Conference Coverage

Genetic Screening Targets Maturity-Onset Diabetes of Youth



PHILADELPHIA – In people aged 20-40 years who have been diagnosed with diabetes, routine genetic screening for maturity-onset diabetes of youth could result in more targeted treatment. But the costs of genetic testing need to come down before routine screening becomes cost effective.

Using a simulation model of type 2 diabetes complications that accounted for the natural history of disease by genetic subtypes, investigators found that genetic screening added 0.01 quality-adjusted life-years (19.22 vs. 19.21 with no screening) at an increased total cost of $1,727 ($41,033 vs. $39,306). The incremental cost-effectiveness ratio (or cost per quality-adjusted life-years) was $143,409.

Dr. Rochelle N. Naylor

Genetic testing becomes more cost effective as the cost of the test decreases. If the prevalence of maturity-onset diabetes of youth (MODY) in the screened population is 5% or greater, and the cost of the test drops to less than $1,000, then the incremental cost-effectiveness ratio would go to $50,000, which is considered to be the conventional cost-effectiveness threshold. If the test cost falls to $200, then the screening policy would be cost saving, presuming that the MODY prevalence in the screened population was 20% or higher, said Dr. Rochelle N. Naylor, a pediatric endocrinology fellow at the University of Chicago’s National Center for Monogenic Diabetes.

MODY is caused by mutations in 11 different genes; just 3 of them account for 80% of cases of MODY. Screening can aid treatment decisions because mutations in either HNF1A or HNF4A lead to a progressive insulin secretory defect for which sulfonylureas are the established first-line therapy. Mutations in GCK, on the other hand, result in permanent but mild blood glucose elevations and don’t require treatment.

But MODY accounts for 2% of diabetes and is rarely diagnosed because genetic testing isn’t routinely obtained. Patients are typically misdiagnosed as having either type 1 or type 2 diabetes, and are treated with insulin or medications other than sulfonylureas, Dr. Naylor said.

The study simulated diabetes costs and complications in incident cases of diabetes that were diagnosed in a hypothetical population of patients aged 20-40 years. Included in the model were variables based on published data on the three MODY subtypes as well as type 2 diabetes complications data from the U.K. Prospective Diabetes Study. The model assumed a MODY prevalence of 2% in the population, with 35% of cases having GCK mutations and 65% having HNF1A or HNF4A mutations, and with a one-time testing cost of $2,000. For the simulated no-testing policy, the model assumed that treatment decisions would be based on the assumed diagnosis of type 2 diabetes.

The model assumed that 75% of MODY patients with HNF1A or HNF4A mutations would be treated with sulfonylureas and that all patients with GCK MODY would discontinue therapy.

A calculator to predict the likelihood of MODY is available at Targeted populations could be expanded as genetic testing costs fall, Dr. Naylor said.

Dr. Naylor said she has no personal disclosures, but that the University of Chicago’s National Center for Monogenic Diabetes receives royalties from Athena Diagnostics for genetic testing for diabetes genes.

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