What is the role of genetics in the etiology of pediatric type 1 diabetes mellitus (DM)?

Updated: Jul 03, 2019
  • Author: William H Lamb, MD, MBBS, FRCP(Edin), FRCP, FRCPCH; Chief Editor: Sasigarn A Bowden, MD  more...
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Answer

Clear evidence suggests a genetic component in type 1 diabetes mellitus. Monozygotic twins have a 60% lifetime concordance for developing type 1 diabetes mellitus, although only 30% do so within 10 years after the first twin is diagnosed. In contrast, dizygotic twins have only an 8% risk of concordance, which is similar to the risk among other siblings.

The frequency of diabetes development in children with a mother who has diabetes is 2-3%; this figure increases to 5-6% for children with a father who has type 1 diabetes mellitus. The risk to children rises to almost 30% if both parents are diabetic.

Human leukocyte antigen (HLA) class II molecules DR3 and DR4 are associated strongly with type 1 diabetes mellitus. More than 90% of whites with type 1 diabetes mellitus express 1 or both of these molecules, compared with 50-60% of the general population.

Patients expressing DR3 are also at risk for developing other autoimmune endocrinopathies and celiac disease. These patients are more likely to develop diabetes at a later age, to have positive islet cell antibodies, and to appear to have a longer period of residual islet cell function.

Patients expressing DR4 are usually younger at diagnosis and more likely to have positive insulin antibodies, yet they are unlikely to have other autoimmune endocrinopathies. The expression of both DR3 and DR4 carries the greatest risk of type 1 diabetes mellitus; these patients have characteristics of both the DR3 and DR4 groups.

Neonatal diabetes, including diagnosis in infants younger than age 6 months, is most likely due to an inherited defect of the iKir6.2 subunit potassium channel of the islet beta cells, and genetic screening is indicated. [24] This is particularly important, because these children respond well to sulphonylurea therapy.


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