The Celiac Disease and Diabetes-Dietary Intervention and Evaluation Trial (CD-DIET) protocol: a randomised controlled study to evaluate treatment of asymptomatic coeliac disease in type 1 diabetes

Farid H Mahmud, Emilia N De Melo, Karima Noordin, Esther Assor, Kamaljeet Sahota, Jolie Davies-Shaw, Ernest Cutz, Gino Somers, Margaret Lawson, David R Mack, Patricia Gallego, Charlotte McDonald, Melanie D Beaton, Kevin Bax, Fred Saibil, Jeremy Gilbert, Susan Kirsch, Bruce A Perkins, Maria Cino, Eva Szentgyorgyi, Dror Koltin, Amish Parikh, Geetha Mukerji, Andrew Advani, Olivia Lou, Margaret A Marcon, Farid H Mahmud, Emilia N De Melo, Karima Noordin, Esther Assor, Kamaljeet Sahota, Jolie Davies-Shaw, Ernest Cutz, Gino Somers, Margaret Lawson, David R Mack, Patricia Gallego, Charlotte McDonald, Melanie D Beaton, Kevin Bax, Fred Saibil, Jeremy Gilbert, Susan Kirsch, Bruce A Perkins, Maria Cino, Eva Szentgyorgyi, Dror Koltin, Amish Parikh, Geetha Mukerji, Andrew Advani, Olivia Lou, Margaret A Marcon

Abstract

Introduction: Coeliac disease (CD) is an autoimmune condition characterised by gluten-induced intestinal inflammation, and observed at a 5-10 fold greater prevalence in type 1 diabetes. While universal screening for CD in patients with diabetes is frequently advocated, objective data is limited as to benefits on diabetes control, bone health or quality of life related to the adoption of a gluten-free diet (GFD) in the large proportion of patients with diabetes with asymptomatic CD. The Celiac Disease and Diabetes-Dietary Intervention and Evaluation Trial (CD-DIET) study is a multicenter, randomised controlled trial to evaluate the efficacy and safety of a GFD in patients with type 1 diabetes with asymptomatic CD.

Methods and analysis: Children and adults (8-45 years) with type 1 diabetes will be screened for asymptomatic CD. Eligible patients with biopsy-proven CD will be randomly assigned in a 1:1 ratio to treatment with a GFD for 1 year, or continue with a gluten-containing diet. The primary outcome will evaluate the impact of the GFD on change in glycated haemoglobin. Secondary outcomes will evaluate changes in bone mineral density, blood glucose variability and health-related quality of life between GFD-treated and the regular diet group over a 1-year period. The study was initiated in 2012 and has subsequently expanded to multiple paediatric and adult centres in Ontario, Canada.

Ethics and dissemination: The findings from this study will provide high-quality evidence as to the impact of GFD treatment on glycaemic control and complications in asymptomatic children and adults with CD and type 1 diabetes.

Trial registration number: NCT01566110.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Figures

Figure 1
Figure 1
Flow diagram illustrating screening phase and eligibility for intervention phase for Celiac Disease and Diabetes-Dietary Intervention and Evaluation Trial (CD-DIET) study (T1D, type 1 diabetes; TTG-IgA, tissue transglutaminase immunoglobulin A).
Figure 2
Figure 2
Intervention phase—outcomes and safety (BMD, bone mineral density; HbA1c, glycated haemoglobin; TTG-IgA, tissue transglutaminase immunoglobulin A).

References

    1. Farrell RJ, Kelly CP. Celiac sprue. N Engl J Med 2002;346:180–8. 10.1056/NEJMra010852
    1. Rubio-Tapia A, Ludvigsson JF, Brantner TL et al. . The prevalence of celiac disease in the United States. Am J Gastroenterol 2012;107:1538–44; quiz 1537, 1545 10.1038/ajg.2012.219
    1. Sud S, Marcon M, Assor E et al. . Celiac disease and pediatric type 1 diabetes: diagnostic and treatment dilemmas. Int J Pediatr Endocrinol 2010;2010:161285 10.1155/2010/161285
    1. Page SR, Lloyd CA, Hill PG et al. . The prevalence of coeliac disease in adult diabetes mellitus. QJM 1994;87:631–7.
    1. Mahmud FH, Murray JA, Kudva YC et al. . Celiac disease in type 1 diabetes mellitus in a North American community: prevalence, serologic screening, and clinical features. Mayo Clin Proc 2005;80:1429–34. 10.4065/80.11.1429
    1. Remes-Troche JM, Rios-Vaca A, Ramirez-Iglesias MT et al. . High prevalence of celiac disease in Mexican Mestizo adults with type 1 diabetes mellitus. J Clin Gastroenterol 2008;42:460–5. 10.1097/MCG.0b013e318046ea86
    1. Smyth DJ, Plagnol V, Walker NM et al. . Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med 2008;359:2767–77. 10.1056/NEJMoa0807917
    1. Mollazadegan K, Fored M, Lundberg S et al. . Risk of renal disease in patients with both type 1 diabetes and coeliac disease. Diabetologia 2014;57:1339–45. 10.1007/s00125-014-3223-y
    1. Mollazadegan K, Kugelberg M, Montgomery SM et al. . A population-based study of the risk of diabetic retinopathy in patients with type 1 diabetes and celiac disease. Diabetes Care 2013;36:316–21. 10.2337/dc12-0766
    1. Sun S, Puttha R, Ghezaiel S et al. . The effect of biopsy-positive silent coeliac disease and treatment with a gluten-free diet on growth and glycaemic control in children with type 1 diabetes. Diabet Med 2009;26:1250–4. 10.1111/j.1464-5491.2009.02859.x
    1. Saadah OI, Zacharin M, O'Callaghan A et al. . Effect of gluten-free diet and adherence on growth and diabetic control in diabetics with coeliac disease. Arch Dis Child 2004;89:871–6. 10.1136/adc.2002.012799
    1. Abid N, McGlone O, Cardwell C et al. . Clinical and metabolic effects of gluten free diet in children with type 1 diabetes and coeliac disease. Pediatr Diabetes 2011;12:322–5. 10.1111/j.1399-5448.2010.00700.x
    1. Hansen D, Brock-Jacobsen B, Lund E et al. . Clinical benefit of a gluten-free diet in type 1 diabetic children with screening-detected celiac disease: a population-based screening study with 2 years’ follow-up. Diabetes Care 2006;29:2452–6. 10.2337/dc06-0990
    1. Sanchez-Albisua I, Wolf J, Neu A et al. . Coeliac disease in children with type 1 diabetes mellitus: the effect of the gluten-free diet. Diabet Med 2005;22:1079–82. 10.1111/j.1464-5491.2005.01609.x
    1. Taler I, Phillip M, Lebenthal Y et al. . Growth and metabolic control in patients with type 1 diabetes and celiac disease: a longitudinal observational case-control study. Pediatr Diabetes 2012;13:597–606. 10.1111/j.1399-5448.2012.00878.x
    1. Bakker SF, Tushuizen ME, von Blomberg ME et al. . Type 1 diabetes and celiac disease in adults: glycemic control and diabetic complications. Acta Diabetol 2013;50:319–24. 10.1007/s00592-012-0395-0
    1. Leeds JS, Hopper AD, Hadjivassiliou M et al. . High prevalence of microvascular complications in adults with type 1 diabetes and newly diagnosed celiac disease. Diabetes Care 2011;34:2158–63. 10.2337/dc11-0149
    1. Simmons JH, Klingensmith GJ, McFann K et al. . Celiac autoimmunity in children with type 1 diabetes: a two-year follow-up. J Pediatr 2011;158:276–81.e1. 10.1016/j.jpeds.2010.07.025
    1. Viljamaa M, Collin P, Huhtala H et al. . Is coeliac disease screening in risk groups justified? A fourteen-year follow-up with special focus on compliance and quality of life. Aliment Pharmacol Ther 2005;22:317–24. 10.1111/j.1365-2036.2005.02574.x
    1. Heikkila K, Pearce J, Maki M et al. . Celiac disease and bone fractures: a systematic review and meta-analysis. J Clin Endocrinol Metab 2015;100:25–34. 10.1210/jc.2014-1858
    1. Diniz-Santos DR, Brandao F, Adan L et al. . Bone mineralization in young patients with type 1 diabetes mellitus and screening-identified evidence of celiac disease. Dig Dis Sci 2008;53:1240–5. 10.1007/s10620-007-9988-9
    1. Simmons JH, Klingensmith GJ, McFann K et al. . Impact of celiac autoimmunity on children with type 1 diabetes. J Pediatr 2007;150:461–6. 10.1016/j.jpeds.2006.12.046
    1. Lunt H, Florkowski CM, Cook HB et al. . Bone mineral density, type 1 diabetes, and celiac disease. Diabetes Care 2001;24:791–2. 10.2337/diacare.24.4.791
    1. Jacobson AM, Braffett BH, Cleary PA et al. . The long-term effects of type 1 diabetes treatment and complications on health-related quality of life: a 23-year follow-up of the Diabetes Control and Complications/Epidemiology of Diabetes Interventions and Complications cohort. Diabetes Care 2013;36:3131–8. 10.2337/dc12-2109
    1. Rashid M, Cranney A, Zarkadas M et al. . Celiac disease: evaluation of the diagnosis and dietary compliance in Canadian children. Pediatrics 2005;116:e754–9. 10.1542/peds.2005-0904
    1. Zarkadas M, Dubois S, MacIsaac K et al. . Living with coeliac disease and a gluten-free diet: a Canadian perspective. J Hum Nutr Diet 2013;26:10–23. 10.1111/j.1365-277X.2012.01288.x
    1. Saukkonen T, Vaisanen S, Akerblom HK et al. . Coeliac disease in children and adolescents with type 1 diabetes: a study of growth, glycaemic control, and experiences of families. Acta Paediatr 2002;91:297–302. 10.1111/j.1651-2227.2002.tb01718.x
    1. Whitaker JK, West J, Holmes GK et al. . Patient perceptions of the burden of coeliac disease and its treatment in the UK. Aliment Pharmacol Ther 2009;29:1131–6. 10.1111/j.1365-2036.2009.03983.x
    1. Ukkola A, Maki M, Kurppa K et al. . Diet improves perception of health and well-being in symptomatic, but not asymptomatic, patients with celiac disease. Clin Gastroenterol Hepatol 2011;9:118–23. 10.1016/j.cgh.2010.10.011
    1. Bystrom IM, Hollen E, Falth-Magnusson K et al. . Health-related quality of life in children and adolescents with celiac disease: from the perspectives of children and parents. Gastroenterol Res Pract 2012;2012:986475 10.1155/2012/986475
    1. Sud S, Marcon M, Assor E et al. . Quality of life in children with diabetes and celiac disease: minimal impact of the ‘double diagnosis’. Pediatr Diabetes 2012;13:163–9. 10.1111/j.1399-5448.2011.00785.x
    1. van Koppen EJ, Schweizer JJ, Csizmadia CG et al. . Long-term health and quality-of-life consequences of mass screening for childhood celiac disease: a 10-year follow-up study. Pediatrics 2009;123:e582–8. 10.1542/peds.2008-2221
    1. Bakker SF, Pouwer F, Tushuizen ME et al. . Compromised quality of life in patients with both type 1 diabetes mellitus and coeliac disease. Diabet Med 2013;30:835–9. 10.1111/dme.12205
    1. Pulido O, Zarkadas M, Dubois S et al. . Clinical features and symptom recovery on a gluten-free diet in Canadian adults with celiac disease. Can J Gastroenterol 2013;27:449–53.
    1. Wolfe F, Kong SX, Watson DJ. Gastrointestinal symptoms and health related quality of life in patients with arthritis. J Rheumatol 2000;27:1373–8.
    1. Mack DR, Langton C, Markowitz J et al. . Laboratory values for children with newly diagnosed inflammatory bowel disease. Pediatrics 2007;119:1113–19. 10.1542/peds.2006-1865
    1. Leffler DA, Dennis M, Edwards George JB et al. . A simple validated gluten-free diet adherence survey for adults with celiac disease. Clin Gastroenterol Hepatol 2009;7:530–6, 536.e531–2 10.1016/j.cgh.2008.12.032
    1. Varni JW, Curtis BH, Abetz LN et al. . Content validity of the PedsQL 3.2 Diabetes Module in newly diagnosed patients with type 1 diabetes mellitus ages 8–45. Qual Life Res 2013;22: 2169–81. 10.1007/s11136-012-0339-8
    1. Wherrett D, Huot C, Mitchell B et al. . Type 1 diabetes in children and adolescents. Can J Diabetes 2013;37(Suppl 1):S153–62. 10.1016/j.jcjd.2013.01.042
    1. International Diabetes Federation ISfPaAD. Other complications and associated conditions. Global IDF/ISPAD Guideline for Diabetes in Childhood and Adolescence 2011:124–8.
    1. American Diabetes Association. Standards of medical care in diabetes—2014. Diabetes Care 2014;37(Suppl 1):S14–80. 10.2337/dc14-S014
    1. Husby S, Koletzko S, Korponay-Szabo IR et al. . European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012;54:136–60. 10.1097/MPG.0b013e31821a23d0
    1. NICE. Coeliac disease. Recognition and assessment of coeliac disease. NICE clinical guideline 2009:86.
    1. Ludvigsson JF, Bai JC, Biagi F et al. . Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology. Gut 2014;63:1210–28. 10.1136/gutjnl-2013-306578
    1. Sud S, Marcon M, Assor E et al. . Health professional attitudes regarding celiac disease screening and treatment in pediatric type 1 diabetes. Can J Diab 2011;35:334–9. 10.1016/S1499-2671(11)54009-2

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever