Coeliac disease (CD) is a complex autoimmune disorder, which occurs in genetically predisposed individuals after exposure to gluten-containing foods. The prevalence of CD is estimated to be 0.5% to 1% in the general population (1), and, in particular, in Italy was 1.2% through a salivary radioimmunological screening among schoolchildren (2).
The disease is characterised by the presence of serum anti-tissue transglutaminase (tTGAb) and anti-endomysium autoantibodies (EMAs), and typical changes on small bowel biopsy: lymphocyte infiltration, crypt hyperplasia, and villous atrophy according to the Marsh-Oberhuber classification (3). A lifelong gluten-free diet (GFD) is, for the time being, the only available and effective treatment for CD.
CD has been traditionally regarded as a malabsorption disorder with attendant diarrhoea and weight loss. The widespread use of serological tests has changed the clinical spectrum of recently diagnosed patients with CD.
In the literature, there are some case reports about the coexistence of CD and overweight/obesity (4–6). Obesity is the most prevalent nutritional disorder among children and adolescents in the United States and in Europe. In Italy, the prevalence of overweight and obesity is 31.1% and 14.3%, respectively (7). In paediatric patients with CD, the prevalence of obesity was below that in general population, with range from 5% to 9% (8–10).
The prevalence of CD among obese paediatric patients has not been determined yet. Our aim was to detect the prevalence of CD in a large series of paediatric overweight/obese patients and the effects of GFD on their nutritional parameters during follow-up.
We retrospectively reviewed the data of 1527 children (727 boys, median age 10.82 years, age range from 2.05 to 24.17 years) who attended the Paediatric Nutrition and Dietetics Centre of “La Sapienza” University of Rome during the period January 1998 to June 2013. Every patient at the admission was evaluated for weight (recorded with a medical, nonelectronic balance to the nearest 100 g), stature (taken with a Harpenden Stadiometer, Loltain, Crosswell, UK), and waist circumference (taken at the end of a normal expiration midway between the inferior margin of the last rib and the ileal crest).
Patients’ weight, height, and body mass index (BMI) were converted to age-specific percentiles and z scores derived from growth charts published by the Centers for Disease Control and Prevention (11). The waist circumference was compared with the cutoff of the 90th percentile according to McCarthy's modified table (12), but, above all, it was measured to obtain the waist/height ratio (WtHR), an index easier to use than waist percentiles, useful to identify, regardless of sex and age, overweight children with a higher likelihood of having metabolic and cardiovascular risks (13). In patients ages >24 months, the BMI percentile was evaluated according to Centers for Disease Control and Prevention 2000 reference tables (cutoff values: 85th percentile for overweight, 95th percentile for obesity).
Every patient was evaluated by a dietician and a psychologist to find possible cases of bulimia. Among others laboratory tests, serum cholesterol (total, high-density lipoprotein [HDL], and low-density lipoprotein [LDL] fraction), triglycerides, aspartate transaminase, alanine aminotransferase, glucose, and insulin were measured using commercial kits. Homeostatic Model Assessment of Insulin Resistance was calculated.
A serological screening for CD, through EMA by an immunoflorescence method (Eurospital, Trieste, Italy) and IgA tTGAb performed using an enzyme-linked immunosorbent assay method (Menarini, Firenze, Italy), was included in the basic laboratory examination.
Patients positive for CD-related autoantibodies were referred to the Coeliac Disease and Malabsorption Disorders Centre of the Paediatric Department of “La Sapienza” University of Rome for further evaluation. Confirmed positive patients underwent upper gastrointestinal endoscopy, after narcosis, using an Olympus PQ20 or GIF-E gastroscope (Olympus, Tokyo, Japan). During each endoscopy at least 5 biopsies (2 from duodenal bulb and 3 from distal duodenum) were taken, oriented on filter paper, and then fixed in 4% formalin. Each fragment was separately embedded in paraffin blocks, serially cut, stained with haematoxylin/eosin, and assessed under light microscopy by a single expert pathologist. The histological lesions of the small intestinal mucosa were evaluated according to the Marsh classification, as modified by Oberhuber et al (3).
The diagnosis of CD was performed according to the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition criteria (14). After CD diagnosis, children were invited to start a nutritionally balanced GFD, with an energy suggested intake in accordance with their ideal weight. Serological and clinical evaluations every 3 months in the first year and then every year had been scheduled. Accordingly, nutritional parameters were evaluated after 1 year of follow-up.
The statistical analysis of the results was performed with the program SPSS version 16.0 (SPSS, Chicago, IL). Unless otherwise indicated, all values were reported as mean ± standard deviation (SD). A χ2 test, or the Fisher exact test if required, was applied for the qualitative analyses. Analysis of variance was performed for quantitative variables. A P value <0.05 was considered significant.
In all of the patients evaluated, the diagnosis of bulimia was excluded. Among the 1527 screened patients, the obese patients numbered 919/1527 (60.18%), whereas 608 (39.82%) were overweight. Seventeen patients (1.11%, 7 boys, mean age 10.88 years) who had a positive test for IgA EMA and/or tTGAb underwent upper gastrointestinal endoscopy with multiple biopsies, showing CD-related duodenal histological lesions (70.58% showed total villous atrophy [type 3c lesions], 23.52% partial villous atrophy [type 3b lesions], and only 1 [5.9%] mild villous atrophy [type 3a lesions]) all with a diffuse distribution. Among children proved to have coeliac disease, 5 (29.4%) presented typical manifestations of the disease (diarrhoea and/or abdominal pain), 2 atypical (11.8%) (iron-deficiency anaemia, headache), and 10 (58.8%) were asymptomatic. All 17 had a negative family history for CD. There was no difference between patients with CD and without CD in terms of mean value of: z BMI, WtHR, total serum cholesterol, LDL, HDL, and triglyceride serum levels (Table 1). Nine of 17 patients with CD were obese (52.94%) and 8 overweight (47.06%); whereas among patients without CD, 910 of 1510 (60.26%) were obese and 600 (39.73%) overweight.
All of the children with CD started a strict GFD with improvement of symptoms in symptomatic patients in approximately 3 to 6 months. All but 1 patient with CD, after starting the GFD, performed at least 1 follow-up examination, in which they received detailed advice about their nutrition and the GFD.
At follow-up 2 of 10 children were not strictly adherent to the GFD and tested weakly positive for tTGAb. At this time, the z BMI mean value was 1.8 ± 0.47, whereas the WtHR mean value was 0.55 ± 0.06. In the group of patients without CD, the z BMI decreases 1.89 ± 0.51 and WtHR 0.56 ± 0.07.
After an average time of 2.7 years, 4 patients lost weight, 7 gained weight, and only 1 maintained the same weight. WtHR was reduced in 6 patients and increased in only 1. z BMI score was reduced in 7 patients.
In this retrospective study we evaluated the prevalence of CD in a large cohort of overweight/obese unrelated children and adolescents consecutively attending our paediatric department because of their nutritional disorders. CD, once considered one of the main causes of malnourishment, is now widely recognised as a multiform clinical entity that may affect almost everyone. Failure to recognise that even obese children may have coeliac disease undoubtedly contributes to both the failure and the delay of CD diagnosis. Coexistence of obesity and CD has already been explained with a compensation theory. According to this hypothesis, nutrients, which cannot be absorbed because of villous atrophy in proximal small bowel, undergo a compensatory absorption in distal small bowel and, as a result, these patients not only do not lose weight (4) but may also become overweight/obese, similarly to anybody else. It is also known that an individual's coefficient for fat absorption remains relatively static; hence, the ability to maintain energy intake is preserved (5). According to the literature, 0.45% to 39.0% of adults with CD at diagnosis are obese (15–20). Sinniah and Roche (20), in a letter to the editor, focus on the rising incidence of obesity in the population with CD and note that none of their patients returned to having a normal BMI after diagnosis and GFD.
This is the first study, to our knowledge, that reverses the point of view evaluating CD in overweight/obese children. The CD prevalence we found in overweight/obese children (1.11%) approximately corresponds to that of the Italian population found in our previous salivary screening among schoolchildren and reflects the increased CD prevalence worldwide (2).
Even if some patients with CD in our cohort showed gastrointestinal symptoms, they had not been complaining about them, and attended the outpatient visit for the nutritional disorder that first drew their attention, sometimes even before the appearance of CD-related symptoms (diarrhoea, abdominal pain, and iron-deficiency anaemia).
All 17 had a negative family history for CD. No difference was found between overweight/obese children with CD and without CD, in terms of age, growth parameters, serum cholesterol (total, HDL, and LDL fraction), and triglyceride levels, so that patients with CD cannot be identified by indirect signs of malabsorption.
The prevalence of obesity in patients with CD is below that in patients without CD: 9 of 17 patients with CD were obese (52.94%) and 8 overweight (47.06%); whereas among patients without CD, 910 of 1510 (60.26%) were obese and 600 (39.73%) overweight.
On the contrary, and similar to previous studies, a high proportion of overweight patients did actually gain further weight on GFD (10,16). A study describes the beneficial impact of GFD on the BMI of CD patients during follow-up: underweight patients gained weight and overweight/obese patients lost weight (17). In our cohort, 23.53% of patients during the follow-up lost weight and 41.18% gained weight. In our study, because patients are growing children, we evaluated, in particular, the harmonious increase in weight and height throughout nutritional measures. The nutritionally balanced diet permitted the WtHR ratio reduction in 6 (35.29%) patients and the increase in only 1 (5.88%); in addition, all 7 patients reached a z BMI score reduction on follow-up.
Stressing the value of a balanced GFD, particularly in obese adolescents, is of major importance. It has been demonstrated that paradoxically among adolescents a strict GFD may even be a nutritional risk factor that alters the already unbalanced diet commonly consumed by healthy adolescents, because it makes these subjects increase the already elevated protein and lipid consumption (21). Unfortunately, the impact of GFD is not conclusive in our study because of the small sample of patients who followed strict GFD and because of the absence of a control group.
In conclusion, our study demonstrates not only that CD can be found in obese subjects, and at a similar rate as that found in the general population, but also that these patients could benefit from a balanced GFD diet. Nevertheless, a strict follow-up and a multidisciplinary approach are needed to ensure harmonious growth and prevent both CD- and obesity-related complications.
1. Fasano A, Berti I, Gerarduzzi T, et al. Prevalence of coeliac disease
in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Intern Med
2. Nenna R, Tiberti C, Petrarca L, et al. The coeliac iceberg: a characterization of the disease in primary school children. J Pediatr Gastroenterol Nutr
3. Oberhuber G, Granditsch G, Vogelsang H. The histopathology of coeliac disease
: time for a standardized report scheme of pathologists. Eur J Gastroenterol Hepatol
4. Furse RM, Mee AS. Atypical presentation of coeliac disease
5. Semeraro LA, Barwick KW, Gryboski JD. Obesity
in celiac sprue. J Clin Gastroenterol
6. Moscheo C, Vieni G, Pellegrino S, et al. The changing face of celiac disease: a girl with obesity
and celiac disease. J Paediatr Child Health
7. Binkin N, Fontana G, Lamberti A, et al. A national survey of the prevalence of childhood overweight and obesity
in Italy. Obesity Rev reviews
8. Venkatasubramani N, Telega G, Werlin SL. Obesity
in pediatric celiac disease. J Pediatr Gastroenterol Nutr
9. Balamtekin N, Baysoy G, Demir H. Differences in the prevalence of obesity
in children with celiac disease. J Pediatr Gastroenterol Nutr
10. Reilly NR, Aguilar K, Hassid BG, et al. Celiac disease in normal-weight and overweight children: clinical features and growth outcomes following a gluten-free diet. J Pediatr Gastroenterol Nutr
11. Kuczmarski RJ, Ogden CL, Guo SS, et al. 2000 CDC Growth Charts for the United States: methods and development. Vital Health Stat
2002; 11: 246:1–190.
12. McCarthy HD, Jarrett KV, Crawley HF. The development of waist circumference percentiles in British children aged 5.0-16.9 y. Eur J Clin Nutr
13. Maffeis C, Banzato C, Talamini G. Waist-to-height ratio a useful index to identify high metabolic risk in overweight children. J Pediatr
14. Hill ID, Dirks MH, Liptak GS, et al. Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr
15. Dickey W, Bodkin S. Prospective study of body mass index in patients with coeliac disease
16. Dickey W, Kearney N. Overweight in celiac disease: prevalence, clinical characteristics, and effect of a gluten-free diet. Am J Gastroenterol
17. Cheng J, Brar PS, Lee AR, et al. Body mass index in celiac disease: beneficial effect of gluten free diet. J Clin Gastroenterol
18. Murray JA, Watson T, Clearman B, et al. Effect of a gluten-free diet on gastrointestinal symptoms in celiac disease. Am J Clin Nutr
19. West J, Logan RF, Card TR, et al. Risk of vascular disease in adults with diagnosed coeliac disease
: a population-based study. Aliment Pharmacol Ther
20. Sinniah R, Roche E. Letter: rising incidence of obesity
in the coeliac population - a malady or maladaptation? Aliment Pharmacol Ther
21. Mariani P, Viti MG, Montuori M, et al. The gluten-free diet: a nutritional risk for adolescence with celiac disease? J Pediatr Gastroenterol Nutr