Gene Variant Type 2 Diabetes

A newly identified gene variant may increase the risk of type 2 diabetes by as much as five times, according to a new study. This research could shape future screening and treatment efforts in a population with one of the highest rates of diabetes.

The study, published in JAMA, examined a previously identified gene, HNF1-alpha, that is involved in a type of diabetes called monogenic diabetes, or MODY. Researchers analyzed DNA samples from more than 3,700 people, both Mexicans and American Latinos, and identified a variant of this gene that was associated with the increased risk. 

“Given its sizable prevalence among Latinos with type 2 diabetes—two percent—and its strong effect size, identifying the mutation in people at risk may lead to more aggressive preventive strategies,” said Jose Florez, M.D., Ph.D., of Massachusetts General Hospital, in an email to Healthline.

In 2006, 14 percent of Mexican adults had type 2 diabetes, and it continues to be one of the leading causes of death in Mexico. Among Mexican-Americans, the prevalence of type 2 diabetes is 10 percent, about double the rate in white Americans.

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Screening for Variant May Improve Treatment

Treatment options for type 2 diabetes include monitoring blood sugar levels, healthy eating, regular exercise, insulin therapy, and medications. Previous research has shown that people with certain gene variants may respond better to specific medications, as is the case with HNF1-alpha.

“People who carry mutations that cause MODY in this gene respond better to sulfonylureas,” said Florez, “rather than metformin, which is the first-line agent used in the treatment of type 2 diabetes worldwide.”

Metformin is generally the first medicine prescribed for people with type 2 diabetes. It works by improving how well your body responds to insulin, which helps to reduce high blood sugar levels. Sulfonylureas are often prescribed only when metformin doesn’t work; they work by increasing the amount of insulin made by your body.

“The hope is that if it is found that carriers of this new variant in the same gene respond better to sulfonylureas,” continued Florez, “this would lead to a change in treatment to a modality that is more appropriate for this group of patients. This is yet to be proven in a clinical trial.”

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Genetic Screening Could Preempt Disease

Genetic screening for this variant of the HNF1-alpha gene has the potential to head off type 2 diabetes before the first symptoms start. However, before early detection is embraced by doctors and the insurance industry, the benefits of screening people in the absence of other risk factors would need to be clear.

“We have yet to demonstrate the clinical utility of such screening,” says Florez, “in that it is not yet established that having this information leads to better clinical outcomes.” 

Genetic screening for other genetic mutations that are known to lead to types of monogenic diabetes is not typically practiced, largely due to the questionable cost-effectiveness.

One reason to test for the new variant of HNF1-alpha is that it affects such a distinct population. That, along with its sizable presence in the Latino population, could bolster the rationale for early screening, with no limit on how early.

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“Such information is present at birth and there is no compelling rationale to wait until symptoms ensue,” said Florez, “at which point the opportunity to implement preventive strategies may have been missed.”

Florez and his colleagues are continuing their research in this area, including the effectiveness of diabetes medications for people with certain gene variants. While screening for this gene variant is not yet available, simple lifestyle changes can reduce the risk of type 2 diabetes—including exercising regularly and eating a healthy diet.

Florez hopes that future screenings will encourage people with a higher risk to embrace these risk-reducing lifestyle choices.

“An informed assessment of future type 2 diabetes risk can help people make healthy choices,” said Florez. "And we believe that genetic information could form part of such an overall assessment.”