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Celiac Disease Triples Risk of Type 1 Diabetes Diagnosis

Nov 14, 2006

Children with celiac disease have a higher likelihood of a subsequent diagnosis of type 1 diabetes — approximately 3-fold higher — than the general population, according to results of a population-based cohort study in Sweden. Lead author Jonas F. Ludvigsson stated that, "We believe that celiac disease predisposes children to type 1 diabetes." Some children receive a type 1 diabetes diagnosis prior to identification of celiac disease, suggesting that the celiac disease has been asymptomatic and ongoing for several years."

In a second study, also published in the November issue of Diabetes Care, Danish researchers established that celiac disease is common in children with type 1 diabetes. In contrast, there has been little focus on patients in whom celiac disease is diagnosed prior to a diagnosis of type 1 diabetes.

For the current paper, Dr. Ludvigsson of the Orebro University Hospital and colleagues used the Swedish National inpatient register for the period between 1964 and 2003 to identify 9243 individuals with celiac disease diagnosed before age 20 years. Using the Total Population Register, they matched these patients to five reference subjects without celiac disease by age, gender, calendar year, and area of residence (n = 45,680).

The median age at celiac disease diagnosis was 1 year, while the median age of type 1 diabetes diagnosis was 10 years among patients with a prior celiac disease diagnosis. To avoid surveillance bias, the investigators first estimated the risk of diabetes diagnosis at least 1 year following the celiac disease diagnosis.

Children with celiac disease had a statistically significantly increased hazard ratio (HR) of 2.4 for a subsequent diagnosis of type 1 diabetes before age 20.

The risk was further elevated when Dr. Ludvigsson’s group included patients diagnosed with diabetes at any time following the first symptoms of celiac disease (HR = 3.9), and when they only included children diagnosed with diabetes 1 to 5 years after their first diagnosis of celiac disease (HR = 2.7).

Neither the age at onset nor subjects’ socioeconomic level affected outcomes.

The researchers post that the association of celiac disease with subsequent type 1 diabetes could be due to autoantibodies expressed after early exposure to gluten in their diet. Other explanations include a common genetic susceptibility or shared human leucocyte antigen (HLA) profiles.

"It could well be that a combination of these factors is responsible for the positive association between celiac disease and type 1 diabetes," Dr. Ludvigsson commented. "Even though our study design does not allow us to examine the etiology of either disease, if I had to choose one factor, it would probably be HLA characteristics."

The Swedish investigators found no strong evidence that an earlier introduction of a gluten-free diet in patients with celiac disease protects against type 1 diabetes.

When asked about the potential implications of his group’s research, Dr. Ludvigsson replied, "Most children being investigated for celiac disease have already had their glucose tested. If blood tests or urinalysis have not been undertaken at diagnosis of celiac disease, I recommend that they be checked."

He continued, "In the absence of increased blood glucose levels or lack of urinary glucose, I do not recommend further testing for type 1 diabetes. However, I inform patients with newly diagnosed celiac disease about typical symptoms of type 1 diabetes and urge them to contact their doctor in case they suspect type 1 diabetes. Such symptoms may include increased thirst, increased urination (polyuria), weight loss and fatigue."

In the Danish study by Dr. Hansen, of Odense University Hospital, and her associates, there was no evidence that HbA1c was affected by the gluten-free diet during 2 years of follow-up.

However, Dr. Ludvigsson added that "I am not convinced by their data that a gluten-free diet has no importance for the HbA1C level." For example, he suggested, longer duration of the diet could lower glucose levels.

Another possibility, the investigator proposed, is that "maybe patients with celiac disease and type 1 diabetes inherently have worse HbA1C levels, and the lack of change in HbA1C in the Hansen et al. study actually represents a relative improvement."
As to how the research team intends to proceed, he said, "Our aim is to describe the spectrum of complications and associated disorders in celiac disease. It would also be interesting to validate some of our earlier findings — the fourfold increased risk of tuberculosis and the twofold risk of depression associated with celiac disease."

Practice Pearls:
· Children with celiac disease have increased risk of developing type 1 diabetes before age 20 years and 1 to 5 years following celiac disease diagnosis, which is unrelated to age of celiac disease diagnosis and socioeconomic status.
· Children with celiac disease have increased risk for ketoacidosis or diabetic coma before age 20 years.
Diabetes Care. 2006;29:2483-2488.


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