Type 1 Diabetes Linked to Higher MS Risk Among Youth

Risk of comorbid multiple sclerosis (MS) was higher in children and adolescents with type 1 diabetes, but environmental factors may modulate risk, according to a database study published online ahead of print August 29 in Diabetes Care (Bechtold et al., 2013).

“Type 1 diabetes and [MS] are organ specific inflammatory diseases, which result from an autoimmune attack against either pancreatic β-cells or central nervous system; a combined appearance has been described repeatedly,” wrote Susanne Bechtold, M.D., a pediatric endocrinologist and diabetologist at Ludwig Maximilians University in München, Germany, and colleagues. “We hypothesize that antibodies (namely diabetes specific antibody, celiac disease or thyroid specific antibodies), BMI, immigrant background or month of birth might have a major impact on the coincidence of type 1 diabetes and MS.”

Using the DPV-Wiss-project database, the investigators estimated the relative risk for MS in a pediatric and adolescent diabetes population and looked for possible modulating factors. From January 1995 to October 2012, there were 56,653 patients under 21 years of age with type 1 diabetes at 248 centers in Germany and Austria. For comparison, the investigators used published data on German and Mid-European prevalence of MS, and they used multivariable regression analysis to examine confounders for co-occurrence of both diseases. This analysis considered age, sex, diabetes duration, migration background, treatment, and daily insulin dose as fixed independent effects, and month of birth, BMI-SDS, thyroid, celiac disease, and diabetes-specific antibodies as dependent variables.

For persons with type 1 diabetes, estimated relative risk for MS was 3.35-4.79 (95% confidence interval [CI]: 1.56-7.21 using German reference data and 2.01-11.39, using mid-European reference data).

Factors affecting MS risk

Factors associated with MS incidence were immigration status for males and females (P < 0.05) and thyroid antibodies for males only (P = 0.05). Compared with the overall type 1 diabetes population, the population with both diseases had a pattern of birth month favoring the spring and summer months. Within the type 1 diabetes-MS population, peak birth months were June and August; fewer subjects were born in April.

“The risk of autoimmune diseases might be linked to month of birth through seasonal maternal vitamin D deficiencies,” the study authors wrote. “Lower UV exposure might predict for a higher autoimmune susceptibility explaining the co-occurrence of several autoimmune diseases in one person.”

Age at diabetes onset, diabetes-specific antibodies, and celiac disease-specific antibodies were not associated with co-occurrence of the two conditions.

“The present cohort study demonstrates a higher risk of co-occurrence of MS in a pediatric and adolescent diabetes population,” the study authors wrote. “… We suggest that environmental factors modulate the individual's risk for the co-occurrence of both diseases.”

The pathophysiology underlying the co-occurrence of type 1 diabetes and MS is still unclear, although both diseases are associated with several immune abnormalities directed against different autoantigens.

A study limitation is that MS-related information was not documented systematically in the diabetes-centered database, so detailed information was not available on family history, number of relapses, type of MS, and medication. The investigators therefore recommend prospective collection of detailed disease-related data from persons with type 1 diabetes and MS.

“Environmental factors like vitamin D and its levels during early pregnancy and immigration background might be a modulator of autoimmune disease,” the study authors concluded. “These specific effects found only in the type 1 diabetes-MS group draw attention to a subtype of immune disease that results in combined autoimmunity against endocrine and neuronal antigens.”

Key open questions

• What is the mechanism underlying the association of type 1 diabetes and MS among youth?
• What would be the implications for prevention or therapy if the underlying mechanism is elucidated?

Disclosures

The German Ministry of Health, the German Diabetes Foundation, the German Diabetes Association, the BMBF competence network for diabetes mellitus and competence net obesity (Förderkennzeichen): 01G1106, excellence center “Metabolism” of the state at Baden Württemberg, the Dr. Bürger-Büsing Foundation, the German Medical Association (BÄK) and Novo Nordisk Germany financially supported the DPV initiative. The study authors reported having no financial disclosures.