Type 1 Diabetes and Celiac Disease: Overview and Medical Nutrition Therapy

Nutrition FYI

Sarah Jane Schwarzenberg, MD, and Carol Brunzell, RD, CDE

In patients with celiac disease (gluten- problems recognized only retrospec- glycemia, but only several months sensitive enteropathy, or GSE), inges- tively as resulting from celiac disease; after initiation. tion of the gliadin fraction of wheat it is common for “asymptomatic” It seems likely that a malabsorp- gluten and similar molecules (pro- patients to report improved health or tive disease could create opportunity lamins) from barley, rye, and possibly sense of well-being when following a for hypoglycemia in diabetes, partic- oats causes damage to the intestinal gluten-free diet. Up to one-third of ularly in patients under tight control. epithelium. The injury results from an patients may have unexplained failure Serological testing for GSE in abnormal T-cell response against to thrive, abdominal pain, or short patients with type 1 diabetes, with gliadin. Thus, GSE is a disease in stature.3,6 early diagnosis of GSE, may reduce which host susceptibility must be More controversial is the question this risk by allowing patients to be combined with a specific environmen- of whether GSE affects blood glucose diagnosed in a pre-symptomatic tal trigger to affect injury.1 control. A study by Acerini et al.7 in a state. It also seems prudent to closely Typically, patients with GSE have type 1 diabetic population found no monitor insulin needs and blood glu- chronic diarrhea and failure to thrive. difference between the celiac and non- cose control during the early phase of However, some patients present with celiac subpopulation in terms of instituting a gluten-free diet. short stature, flatulence, or recurrent hemoglobin A1c or total insulin needs. abdominal pain. Dermatitis herpeti- Some celiac patients had morning Testing People With Diabetes for GSE formis, a pruritic papular rash, is hypoglycemia after starting a gluten- Serological testing is an important directly related to GSE.2 Other atypi- free diet, but no statistically signifi- screening tool for patients with atypi- cal presentations are increasingly rec- cant change in insulin needs was cal or silent celiac disease or family ognized, among them iron-deficiency found. Another study8 of adults with members of patients with GSE. While anemia, osteopenia/osteoporosis, type 1 diabetes and GSE found no dif- the evolving nature of serological test- short stature, dental enamel hypopla- ference in metabolic control of dia- ing for GSE makes any recommenda- sia, arthritis and arthralgia, chronic betes with treatment of GSE. tion difficult, most investigators hepatitis/hypertransaminasemia, and It has been observed that patients would advocate a profile consisting of neurological problems. GSE has also with GSE have hypoglycemic episodes three antibody assays: 1) anti-gliadin been found in asymptomatic individu- and reduced insulin needs before diag- IgG, 2) anti-gliadin IgA, and 3) either als who nonetheless have evidence of nosis, presumably because of malab- an anti-endomysial or an anti-tissue intestinal mucosal injury on biopsy.1 sorption.9 In a detailed study of transglutaminase assay. Serum IgA growth parameters, blood glucose must be quantitated in all patients Celiac Disease and Type 1 Diabetes control, and dietary intake in a group because the most specific antibodies An association of diabetes with GSE of children and adolescents with GSE are IgA, and GSE is more common in has been observed since the late and type 1 diabetes, Westman et al.10 patients with IgA deficiency.12–14 1960s. In recent years, it has become found no differences between GSE Patients with positive serological clear that the incidence of GSE in and non-GSE patients. This popula- tests and those who have symptoms patients with type 1 diabetes is sub- tion was screened annually for GSE compatible with GSE and negative stantial. A prevalence rate of 4–6% and so were diagnosed at an asympto- serology should be referred to a gas- in type 1 diabetes has been report- matic point of the illness. In a case- troenterologist for further diagnostic ed.3–5 Some of the variation in preva- controlled study of the incidence of studies. In the past, the diagnosis of lence can be attributed to the differ- hypoglycemia in patients with GSE required three small-bowel biop- ent diagnostic criteria used in the untreated GSE, Mohn et al.11 found sies generally performed endoscopi- studies. that there were significantly more cally. The first, done while the patient The majority of patients with GSE episodes of hypoglycemia in the GSE was symptomatic, would show are asymptomatic4 or are not aware of patients than in controls. Institution mucosal injury. A second biopsy symptoms. Some patients present with of a gluten-free diet reduced hypo- would be performed after a minimum 197 Diabetes Spectrum Volume 15, Number 3, 2002 Nutrition FYI

of 1 year on a gluten-free diet. If the lymphoma diagnoses in children To aid patients in maintaining the those results were normal, the patient in this region; the risk may rise in diet, they should be tested regularly then would be challenged carefully adults, particularly if the diet is not for ingestion of gluten (at least yearly with gluten, and a third biopsy, maintained. This constitutes the most and perhaps more often for those who which would again show abnormali- compelling reason to advocate strict have difficulty following the diet). ties, would be performed either when adherence to the diet. Antigliadin antibodies rise within the patient was symptomatic or after Many GSE patients, despite their weeks of gluten ingestion in patients 1 year on gluten.15 The evolution of resistance to the diet, find they feel with GSE and constitute a useful serological testing has allowed modi- better and have more energy when marker of dietary management. fication of this protocol, although their diets are gluten-free. Frequently, Patients may inadvertently ingest individual patients may still require both children and adults have more gluten because of its abundant use in multiple biopsies to distinguish GSE energy, feel less irritable and cranky, many prepared foods. Contamination from diseases that produce a similar display better skin color, and report of gluten-free foods in a family toaster histopathological injury.16 better overall health following treat- full of wheat crumbs, for example, There are limitations to serological ment of GSE. Some people with dia- may be discovered by interviewing the testing. First, a positive serological betes and GSE report that blood glu- family after a positive antigliadin anti- test is not diagnostic of GSE. Small- cose control is easier to maintain body test. bowel biopsy is required to confirm when they follow the gluten-free diet. Most studies suggest that osteope- the diagnosis. Second, patients under While these are not universal benefits, nia and vitamin and mineral deficien- the age of 2 years may have false-neg- they should be noted in discussions cies associated with GSE resolve on ative results on serology. When celiac with patients. the gluten-free diet. Thus, in patients disease is strongly suspected in Finally, patients with untreated adhering to the diet, little long-term patients within this age-group, they celiac disease are at risk of multiple screening for these deficiencies is war- should have a small-bowel biopsy deficiencies of micronutrients and vit- ranted. despite negative antibody testing. If amins because of the malabsorption It should be noted that immediately they are asymptomatic, they should of these nutrients by the injured small after diagnosis, some supplements and be re-tested at an older age. Third, it intestine. Among the reported prob- dietary modifications may be neces- is clear that a single serological test lems are iron and vitamin B12 defi- sary that will be unnecessary after the with negative results does not pre- ciency. At diagnosis, many celiac intestinal mucosa is healed. Patients clude the later development of celiac patients have osteopenia, which are frequently lactose-intolerant at disease. Although clear recommenda- resolves on a gluten-free diet. Clearly, diagnosis because of injury to the di- tions are not available, many centers the risk of malnutrition is another saccharidases in the small intestine. test yearly for the first 3 years of important reason to advocate a strict Patients should be screened at diagno- diagnosed diabetes, every 3–5 years gluten-free diet. sis for iron, zinc, B12, folate, calcium, thereafter, and whenever symptoms Celiac disease is a lifelong condi- magnesium, and fat-soluble vitamin develop. tion; thus, the diet is a permanent deficiencies and treated if abnormali- change for these patients. Many ties are found. Most specific supple- Treatment of GSE patients become exquisitely sensitive ments can be stopped 6–12 months Current U.S. and Canadian recommen- to the ingestion of even small amounts into therapy. dations for the treatment of GSE of gluten after a gluten-free period. Because gluten-free foods may be include a strict gluten-free diet to be Violent vomiting, severe diarrhea, lower in B vitamins, folate, iron, and maintained for life. For many patients abdominal cramping, and even shock fiber, careful planning is necessary to with diabetes, this may seem unreason- may occur in these patients. ensure adequate intake of these nutri- able given the changes they have no In some patients, ingestion of small ents.19,20 A daily multivitamin may be doubt already made to their diet after amounts of gluten will not produce recommended for patients with GSE. their diabetes diagnosis. However, the overt symptoms. Some patients expe- stringency of this recommendation is rience a reduction in response to The Diet based on sound reasoning. gluten during their teens—the so- Ideally, a gluten-free diet would elimi- First, strict elimination of gluten called “honeymoon period.” nate any prolamin or similar protein has been shown to lower the risk of Unfortunately, despite the lack of per- capable of stimulating an adverse T- small-bowel lymphoma associated ceived symptoms, biopsies of the cell response. (See Tables 1 and 2.) with GSE.17 Although there are no small intestine in these patients Unfortunately, there is no way to reliable incidence figures for lym- demonstrate ongoing mucosal injury directly determine the capacity of phoma in GSE, a recent survey by the associated with gluten ingestion. It is individual grains to elicit a response, European Society for Paediatric believed that this persistent recurrent and current recommendations rely on Gastroenterology, Hepatology, and injury to the intestine is the factor that in vivo testing. As a result, there is Nutrition18 reported five cases of predisposes these patients to lym- controversy regarding the most appro- small-bowel lymphoma with respons- phoma. Thus, absence of symptomatic priate diet for patients with GSE. For es from about half their membership. response to gluten ingestion should example, moderate consumption of All five patients were eating gluten. It not be construed as indicating that oats has been shown in several short- should be noted that this reflects only gluten intake is safe. term studies to be safe;21–24 however, 198 Diabetes Spectrum Volume 15, Number 3, 2002 Nutrition FYI

Table 1. Starches, Grains, and Other Foods Appropriate on a the United States and Canada should be aware that the term “gluten-free” Gluten-Free Diet on imported foods purchased through • Amaranth,* arrowroot, whole-bean flour, buckwheat,* corn, cornstarch, corn- direct mail order may not have the meal, flax, millet,* nut flours, oats,* oat bran,* oat gum,* pea flour, potato, sweet same implication it would if the food potato and yam, potato flour, potato starch, quinoa,* rice and wild rice, rice bran, were produced locally. rice flour, sago, sorghum, soy, tapioca, teff* • Fresh, frozen, or canned unprocessed fruits and vegetables Other Hidden Sources of Gluten • Fresh meats, poultry, seafood, fish, game, eggs, some processed meats with gluten- Complete removal of gluten-contain- free ingredients, tofu, dried peas, beans, and lentils ing grains is challenging. Hidden • Milk, yogurt, and cheese made with gluten-free ingredients sources of gluten/prolamins may be found in the ingredients of many • Oils, tree nuts, seeds, natural peanut butter, and salad dressings and spreads with processed foods in the form of addi- gluten-free ingredients tives, stabilizers, thickeners, flavor- • Honey, sugar, pure maple syrup, corn syrup, jams, jellies, candy, and ice cream ings, extracts, emulsifiers, hydrolyzed with gluten-free ingredients textured vegetable proteins, and cer- • Pure spices and herbs, salt, wheat-free soy sauce, vinegar with gluten-free ingredi- tain ground spices. Other sources of ents prolamins include grain alcohol, some • Coffee ground from whole beans, brewed tea, carbonated beverages, some root prescription and over-the-counter beer medications, certain multivitamins, This is only a partial listing. Patients are encouraged to read all labels and to seek toothpastes, lip balms, mouthwash, comprehensive food and additive lists from celiac organizations and the American and adhesive on stamps and Dietetic Association. envelopes. Ingredient reference lists *Recommendations about acceptability are inconsistent. Many physicians restrict are extensive and must be available to these grains for the first 6 months after diagnosis or until patients are in full remis- all patients and health care providers. sion. Patients with dermatitis herpetiformis need to check labels and/or manufac- many celiac organizations and the small amounts of toxic prolamins turers for prolamins in lotions, American Dietetic Association are not until further studies can confirm its creams, and cosmetics. Patients must yet recommending oats as safe for safety.29 become lifelong label readers because consumption. It is also unclear It is important to inform patients ingredients in food and non-food whether several other grains, such as traveling to countries adhering to items may change over time. buckwheat and amaranth, are accept- Codex standards of this labeling dis- The potential for cross-contamina- able on a gluten-free diet.25 A consen- crepancy. In addition, individuals in tion is also of concern. Equipment sus is needed among the various organizations to minimize confusion for Table 2. Grains and Other Foods/Ingredients Not Appropriate practitioners and patients.26 on a Gluten-Free Diet

Codex Standards • Barley, bran, bulgur, couscous, durum flour, farina, graham flour, hydrolyzed The Codex Alimentarius Commission plant protein (HPP), hydrolyzed vegetable protein (HVP), kamut, malt, malt of the World Health Organization extract, malt flavoring, malt syrup, semolina, rye, spelt (dinkel), triticale, wheat, and the Food and Agriculture wheat bran, wheat germ, wheat starch Organization of the United Nations • Imported foods that are labeled “gluten-free” but that may contain wheat starch* provides the only international • Processed meats and luncheon meats containing HVP or HPP, breaded meats, gluten-free food standards for manu- meats with sauces or gravies, casseroles facturers. The standards for gluten- • Fruits and vegetables with sauces, breading, or thickeners free foods as defined by the commission allow small amounts of prolamin • Flavored milk, yogurt, processed cheese, and spreads made with gluten-containing in foods that are designated gluten- ingredients free.27 In Europe, the United • Canned soups, soup mixes, bouillon, miso Kingdom, and Scandinavia, ingestion • Candy, snack foods, desserts, frozen yogurt, and ice cream with gluten-containing of wheat starch that has been ren- ingredients dered gluten-free is permitted. • Ground spices, condiments, and soy sauce with gluten-containing ingredients European Codex Alimentarius-quali- • Margarine, salad dressing, and dips with gluten-containing ingredients ty wheat starch has been used in • Instant coffee, instant tea, instant cocoa mixes, some root beer, grain alcohol some European countries for several decades and is considered safe.28 This is only a partial listing. Patients are encouraged to read all labels and to seek However, the United States and comprehensive food and additive lists from celiac organizations and the American Canada have adopted a strict gluten- Dietetic Association. free regimen and do not recommend *Food produced in the United States or Canada and labeled “gluten-free” does not the use of wheat starch that contains contain gluten or wheat starch. 199 Diabetes Spectrum Volume 15, Number 3, 2002 Nutrition FYI

used for processing and shipping Table 3. GSE Support acteristics of celiac disease in juvenile diabetes in grains (bins, rail cars, trucks) and Wisconsin. J Pediatr Gastroenterol Nutr grains sold in bulk at natural food Organizations in the United 33:462–465, 2001 sections/stores may be contaminated States and Canada 4Cronin CC, Feighery A, Ferriss JB, Liddy C, via cross-use of equipment, bins, and Shanahan F, Feighery C: High prevalence of celi- scoops with prohibited grains. Pamphlets, books, recipes, cookbooks, ac disease among patients with insulin-dependent specialty food companies, reference (type I) diabetes mellitus. Am J Gastroenterol Eating in restaurants poses addi- materials, and local support groups can 92:2210–2212, 1997 tional challenges. A gluten-free item be accessed through these organiza- 5Vitoria JC, Castano L, Rica I, Bilbao JR, Arrieta may be cooked in a pan or on a grill tions: A, Garcia-Masdevall MD: Association of insulin- that is also used to cook problem dependent diabetes mellitus and celiac disease: a foods and that may not be cleaned American Celiac Society study based on serologic markers. J Pediatr between food orders. Deep-fat fryers 59 Crystal Ave. Gastroenterol Nutr 27:47–52, 1998 are also a source of contamination. West Orange, NJ 07052 6Madacsy L, Arato A, Korner A: Celiac disease Patients must be prepared to ask 973-325-8837 as a frequent cause of abdominal symptoms in detailed questions about menu items E-mail: [email protected] children with insulin-dependent diabetes melli- and preparation. tus. Clin Pediatr (Phila) 36:185–186, 1997 Celiac Disease Foundation 7 Cross-contamination in the home 13251 Ventura Blvd., Suite 3 Acerini CL, Ahmed ML, Ross KM, Sullivan PB, Bird G, Dunger DB: Coeliac disease in children may occur from toasters, kitchen Studio City, CA 91604 counters, and containers of jam, and adolescents with IDDM: clinical characteris- 818-990-2354 tics and response to gluten-free diet. Diabet Med peanut butter, and other spreads. 15:38–44, 1998 Gluten Intolerance Group of North Some patients have separate cooking 8 utensils, toasters, mixers, storage con- America Kaukinen K, Salmi J, Lahtela J, Siljamaki- 15110 10th Ave. SW, Suite A Ojansuu U, Koivisto AM, Oksa H, Collin P: No tainers, and other kitchen items. effect of gluten-free diet on the metabolic control Health care institutions, diabetes Seattle, WA 98166-1820 of type 1 diabetes in patients with diabetes and camps, daycare providers, schools, 206-246-6652 celiac disease: retrospective and controlled and other care providers must be www.gluten.net prospective survey. Diabetes Care knowledgeable about gluten-free diets 22:1747–1748, 1999 Celiac Sprue Association/USA, Inc. 9 and the potential for cross-contami- P.O. Box 31700 Iafusco D, Rea F, Chiarelli F, Mohn A, Prisco F: nation. Effect of gluten-free diet on the metabolic control Omaha, NE 68131-0700 of type 1 diabetes in patients with diabetes and 402-558-0600 celiac disease. Diabetes Care 23:712–713, 2000 Educational Materials www.csaceliacs.org 10 Referring patients to a registered Westman E, Ambler GR, Royle M, Peat J, dietitian who has expertise in medical Canadian Celiac Association Chan A: Children with celiac disease and insulin 190 Britannia Road East, Unit 11 dependent diabetes mellitus: growth, diabetes nutrition therapy (MNT) for GSE is control and dietary intake. J Pediatr Endocrinol imperative. An MNT protocol has Misissauga, ON L4Z 1W6 Metab 12:433–442, 1999 Canada been developed and is a valuable tool 11 905-507-6208 or 800-363-7296 Mohn A, Cerruto M, Lafusco D, Prisco F, for ensuring comprehensive education www.celiac.ca Tumini S, Stoppoloni O, Chiarelli F: Celiac dis- for patients with GSE.30 Patients also ease in children and adolescents with type I dia- must be strongly encouraged to join American Dietetic Association betes: importance of hypoglycemia. J Pediatr Gastroenterol Nutr 32:37–40, 2001 national and local support groups 216 West Jackson Blvd., Suite 800 (Table 3) for access to the latest infor- Chicago, IL 60606-6995 12Leon F, Camarero C, R-Pena R, Eiras P, Sanchez mation, educational materials, and 312-899-0040 or 800-366-1655 L, Baragano M, Lombardia M, Bootello A, Roy support. www.eatright.org G: Anti-transglutaminase IgA ELISA: clinical potential and drawbacks in celiac disease diagno- There is a need for educational sis. Scand J Gastroenterol 36:849–853, 2001

materials that combine MNT for celi- 13 ac disease and MNT for diabetes. Roldan MB, Barrio R, Roy G, Parra C, Alonso Acknowledgments M, Yturriaga R, Camarero C: Diagnostic value Gluten-free foods are not always Dr. Schwarzenberg’s work is funded, of serological markers for celiac disease in dia- equivalent in carbohydrates to similar in part, by a grant from the Cystic betic children and adolescents. J Pediatr gluten-containing foods. Other dia- Fibrosis Foundation. Endocrinol Metab 11:751–756, 1998 betes educational materials, such as 14Russo PA, Chartrand LJ, Seidman E: instructions for treatment of hypo- Comparative analysis of serologic screening tests glycemia with specific foods, should References for the initial diagnosis of celiac disease. Pediatrics 104:75–78, 1999 also be available in versions for 1Fasano A, Catassi C: Current approaches to patients with GSE. diagnosis and treatment of celiac disease: an 15Meeuwisse GW: Diagnostic criteria in coeliac Because of the overwhelming num- evolving spectrum. Gastroenterology disease. Acta Paediatr Scand 59:461–463, 1970 120:636–651, 2001 ber of foods containing gluten, inten- 16Walker-Smith JA, Guandalini S, Schmitz J, sive patient training is imperative. 2Reunala T, Collin P: Diseases associated with Shmerling DH, Visakorpi JK: Revised criteria for Dietitians must be prepared to help dermatitis herpetiformis. Br J Dermatol diagnosis of coeliac disease. Arch Dis Child patients navigate the conflicting 136:315–318, 1997 65:909–911, 1990 information from various organiza- 3Aktay AN, Lee PC, Kumar V, Parton E, Wyatt 17Holmes GK: Celiac disease and malignancy. J tions and health care providers. DT, Werlin SL: The prevalence and clinical char- Pediatr Gastroenterol Nutr 24:S20–S24, 1997 200 Diabetes Spectrum Volume 15, Number 3, 2002 Nutrition FYI

18Schweizer JJ, Oren A, Mearin ML: Cancer in Silano M, De Vincenzi M: Immunologic evidence herpetiformis: a long-term follow-up study. children with celiac disease: a survey of the of no harmful effect of oats in celiac disease. Am Scand J Gastroenterol 34:163–169, 1999 European Society of Paediatric Gastroenterology, J Clin Nutr 74:137–140, 2001 29Thompson T: Wheat starch, gliadin, and the Hepatology, and Nutrition. J Pediatr 24 Gastroenterol Nutr 33:97–100, 2001 Srinivasan U, Leonard N, Jones E, Kasarda gluten-free diet. J Am Diet Assoc DD, Weir DG, O’Farrelly C, Feighery C: 101:1456–1459, 2001 19Thompson T: Thiamin, riboflavin, and niacin Absense of oats toxicity in adult coeliac disease. contents of the gluten-free diet: is there a cause BMJ 313:1300–1301, 1996 30Inman-Felton AE: Overview of gluten-sensitive for concern? J Am Diet Assoc 99:858–862, 1999 25Thompson T: Case problem: questions regard- enteropathy (celiac sprue). J Am Diet Assoc 20 Thompson T: Folate, iron, and dietary fiber ing the acceptability of buckwheat, amaranth, 99:352–362, 1999 contents of the gluten-free diet. J Am Diet Assoc quinoa, and oats from a patient with celiac dis- 100:1389–1396, 2000 ease. J Am Diet Assoc 101:586–587, 2001 21 Janatuinen EK, Pikkarainen PH, Kemppainen 26Thompson T: Questionable foods and the Sarah Jane Schwarzenberg, MD, is an TA, Kosma V-M, Jarvinen RMK, Uusitupa MIJ, gluten-free diet: survey of current recommenda- associate professor of pediatrics in the Julkunen RJK: A comparison of diets with and tions. J Am Diet Assoc 100:463–465, 2000 without oats in adults with celiac disease. N Engl Division of Pediatric Gastroenterology, J Med 333:1033–1037, 1995 27Joint FAO/WHO Food Standards Program: Hepatology, and Nutrition at the 22Janatuinen EK, Kemppainen TA, Pikkarainen Codex Committee on Nutrition and Foods for University of Minnesota in PH, Holm KH, Kosma V-M, Uusitupa MIJ, Special Dietary Uses: Draft revised standard for Minneapolis. Carol Brunzell, RD, Maki M, Julkunen RJK: Lack of cellular and gluten-free foods. CX/NFSDU 98/4. July, CDE, is a diabetes educator at humoral immunological responses to oats in 1998:1–4 Fairview-University Medical Center adults with coeliac disease. Gut 46:327–331, 28 2000 Kaukinen K, Collin P, Holm K, Rantala I, Diabetes Education and Self- Vuolteenaho N, Reunala T, Maki M: Wheat 23Picarelli A, Ki Tola M, Sabbatella L, Gabrielli starch-containing gluten-free flour products in Management Program, Pediatric and F, Di Cello T, Anania MC, Mastracchio A, the treatment of coeliac disease and dermatitis Adult Divisions, in Minneapolis, Minn.

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