Frugal Finance: Research: Celiac Disease and Risk of Subsequent Type I Diabetes

Article Critiqued By Frugal Fitness From "The Journal of Diabetes Care"

About Celiac Disease

• Definition: 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 cross-contamination with gluten containing products

• Occurs in about 1% of North American and European populations but increasing reports due to screening asymptomatic individuals

Cell-Mediated Immune Response

• 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.

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)

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

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

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.

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

• 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.

• This study did not give incidence ratios

• It was unclear if individuals with type 1 diabetes and simultaneously diagnosed with celiac disease were included.

• 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.

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.

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

• 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.

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

• 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

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.

• 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

• The association could be a result of shared HLA characteristics or an interaction between food introduction and genetic susceptibility.

• Approximately 1/3^rd 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.

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.

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

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 Gastroenterol Nutr 23:524-527,1996

Frugal Fitness Fun For Everyone! Subscribe Today

For More Great Tips, Get My Best-Seller On Amazon: