Gastroenterology

Gastroenterology

Volume 137, Issue 1, July 2009, Pages 88-93
Gastroenterology

Clinical—Alimentary Tract
Increased Prevalence and Mortality in Undiagnosed Celiac Disease

https://doi.org/10.1053/j.gastro.2009.03.059Get rights and content

Background & Aims

The historical prevalence and long-term outcome of undiagnosed celiac disease (CD) are unknown. We investigated the long-term outcome of undiagnosed CD and whether the prevalence of undiagnosed CD has changed during the past 50 years.

Methods

This study included 9133 healthy young adults at Warren Air Force Base (sera were collected between 1948 and 1954) and 12,768 gender-matched subjects from 2 recent cohorts from Olmsted County, Minnesota, with either similar years of birth (n = 5558) or age at sampling (n = 7210) to that of the Air Force cohort. Sera were tested for tissue transglutaminase and, if abnormal, for endomysial antibodies. Survival was measured during a follow-up period of 45 years in the Air Force cohort. The prevalence of undiagnosed CD between the Air Force cohort and recent cohorts was compared.

Results

Of 9133 persons from the Air Force cohort, 14 (0.2%) had undiagnosed CD. In this cohort, during 45 years of follow-up, all-cause mortality was greater in persons with undiagnosed CD than among those who were seronegative (hazard ratio = 3.9; 95% confidence interval, 2.0–7.5; P < .001). Undiagnosed CD was found in 68 (0.9%) persons with similar age at sampling and 46 (0.8%) persons with similar years of birth. The rate of undiagnosed CD was 4.5-fold and 4-fold greater in the recent cohorts, respectively, than in the Air Force cohort (both P ≤ .0001).

Conclusions

During 45 years of follow-up, undiagnosed CD was associated with a nearly 4-fold increased risk of death. The prevalence of undiagnosed CD seems to have increased dramatically in the United States during the past 50 years.

Section snippets

Subjects

We concurrently tested serum samples for CD antibodies in 3 cohorts (Table 1). The first cohort, the Warren Air Force Base (WAFB) cohort, was a large sample of healthy young men whose serum was collected from 1948 to 1954 and stored frozen as part of a series of studies and surveillance activities related to streptococcal infection.12, 13 The cohort was subsequently used successfully to study the prevalence and outcomes of hepatitis C infection. The repository and construction of the study

Demographic data

The cohort total was 9133 persons. Of 7950 whose date of birth was known, 7511 (94.5%) were <25 years old, 426 (5.4%) were 25–40 years old, and 13 (0.2%) were >40 years at sampling. Of 6676 persons whose gender was known, 6579 (98.6%) were men. Among 6465 persons whose ethnicity was known, 5774 (89.3%) were white, 668 (10.3%) were African American, and 23 (0.4%) were of another race.

Serologic data

Among 9133 persons tested, the tTGA titer was negative in 9090 (99.5%), weakly positive in 30 (0.4%), and

Discussion

This study yielded 2 major findings. First, undiagnosed CD was associated with a nearly 4-fold increased risk of death compared with subjects without serologic evidence of CD. Second, the prevalence of CD seems to have increased dramatically in the United States during the past 50 years.

These results are important because, by testing a unique collection of sera obtained from 1948 to 1954, we were able to study the long-term natural history of CD. Our results confirm recent data19 showing that

Acknowledgments

Portions of this manuscript have been published in abstract form: Gastroenterology 2008;134(Suppl 1):A-80–81.

The opinions and assertations herein are of the authors and not to be construed as reflecting the views or positions of the National Academies, the Institute of Medicine, or the National Research Council.

References (33)

  • N.J. Talley et al.

    Epidemiology of celiac sprue: a community-based study

    Am J Gastroenterol

    (1994)
  • C. Catassi

    The world map of celiac disease

    Acta Gastroenterol Latinoam

    (2005)
  • T. Not et al.

    Celiac disease risk in the USA: high prevalence of antiendomysium antibodies in healthy blood donors

    Scand J Gastroenterol

    (1998)
  • A. Fasano et al.

    Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study

    Arch Intern Med

    (2003)
  • O.H. Nielsen et al.

    Non-tropical sprue: malignant diseases and mortality rate

    Scand J Gastroenterol

    (1985)
  • P. Collin et al.

    Coeliac disease: associated disorders and survival

    Gut

    (1994)
  • Cited by (0)

    This article has an accompanying continuing medical education activity on page 373. Learning Objective: Upon completion of this CME exercise, successful learners will be able to understand the potential impact of the changing prevalence of undiagnosed celiac disease in its potential effect on long-term outcome.

    Conflicts of interest The authors disclose no conflicts.

    Funding Supported in part by the National Institutes of Health (NIH) under Ruth L. Kirschstein National Research Service Award/Training Grant in Gastrointestinal Allergy and Immunology Research T32 AI07047 (A.R.-T.), NIH grants DK57892, DK070031, AR30582 (J.A.M.), DK61617 (W.R.K.), and CA62242 (R.A.K.), and the CTSA grant 1UL1RR024150-01 from the National Center for Research Resources.

    View full text