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1 From the Department of Pediatrics and the Laboratory of Pediatric Endocrinology, Scientific Institute H San Raffaele, University of Milan, Italy.
2 Address reprint requests to S Mora, Laboratory of Pediatric Endocrinology, Scientific Institute H San Raffaele, via Olgettina 60, 20132 Milano, Italy. E-mail: mora.stefano{at}hsr.it.
ABSTRACT
Background: Celiac disease is the most common cause of malnutrition in children of Western countries.
Objective: The objective was to measure body composition in children at the time celiac disease was diagnosed and after consumption of a gluten-free diet (GFD).
Design: We assessed body composition by dual-energy X-ray absorptiometry in 29 children and adolescents with a mean (±SD) age of 9.5 ± 3.4 y at the time celiac disease was diagnosed and in a subset of 20 patients after 1.2 ± 0.2 y of a GFD. We also studied 23 patients aged 21.2 ± 4.6 y who consumed a GFD for 10.6 ± 4.5 y. Each patient was matched with a healthy control subject of the same age and sex.
Results: Untreated patients weighed less than control subjects (P = 0.04). Fat mass and bone mineral content were lower in the patients than in the control subjects (P < 0.01), as was lean mass of the limbs (P = 0.0013). After 1 y of the GFD, there were no significant differences in body-composition values between patients and control subjects. Similarly, body-composition values of celiac disease patients who consumed the GFD long term were comparable with those of healthy subjects.
Conclusions: Remarkable abnormalities in body composition were found in children at the time of diagnosis of celiac disease. Appropriate dietary treatment reverses body-composition abnormalities quickly and the beneficial effects of gluten withdrawal are persistent. Because these results are harder to achieve if celiac disease is first diagnosed in adulthood, efforts to encourage early diagnosis of celiac disease should be made.
Key Words: Body composition • celiac disease • children • dual-energy X-ray absorptiometry • gluten-free diet
INTRODUCTION
Undernutrition is a common contributor to morbidity and mortality. Consideration must be given to the mass of the major body components, which are markedly altered by nutritional deficiencies. Because of continuing interest in body composition in clinical disorders, several methods have been developed in the last 2 decades. The most accurate noninvasive method for the assessment of body composition is dual-energy X-ray absorptiometry (1, 2). The accuracy of this technique was directly validated by chemical analysis of carcasses (3, 4). Dual-energy X-ray absorptiometry provides direct measurements of bone mineral content (BMC) and fat mass and indirect measurements of lean mass; it detects even small changes in body composition (5).
Celiac disease is probably the most common cause of overt or latent malnutrition in children in Western countries, with a prevalence of 1:250 on the basis of population studies (6, 7). In untreated adult celiac disease patients, body-composition analysis showed abnormal measurements for many body components (8–13). Abnormal measurements of one or more body-composition compartments persisted in most studies even after treatment (8–11, 13). Few studies in children and adolescents with celiac disease are available (14, 15), and the results of these studies are controversial, probably because of the different techniques used and because of differences in study design. Moreover, it has been suggested that a gluten-free diet (GFD) contributes to the poor dietary status of adolescents with celiac disease, who often consume an unbalanced diet (16).
The present study was designed to assess body composition in a group of children with celiac disease at the time of diagnosis, to determine the effect on body composition of short-term (1 y) dietary treatment in this same group of children, and to determine the effect on body composition of long-term (>5 y) dietary treatment in a group of adult patients with celiac disease. The results of body-composition measurements were compared with those of healthy control subjects matched for sex and age.
SUBJECTS AND METHODS
Subjects
We studied 29 (14 boys and 15 girls) consecutive white patients at diagnosis of celiac disease with a mean (±SD) age of 9.54 ± 3.42 y. Diagnosis of celiac disease was made according to the criteria of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (17); All patients had anti-endomysium antibodies. Histologic evaluation of intestinal mucosa specimens was done by conventional microscopy; in all cases we found subtotal villous atrophy. Four patients presented with typical intestinal symptoms; the remaining subjects had short stature, iron deficiency anemia, or a sibling with celiac disease. A subset of 20 patients (10 boys and 10 girls) aged 10.12 ± 3.07 y was studied at diagnosis and after 1.02 ± 0.15 y of consuming a GFD (longitudinal study). Compliance with the diet was ascertained by measuring serum antiendomysium antibodies during the follow-up period. The patients did not take dietary supplements, except for iron and folate.
To monitor the efficacy of a long-term GFD in maintaining body composition, we also studied 23 young adults (8 men and 15 women) aged 21.20 ± 4.62 y with celiac disease who had begun a GFD during childhood or adolescence. These subjects consumed the GFD for 10.6 ± 4.5 y (range: 5–21 y).
Each patient was matched by sex and chronologic age to a healthy control subject. The ages of each pair of subjects differed by <6 mo. We therefore studied 3 distinct groups of healthy subjects. Control subjects were all in good health and appropriately physically active for their age. Candidates were excluded if they had a chronic illness or if they had taken any medication known to interfere with bone metabolism. All subjects underwent a physical examination and measurements of weight and height were made. Informed consent was obtained from all parents of the patients and control subjects and from all adult subjects. The study was performed according to the principles of the Declaration of Helsinki and it was approved by the ethics committee of our Institution.
Methods
Weight was measured with an electronic scale while the subjects were wearing minimal clothing. Height was measured to the nearest millimeter with a wall-mounted Harpenden stadiometer (British Indicators Ltd, London). Body mass index (BMI) was calculated as weight (kg)/height2 (m). Body composition was assessed with dual-energy X-ray absorptiometry by using a DPX-L scanner (Lunar Corp, Madison, WI) equipped with pediatric software (version 1.5e). Scans were performed with the subject in the supine position; the younger children did not require sedation. The pediatric medium scan mode was used for children who weighed <30 kg, as recommended by the manufacturer. The fast adult scan mode was used for all other subjects. The entire body of each subject was scanned, beginning at the top of the head. Measurement times varied according to the height of the subject. Effective radiation exposure was <1 µSv for each scan (18). Fat mass was expressed in kilograms and as a percentage of total-body tissue mass (% fat mass); total lean mass was expressed in kilograms and as a ratio to height. Total body scans were divided into several regions (19) and the lean mass of the limbs was calculated and expressed in kilograms. BMC was expressed as total bone mass (g). Daily quality-assurance tests were performed according to the manufacturer's instructions. The precision of the instrument was calculated as 0.7% for fat mass, 0.9% for lean mass, and 1.5% for BMC.
Statistical analysis
All results are expressed as means ± SDs. The normalcy of the distribution of the data was tested by using the Shapiro-Wilk test; all variables were normally distributed; therefore, differences between patients and control subjects were analyzed by using Student's t test for paired samples. All tests were conducted at the = 0.05 level and were two tailed. Statistical analyses were performed by using the software program JMP IN (SAS Institute, Inc, Cary, NC).
RESULTS
Prospective study
Age and anthropometric and body-composition measurements are shown in Table 1. By design, there was no significant difference in the chronologic age of the 29 matched pairs of children. Celiac disease patients were shorter than their matched pairs, but the difference was not significant. However, children with celiac disease weighed significantly less than control children. Lean mass was 8.5% lower in the patients than in the control subjects, but the difference was not significant, even after correction for height. In contrast, there was a mean difference of 2.4 kg (equal to 22.2% of the mean value of control subjects) in the lean mass of the limbs between groups. Fat mass and % fat mass were also significantly lower in celiac disease patients. Finally, the celiac disease patients had a BMC that was 250 g lower on average than that of control subjects.
View this table:
TABLE 1.. Age and anthropometric and body-composition measurements in untreated celiac disease patients and healthy control subjects matched for sex and age1
Longitudinal study
At diagnosis, the subset of 20 celiac disease patients did not differ significantly from the control subjects in chronologic age, height, BMI, or lean mass (Table 2). Untreated celiac disease patients weighed significantly less than their matched control subjects. Fat mass expressed in kilograms and as a percentage was significantly lower in the untreated celiac disease patients than in their matched control subjects. Lean mass did not differ significantly between the control subjects and the untreated or treated celiac disease patients, even when corrected for height. Conversely, lean mass of the limbs and BMC were significantly lower in the untreated patients than in the control subjects.
View this table:
TABLE 2.. Age and anthropometric and body-composition measurements in 20 celiac disease patients at diagnosis and after consumption of a gluten-free diet (GFD) for 1.02 ± 0.15 y compared with 2 distinct groups of healthy control subjects matched for sex and age1
Compliance with the diet was good in all patients, as evidenced by the absence of anti-endomysium antibodies. After consuming the GFD for 1.02 ± 0.15 y, the patients' weight, fat mass, % fat mass, lean mass of the limbs, and BMC values no longer differed significantly from those of matched healthy control subjects (Table 2). The difference in lean mass of the limbs between the 2 groups was 0.6 kg, or 5% of the mass of control subjects.
Long-term gluten-free diet
By design, the 23 pairs of subjects did not differ significantly by age (Table 3); however, celiac disease patients weighed less and were significantly shorter (t = -4.2, P = 0.004) than their age- and sex-matched control subjects. Fat mass, % fat mass, lean mass, lean mass:height, lean mass of the limbs, and BMC measurements of celiac disease patients did not differ significantly from those of control subjects. The difference in lean mass of the limbs between the 2 groups was 1.2 kg, or 6.5% of the mass of control subjects. Compliance with the diet, assessed by measurements of antiendomysium antibodies, was good: only 3 patients had antibodies at the time of examination. The exclusion of these 3 subjects from the group did not alter the results of the statistical analyses.
View this table:
TABLE 3.. Age and anthropometric and body-composition measurements in celiac disease patients after consumption of a gluten-free diet for 10.6 ± 4.5 y and in healthy control subjects matched for sex and age1
DISCUSSION
In the present study, we describe changes in body composition in celiac disease patients studied at diagnosis and after a short-term and long-term GFD. For ethical reasons, we did not study healthy control subjects longitudinally. Therefore, 3 different groups of healthy subjects were matched to the celiac disease patients for age and sex to avoid biases due to the striking variability in anthropometric variables that is expected in growing subjects. Dual-energy X-ray absorptiometry was used to assess body composition because it is the most accurate method available clinically and because of its versatility, high accuracy and precision, short scanning time, and low radiation exposure. Healthy control subjects were not screened for celiac disease; they were selected after a careful evaluation of their clinical history and on the basis of being healthy as determined by physical examination. The prevalence of celiac disease in our population was 1:200 (6); therefore, the estimated probability of having included a subject with celiac disease in our control group was not very high. Nevertheless, if this occurred it would have strengthened our results.
We found that weight, fat mass, and BMC were significantly lower in untreated patients than in control subjects. Interestingly, the lean mass of celiac disease patients was on average 8.5% lower than that of the healthy control subjects. Nevertheless, the difference was not significant. We assessed separately the lean mass of the limbs, which was shown previously to be closely related to total-body muscle mass in both experimental (20) and clinical (21) studies. Despite mild signs of nutritional imbalance, the extent of muscle mass depletion should not be underscored: our data showed for the first time that a change in lean mass was sustained by a remarkable reduction in muscle mass rather than by a decrease in visceral mass. Muscle tissue represents an important source of amino acids that can be used, if necessary, to produce glucose and energy (22). In contrast, visceral organs have virtually no energy reserves (23). Previous studies that examined changes in body composition in subjects with naturally evolving chronic undernutrition showed that muscle mass was more likely to be reduced than was nonmuscle lean or visceral mass in cases of mild-to-moderate energy deficiency, whereas visceral lean mass mobilization occurred only in severe forms of undernutrition (24).
The introduction of a GFD in children with celiac disease promotes a faster growth rate and faster bone maturation (25, 26) and may lead to the intake of hyperenergetic foods and secondary overweight (27). Consumption of the GFD for 1 y promoted a remarkable increase in body-compartment masses in our patients: the differences from healthy subjects observed before the dietary treatment began were no longer present. Our data confirm the results of a previous study based on anthropometric measurements and single-photon absorptiometry in pediatric patients (14). A second study showed low BMC values in a group of children with celiac disease after they consumed a GFD short term (<1 y) and showed complete recovery in BMC in another group of patients who consumed a GFD for a longer time (>1 y) (15). This discrepancy was probably due to the heterogeneous population studied by Scotta et al: their group of patients receiving a GFD short-term included 9 untreated patients as well as patients who consumed a GFD for a short time.
The results of studies in adults are controversial. Some showed incomplete recovery in one or more body-composition compartments after consumption of a GFD: Capristo et al (11) described lower than normal fat mass and fat-free mass but normal % fat mass in 18 patients studied by anthropometry and bioimpedance. Kemppainen et al (28) found no differences in anthropometric measurements (BMI, skinfold thicknesses, midarm muscle circumference, fat-free mass, and % fat mass) between 52 celiac disease patients who consumed a GFD for 12 mo and 40 untreated celiac disease patients. Results of longitudinal studies of celiac disease patients were published by another group (12, 13). Mautalen et al (12) studied 14 patients at the time of diagnosis and after 12 mo of a GFD; results showed that only fat mass and BMC were lower than normal in untreated patients, who had normal values after consuming the GFD. The study by Smecuol et al (13) assessed body composition in 25 patients before and after 3 y of consuming a GFD. Fat mass and bone mass increased significantly after treatment; in contrast, fat-free mass did not increase significantly. No comparison with healthy control subjects was made in either study. Therefore, it seems likely from our and previous data that a GFD initiated during childhood restores body composition faster and more completely than it does during adulthood.
In the adult celiac disease patients who consumed a GFD long term, we found normal BMI, lean mass, lean mass of the limb, fat mass, and BMC values. On the contrary, Gonzalez et al (9) reported low bone mass and fat mass values, but normal BMI and fat-free mass values in 12 adult patients who consumed a GFD for a mean of 16 y (range: 2–26 y). Bodé et al (8) reported low fat mass and BMC values, but high fat-free mass values in 22 adult patients who consumed a GFD for a mean of 3.6 y (range: 1–24 y) studied by dual-energy X-ray absorptiometry. Our group of treated celiac disease patients was significantly shorter than control subjects; this finding could be explained by the large percentage of patients' parents who were of short stature (25) rather than by poor nutritional status.
In conclusion, our data show lower than normal fat mass, muscle mass, and BMC values in untreated celiac disease patients; visceral lean mass was normal in these patients. The longitudinal study showed that a GFD initiated during childhood and adolescence allows complete recoveries of fat mass, lean mass, and bone mass; moreover, a long-term GFD maintains normal body composition in young adults. Because these results are harder to achieve if celiac disease is first diagnosed in adulthood, efforts to encourage early diagnosis of celiac disease should be made.
REFERENCES