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It Is High Time for Personalized Dietary Counseling in Celiac Disease: A Systematic Review and Meta-Analysis on Body Composition.
Vereczkei, Z, Farkas, N, Hegyi, P, Imrei, M, Földi, M, Szakács, Z, Kiss, S, Solymár, M, Nagy, R, Bajor, J
Nutrients. 2021;(9)
Abstract
The body composition of patients with celiac disease (CD), on which the effects of a gluten-free diet (GFD) are controversial, differs from that of the average population. In this study, we aimed to compare the body composition across CD patients before a GFD, CD patients after a one-year GFD and non-celiac control subjects. A systematic search was conducted using five electronic databases up to 15 July 2021 for studies that reported at least one of the pre-specified outcomes. In meta-analyses, weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated. A total of 25 studies were eligible for systematic review, seven of which were included in meta-analysis. During a ≥1-year GFD, fat mass of CD patients, compared to that at baseline, significantly increased (WMD = 4.1 kg, 95% CI = 1.5 to 6.6, three studies). In CD patients after a ≥1-year GFD, compared to non-celiac controls, fat mass (WMD = -5.8 kg, 95% CI = -8.7 to -2.9, three studies) and fat-free mass (WMD = -1.9 kg, 95% CI = -3.0 to -0.7, three studies) were significantly lower. In conclusion, body composition-related parameters of CD patients differ from that of the non-celiac control subjects even after a longstanding GFD.
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Psychiatric Manifestations of Coeliac Disease, a Systematic Review and Meta-Analysis.
Clappison, E, Hadjivassiliou, M, Zis, P
Nutrients. 2020;(1)
Abstract
BACKGROUND Coeliac disease (CD) is increasingly prevalent and is associated with both gastrointestinal (GI) and extra-intestinal manifestations. Psychiatric disorders are amongst extra-intestinal manifestations proposed. The relationship between CD and such psychiatric disorders is not well recognised or understood. AIM: The aim of this systematic review and meta-analysis was to provide a greater understanding of the existing evidence and theories surrounding psychiatric manifestations of CD. METHODOLOGY An online literature search using PubMed was conducted, the prevalence data for both CD and psychiatric disorders was extracted from eligible articles. Meta analyses on odds ratios were also performed. RESULTS A total of 37 articles were included in this review. A significant increase in risk was detected for autistic spectrum disorder (OR 1.53, 95% CI 1.24-1.88, p < 0.0001), attention deficit hyperactivity disorder (OR 1.39, 95% CI 1.18-1.63, p < 0.0001), depression (OR 2.17, 95% CI 2.17-11.15, p < 0.0001), anxiety (OR 6.03, 95% CI 2.22-16.35, p < 0.0001), and eating disorders (OR 1.62, 95% CI 1.37-1.91, p < 0.00001) amongst the CD population compared to healthy controls. No significant differences were found for bipolar disorder (OR 2.35, 95% CI 2.29-19.21, p = 0.43) or schizophrenia (OR 0.46, 95% CI 0.02-10.18, p = 0.62). CONCLUSION CD is associated with an increased risk of depression, anxiety, eating disorders as well as ASD and ADHD. More research is required to investigate specific biological explanations as well as any effect of gluten free diet.
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Celiac Disease and Bone Health in Children and Adolescents: A Systematic Review and Meta-Analysis.
Fedewa, MV, Bentley, JL, Higgins, S, Kindler, JM, Esco, MR, MacDonald, HV
Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry. 2020;(2):200-211
Abstract
CONTEXT Celiac disease is characterized by deficits in bone mineral accrual and longitudinal growth. OBJECTIVE The purpose of this study was to determine the differences in bone health and stature among children and adolescents with celiac disease versus healthy controls. DATA SOURCES Articles published before February 27, 2018 were located using searches of the Physical Education Index (n = 186), PubMed (n = 180), Scopus (n = 3), SPORTDiscus (n = 3), and Web of Science (n = 4). STUDY SELECTION Bone mineral content (BMC) and areal bone mineral density (aBMD) were assessed via dual-energy X-ray absorptiometry, and height was measured using a stadiometer. DATA EXTRACTION Effect sizes (ES) were calculated as follows: the mean difference of the celiac disease group and healthy control group, divided by the pooled standard deviation. The inverse variance weight was used to calculate the overall mean ES. Random-effects models were used to aggregate a mean ES, 95% confidence intervals (CIs) and to identify potential moderators. RESULTS The results of 30 effects gathered from 12 studies published between 1996 and 2017 indicated BMC (ES = -0.54, 95% CI: -0.69 to -0.40; p < 0.0001) and aBMD (ES = 0.72, 95% CI: -0.96 to -0.47; p < 0.0001) were lower in youth with celiac disease. LIMITATIONS These results were limited to only cross-sectional and baseline data from longitudinal studies reporting BMC and BMD, however did not assess changes in bone health over time. CONCLUSION Children and adolescents with celiac disease have suboptimal bone health and shorter stature.
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Determination of gluten consumption in celiac disease patients on a gluten-free diet.
Syage, JA, Kelly, CP, Dickason, MA, Ramirez, AC, Leon, F, Dominguez, R, Sealey-Voyksner, JA
The American journal of clinical nutrition. 2018;(2):201-207
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Abstract
BACKGROUND Celiac disease (CD) patients adhering to a gluten-free diet (GFD) are exposed frequently to low levels of gluten that contribute to symptoms and persistent intestinal histologic damage. OBJECTIVE We analyzed prior clinical data to determine how much gluten is accidentally consumed while on a GFD. The aim was to understand the range of gluten consumption for a wide distribution of CD patients. DESIGN A meta-analysis was conducted on data from 2 different clinical programs: 1) measurements of gluten in stool and urine in CD and non-CD populations; and 2) analysis of data from trials for the investigational therapeutic latiglutenase. The stool and urine studies included controlled gluten challenges. A calibration factor was applied that allowed normal ingestion of gluten to be computed from the urine and stool measurements. From the latiglutenase trial data, a determination of gluten consumption was made by estimating how much gluten was eliminated from patients' diets due to a trial effect that led to improved histology even in the placebo group. RESULTS The average inadvertent exposure to gluten by CD individuals on a GFD was estimated to be ∼150-400 (mean) and ∼100-150 (median) mg/d using the stool test and ∼300-400 (mean) and ∼150 (median) mg/d using the urine test. The analyses of the latiglutenase data for CD individuals with moderate to severe symptoms indicate that patients ingested significantly >200 mg/d of gluten. CONCLUSIONS These surrogate biomarkers of gluten ingestion indicate that many individuals following a GFD regularly consume sufficient gluten to trigger symptoms and perpetuate intestinal histologic damage.
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Systematic review with meta-analysis: Dietary adherence influences normalization of health-related quality of life in coeliac disease.
Burger, JPW, de Brouwer, B, IntHout, J, Wahab, PJ, Tummers, M, Drenth, JPH
Clinical nutrition (Edinburgh, Scotland). 2017;(2):399-406
Abstract
BACKGROUND & AIMS Gluten-free diet is the keystone of coeliac disease treatment. Despite adherence, some patients continue to suffer from symptoms that negatively influence health-related quality of life (HRQoL). Therefore we performed a systematic review and meta-analysis to assess the effect of gluten-free diet on HRQoL in coeliac disease. We specifically sought for determinants that negatively influenced HRQoL. METHODS We systematically searched PubMed, EMBASE, CINAHL, PsycINFO and Cochrane Library for studies assessing HRQoL in untreated or treated adults using validated HRQoL-questionnaires from 1960 to September 2015, comparing HRQoL: (1) before and after gluten-free diet initiation or (2) in patients and non-coeliac controls. RESULTS We included eighteen studies and sixteen were suitable for meta-analysis. Gluten-free diet significantly improves HRQoL, for psychological general well-being (PGWB)-Total (mean difference (MD) 7.34, 95% confidence interval (CI) [1.96; 12.72]; p = 0.008), SF-36 Mental Component Score (MCS) (MD 7.37, 95% CI [1.84; 12.90]; p = 0.009) and SF-36 Physical Component Score (PCS) (MD 5.72, 95% CI [1.50; 9.95]; p = 0.008). Treated patients had similar HRQoL compared with controls for PGWB-Total (MD -0.72, 95% CI [-2.71; 1.27]; p = 0.48), but significantly lower levels for SF-36 MCS (MD -4.09, 95% CI [-6.17; -2.01]; p = 0.0001) and PCS (MD -4.57, 95% CI [-6.97; -2.17]; p = 0.0002). Symptom-detected gluten-free diet adhering patients have lower HRQoL compared with screening-detected patients (MD -3.73, 95% CI [-6.77;-0.69]; p = 0.02) Strict adhering patients have better HRQoL compared with non-strict adhering patients for SF-36 MCS (MD 7.70, 95% CI [4.61; 10.79]; p < 0.00001) and for SF-36 PCS (MD 3.23, 95% CI [1.33; 5.14]; p = 0.0009). CONCLUSIONS Gluten-free diet significantly improves but does not normalize HRQoL in adults with coeliac disease. Dietary adherence improves HRQoL. Better (self-reported) dietary adherence results in higher HRQoL.
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Celiac disease and obstetric complications: a systematic review and metaanalysis.
Saccone, G, Berghella, V, Sarno, L, Maruotti, GM, Cetin, I, Greco, L, Khashan, AS, McCarthy, F, Martinelli, D, Fortunato, F, et al
American journal of obstetrics and gynecology. 2016;(2):225-234
Abstract
The aim of this metaanalysis was to evaluate the risk of the development of obstetric complications in women with celiac disease. We searched electronic databases from their inception until February 2015. We included all cohort studies that reported the incidence of obstetric complications in women with celiac disease compared with women without celiac disease (ie, control group). Studies without a control group and case-control studies were excluded. The primary outcome was defined a priori and was the incidence of a composite of obstetric complications that included intrauterine growth restriction, small for gestational age, low birthweight, preeclampsia and preterm birth. Secondary outcomes included the incidence of preterm birth, intrauterine growth restriction, stillbirth, preeclampsia, small for gestational age, and low birthweight. The review was registered with PROSPERO (CRD42015017263) before data extraction. All authors were contacted to obtain the original databases and perform individual participant data metaanalysis. Primary and secondary outcomes were assessed in the aggregate data analysis and in the individual participant data metaanalysis. We included 10 cohort studies (4,844,555 women) in this metaanalysis. Four authors provided the entire databases for the individual participant data analysis. Because none of the included studies stratified data for the primary outcome (ie, composite outcome), the assessment of this outcome for the aggregate analysis was not feasible. Aggregate data analysis showed that, compared with women in the control group, women with celiac disease (both treated and untreated) had a significantly higher risk of the development of preterm birth (adjusted odds ratio, 1.35; 95% confidence interval, 1.09-1.66), intrauterine growth restriction (odds ratio, 2.48; 95% confidence interval, 1.32-4.67), stillbirth (odds ratio, 4.84; 95% confidence interval, 1.08-21.75), low birthweight (odds ratio, 1.63; 95% confidence interval, 1.06-2.51), and small for gestational age (odds ratio, 4.52; 95% confidence interval, 1.02-20.08); no statistically significant difference was found in the incidence of preeclampsia (odds ratio, 2.45; 95% confidence interval, 0.90-6.70). The risk of preterm birth was still significantly higher both in the subgroup analysis of only women with diagnosed and treated celiac disease (odds ratio, 1.26; 95% confidence interval, 1.06-1.48) and in the subgroup analysis of only women with undiagnosed and untreated celiac disease (odds ratio, 2.50; 95% confidence interval; 1.06-5.87). Women with diagnosed and treated celiac disease had a significantly lower risk of the development of preterm birth, compared with undiagnosed and untreated celiac disease (odds ratio, 0.80; 95% confidence interval, 0.64-0.99). The individual participant data metaanalysis showed that women with celiac disease had a significantly higher risk of composite obstetric complications compared with control subjects (odds ratio, 1.51; 95% confidence interval, 1.17-1.94). Our individual participant data concurs with the aggregate analysis for all the secondary outcomes. In summary, women with celiac disease had a significantly higher risk of the development of obstetric complications that included preterm birth, intrauterine growth restriction, stillbirth, low birthweight, and small for gestational age. Since the treatment with gluten-free diet leads to a significant decrease of preterm delivery, physicians should warn these women about the importance of a strict diet to improve obstetric outcomes. Future studies calculating cost-effectiveness of screening for celiac disease during pregnancy, which could be easily performed, economically and noninvasively, are needed. In addition, further studies are required to determine whether women with adverse pregnancy outcomes should be screened for celiac disease, particularly in countries where the prevalence is high.
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Risk of venous thromboembolism in patients with celiac disease: A systematic review and meta-analysis.
Ungprasert, P, Wijarnpreecha, K, Tanratana, P
Journal of gastroenterology and hepatology. 2016;(7):1240-5
Abstract
BACKGROUND AND AIM Patients with celiac disease (CD) might be at an increased risk of developing venous thromboembolism (VTE) due to chronic inflammation and vitamin deficiency. However, epidemiologic studies attempting to investigate this risk have yielded inconsistent results. We conducted this meta-analysis with the aims to better characterize this possible association. METHODS We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio comparing the risk of VTE in patients with CD versus participants without CD. Generic inverse variance method of DerSimonian and Laird was used to calculate the pooled risk ratio. RESULTS Out of 279 potentially relevant articles, four studies met the inclusion criteria and were included in the meta-analysis. We found a statistically significant increased risk of VTE among patients with CD with the pooled risk ratio of 1.25 (95% confidence interval, 1.02-1.53). The statistical heterogeneity was moderate with an I(2) of 69%. CONCLUSIONS A significantly increased risk of VTE among patients with CD was demonstrated in this meta-analysis. Further studies are required to clarify how this risk should be addressed in clinical practice.
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Increased Incidence of Thyroid Disease in Patients with Celiac Disease: A Systematic Review and Meta-Analysis.
Sun, X, Lu, L, Yang, R, Li, Y, Shan, L, Wang, Y
PloS one. 2016;(12):e0168708
Abstract
The prevalence of thyroid disease is likely increased among individuals with celiac disease (CD). In addition, exposure to gluten-free treatment may be associated with a risk of thyroid disease, but this association remains controversial. A systematic review was performed to evaluate the association between thyroid disease and CD. The articles were obtained from the PubMed, Web of Science, Embase, and Chinese WanFang bibliographical databases for the period up to May 2016. The results were analysed in a meta-analysis with odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs). There were 13 articles in this meta-analysis, including 15629 CD cases and 79342 controls. Overall, the prevalence of thyroid disease in patients with CD was significantly increased compared with that in the control groups (OR 3.08, 95% CI 2.67-3.56, P<0.001). Moreover, there was no significant difference in the OR between the gluten-treated and untreated groups (OR 1.08, 95% CI 0.61-1.92, P = 0.786). The results of our meta-analysis support the hypothesis that the prevalence of thyroid disease in patients with CD is increased compared with that in controls, which suggests that CD patients should be screened for thyroid disease. The effect of gluten-free treatment on thyroid disease needs further investigation.
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TNF-α -308 G > A (rs1800629) Polymorphism is Associated with Celiac Disease: A Meta-analysis of 11 Case-Control Studies.
Khan, S, Mandal, RK, Jawed, A, Dar, SA, Wahid, M, Panda, AK, Areeshi, MY, Ahmed Khan, ME, Haque, S
Scientific reports. 2016;:32677
Abstract
Celiac disease (CD) remains one of the most significant autoimmune diseases worldwide. The pathogenesis of CD is not clearly understood and is probably attributed to genomic variations and host genetic make-up. Case-control and cohort studies of the association between the TNF-α -308 G > A (rs1800629) polymorphism and CD susceptibility have yielded inconsistent results. In this study, PubMed, EMBASE, and Google Scholar web-databases were searched for pertinent reports showing association of TNF-α -308 G > A gene with CD risk. A total of eleven reports involving 1774 controls and 1147 CD cases were included. Significant associations in four genetic models, viz. variant allele (A vs. G: p = 0.001; OR = 2.051, 95% CI = 1.452-2.895), variant homozygous (AA vs. GG: p = 0.001; OR = 6.626, 95% CI = 3.569-12.300), recessive (AA vs. GG + AG: p = 0.001; OR = 4.766, 95% CI = 3.177-7.152) and dominant (AA + AG vs. GG: p = 0.008; OR = 1.910, 95% CI = 1.181-3.088) were found in comparison with wild type homozygous GG genotype. However, heterozygous genetic model did not show any association. Sensitivity analysis revealed stable and statistically robust results. Our results suggest that TNF-α -308 G > A gene polymorphism significantly contributes to CD susceptibility.
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Celiac disease and bone fractures: a systematic review and meta-analysis.
Heikkilä, K, Pearce, J, Mäki, M, Kaukinen, K
The Journal of clinical endocrinology and metabolism. 2015;(1):25-34
Abstract
CONTEXT Celiac disease, an autoimmune disease induced by dietary gluten, is associated with metabolic bone disorders, such as low bone mineral density. However, it is unclear whether this translates into an association between celiac disease and such hard clinical outcomes as bone fractures. OBJECTIVE To systematically review and pool the evidence for the relationship of celiac disease with prevalence and incidence of bone fractures. DATA SOURCES We systematically searched Pubmed, Scopus, Web of Science, and Cochrane Library in January 2014 for studies of celiac disease and bone fractures. STUDY SELECTION Observational studies of any design, in which bone fracture outcomes were compared in individuals with and without celiac disease were included. DATA EXTRACTION Two investigators independently extracted results from eligible studies. DATA SYNTHESIS In the meta-analyses of case-control and cross-sectional studies, bone fractures were almost twice as common in individuals with a clinically diagnosed celiac disease as in those without the disease. In the meta-analyses of prospective studies, celiac disease at baseline was associated with a 30% increase (95% confidence interval [CI]: 1.14, 1.50) in the risk of any fracture and a 69% increase in the risk of hip fracture (95% CI: 1.10, 2.59). The two studies of unrecognized celiac disease (elevated circulating concentrations of celiac disease-specific autoantibodies but no celiac disease diagnosis) had contradicting findings. CONCLUSION Our findings suggest that clinically diagnosed celiac disease and bone fractures co-occur and that celiac disease was associated with an increased risk of hip fractures as well as fractures in general. Further research would be needed to determine whether unrecognized celiac disease is associated with the risk of bone fractures.