Gluten Intake and Development of Celiac Disease -Two Studies

  • NA Lund-Blix et al. Am J Gastroenterol 2019; 114: 1299-1306.
  • K Marild et al. Am J Gastroenterol 2019; 114: 1307-14.

Thanks to Ben Gold for these references.

In the first study, the authors used an observational prospective nationwide cohort study, the Norwegian Mother and Child Cohort Study (MoBa) with 67,608 children born between 2000-2009 and with a mean followup of 11.5 years.

Key findings:

  • Celiac disease (CD) was diagnosed in 738 children (1.1%)
  • The adjusted relative risk of CD was 1.1 per standard deviation increase in daily gluten amount at age 18 months.
  • Compared to children in the lowest quartile of gluten ingestion, those in the upper quartile had an adjusted relative risk of 1.29.
  • Timing of gluten introduction, ≥6 months or before 4 months, was also an independent risk factor for CD. In those before 4 months the aRR was 1.45 and for those ≥6 months the aRR was 1.34

In the second study, the authors used the prospective Diabetes Autoimmunity Study in the Young cohort with 1875 at-risk children.

Key findings:

  • Children in the highest tertile of gluten intake between ages of 1 and 2 had a 2-fold greater hazard of developing CD autoimmunity (positive tTG antibodies) (aHR 2.17) than those in the lowest tertile.
  • The risk of CDA increased by 5% per daily gram increase in gluten intake in 1 year olds.

My take: Taken together, these studies indicate that higher gluten exposure (between 1-2 years) is associated with a modestly-higher risk of CD; in addition, early (<4 months) and late exposure (>6 months) may increase the risk as well.

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Spoiler alert: This case study by A Fasano et al. NEJM 2020; 382: 180-9. describes a presentation of celiac disease and Addision’s disease. I recently had a teenager present with similar symptoms who had Addison’s alone (clues were fatigue, low sodium and hyperpigmentation)

Dietary Patterns in First Year of Life May Increase Risk of Celiac Autoimmunity

M Barroso et al. Gastroenterol 2018; 154: 2087-96.

Background: “Western-like diets –mainly characterized by high intake of red and processed meats, refined grains, simple sugars, and saturated fats and low intake of fruits, vegetables, and whole grains– have been associated with low-grade chronic inflammation, which is involved in the etiology of inflammatory conditions.” Ref: Br J Nutr 2015; 114: 999-1012.

To examine how diet may influence the development of celiac autoimmunity, defined by TG2A positivity, the authors examined a subset of patients (n=1997) from the prospective Generation R study (Netherlands); 27 in this cohort developed celiac autoimmunity (1.4%).

Key finding:

  • Higher adherence to a “prudent” diet which had a higher intake of vegetables, vegetable oils, pasta, and grains and low consumption of refined cereals and sweet beverages at 1 year of age was associated with a lower odds of celiac autoimmunity at 6 years of age with an odds ratio of 0.67.

This study is limited by the relatively low number who had celiac autoimmunity and by its use of a food questionnaire.

My take: This study indicates that diet plays a role in the development of celiac along with other disease, but this likely involves a complex mix of components rather than a single toxic agent.

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Celiac Disease Risk -TEDDY Study

“The Environmental Determinants of Diabetes in the Young (TEDDY) is a multinational study that follows children at high genetic risk for type 1 diabetes, with the development of celiac disease as a secondary outcome.”  A recent publication provides excellent data with regard to the longitudinal risk of developing celiac disease (CD) (NEJM 2014; 371: 42-9).

Methods: 424,788 newborns were screened for at-risk HLA genotypes (from 2004 to 2010) in four countries (U.S, Finland, Germany, and Sweden).  21,589 had one of nine HLA genotypes of interest to the investigators –>8677 infants were enrolled in the study; 6403 of this group had one of the four HLA genotypes reported in this study:

  1. DR3-DQ2 homozygotes
  2. DR3-DQ2/DR4-DQ8
  3. DR4-DQ8 homozygotes
  4. DR4-DQ8/DR8-DQ4

Median follow-up: 60 months

Definitions for study:

  • Celiac autoimmunity: presence of tTG antibodies on two consecutive tests at least 3 months apart
  • Celiac disease: CD diagnosis based on biopsy (Marsh 2 or higher) or persistently high tTG (≥100 units) on at least two tests at least 3 months apart

Key findings:

  • Overall 786 children developed celiac autoimmunity (12%) and 291 had confirmed CD.
  • Children with DR3-DQ2 homozygosity had more than 5 times the risk of CD than the lowest-risk groups; in addition, the risk was 2.5 times more than the risk for a heterozygote (single DR3-DQ2) haplotype.
  • By 5 years of age, celiac autoimmunity developed in 26% and 12% respectively among children with DR3-DQ2 homozygosity  and in 11% and 3% of those children with DR3-DQ2 heterozygosity.
  • Residence in Sweden increased risk for CD with hazard ratio of 1.9.  The fact that residents with same genetic haplotypes had increased risk suggests that an environmental factor is playing a role.  It was noted that these children were given gluten-containing cereals at the earliest age.
  • CD was more common in females with HR of 2.16 (P<0.001) and in those with family history of CD HR 2.95 (P<0.001)

Take-home message: This prospective TEDDY study is providing useful information about how likely an individual with a genetic predisposition will develop CD and how quickly this develops.

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