UF Health researchers propose an update to Type 1 diabetes staging system

GAINESVILLE, Fla. — The understanding of Type 1 diabetes races forward, propelled by Big Data, technological advances, and the urgent hopes of millions globally who long for new treatments or an elusive cure.

Now, some researchers suggest the model used to assess the risk of developing Type 1 diabetes in individuals with early, symptomless markers of the disease is ready for an update.

And it’s barely 9 years old, a reflection of the meteoric pace of science and medicine.

University of Florida Health diabetes researchers and collaborators last week issued a call to action in The Lancet Diabetes & Endocrinology, one of the most prestigious journals in the field, urging the development of a more precise method of calculating Type 1 diabetes risk.

The hope is that a revised calculation incorporates new knowledge generated by researchers worldwide since the current staging model was published in 2015.

Since the model informs treatment decisions, researchers said a change would enhance patient care.

“What we’re proposing, and this is our personal view, is that we create a more individualized risk tool that the diabetes community can agree on,” said pediatric endocrinologist Laura Jacobsen, M.D., an assistant professor in the UF College of Medicine’s Department of Pediatrics. “We should continue to evolve and get better and better at our prediction.”

A more precise risk calculation also benefits diabetes screening programs that have become more common in the United States and around the world.

Jacobsen, the lead author in the “personal views” paper, is joined by co-author Mark Atkinson, Ph.D., a professor in the UF College of Medicine’s Department of Pathology, Immunology and Laboratory Medicine and former director of the UF Diabetes Institute. Both are members of the institute.

Atkinson is one of the most-cited Type 1 diabetes investigators globally and is the American Diabetes Association Eminent Scholar for Diabetes Research.

Other co-authors are Jay M. Sosenko, M.D., a professor at the University of Miami, and senior author Stephen E Gitelman, M.D., a professor at the University of California, San Francisco.

Type 1 diabetes is a disease in which the body’s immune system mistakenly attacks and kills the beta cells of the pancreas that produce insulin. The telltale signs of the disease are present even years before someone is diagnosed with full-blown diabetes.

Specific autoantibodies, proteins the immune system produces in response to an attacker such as a virus, can be found in these individuals. However, in Type 1 diabetes, the immune system mistakes the insulin-producing cells in the pancreas as a foreign invader.

The autoantibodies are found in the blood and are evidence of the immune response, like fingerprints tying a thief to a crime scene. They can serve as a marker of the disease before someone exhibits symptoms.

Under the current staging system, this is Stage 1 of the disease, when a patient does not yet have elevated blood sugar but has two or more of these autoantibodies in the blood.

Stage 2 is diagnosed when blood sugar begins to rise, indicating a dysfunctional pancreas in a patient who does not yet have clinical Type 1 diabetes. That comes in Stage 3 with high blood sugar and, eventually, the classic symptoms of the disease, including frequent urination, weight loss, and fatigue.

Jacobsen, however, said the staging system requires more precision. This is especially important as the current staging model determines if a patient is eligible to receive a drug therapy called teplizumab, the only Food and Drug Administration-approved medication that can delay the onset of Type 1 diabetes by an average of two years. The drug is administered to individuals in Stage 2 who are at very high risk of progressing to Stage 3, or clinical Type 1 diabetes.

The staging system, however, does not include a patient’s age, which can be tremendously important in predicting risk, especially in children, Jacobsen said.

“It doesn’t provide, in our opinion, enough granular detail to decide whether a person should enter a clinical trial or receive an FDA-approved therapy such as teplizumab,” Jacobsen said.

Additional markers that would be important to consider include a greater array of abnormal metabolic measures beyond blood sugar and the presence of more autoantibodies.

“We’re promoting the idea that, as a field, we need to be thinking beyond the stages,” she said.