Celiac Autoimmunity in Children with Type 1 Diabetes: A Two-Year Follow-Up

Abstract

Objective-To determine the benefits of screening for celiac autoimmunity via IgA transglutaminase autoantibodies (TG) in children with type 1 diabetes (T1D).Study design-We followed 79 screening-identified TG+ and 56 matched TG− children with T1D for 2 years to evaluate growth, bone mineral density, nutritional status, and diabetes control. TG+ subjects self-selected to gluten-free or gluten-containing diet.Results-Of the initial cohort, 80% were available for re-examination after 2 years. TG+ subjects had consistently lower weight z-scores and higher urine N-telopeptides than TG− subjects, but similar measures of bone density and diabetes outcomes. TG+ children who remained on a gluten-containing diet had lower IGF-BP3 z-scores compared with TG+ subjects who reported following a gluten-free diet. Children who continued with high TG index throughout the study had lower bone mineral density z-scores, ferritin, and vitamin D 25OH levels, compared with the TG− group.Conclusions-No significant adverse outcomes were identified in children with T1D with screening-identified TG+ who delay GFD therapy for 2 years. Children with persistently high levels of TG may be at greater risk. The optimal timing of screening and treatment for CD in children with T1D requires further investigation.Keywords type 1 diabetes; pediatric; celiac disease; tissue transglutaminase autoantibodies; screening; gluten; diet Up to 16% of children with type 1 diabetes mellitus (T1D) have celiac disease (CD) 1,2,3,4,5 . Routine screening using IgA transglutaminase autoantibody (TG) has been recommended Corresponding author and reprint request author: Jill Simmons, MD, 11136 Doctors' Office Tower, 2200 Children's Way, Nashville, TN 37232-9170, (615) 936-1874 (office) (615) 343-5845 (fax), jill.h.simmons@vanderbilt.edu. The authors declare no conflicts of interest.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript 6,7 . However, important unanswered questions remain regarding benefit of gluten-free diet (GFD) in screening-identified TG+ children with T1D. Even though high TG levels are specific for biopsy-confirmed CD, low-positive TG may be associated with negative biopsy but may be a risk factor for future CD. The optimal timing of GFD initiation in screeningidentified TG+ children, with or without T1D, remains unclear. The child with T1D and CD faces two life-long changes in diet, yet untreated CD has been associated with recurrent hypoglycemia and poor glycemic control.We previously reported baseline data reg...

High Rate of Spontaneous Normalization of Celiac Serology in a Cohort of 446 Children With Type 1 Diabetes: A Prospective Study

“…The discordant findings among studies, the small numbers of patients, and the lack of distinction between symptomatic and asymptomatic patients make it difficult to comment on the real effect of adherence to a GFD in patients with T1DM. Recent studies suggest that no significant adverse outcomes take place in anti-tTG-positive children with T1DM who delay starting a GFD for 2 years (29) and that positive antibodies are insufficient to cause a noticeable effect on important outcomes (microvascular complications, neuropathy) for which coexisting enteropathy is required (30).…”

Children diagnosed with both Type 1 diabetes and Celiac disease - An Immunological challenge

“…Neither could the same intervention study, at a follow-up at the age of 8 years, indicate that delayed gluten introduction can decrease the risk of developing autoimmune T1D [119] . Also, in a 2-year prospectively followed cohort of subjects with already diagnosed T1D, with and without celiac autoimmunity, no significant adverse outcome was found in children with a delayed introduction of gluten [120] . Thus, there is still a controversial regarding the effect of gluten-free diet in T1D patients with celiac disease.…”

Organ specific autoimmune disorders in type 1 diabetes mellitus

“…5,[32][33] In India, prevalence of celiac autoimmunity was reported to be 8%-22% among patients with established T1DM (Table 4). 24,[35][36][37][38][39][40] A two year follow-up study 41 was done at Barbara Davis Center for Childhood Diabetes to determine the impact of screening-detected celiac disease autoimmunity via IgA anti TTG antibodies in children with T1DM and GFD on growth, bone mineralization, and glycaemic control. It was found that anti TTG antibody positive subjects had consistently lower weight z-scores and higher urine N-telopeptides (a marker of bone turnover) than anti TTG antibody negative subjects, but had similar measures of bone densit y and diabet es outcomes.…”

“…Children who continued with high TTG index throughout the study had lower bone mineral density z-scores, serum ferritin and 25-hydroxy vitamin D, compared with the antibody negative group. 41 A study from university of Toronto compared CD associated with T1DM to CD alone. After following patients for 3 years it was found that CD associated with T1DM represents a distinct and a possibly milder form.…”