- A new research study in Germany shows that screening for type 1 diabetes (T1D) in preschool-aged children is worthwhile and scalable to the general population.
- If conducted broadly, this type of screening could significantly reduce the likelihood of diabetic ketoacidosis (DKA) in children, a dangerous complication of T1D.
- Another study showed that the immunotherapy treatment Teplizumab reduced new T1D diagnoses in at-risk children and adults by 59 percent, and it may delay disease onset by as long as 2 years.
Big questions often arise when kids are diagnosed with type 1 diabetes: Why didn’t anyone prescreen? Could anything have been done ahead of time to avoid the dangerous high blood sugars that mark the onset of this disease?
Historically, there hasn’t been a reliable method for advanced screening that could detect or possibly ward off this autoimmune condition.
There may now be hope on the horizon.
Results show that this type of prescreening by primary care physicians is possible on a broader scale for the general population, signaling an opportunity for not only families of young children but also adults to eventually get advanced notice that they’re at risk for developing diabetic ketoacidosis (DKA) — often the dramatic start of a diagnosis.
The 4-year program, dubbed “Fr1da,” included more than 90,000 children ages 2 to 5 years old. They were screened by primary care doctors in Bavaria, Germany. More than 600 pediatricians implemented screenings into their routine well-baby exams.
“The message is that, if done well, testing for islet autoantibodies will identify the majority of children who will develop type 1 diabetes,” said Dr. Anette-Gabriele Ziegler, lead study author and director of the Institute of Diabetes Research at Helmholtz Zentrum München in Germany.
“Screening must be cheap, easy, and reliable. I think that we have a blueprint for how to do it that can be adapted to practices in different countries and states,” Ziegler said.
This, combined with other recent research findings that a novel drug could delay the disease onset by years, gives the Diabetes Community a lot to be optimistic about on the topic of early T1D detection.
Specifically, the German study found that 31 percent of the kids screened were identified as “high-risk” for developing T1D through the presence of two or more key islet autoantibodies, which indicate a likelihood for diabetes.
Roughly 25 percent of those 280 children went on to develop type 1.
Interestingly, only two of the high-risk kids in the study who went on to develop T1D developed DKA at the time of their diagnosis — a low rate compared to
Imagine the possibilities if early screening signaled potential T1D, and, as a result, the family or patient could be aware and on the lookout for symptoms.
These symptoms can include things like extreme thirst, frequent urination, rapid weight loss, and vomiting. They’re often overlooked or mistaken for other ailments until the patient is rushed to the hospital with DKA.
“I think we have shown that a screening program can achieve a DKA rate of less than 5 percent, and I expect that with more experience and awareness, the primary healthcare providers could consistently bring it down to such a level,” Ziegler said.
However, she has some words of caution.
“Screening will decrease but not prevent DKA completely. Apart from the cases that are missed because they are too young or they have a very rapid progression to clinical disease, there are also some families who will not change how they behave when their child is given a pre-diagnosis,” Ziegler said.
The Fr1da study does have implications for all ages, Ziegler says, even though the most favorable conditions for T1D autoantibody detection are typically during the preschool years.
Screening infants younger than 2 can be most challenging, she notes. And expanding to testing an older population would certainly increase the cost and scope of any screening infrastructure.
“To catch all cases, children will need to be tested repeatedly, but this will greatly increase the cost,” Ziegler told DiabetesMine via email.
“We have an ongoing Fr1da Plus study where children are also tested at age 9 years, to help us learn about the potential impact of later testing. Another possibility is that children with an increased genetic risk, such as a family history of the disease, are tested repeatedly,” she said.
Ziegler says any prescreening policy that eventually materializes would need to be coupled with care and counseling for pre-diagnosed families.
She says her clinic is researching how to set up that infrastructure to support this type of screening.
Next steps are assessing cost data and compiling estimates on how many T1D cases could be detected or missed — key factors in moving forward on any policy discussion or implementation.
She also points out that an important element of any screening protocols would emphasize that the first autoantibody screening happens locally so a family wouldn’t need to travel far to have the test done.
Ziegler and her co-researchers are working with health economists to assess what a prescreening might cost.
The JDRF and Helmsley Charitable Trust are also involved in that work.
Meanwhile, related research is underway to tackle many unanswered questions.
One study called Fr1dolin is ongoing in Lower Saxony, Germany, and another called ASK is ongoing in Colorado.
Ziegler says she’s aware of other efforts in states and countries worldwide, exploring the issues related to screening for T1D.
“Ultimately, cost-effectiveness will only be guaranteed if we can delay or prevent clinical disease altogether,” she said.
“So we are more than hopeful that by working together we will have a widespread cost effective screening program that reduces DKA and the number of cases of clinical type 1 diabetes.”
Assuming T1D screening could be put in place more broadly, the next big question after getting a result signaling a possible T1D diagnosis down the road is, now what?
Last summer gave us a potentially game-changing answer to that question, with results from a type 1 prevention consortium being unveiled at the American Diabetes Association (ADA) Scientific Sessions conference in June 2019.
The research, while small with only 76 participants, found that a 14-day single dose of this immunotherapy treatment reduced T1D diagnosis for at-risk children and adults by 59 percent versus the placebo’s effect.
Significantly, it delayed that diagnosis by as long as 2 years by allowing patients’ insulin secretion to be prolonged.
A second trial involving the drug anti-thymocyte globulin (ATG), which is typically used for preventing kidney transplant rejection, also showed similar positive effects.
A low dose was given to newly diagnosed T1s, showing a preservation of insulin production and lower glucose trends for as long as two years (compared to what might otherwise been seen for newly-diagnosed T1Ds).
Coupled with Ziegler’s Fr1da study, these are promising results with respect to catching the effects of T1D diagnosis early.
“It’s exciting to have a confluence of these things,” said Dr. Michael Haller at the University of Florida, lead study author and TrialNet’s ATG study chair.
Regarding the ATG compound used in the study, Haller says it’s currently only Food and Drug Administration (FDA) approved for the kidney transplant rejection purpose, not for treatment of type 1 diabetes.
Still, after his research using ATG off-label in a clinical setting showed the delay of T1D onset, Haller says he’s more comfortable with the treatment process. To date, insurers have been paying for the treatments.
Teplizumab, on the other hand, received breakthrough therapy designation from the FDA last autumn for the prevention or delay of type 1 diabetes in at-risk individuals.
This designation means the drug, made by the New Jersey biopharma company Provention Bio, can move more quickly through the regulatory process to get to market.
The company plans to finish its FDA filing by the end of the year.
While early testing and intervention drugs won’t stop type 1 completely or even prevent all cases of DKA, it could spare a lot of people pain and suffering, and potentially prevent deaths.
In other words, it matters immensely to the increasing numbers of people affected by T1D.
Ask any parent of a child ever diagnosed who’d gone into DKA or gotten viciously ill from high blood sugars leading into their diagnosis.
Ask the loved ones of those who weren’t diagnosed in time but fell into extreme DKA and didn’t make it to the other side.
“Since DKA at diagnosis still happens and can be fatal, giving these families at least a heads-up that their child may be at risk for developing type 1 is likely to save lives,” said Ohio D-Dad Jeff Hitchcock, founder and president of the nonprofit Children with Diabetes, whose daughter Marissa was diagnosed at 24 months old.
“The science also shows that children who begin treatment before DKA have an easier time achieving metabolic goals than kids who were in DKA, meaning that early identification of risk, even if T1D cannot be prevented, can have lifelong positive impact,” he said.
Tom Karlya from New York, another D-Dad and advocate (whose adult son and daughter were both diagnosed as kids), also sees the potential here.
Years ago, Karlya spearheaded a “Cry for Change” aimed at raising awareness about type 1 and DKA in schools and communities.
He helped push Reegan’s Rule into law in North Carolina, which encourages pediatricians to teach T1D symptoms to the families of children ages 1 to 6 years old.
“This all has a snowball effect,” Karlya said. “This research leads to other studies, and that leads to education and awareness within the community and pediatricians’ offices. Imagine going in to get your cholesterol tested, and when they ask about any family connection to T1D, they put in another test to screen. This could be a first step to that becoming part of the language.”
“The thing about research is that it doesn’t just open a door, it opens a hallway of doors. You start with a pin-light, that turns into a flashlight, a headlight, a floodlight… and then a zenith,” Karlya added.
Still, the question of prescreening isn’t a simple one for some families, who may be worried that a positive result could cause emotional harm if there’s nothing that can be done to prevent the oncoming T1D diagnosis.
That’s something each family must grapple with and decide for themselves.
In the meantime, before any of this research materializes into possible screening and treatment, we appreciate resources that exist to help families and the general public recognize T1D symptoms and possible dangerous DKA complications, including: