0
Celiac Disease and Risk
of Subsequent Type I
Diabetes: A general
population cohort study
of children and
adolescents
Journ...
Celiac Disease
• Aka: Gluten Intolerance
• Not to be confused with a wheat allergy, body
•
•
•

reacts to wheat protein on...
Cell-mediated Immune Responses
• Upon exposure to gliadin, the
enzyme tissue transglutaminase
modifies the protein and imm...
Symptoms of Celiac Disease
•
•
•
•
•
•
•
•
•
•
•

Often diagnosed as IBS before proper screening
Diarrhoea or constipation...
Malabsorption-Related
Problems
• Fatigue or lack of energy due to carbohydrate
•
•
•

and fat malabsorption
Reduced Vitami...
Diagnosis

• All tests lose there usefullness if patient consuming a
•
•
•
•

gluten-free diet
Intestinal damage begins to...
Pathology determined by the "Marsh classification”:
• Marsh stage 0: Normal mucosa
• Marsh stage 1: Increased number of in...
Prophylaxis/Treatment
• One study suggested that exposure to wheat,
•
•
•
•

barley, or rye before full GI development cau...
Introduction
• Looks at incidence of type 1 diabetes
•
•
•

diagnosis prior to celiac diagnosis.
Previous studies looked a...
Introduction
• Majority of individuals with celiac disease exhibit

HLA-DQ2, with a smaller group being positive for
HLA-D...
Introduction
• This study did not give incidence ratios
• It was unclear if individuals with type 1

diabetes and simultan...
Introduction
• The main objective was to estimate the

association of celiac disease with subsequent type
1 diabetes (befo...
Research/Methods
• Approved by research ethics committee of Karolinska
•
•
•
•

•

Institute.
No participants contacted, i...
Methods
• Follow up time began 1 year after study entry.
• Ended on the date of first discharge diagnosis of
•
•
•
•

type...
Methods
• Used cox regression to estimate association of celiac disease
•
•
•
•
•

with type 1 diabetes.
Estimated the ris...
Results
•
•
•

Median age was 1 year (range 0-19).
Majority was female.
Median age at first diabetes diagnosis was
10 year...
Table 1

Atopic
Dermatitis of
the Arm
(celiac
patient)
Results
• Children with celiac disease were at increased risk
•
•
•
•

of type one diabetes (based upon 300 positive
resul...
Conclusion
• The study found a statistically significant positive
•

•
•
•

association of celiac disease with subsequent ...
Table 2
Conclusion
• Increased risk of diabetes was seen (300 cases) 2-3 fold greater
•
•
•
•
•
•
•

than reference individuals
Co...
Conclusion
• The association could be a result of shared HLA characteristics
•
•
•
•
•

or an interaction between food int...
Experiment Critique
• Family history of subjects not taken into account
• Many subjects taken from decades ago and the

di...
Further Experimentation
• Use more current records to account for

present day type 1 diabetes diagnosis,
compare rate of ...
Works Cited
• Bao F, Yu L, Babu S, Wang T, Hoffenberg EJ, Rewers M, Eisenbarth GS: One

•

•

•
•
•

third of HLA DQ2 homo...
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Nutritional Science Research: Celiac Disease & Risk of Subsequent Type I Diabetes

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Nutritional Science Research: Celiac Disease & Risk of Subsequent Type I Diabetes

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Transcript of "Nutritional Science Research: Celiac Disease & Risk of Subsequent Type I Diabetes"

  1. 1. Celiac Disease and Risk of Subsequent Type I Diabetes: A general population cohort study of children and adolescents Journal of Diabetes Care Mike Schiemer and Ryan Blaney
  2. 2. Celiac Disease • Aka: Gluten Intolerance • Not to be confused with a wheat allergy, body • • • reacts to wheat protein only Autoimmune Disease of small bowel Reaction to gliadin, a gluten protein found in wheat and hybrid wheat/rye Triticeae proteins, some also react to oats due to crosscontamination with gluten containing products Occurs in about 1% of North American and European populations but increasing reports due to screening asymptomatic individuals
  3. 3. Cell-mediated Immune Responses • Upon exposure to gliadin, the enzyme tissue transglutaminase modifies the protein and immune system cross-reacts with bowel tissue, creating inflammation • leads to flattening of the lining of the small intestine, significantly reducing nutrient absorption.
  4. 4. Symptoms of Celiac Disease • • • • • • • • • • • Often diagnosed as IBS before proper screening Diarrhoea or constipation Weight Loss Stunted Growth in Children Fatigue Primarily a bowel disease but these symptoms may be limited or absent Older children and adults have malabsorptive problems and anaemia due to reduced iron absorption Abdominal pain, cramping, bloating, abdominal distention due to gas production Mouth ulcers may be present Lactose intolerance can develop as symptoms worsen Longstanding disease may cause ulcering of the small bowels or stricturing (narrowing due to scarring)
  5. 5. Malabsorption-Related Problems • Fatigue or lack of energy due to carbohydrate • • • and fat malabsorption Reduced Vitamin D and Calcium absorption may lead to osteopenia or osteoporosis. 10% of those with Celiac have coagulation problems due to decreased Vitamin K absorption Can potentially cause bacterial overgrowth of small intestine leading to further malabsorption even after treatment
  6. 6. Diagnosis • All tests lose there usefullness if patient consuming a • • • • gluten-free diet Intestinal damage begins to heal within weeks of gluten being removed from the diet, and antibody levels decline over months, if no gluten consumed a 10g per day intake will elicit a proper diagnosis Serology by blood test is 98% effective, all positive blood tests must be followed by endoscopic examination and a biopsy of 4-8 sites in duodenum to be 100% sure Blood tests detect IgA against endomysium or tissue transglutaminase Some experts also require or encourage blood tests for electrolyte, calcium, liver enzymes, vitamin B12, and folic acid levels. Coagulation testing for Vitamin K deficiency, bone scan for checking Vitamin D or calcium deficiencies
  7. 7. Pathology determined by the "Marsh classification”: • Marsh stage 0: Normal mucosa • Marsh stage 1: Increased number of intra-epithelial lymphocytes • Marsh stage 2: Proliferation of the crypts of Lieberkuhn • Marsh stage 3: Partial or complete villous atrophy • Marsh stage 4: Hypoplasia of small bowel architecture
  8. 8. Prophylaxis/Treatment • One study suggested that exposure to wheat, • • • • barley, or rye before full GI development caused five times the risk over those exposed at 4 to 6 months Another study contradicts these results and shows early exposure can be protective to disease development Breastfeeding may also reduce risk significantly for the first 6 months before gluten exposure Only real “cure” is the preventative measure of a lifelong diet avoiding gluten although some major symptoms may still occur even with strict dieting Now there is a much higher selection of gluten-free foods at supermarkets, restaurants, etc.
  9. 9. Introduction • Looks at incidence of type 1 diabetes • • • diagnosis prior to celiac diagnosis. Previous studies looked at prevalence of opposite scenario Focused on children diagnosed before the age of 20. Hypothesized that prior celiac diagnosis will result in significant increased risk for type 1 diabetes
  10. 10. Introduction • Majority of individuals with celiac disease exhibit HLA-DQ2, with a smaller group being positive for HLA-DQ8 • Studies have proven that children with diabetes are at increase risk for celiac disease (5 to 10 fold risk increased for celiac) • It has also been suggested that early gluten introduction may be a common risk factor for both diseases. • Cronin and Shanahan have demonstrated that some 15% of individuals with both diseases may first receive diagnosis of celiac disease.
  11. 11. Introduction • This study did not give incidence ratios • It was unclear if individuals with type 1 diabetes and simultaneously diagnosed with celiac disease were included.
  12. 12. Introduction • The main objective was to estimate the association of celiac disease with subsequent type 1 diabetes (before 20yoa) p=9,243 with celiac disease compared with 45,680 age + sex matched individuals without celiac disease • The second objective was to study the risk of type 1 diabetes stratified for age at diagnosis of celiac disease. • Hypothesis: celiac disease diagnosed at early age and consequent early introduction of gluten-free diet would be associated with a lower risk of type 1 diabetes.
  13. 13. Research/Methods • Approved by research ethics committee of Karolinska • • • • • Institute. No participants contacted, information was made anonymous before analysis Used hospital inpatient diagnosis of celiac disease between 1964 and 2003 through Sweedish national inpatient register. Celiac diagnosed by various ICD codes. For each individual with celiac disease, Statistics Sweden indentified up to five reference individuals matched for age, sex, calendar, year, and area of residence at time of diagnosis Restricted measurements to individuals diagnosed with type 1 diabetes before age of 20.
  14. 14. Methods • Follow up time began 1 year after study entry. • Ended on the date of first discharge diagnosis of • • • • type 1 diabetes, emigration, death, or age 20 years Identified 9,733 individuals with celiac disease between 1964 and 2003 Excluded 233 individuals with type 1 diabetes diagnosed before celiac disease. Study based upon 9,243 individuals with celiac disease diagnosed before 20yo and 45,680 age, period, and sex matched individuals without celiac disease All participants were type 1 free at start of follow up
  15. 15. Methods • Used cox regression to estimate association of celiac disease • • • • • with type 1 diabetes. Estimated the risk of ketoacidosis before age 20 years. Individuals only compared with matched reference individuals Stratification for sex and age was chosen <2 or 3 years to maximize study power Individuals diagnosed with celiac disease between 0-1yo were used as the reference category and compared with those between 1 and <2yo At a significance level of 5% the study had an 80% power to detect an increased risk of subsequent type 1 diabetes.
  16. 16. Results • • • Median age was 1 year (range 0-19). Majority was female. Median age at first diabetes diagnosis was 10 years (2-19) • The median duration from diagnosis of celiac to diagnosis of diabetes was 8.1 years
  17. 17. Table 1 Atopic Dermatitis of the Arm (celiac patient)
  18. 18. Results • Children with celiac disease were at increased risk • • • • of type one diabetes (based upon 300 positive results) Age of first celiac diagnosis displayed no significance to subsequent diagnosis of diabetes (p=.211) Risk estimates after stratification for age at diagnosis and sex were similar to risk estimates for type 1 diabetes before age of 20. Individuals with celiac disease were at a significantly increased risk of subsequent ketoacidosis. (based upon 13 positive results) Results were only significant for females
  19. 19. Conclusion • The study found a statistically significant positive • • • • association of celiac disease with subsequent type 1 diabetes and with ketoacidosis before the age of 20. There was no statistically significant difference in risk of subsequent type 1 diabetes between individuals with a diagnosis of celiac disease at 0-2 years and those diagnosed after 2 years of age. To knowledge of authors, there exists only one previous similar study though no incidence ratios were given. The significance of the studies results is only further enhanced by the use of several reference individuals for each of the studied individuals. The large population provided high statistical power and allowed for sub analysis.
  20. 20. Table 2
  21. 21. Conclusion • Increased risk of diabetes was seen (300 cases) 2-3 fold greater • • • • • • • than reference individuals Could be attributed to various factors such as environmental or genetic susceptibility. Gluten is a necessary trigger for celiac disease so feeding pattern may have been a factor. Daisy and BABY DIAB studies found a four to fivefold increase risk in children exposed to gluten before age of 4 months. Risk estimates were substantially lower than prior findings of diabetes diagnosis followed by celiac disease An explanation could be that those with more severe autoimmune disease have an earlier symptomatic onset of type 1 diabetes. An alternative explanation is that the inflammation associated with celiac disease remained for a period after diagnosis. No strong evidence suggested that early diagnosis of celiac disease could help protect against type 1 diabetes
  22. 22. Conclusion • The association could be a result of shared HLA characteristics • • • • • or an interaction between food introduction and genetic susceptibility. Approximately 1/3rd of celiac patients are positive for HLA-DQ2 and this is a positive risk factor for type 1 diabetes so the increased risk could be attributed entirely to HLA characteristics. False negative celiac disease is unlikely since <1% of reference population should be affected by celiac disease. All children in Sweden are hospitalized upon diagnosis of type 1 diabetes so sensitivity to diabetes should be high in this study. In conclusion, the cohort study found a 2-3fold risk increase of type 1 diabetes before age of 20. Shared nutritional factors and common HLA profiles may explain the significance. The risk increase for type 1 diabetes is low considering that 95% of individuals with celiac disease are HLA-DQ2 positive.
  23. 23. Experiment Critique • Family history of subjects not taken into account • Many subjects taken from decades ago and the diagnosis of type 1 diabetes may have been inconsistent with rates from the last few years • Study isolated to a set of hospital records in Sweden, primarily Caucasian and middle class. • Subjects were anonymous so there was no telling what these subjects diet consisted of. • Also the prevalence of celiac disease within the subjects siblings and parents could not be noted.
  24. 24. Further Experimentation • Use more current records to account for present day type 1 diabetes diagnosis, compare rate of increased susceptibility from this study to a current one • Focus on other geographical or demographical areas • Take more detailed records of subjects to determine secondary variables that could account for different results
  25. 25. Works Cited • Bao F, Yu L, Babu S, Wang T, Hoffenberg EJ, Rewers M, Eisenbarth GS: One • • • • • third of HLA DQ2 homozygous patients with type 1 diabetes express celiac disease-associated transglutaminase autoantibodies. ] Autoimmun 13:143-148, 1999. Dube C, Rostom A, Sy R, Cranney A, Saloojee N, Garritty C, Sampson M, Zhang L, Yazdi F, Mamaladze V, Pan I, Macneil J, Mack D, Patel D, Moher D: The prevalence of celiac disease in average-risk and at-risk Western European populations: a systematic review. Gastroenterology 128: S57-S67, 2005 Ekbom, Anders; Jonas F Ludvigsson, Johnny Ludvigsson, Scott M Montgomery. Celiac Disease and Risk of Subsequent Type 1 Diabetes: A general population cohort study of children and adolescents. J. Diabetes Care . Alexandria: Nov 2006. Vol. 29, Iss. 11; pg. 2483. Green PHR, Stavropoulos SN, Panagi SG, Goldstein SL, McMahon DJ, Absan H, Neugut AI: Characteristics of adult celiac disease in the USA: results of a national survey. Am J Gastroenterol 96:126-131, 2001 Murray JA: Celiac disease in patients with an affected member, type 1 diabetes, irondeficiency, or osteoporosis? Gastroenterology 128:552-556, 2005 Rapoport MJ, BistritzerT, Vardi O, Broide E, Azizi A, Vardi P: Increased prevalence of diabetes-related autoantibodies in celiac disease. J Pediatr
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