 3.4) | 3.5 (5.3, 3.0) | 0.30 |
| Intake energy, kcal/d | 1200.0 (1659.0, 900.0) | 1723.5 (1996.0, 900.0) | 1.06 |
| Alb, g/dL | 3.5 (4.0, 3.3) | 3.3 (4.2, 2.9) | 0.57 |
| T-cho, mg/dL | 166.0 (232.0, 140.0) | 211.5 (270.0, 151.0) | 0.76 |
| WBC, µL | 58.4 (75.6, 39.5) | 47.3 (71.7, 37.7) | 0.42 |
| TLC, µL | 1611.2 (2870.4, 903.2) | 1529.0 (2086.5, 1108.4) | 0.31 |
| CONUT, score | 2 (4, 0) | 3 (6, 1) | 1.04 |
Median (maximum, minimum).
BMI = body mass index, CPF = cough peak flow, CONUT = controlling nutritional status, CTG = cytosine-thymine-guanine, d = effect size, FEV1 = forced expiratory volume in 1 second, FFMI = fat free mass index, FMI = free mass index, HR = heart rate, LL = lower limbs, REE = resting energy expenditure, SMI = skeletal mass index, TLC = total lymphocyte count, UL = upper limb, VC = vital capacity, WBC = white blood cells.
P < .05.
P < .01.
The DMI severity in patients is categorized into 4 groups based on the number of CTG repeats as follows: mild phenotype, with an expansion of 50 to 150 CTG repeats; classic phenotype, with symptoms spanning from mild to severe and an expansion of 50 to 1000 CTG repeats; childhood/juvenile phenotype, with early onset and typically >800 CTG repeats; and the most severe congenital form, usually with >1000 CTG repeats.[45] This study involved 8 severe congenital types, 3 classic types, and childhood/juvenile types. Comparatively, BW, BMI, %VC, and CPF were significantly higher in healthy volunteers.
The CONUT rating revealed 5 normal types, 6 mild types, and 1 moderate type. For the feeding mode, 2 patients were normal meals (solid staple and side dishes), 7 patients were swallowing meals (blender or coarsely chopped or soft rice staple food and side dish), and 3 patients were tube feedings (enteral nutrition).
3.1. Comparison between REE and BEE within each group (Table 3 )
Table 3.
Comparison between REE and BEE within each group.
| DM1 group (n = 12) | Control group (n = 16) | |
|---|---|---|
| BEE (kcal/d) | 1367 (1709, 935)* | 1488 (1755, 1301) |
| REE (kcal/d) | 1033 (1439, 819) | 1719 (2201, 1350)* |
Median (maximum, minimum).
BEE= basal energy expenditure, DM1 = myotonic dystrophy type 1, REE = resting energy expenditure.
P < .05.
Patients with DM1 had significantly higher BEE than REE (1033 vs 1367 kcal/day, P < .05), whereas healthy volunteers had significantly higher REE than BEE (1719 vs 1488 kcal/day, P < .05).
3.2. Comparison of metabolism and expired gas index and body composition (Table 4 )
Table 4.
Comparison between 2 groups of metabolism and expired gas index and body composition.
| DM1 group (n = 12) | Control group (n = 16) | d | |
|---|---|---|---|
| VO2, L/min | 0.16 (0.20, 0.09)** | 0.25 (0.34, 0.19) | 2.08 |
| VCO2, L/min | 0.13 (0.18, 0.08)** | 0.22 (0.30, 0.15) | 2.08 |
| TV, L | 0.3 (0.5, 0.2)* | 0.6 (1.2, 0.4) | 2.16 |
| RR, bpm | 17 (26, 10) | 13 (22, 9) | 0.97 |
| VE, L/min | 5.4 (7.3, 3.7)** | 8.8 (11.7, 6.1) | 2.05 |
| HR, bpm | 70 (96, 53) | 64 (92, 47) | 0.97 |
| VO2/HR, mL | 1.9 (3.8, 1.7)** | 3.9 (5.3, 2.7) | 2.88 |
| REE, kcal/d | 1033 (1439, 819)** | 1719 (2201, 1350) | 2.89 |
| REE/BW, kcal/kg | 19.0 (27, 12)** | 25.0 (30, 19) | 2.79 |
| REE/FM, kcal/kg | 52.4 (87.9, 32.7)** | 117.0 (250, 68) | 2.59 |
| REE/LBM, kcal/kg | 34.2 (43.3, 20.8) | 32.0 (42, 25) | 0.71 |
| %REE, % | 79 (123, 56)** | 115 (131, 85) | 2.79 |
| UL FMI, kg/m2 | 0.9 (1.8, 0.6)** | 0.7 (1.0, 0.2) | 1.68 |
| Trunk FMI, kg/m2 | 6.0 (9.7, 4.6)** | 2.9 (5.2, 0.9) | 2.64 |
| LL FMI, kg/m2 | 2.2 (2.9, 1.3)** | 1.5 (2.0, 0.7) | 2.59 |
| Whole FMI, kg/m2 | 7.3 (9.7, 5.2)** | 5.3 (8.5, 2.2) | 2.83 |
| UL FFMI, kg/m2 | 1.0 (2.0, 0.7)** | 2.2 (2.4, 1.6) | 3.36 |
| Trunk FFMI, kg/m2 | 6.7 (7.7, 5.2)** | 9.1 (9.7, 7.6) | 9.60 |
| LL FFMI, kg/m2 | 3.0 (4.5, 2.2)** | 6.1 (7.3, 4.9) | 5.83 |
| Whole FFMI, kg/m2 | 12.0 (15.1, 9.5)** | 18.5 (20.5, 15.6) | 5.48 |
| SMI, kg/m2 | 3.9 (6.5, 3.0)** | 8.1 (9.6, 6.5) | 5.32 |
Median (maximum, minimum).
BW = body weight, d = effect size, DM1 = myotonic dystrophy type 1, FFMI = fat free mass index, FM = fat mass, FMI = free mass index, HR = heart rate, LBM = lean body mass, LL = lower limbs, REE = resting energy expenditure, RR = respiratory rate, SMI = skeletal mass index, TV = tidal volume, UL = upper limb, VCO2 = carbon dioxide output, VE = minute ventilation, VO2/HR = O2 pulse, VO2 = oxygen intake.
P < .05,
P < .01.
Patients with DM1 had significantly lower REE (1033 vs 1719 kcal/day, P < .01), REE/BW (19 vs 25 kcal/kg, P < .01), and REE/FM (52 vs 117 kcal/kg, P < .01). However, there was no significant difference in the REE/LBM (34 vs 32 kcal/kg). The DM1 group had significantly lower VO2 (0.16 vs 0.25 L/min, P < .01), VCO2 (0.13 vs 0.22 L/min, P < .01), VO2/HR (1.9 vs 3.9 mL, P < .01), TV (0.3 vs 0.6 L/min, P < .05), and VE (5.4 vs 8.8 L/min, P < .01). There was no significant difference in respiratory rate and HR.
The body composition of the UL FMI (0.9 vs 0.7, P < .01), LL FMI (2.2 vs 1.5, P < .01), trunk FMI (6.0 vs 2.9, P < .01), and whole-body FMI (7.3 vs 5.3, P < .01) in patients with DM1 were significantly higher. Conversely, UL FFMI (1.0 vs 2.2, P < .01), trunk FFMI (6.7 vs 9.1, P < .01), LL FFMI (3.0 vs 6.1, P < .01), whole-body FFMI (12.0 vs 18.5, P < .01), and SMI (3.9 vs 8.1, P < .01) were significantly lower in patients with DM1.
3.3. Relationship between body composition and REE (Table 5 )
Table 5.
Relationship between body composition and REE.
| DM1 group (n = 12) | Control group (n = 16) | |||
|---|---|---|---|---|
| rs | r | rs | r | |
| Weight, kg | 0.20 | – | 0.57* | – |
| BMI, kg/m2 | 0.27 | 0.27 | 0.53* | 0.19 |
| Whole FM, kg | 0.15 | 0.15 | 0.37 | −0.19 |
| Whole LBM, kg | 0.22 | 0.22 | 0.57* | 0.16 |
| UL FMI, kg/m2 | 0.13 | 0.13 | 0.26 | −0.02 |
| Trunk FMI, kg/m2 | 0.15 | 0.15 | 0.32 | −0.14 |
| LL FMI, kg/m2 | 0.04 | 0.04 | 0.25 | −0.03 |
| Whole FMI, kg/m2 | 0.15 | 0.15 | 0.31 | −0.10 |
| UL FFMI, kg/m2 | −0.03 | −0.03 | 0.45 | 0.18 |
| Trunk FFMI, kg/m2 | 0.36 | 0.36 | 0.66** | 0.45 |
| LL FFMI, kg/m2 | 0.27 | 0.27 | 0.50* | 0.11 |
| Whole FFMI, kg/m2 | 0.28 | 0.28 | 0.64** | 0.39 |
| SMI, kg/m2 | 0.17 | 0.17 | 0.53* | 0.17 |
BMI = body mass index, DM1 = myotonic dystrophy type 1, FFMI = fat free mass index, FM = fat mass, FMI = free mass index, LBM = lean body mass, LL = lower limbs, r = partial correlation coefficient (body weight: confounding variable), rs = Spearman rank correlation coefficient, REE = resting energy expenditure, SMI = skeletal mass index, UL = upper limb.
P < .05,
P < .01.
Body composition and REE in patients with DM1 had a low correlation coefficient and were not related; however, they showed moderate-to-high positive significant correlation coefficient in healthy volunteers (BW, rs = 0.57, whole-LBM, rs = 0.57, trunk FFMI, rs = 0.66, LL FFMI, rs = 0.50, whole-FFMI, rs = 0.64, SMI, rs = 0.53). The partial correlation coefficients were not significantly related in both groups.
3.4. Relationship between body composition, pulmonary function, and analysis of expired gas (Table 6 )
Table 6.
Relationship between body composition, pulmonary function and expired gas analysis index.
| DM1 group (n = 12) | Control group (n = 16) | ||
|---|---|---|---|
| Parameter | rs | rs | |
| %VC | BMI | 0.61* | −0.10 |
| Trunk FFMI | 0.76** | 0.02 | |
| Whole-body FFMI | 0.61* | 0.00 | |
| CPF | BMI | 0.66* | −0.37 |
| Trunk FFMI | 0.61* | −0.43 | |
| HR | Trunk FMI | 0.71** | 0.12 |
| Whole-body FMI | 0.71* | 0.08 | |
| TV | BMI | 0.58* | −0.07 |
| Trunk FFMI | 0.61* | −0.01 |
Note: Only correlated parameters are shown in patients with DM1.
BMI = body mass index, CPF = cough peak flow, DM1 = myotonic dystrophy type 1, FFMI = fat free mass index, FMI = free mass index, HR = heart rate, rs = Spearman rank correlation coefficient, TV = tidal volume, VC = vital capacity.
P < .05.
P < .01.
In patients with DM1, %VC was positively correlated with BMI (rs = 0.61), trunk FFMI (rs = 0.76), and whole-body FFMI (rs = 0.61). CPF showed a significant positive correlation between BMI (rs = 0.66) and trunk FFMI (rs = 0.61). HR was significantly positively correlated with trunk FMI (rs = 0.71) and whole-body FFMI (rs = 0.71). TV showed a significant positive correlation with BMI (rs = 0.58) and trunk FFMI (rs = 0.61).
3.5. Comparison of body composition, pulmonary function, and analysis of expired gas in the follow-up period (Table 7 )
Table 7.
Comparison of body composition, pulmonary function, and expired gas analysis index in the follow-up period.
| DM1 group (N = 7) | Control group (N = 14) | |||||
|---|---|---|---|---|---|---|
| Baseline | After 12 mo | r | Baseline | After 12 mo | r | |
| %VC, % | 55.0 (72.7, 42.3) | 49.2 (83.0, 38.0) | .41 | 114.5 (142.3, 85.0) | 113.5 (138.0, 85.0) | .54 |
| FEV1, % | 79.9 (97.9, 65.8) | 55.0 (96.8, 32.1) | .65 | 80.0 (90.0, 76.0) | 81.0 (88.0, 75.0) | .41 |
| CPF, L/min | 141.0 (522.0, 37.1) | 173.4 (524.5, 51.6) | .33 | 455.0 (580.0, 180.0) | 440.5 (573.0, 178.0) | .56 |
| TV, L/min | 0.4 (0.5, 0.2) | 0.3 (0.5, 0.2) | .56 | 0.6 (1.2, 0.5) | 0.7 (1.8, 0.5) | .53 |
| VE, L/min | 5.7 (6.7, 4.7) | 5.9 (9.2, 4.1) | .28 | 9.7 (11.9, 6.1) | 8.9 (12.5, 6.3) | .31 |
| RR, bpm | 15 (26, 10) | 19 (36, 12) | .37 | 14 (23, 8) | 13 (18, 6) | .55 |
| VO2, L/min | 0.16 (0.20, 0.09) | 0.15 (0.21, 0.08) | .19 | 0.26 (0.34, 0.19) | 0.27 (0.32, 0.22) | .24 |
| VO2/kg, L/min | 2.63 (3.91,1.96) | 2.80 (3.72, 1.71) | .06 | 3.6 (5.6, 2.7) | 3.8 (4.5, 3.3) | .15 |
| HR, bpm | 67 (96, 53) | 70 (101. 48) | .22 | 66 (92, 56) | 63 (83, 57) | .28 |
| VCO2, L/min | 0.13 (0.18, 0.08) | 0.12 (0.16, 0.07) | .71 | 0.22 (0.30, 0.15) | 0.23 (0.36, 0.19) | .16 |
| REE, kcal/d | 1059.7 (1438.7, 818.6) | 1043.0 (1447.0, 638.0) | .26 | 1775.5 (2201.0, 1350.0) | 1920.0 (2391.0, 1552.0) | .67 |
| REE/kg, kcal/kg/d | 17.9 (27.2, 16.1) | 19.4 (25.5, 13.8) | .13 | 24.5 (29.6, 19.3) | 26.7 (34.0, 23.7) | .65 |
| REE/FM, kcal/kg/d | 45.9 (87.9, 41.9) | 48.9 (81.7, 40.9) | .46 | 117.3 (242.1, 67.7) | 115.2 (254.9, 86.2) | .25 |
| REE/LBM, kcal/kg/d | 30.1 (40.1, 23.2) | 32.6 (41.3, 23.9) | .71 | 31.9 (41.5, 25.4) | 36.6 (45.3, 30.5)* | .61 |
| %REE, % | 78.3 (122.6, 68.3) | 81.4 (117.6, 54.8) | .19 | 113.4 (130.5, 84.9) | 125.5 (151.0, 112.0)* | .69 |
| BW, kg | 54.5 (67.9, 43.0) | 53.7 (71.3, 41.5) | .55 | 71.0 (82.8, 55.0) | 71.5 (85.0, 56.0) | .29 |
| BMI, kg/m2 | 20.3 (22.4, 18.7) | 19.0 (23.5, 16.6) | .66 | 26.2 (28.4, 20.7) | 25.9 (28.8, 20.7) | .33 |
| BEE, kcal/d | 1284.3 (1538.6, 934.5) | 1281.5 (1578.8, 900.4) | .56 | 1537.0 (1755.0, 1301.0) | 1557.0 (1753.0, 1305.0) | .04 |
| UL FMI, kg/m2 | 0.9 (1.2, 0.7) | 0.9 (1.0, 0.5) | .30 | 0.7 (1.0, 0.3) | 0.7 (0.9, 0.3) | .65 |
| Trunk FMI, kg/m2 | 6.1 (9.7, 4.6) | 3.7 (5.9, 2.4)** | .96 | 3.1 (5.2, 1.3) | 3.0 (4.7, 1.4) | .53 |
| LL FMI, kg/m2 | 2.2 (2.9, 1.3) | 2.1 (2.8, 1.3) | .61 | 1.5 (2.0, 0.8) | 1.5 (2.1, 0.7) | .03 |
| Whole FMI, kg/m2 | 7.0 (9.7, 6.1) | 6.6 (9.9, 4.7) | .61 | 5.8 (8.5, 2.7) | 5.8 (7.7, 2.8) | .23 |
| UL FFMI, kg/m2 | 1.0 (1.3, 0.8) | 0.9 (1.2, 0.8) | .84 | 2.2 (2.4, 1.6) | 2.1 (2.3, 1.6) | .67 |
| Trunk FFMI, kg/m2 | 11.8 (13.1, 9.4) | 7.0 (7.3, 5.3)** | .99 | 9.1 (9.7, 7.6) | 9.1 (10.2, 7.5) | .07 |
| LL FFMI, kg/m2 | 3.1 (3.8, 2.3) | 3.0 (3.4, 2.2) | .57 | 6.1 (7.3, 4.9) | 5.9 (7.5, 4.8) | .15 |
| Whole FFMI, kg/m2 | 12.7 (15.8, 11.6) | 12.2 (12.8, 9.6) | .90 | 18.9 (20.5, 15.6) | 18.6 (21.2, 15.3) | .20 |
| SMI, kg/m2 | 4.0 (5.1, 3.4) | 3.8 (4.6, 3.1) | .71 | 8.3 (9.6, 6.5) | 8.1 (9.7, 6.3) | .40 |
| Albumin, g/dL | 3.5 (4.0, 3.3) | 3.4 (4.2, 3.3) | .30 | – | – | – |
| Total cholesterol, mg/dL | 166 (232, 140) | 174 (220, 134) | .31 | – | – | – |
| Total lymphocyte, μL | 1611 (2870, 903) | 1548 (2102, 1028) | .30 | – | – | – |
| CONUT score | 2 (4, 0) | 2 (5, 1) | .58 | – | – | – |
| Intake energy, kcal/d | 1200 (1659, 900) | 1100 (1665, 900) | .30 | – | – | – |
| FIM total score | 88 (118, 46) | 70 (107, 45) | .46 | – | – | – |
| FIM motor score | 56 (83, 22) | 37 (72, 21) | .48 | – | – | – |
| FIM cognitive score | 30 (35, 16) | 30 (35, 16) | .38 | – | – | – |
Median (maximum, minimum).
BEE= basal energy expenditure, BMI = body mass index, BW = body weight, CONUT = controlling nutritional status, CPF = cough peak flow, DM1 = myotonic dystrophy type 1, FEV1 = forced expiratory volume in 1 second, FFMI = fat free mass index, FIM = functional independence measure, FM = fat mass, FMI = free mass index, HR = heart rate, LBM = lean body mass, LL = lower limbs, r = effect size, REE = resting energy expenditure, RR = respiratory rate, SMI = skeletal mass index, TV = tidal volume, UL = upper limb, VC = vital capacity, VCO2 = carbon dioxide output, VE = minute ventilation, VO2/HR = O2 pulse, VO2 = oxygen intake.
P < .05.
P < .01.
REE, REE/kg, and %REE were not significantly different in patients with DM1. Despite no decrease in the BW and BMI of patients with DM1, there was a significant decrease in trunk FMI (6.8 ± 1.9, 3.8 ± 1.2, P < .01) and trunk FFMI (11.3 ± 1.5, 6.5 ± 0.9, P < .01). In individual CONUT assessments, there were 3 unchanged cases, 3 worsened cases, and 1 improved case.
4. Discussion
The purpose of this study was to examine the associations and characteristics of body composition, REE, and pulmonary function and to investigate changes over 1 year in male patients with DM1 who were unable to walk. The analysis of expired gas was significantly lower VO2, VCO2, TV, and VE. REE, REE/BW, REE/FM, and %REE were also significantly lower. The appendicular, trunk, and whole-body FMI of patients with DM1 were significantly higher, and limb, trunk, whole-body FFMI was significantly lower. There was no correlation between body composition and REE; %VC was significantly correlated with trunk and whole-body FFMI; and HR was significantly correlated with trunk and whole-body FMI. At 1-year follow-up, trunk FMI and FFMI were significantly reduced.
The low REE of patients with DM1 may be due to low VO2 and VCO2. VO2 is affected by stroke volume, HR, and arteriovenous oxygen difference (AVO2). The cause of the decrease in VO2 was considered the decrease in AVO2. AVO2 reduction is caused by an increase in mixed venous oxygen content, which, in turn, is caused by impaired cardiac function and hemodynamics. VO2/HR of patients with DM1 was significantly reduced. It was considered that the cardiac output and the ability to take in oxygen were reduced. Cardiac function is unclear because it was not measured. In other words, it is not clear whether the decreased VO2/HR is due to reduced cardiac function, ventilatory failure alone, inability of tissues to take up oxygen, severity of illness or multisystemic failure. Therefore, the energy requirement of patients with DM1 was overestimated, suggesting that true metabolism was low.[5] The lower REE for patients with DM1 was similar to previous studies.[4,30,33]
There was no association between REE and body composition in patients with DM1. Factors associated with REE are LBM and a decreased metabolic rate of skeletal muscle and organs.[46,47] The percentage contributing to REE decreased due to decreased LBM and skeletal muscle mass in patients with DM1. Therefore, no association was found between REE and body composition. Previous studies have suggested that basal metabolism of DM1 is associated with LBM, but this was different in this study.[30,47] The patient was male, unable to walk, and severe, suggesting limited results. Furthermore, body composition alone was inadequate to explain the REE reduction[48]; therefore, high-metabolic-rate organs, such as the heart, kidneys, and liver, should be considered.[49] The patients with DM1 in this study exhibited restrictive ventilatory disturbance,[26] something that is consistent with previous research, in which it manifested as a decrease in VC associated with respiratory muscle weakness. %VC showed a positive correlation between trunk and whole-body FFMI.
There was a significant negative correlation between respiratory function and BMI, %VC, and whole-body FMI in previous studies.[18] Fat infiltration and trunk muscle size in patients with DM1 were associated with decreased FVC.[25] Therefore, a decrease in FM and an increase in LBM are important for improving respiratory function. However, FMI and FFMI are not independent factors affecting respiratory function, and it is necessary to consider the progression of the primary disease.[18] When %VC is below 80%, FVC and FEV1, measured in the supine position, are reported to decline significantly.[50] That is, when respiratory muscle strength is reduced, the respiratory motion is affected by the posture. Patients with DM1 in this study had restricted diaphragm movement in the supine position due to restrictive ventilatory impairment and obesity.[27,50,51]
In preliminary research concerning the association between HR and arteriosclerosis risk factors, HR was positively correlated with BMI and triglycerides.[52,53] We found a correlation between HR and FMI. Furthermore, according to a meta-analysis of coronary artery disease prognosis, the total mortality and cardiovascular mortality increase as the number of HR increases, and the risk increases by approximately 10% for every 1 standard deviation increase.[54] In fact, in a longitudinal cohort study of survival in patients with DM1, a systolic blood pressure of <110 mm Hg and an HR of >63 bpm were independently associated with overall survival.[55] Conversely, patients with slow HR were associated with a better vital prognosis.[55] Generally, patients with DM1 have cardiac abnormalities, such as impaired ventricular conduction, arrhythmia, and left ventricular hypertrophy.[56] These might be caused by lesion regions of myocardial fibrosis and fat infiltration, as shown in magnetic resonance imaging and endomyocardial biopsies.[57,58] Therefore, treatment for body composition and heart damage is important from the viewpoint of life prognosis.
The body composition of DM1 was high in FMI and low in FFMI. It is known that fat levels are high in patients with DM1.[18,59] Generally, it has been reported that fat in the trunk and appendicular is increased.[21,31,60] Sarcopenia obesity is defined as an SMI <7.26 kg/m2 and a body fat percentage >28% for men and an SMI <5.45 kg/m2 and a body fat percentage >40% for women.[61] As in the previous study, it is a condition of sarcopenia obesity. The assessment of body composition with DEXA is recommended because SMI correlates with physical performance, such as residual muscle strength, walking speed, and respiratory function.[39] In the course of 1 year, patients with DM1 had significantly reduced trunk FFMI and FMI. However, the other parameters did not change. In the future, it is necessary to consider the long-term progress. In this study, the cause of partial fat atrophy cannot be clarified. However, “The Diagnosis and Management of Lipodystrophy Syndromes: A Multi-Society Practice Guideline” was published in 2016.[62] Lipodystrophy syndromes are metabolic disorders caused by severe insulin resistance, diabetes, high neutral hyperlipemia, and fatty liver. This is unrelated to the intake energy. Here, the cause of partial fat atrophy could not be clarified. With regard to lipodystrophy syndromes, large-scale clinical trials for natural history and the analysis of body composition are necessary.
There are 3 limitations of this study. The first is selection bias: the recruiting method was based on a single posture. The second was confounding bias: in relation to metabolism and body composition, it was necessary to consider highly metabolized organs.[63] The third was dropout bias: we could not follow-up patients with DM1 with reduced respiratory function. It may have been difficult to generalize.
5. Conclusion
Patients with DM1 had poor metabolism that was not related to body composition. FM was high and LBM was low. In the course of 1 year, not only the FFMI but also the core FMI declined. Measurement of body composition and REE leads to understanding of body function and nutritional status.
Acknowledgments
We are grateful to patients, neurology physicians, and medical staff at the National Hospital Organization Akita Hospital in Japan.
Author contributions
KK performed informed consent in the design of the study, measurement of data, writing the text, statistical analysis, risk management, and consent and explanation of the study. MS devised the research design, wrote the paper, and conducted statistical analysis. YF devised a research design, wrote a paper, and performed statistical analysis. YT devised a research design, wrote a paper, and conducted statistical analysis. All authors have read and approved the manuscript.
Conceptualization: Kikuchi Kazuto, Yutaka Furukawa.
Data curation: Kikuchi Kazuto.
Formal analysis: Kikuchi Kazuto, Yutaka Furukawa.
Funding acquisition: Kikuchi Kazuto.
Investigation: Kikuchi Kazuto.
Methodology: Kikuchi Kazuto, Masahiro Satake, Yutaka Furukawa.
Project administration: Kikuchi Kazuto, Masahiro Satake, Yutaka Furukawa.
Resources: Kikuchi Kazuto.
Software: Kikuchi Kazuto, Yoshino Terui.
Supervision: Kikuchi Kazuto, Masahiro Satake, Yoshino Terui.
Validation: Masahiro Satake, Yoshino Terui.
Visualization: Masahiro Satake, Yutaka Furukawa, Yoshino Terui.
Writing – original draft: Kikuchi Kazuto, Masahiro Satake, Yoshino Terui.
Writing – review & editing: Masahiro Satake, Yoshino Terui.
Abbreviations:
- BEE =
- basal energy expenditure
- BMI =
- body mass index
- BW =
- body weight
- CONUT =
- controlling nutritional status
- CPF =
- cough peak flow
- CTG =
- cytosine-thymine-guanine
- DEXA =
- dual-energy X-ray absorptiometry
- DM1 =
- myotonic dystrophy type 1
- FEV1 =
- forced expiratory volume in 1 second
- FFMI =
- fat free mass index
- FM =
- fat mass
- FMI =
- fat mass index
- FVC =
- forced vital capacity
- HR =
- heart rate
- LBM =
- lean body mass
- MIRS =
- muscular disability rating scale
- REE =
- resting energy expenditure
- RR =
- respiratory rate
- SMI =
- skeletal mass index
- TV =
- tidal volume
- VC =
- vital capacity
- VCO2 =
- carbon dioxide output
- VE =
- minute ventilation
- VO2/HR =
- O2 pulse
- VO2 =
- oxygen intake
All data generated or analyzed during this study are included in this published article [and its supplementary information files].
This study was approved by the ethics committee of the National Hospital Organization, Akita Hospital (IRB No. 30/16). In addition, the study was conducted in accordance with the Helsinki Statement. We have obtained written and verbal consent from the participants to participate in the study.
The authors have no funding and conflicts of interest to disclose.
How to cite this article: Kikuchi K, Satake M, Furukawa Y, Terui Y. Assessment of body composition, metabolism, and pulmonary function in patients with myotonic dystrophy type 1. Medicine 2022;101:36(e30412).
Contributor Information
Masahiro Satake, Email: satake@hs.akita-u.ac.jp.
Yutaka Furukawa, Email: erecan328@gmail.com.
Yoshino Terui, Email: terui@hs.akita-u.ac.jp.
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