SAN DIEGO (FRONTLINE MEDICAL NEWS)Routine genetic testing for maturity-onset diabetes of the young has become compellingly cost effective in selected populations of diabetic patients, Dr. Siri Atma W. Greeley asserted at the annual meeting of the Pediatric Academic Societies.

“We’re not quite at the point of saying test everyone with diabetes for monogenic causes, but as the cost of genetic testing goes down that could actually happen,” said Dr. Greeley, a pediatric endocrinologist at the University of Chicago.

Today, however, the genetic testing is greatly underutilized and the insurance industry remains balky about providing coverage. That’s starting to change, though, as Dr. Greeley and other MODY experts meet with insurers and explain the dollars-and-cents benefits. Encouragingly, Aetna has led the way forward by publishing its rules for coverage of MODY genetic testing in 2015.

Dr. Greeley was coauthor of a study that evaluated the cost-effectiveness of testing for mutations in three genes responsible for more than 90% of cases of MODY with a known cause. The study, led by his University of Chicago colleague Dr. Rochelle N. Naylor, involved a hypothetical cohort of 25- to 40-year-olds presumed to have type 2 diabetes. Various studies indicate that roughly 2% of such patients actually turn out to have MODY. The question asked by the researchers was, is it cost effective to find them?

With a 2% MODY prevalence, the answer turned out to be no. However, if the population undergoing genetic testing could be enriched through application of clinical criteria associated with increased risk of MODY, then testing does become cost effective even when it identifies a case only 6% of the time. Under that scenario, at a genetic testing cost of $2,580, the incremental cost-effectiveness ratio is $50,000 per additional quality-adjusted life year, which meets the definition of cost-effectiveness widely accepted by health policy makers.

The improvement in quality-adjusted life years is achieved in the case of MODY on the basis of reduced lifetime costs of treatment and complications because one relatively common type of MODY known as glucokinase MODY, or MODY 2, requires no treatment and has essentially no vascular complications, while other common forms of MODY generally respond well to low-dose sulfonylureas rather than more elaborate insulin regimens.

The analysis also concluded that routine testing in a population with a 2% prevalence of MODY would become cost effective if the price tag for testing decreased to $700, as seems highly plausible with further advances in sequencing. And if the MODY prevalence is 31%, a policy of routine genetic testing for MODY actually becomes cost saving rather than just cost effective ( Diabetes Care 2014;37:202-9 ).

This cost-effectiveness analysis doesn’t take into account the added value of genetic testing in terms of family counseling. MODY is transmitted in autosomal dominant fashion, so first-degree relatives of an affected individual have a 50% chance of inheriting a MODY gene mutation, Dr. Greeley noted.

He assisted University of Chicago laboratory scientists in creating a commercially available panel that tests for more than 40 genes known to cause diabetes, including all of the genes known to cause the various types of MODY.

The American Diabetes Association, in its standards of care for 2015, lists a series of criteria that boost the likelihood of monogenic diabetes above the background 2% rate, including diabetes with negative autoantibodies and no signs of insulin resistance or obesity. Moreover, investigators at the University of Exeter (England) have developed an eight-question MODY probability calculator to guide genetic testing decisions, although this tool requires validation. The Exeter group also has shown that among women with gestational diabetes who meet the dual criteria of a body mass index below 25 kg/m2 plus a fasting blood glucose of 5.5 mmol/L or more, genetic testing will identify one case of glucokinase MODY for every 2.7 such women tested (Diabetes Care 2014;37:1230-6).

Dr. Greeley’s research is funded by the National Institutes of Health, the American Diabetes Association, and the Kovler Family Foundation. He reported having no financial conflicts and emphasized that he has no financial ties to the University of Chicago’s genetic testing lab.