原著論文

Resting energy expenditure and regional body composition
in myotonic dystrophy type 1 patients
Kosuke Yoshida, MD, Yoko Aburakawa, MD, PhD, Yasuhiro Suzuki, MD, PhD,Kenji Kuroda, MD, PhD and Takashi Kimura, MD, PhD
Depertment of Neurology, Asahikawa Medical Center, National Hospital Organization, Asahikawa, Japan

ABSTRUCT
Objectives: In this study, we compared regional body composition and resting energy expenditure (REE)
in myotonic dystrophy type 1 (DM1) patients with matched controls. We evaluated the relationshipbetween regional body composition and REE in DM1 patients.
Methods: REE was studied by indirect calorimetry, and fat mass and fat-free mass were calculated bydual-energy X-ray absorptiometry in 18 DM1 patients and 10 age-matched healthy volunteers. In DM1
patients, we evaluated body muscle computed tomography and blood examination.
Results: DM1 patients had lower fat-free mass than controls (P < 0.05 - 0.001), but there were no groupdifferences in age, height, weight, or fat mass. REE was lower in DM1 patients than controls (P <0.01). In a multiple linear regression analysis, REE correlated with fat-free mass (beta 0.805, P < 0.001)
and serum gamma glutamyl transpeptidase (beta 0.352, P = 0.01) in DM1 patients. In controls, REE
correlated with weight (beta 0.86, P = 0.001).
Conclusion: REE decreased in DM1 patients. REE is proportional to whole body fat-free mass and serum
gamma glutamyl transpeptidase in DM1 patients. Thus, REE should be a good indicator for evaluating
new therapies targeting muscles even if patients cannot walk.
symptoms arise from abnormal RNA １）. Clinical features ofINTRODUCTION

DM1 include progressive muscle atrophy and weakness, grip

Myotonic dystrophy type 1 (DM1) is an autosomal

and percussion myotonia, hatchet face, and involvement of

dominant inherited disorder related to the extension of athe central nervous system, eyes, heart, and endocrine

trinucleotide (CTG) repeat in the 3 -untranslated region ofsystem. Expansion of the CTG repeats modifies clinicalthe myotonic dystrophy protein kinase gene. Although thisseverity and age of onset. New therapeutic strategies have

expanded region is in a non-coding sequence, many

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Kosuke Yoshida4048 Hanasaki cho 7 chome, Asahikawa, Hokkaido, Japantelephone +81 166 51 3161 fax +81 166 53 9184
email yoshidak@asahikawa.hosp.go.jp.

―7―DM1 patients have metabolic syndromes including
insulin resistance, increased body fat mass, and2200c (COSMED S.r.l., Rome, Italy). We measured at least
one hour from the most recent meal.

hypertriglyceridemia. A previous study reported decreased４）

Regional body composition was obtained by dual. REEenergy X-ray absorptiometry. All scans were performed

is decreased in Duchene muscular dystrophy and Becker

and analyzed by a certified technician in our hospital. To

resting energy expenditure (REE) in DM1 patients
muscular dystrophy

５）

muscular dystrophy

６）

but increased in Emery-Dreifussmeasure regional body composition, the software divided. It is difficult to measure total

the body into trunk (except for the head), left and rightenergy expenditure and basal energy expenditure, but REE

entire arms, and left and right entire legs. The whole bodymay be measured by indirect calorimetry.

measurement was the sum of these components. The arm

Body mass index is not useful for fat mass assessment

regions were delineated by a vertical line passing throughin neuromuscular disorder patients because these patientsthe shoulder joint, and the leg regions were delineatedhave higher fat/muscle ratios due to fat infiltration into

by an oblique line passing through the femoral neck. The

atrophied muscles. Dual energy X-ray absorptiometry is ascans were analyzed with the enCORE software for bodynoninvasive technique that provides regional estimations ofcomposition assessment: soft tissue mass; fat mass; fat-fat-free mass, fat mass and bone mineral content７，８）

and isuseful for assessment in these patients.

free mass; and bone mineral content. Body mass index wascalculated by dividing body weight (kg) by height squaredThis study aims to compare fat-free mass to fat mass(m2).

in DM1 patients with matched controls and to evaluate

To estimate body muscle annually, all patients withthe relationship of REE with whole and regional body

DM 1 underwent CT scans. Thus, we estimated volumes

composition in DM1 patients.

of hypermetabolic organs from CT. REE for each of theseorgans was assessed using the specific resting metabolic

METHODSrates (Ki, in kcal/kg per day) suggested by Elia et al.10）forheart, liver, kidney, adipose tissue, and skeletal muscle.

Participants
Eighteen DM 1 patients aged 35 to 70 years (mean:48.89,Skeletal muscle was calculated by subtracting total

sd:11.17) were recruited from our neurology department.

volume of heart, liver, and kidney from the fat-free massDM1ZDVGLDJQRVHGE\FRQ¿UPLQJWKHH[SDQVLRQRI&7*

measurement.

repeats on genomic DNA extracted from peripheral blood

Statistical Analysis.

leucocytes using Southern blot analysis in all patients.

All analyses were performed using SPSS Version

Disease severity was assessed using the muscular disability

20 (IBM) with a P-value of 0.05 as significant. Group９）. Computed tomography (CT) wascomparisons between DM1 subjects and respective age-performed in all patients to evaluate body muscle. We also

matched controls were performed using paired Student

studied blood cell counts, serum biochemistry and thyroid

t-tests; chi-square tests were used for categorical variables.

function.

Within each group, we calculated Pearson correlation

rating scale (MIRS)

Ten healthy volunteers were screened from our hospitalcoefficients between REE and other variables, andco-worker as controls. They were matched with patients byperformed multiple linear regression using variables thatage and gender.

had P-values less than 0.20.

Standard Protocols and Patient Consents
Ethic approval was obtained from the National Hospital
Organization Asahikawa Medical Center Ethic Committee.

RESULTS
Demographics and Regional Body Composition.
Whole body and regional fat-free and fat masses

All participants provided informed consent.

were obtained from each participant. Demographic andMeasurements
REE was estimated by indirect calorimetry, using Fit

anthropometric data are showed in Table 1. Body mass―8―

index was greater than 25 kg/m2 in 4/18 of DM1 patientsweight, and body mass index.

and 3/10 of controls. There was no significant difference

Fat-free mass was lower in DM1 patients compared tobetween DM1 patients and controls for age, gender, height,controls (30.2 ± 5.93 kg vs. 44.8 ± 9.46 kg, P < 0.001).

Table 1. Demographics and anthropometric data.

―9―

There was also a trend for fat mass to be higher in DM1= 0.775; P = 0.004), fat-free mass in trunk (r = 0.850; P =patients (23.3 ± 6.84 kg vs. 18.7 ± 6.56 kg, P = 0.097).

0.001), fat-free mass in left arm (r = 0.737; P = 0.008), fat-General characteristics of DM1 patients

free mass in right arm (r = 0.781; P = 0.004), fat-free mass

The mean CTG repeat expansion was 1426 (all patientsin left leg (r = 0.808; P = 0.002), fat-free mass in right leg

range: 400-2025) in DM1 patients. One patient (5.6%) was(r = 0.799; P = 0.003), and fat-free mass of the whole bodyassigned MIRS = 3, four patients (22.2%) were MIRS = 4,

(r = 0.837; P = 0.001). We further analyzed the relationshipand 13 patients (72.2%) were MIRS = 5. For all patients,

between REE and these variables using multiple linear

we estimated the mean volumes of major organs fromregression. In the multiple linear regression analysis, REE ofCT scans. Table 2 provides the mean estimated volumes

controls correlated only with weight (beta = 0.86; P = 0.001).

of liver, heart, and kidneys, as well as adipose tissue andThe regression equation was REE = 20.81 ± weight (kg) +skeletal muscle. The results of blood tests in DM1 patients224.

are shown in Table 3. One patient was diagnosed withIn DM1 patients, REE correlated with fat-free mass inhypothyroidism and treated by levothyroxine sodium

all body composition (Table 1) measurements and somehydrate.

blood measurements (Table 3). We applied linear multiple
regression using variables that had P < 0.20 for bivariate

REEcorrelations. REE correlated with fat-free mass of whole

The REE was lower in DM1 patients than in controls

body (beta = 0.805, P < 0.001) and gamma glutamyl(1178 ± 221 kcal/day vs. 1560 ± 280 kcal/day, P = 0.002).

transpeptidase (GGT) (beta = 0.352; P = 0.01) (Figure 1)

REEs from each organ were estimated in DM1 patients. Wewith a regression equation of REE (DM1) = 30.0 ± WB

did not estimate from the brain (Table 2).

FFM + 1.49 ± GGT + 140. We divided the DM1 patients

In controls, REE correlated with weight (r = 0.862; P =into two groups based on severity (MIRS of 5 vs. lower0.001), height (r = 0.749; P = 0.006), body mass index (rMIRS). The REE was lower in patients with MIRS of 5

Table 2. Volume and REE of major organs in DM1 patients.

― 10 ―

Table 3. Blood counts, serum biochemistry, and thyroid measures in DM1 patients.

― 11 ―

Figure 1. Scatter plot between REE and FFM or GGT.

(1095 ± 173.5 kcal/day vs. 1394 ± 192.9 kcal/day; P =The elevated serum GGT in DM1 patients seems to be0.006).

from nonalcoholic fatty liver disease. However, it is unclearthat the relationship between fatty liver disease and REE.

DISCUSSION

On the other hands, Generally elevation of serum GGT isWe demonstrated that REE in DM1 patients wasassociated with oxidant stress especially in liver cirrhosis

decreased compared with healthy controls. In addition, REE

patients 11）. Liver cirrhosis patients have higher REE

in DM1 patients correlated with fat-free mass of wholethan normal controls 12）. DM1 patients frequently havebody and serum GGT.

nonalcoholic fatty liver disease, which is associated with

REE in healthy controls correlated with body weight.

insulin resistance and features of metabolic syndromes13）.

We found that the difference between DM1 and controls

Serum GGT is a marker of nonalcoholic fatty liver disease

in body composition was fat-free mass; there were noin patients with metabolic syndrome14） and not only insignificant differences in fat mass in any region. Fat-free

DM1; it may also be elevated by a biliary system disordermass in this study is mainly composed from skeletal muscle

such as gallstones. However, we could not detect gallstones

and smooth muscle because bone mineral content wasin our DM1 patients in body muscle CT. This result

measured separately from other body composition in ourindicates that liver dysfunction associated with REE indual energy X ray absorptiometry. We analyzed the REEs

DM1 patients is similar to those of liver cirrhosis patients.

of major organs as predictor variables in multiple linear

REE measured by indirect calorimetry is all metabolic

regressions. Finally these variables were excluded. This fact

HQHUJ\WKDWLVQRWFRUUHFWHGIURPERG\SUR¿OH2QWKHRWKHU

indicates that skeletal muscle plays an important role about

hand, the Harris-Benedict equation is corrected from bodyREE.

profile. REE is more important than the Harris-Benedict

Serum GGT is another predictor variable for REE inequation in nutrition management of neuromuscular diseaseDM1 patients. Serum GGT reflects mainly liver disease.

in abnormal body profile. We consider that body mass

― 12 ―

index and other body region index are not useful in same

6. Vaisman N, Katzenellenbogen S, Nevo Y. Increased restingenergy expenditure in subjects with Emery-Dreifuss muscularreason.

dystrophy. Neuromuscular Disorders: NMD. 2004 ;14(2):142–

This study has some limitations. First, the DM1 patients
participated in this study are severely disabled. Seventeen
patients had MIRS ratings greater than 4. Thereby we146.
7. Evans E, Misic M, Mallard D. A technique to assess bodycomposition and sarcopenia using DXA: application

could not examine completely the relationship between

for an obese population. European Journal of Clinical

REE and MIRS stages. Second, we estimated REE ofNutrition.2009;64(2):218.

major organs by evaluating their volumes with muscle CT.

8. LaForgia J, Dollman J, Dale MJ, Withers RT, Hill AM.
Validation of DXA body composition estimates in obese men

However, body muscle CT was originally performed toobserve muscle atrophy and its distribution. It is difficultand women. Obesity. 2009;17(4):821–826.
9. Mathieu J, Boivin H, Meunier D, Gaudreault M, Bégin P.

to measure the area of major organs exactly. We could notAssessment of a disease-specific muscular impairment rating¿QGDFRUUHODWLRQEHWZHHQ5((DQGPDMRURUJDQVEXWRQH

scale in myotonic dystrophy. Neurology. 2001;56(3):336–340.

may exist. Third, healthy controls were recruited from our

10. Elia M. Organ and tissue contribution to metabolic rate.

hospital. This may be a bias because hospital workers may

In: Kinney J, Tucker H, editors. Energy Metabolism: Tissue
Determinants and Cellular Corollaries. New York: Raven Press;

have greater knowledge about health. This may result in
more differences between the two groups.

1992. p. 61.
11. Müller MJ, Lautz HU, Plogmann B, Bürger M, Körber J,

In conclusion, we demonstrated the following twoSchmidt FW. Energy expenditure and substrate oxidation inthings. First, REE in DM1 patients was decreased relative

patients with cirrhosis: the impact of cause, clinical staging andnutritional state. Hepatology. 1992;15(5):782–794.

to healthy controls. Second, REE in DM1 patients isproportional to the fat-free mass of whole body and gamma

12. Müller MJ, Böttcher J, Selberg O, et al. Hypermetabolism
in clinically stable patients with liver cirrhosis. The American

glutamyl transpeptidase. This fact indicates that REE in

Journal of Clinical Nutrition. 1999;69(6):1194–1201.

DM1 is associated with muscle volume and liver function.

13. Shieh K, Gilchrist JM, Promrat K. Frequency and predictors ofThus, REE will be a good indicator of evaluating newnonalcoholic fatty liver disease in myotonic dystrophy. Muscle

therapies targeting muscles even if patients cannot walk.

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