Genetic Testing for People Diagnosed with Type 1 Diabetes Could Rule Out Disease

Juvenile diabetes patient checking his blood glucose levels at home
Juvenile diabetes patient checking his blood glucose levels at home using a glaucometer and lancet

A new study suggests that all young people with newly diagnosed Type 1 diabetes should be tested for a genetic mutation that could be responsible for their disease. They may not have Type 1 diabetes at all, but a rare form of the disease called monogenic diabetes—a non-autoimmune inherited condition that may not require insulin treatment.

Type 1 diabetes results from the destruction of insulin-producing pancreatic betacells by a beta cell-specific autoimmune process. Researchers studied a large cohort of people with Type 1 diabetes, as well as studying the pancreases of deceased people with the disease. All had Type 1 diabetes and were on insulin for at least 50 years.

“This is the first study to our knowledge to document the natural history of beta cell function and pathology in the same group of individuals with very long-duration Type 1 diabetes,” the study’s authors wrote. Their findings were published in the July 2, 2019 issue of the Journal of Clinical Investigation.

Diabetes affects more than 1 million Americans, with about 5 percent of those having the Type 1 kind. Complications from diabetes include cardiovascular disease, kidney failure and blindness. Monogenic diabetes is produced by a mutation in at least one gene that affects insulin secretion. The condition makes up something between 1 and 5 percent of diabetes cases, many in a form known as mature onset diabetes of the young (MODY).

According to the Monogenic Diabetes Registry, infants are more likely to have monogenic neonatal diabetes rather than Type 1 diabetes. They may have learning and developmental problems not associated with Type 1 diabetes. And they may respond to treatments other than insulin, including sulfonylureas, that lower blood glucose levels by stimulating insulin release from the Beta cells of the pancreas.

“Our finding has clinical implications,” said George King, M.D., senior author of the paper in a press release. “We are recommending that everyone under 18 who is diagnosed with Type 1 diabetes be screened for monogenic diabetes, which is not being done at this time.”

King is the Senior Vice President and Chief Scientific Officer at the Joslin Diabetes Center. The center was founded in 1983 when the Joslin Diabetes Foundation was named. It has its roots in the medical practice of Elliot Joslin, M.D. who began a diabetes registry in 1893 and treated more than 130,000 diabetics in his lifetime. He participated in the first clinical trial of insulin and, in 1931, began the tradition of awarding medals to diabetics who had been on insulin long-term. The Center still carries out the tradition and the medalists are now important research participants.

In the current study, a team of investigators from the Joslin Center, Harvard and the University of Utah looked at 29 genes implicated in Type 1 diabetes in 1,019 medalists. They found that about 8 percent had a monogenic diabetes mutation that might drive disease. Within that group, slightly less than half did not exhibit the genetic variations that needed to trigger Type 1 diabetes—which suggested that they might respond well to oral drugs rather than only to insulin. In the remainder of the group, who displayed both Types of genetic alterations, “we don’t really know which genetic condition is causing their diabetes,” King said.

Researchers found that 14 of the 68 pancreases they examined had many insulin-containing beta cells. This suggests that these diabetics may have benefitted from treatment with sulfonylureas.

Joslin investigators expect to launch a clinical trial within months to see if oral diabetes drugs can help medalists with mutated monogenic diabetes genes manage their disease more effectively. “This will be the first clinical study looking at the administration of oral drugs in an older population with monogenic diabetes,” said first author on the paper, Marc Gregory Yu, M.D., in the press release.The results of the trial may prompt changes in the standard of care for tens of thousands of people in the U.S. who have been diagnosed with Type 1 diabetes.

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