Should We Be Screening Every Single Child for Type 1 Diabetes Risk?

If Type 1 diabetes struck you or a family member, it may well have seemed completely random, unpredictable, and unpreventable.

It’s less random than it might seem—with a drop of blood, doctors can roughly estimate the risk of developing the condition, even in a newborn baby. And while the condition cannot yet be prevented, education and awareness can make its onset significantly less damaging, possibly resulting in lifelong health gains.

Screening for type 1 diabetes risk could become a routine element of childhood checkups, applied to all children. Should it be?

How Screening Works

There are, generally speaking, two ways of screening for type 1 diabetes risk.

The first, autoantibody screening, tests the blood for the immune proteins that cause type 1 diabetes when they attack the pancreas’ Beta cells. Autoantibodies emerge unpredictably, and are best assessed in early childhood, when the risk of disease onset is at its highest.

The second, genetic screening, tests a patient’s DNA for variations that are associated with type 1 diabetes. Genetic screening can be accomplished immediately after birth.

Screening of either sort rarely gives a definitive answer as to the likelihood that any one person will or will not develop type 1 diabetes—it places a patient in a bracket of higher or lower risk. One exception is when a blood test finds multiple autoantibodies present in one person, which can be said to indicate very early (subclinical) type 1 diabetes. In these cases, it may be years before the symptoms become noticeable.

Much of the data linking antibody presence with risk factors comes from the long-running Trialnet Pathway to Prevention study. TrialNet has been celebrated in the diabetes community for providing simple and free screening to so many. Click the link, and you can contribute to the body of knowledge by getting yourself (or a family member) screened.

Genetic and autoantibody screening can be used separately, but the most accurate projections use the two (along with any family history of diabetes) in concert.

The Benefits of Screening

Type 1 diabetes isn’t, so far as we know, preventable. So why screen for it at all?

Perhaps the single largest benefit to type 1 diabetes screening is the reduced incidence of diabetic ketoacidosis (DKA). When doctors, patients, parents, and caregivers are all aware that one patient has an increased risk, they’ll be more likely to identify hyperglycemia early, before it progresses to a critical state.

Avoiding DKA, a dangerous and incredibly painful condition, is just the start of it: studies have also shown that patients that got an early warning of the risk of type 1 diabetes also go on to have reduced A1c, fewer diabetes symptoms, and increased residual beta cell functioning. The earlier you catch the progression of type 1 diabetes, the healthier you’re likely to be in the coming years and perhaps even decades.

While researchers can’t always prove a causal relationship, mounting evidence appears to show that the severity of hyperglycemia at diagnosis can have a lasting and possibly even lifelong effect. In our recent article on diabetes and the brain, for instance, we learned that children that experience severe DKA at diagnosis have measurably worse cognitive impairment compared to children that did not have DKA. This effect lasts for years, and may be permanent.

And then there’s the game-changing drug teplizumab, which appears to delay the progression of symptomatic diabetes for years when given to patients that already have two or more antibodies. Those delays can be hugely valuable to families, meaning both enhanced health and emotional well-being. An expert panel recently voted to recommend that the FDA approve the drug. If teplizumab proves to be as effective as hoped, it would significantly strengthen the case for large-scale type 1 diabetes risk screening.

Teplizumab may just be the start, as doctors are working on other novel approaches to delaying (or preventing) type 1 diabetes. At the moment, for example, trials are underway to see if infants with a genetic predisposition to the condition will be less likely to develop the disease if given the probiotic B. infantis or insulin powder. Who knows what other therapies the future could bring?

Experiments with Universal Screening

At the recent American Diabetes Association Scientific Sessions, Germany’s Dr. Anette-Gabriele Ziegler discussed the results of two different experiments in universal diabetes screening. In these studies, all children within a certain area were tested for type 1 diabetes antibodies, regardless of family history.

The first, named the Fr1da study, tested children aged 2-5 during their regular check-ups in Bavaria, Germany. Only 0.29% of these Bavarian children got the bad news that they had the antibodies indicating subclinical type 1 diabetes.

While this was a very thin slice of the population, that knowledge still made a big difference. 81 tested Bavarian children went on to develop full-blown type 1 diabetes within the next three years; of those 81, only three developed DKA, an astoundingly low 3.7%. This was an immense improvement over the status quo – elsewhere in Germany, about 45% of newly diagnosed children developed DKA. And even that 3.7% seems somewhat inflated – of the three kids that suffered DKA, two of them belonged to families that declined diabetes education after receiving the positive test results.

In short, testing about 140,000 kids saved about 36 (and counting) from DKA and from whatever other long-term health deficits that acute hyperglycemia might have caused in the future. It also significantly reduced stress in the parents of newly diagnosed children.

A similar effort in Colorado, named ASK, delivered similar results. While only 0.52% of the participants were found to have subclinical type 1 diabetes, only 6% of them developed DKA, a vast improvement over usual rates.

Dr. Ziegler said, “We would like to screen everybody.”

The Downside of Screening Too Many

So why not start screening every child now? It costs money. Insurance companies will need to be convinced that it’s worth paying for.

The cost of screening may be significant, and the cost of follow-up education can be even higher.

Even if we can screen all children for type 1 diabetes, it’s not at all clear how many families should receive diabetes education, as Dr. Richard Oram of the UK’s University of Exeter expressed in a presentation at the conference.

Suppose, for example, that we had a universal genetic testing program – every newborn child in the country gets his or her drop of blood analyzed. At what level of genetic risk do you begin to apply education and intervention?

If you draw the line at the infants in the top 10% highest risk, you’ll identify nearly 80% of the kids that are going to develop type 1 in the coming years … but that’s only 2.4% of the kids selected for extra attention, meaning it’s likely a waste of time for the remaining 97.6%. On the other hand, if you only choose to educate the tiny minority of kids with the highest risks, you’ll waste less time, but ultimately only identify less than 10% of the children that will go on to develop type 1.

Public health experts are not ready to just brush aside all that education delivered to families that don’t really need it. And it’s not just a question of wasted time or money – as noted by Dr. Laura Smith, a clinical psychologist at USF, studies have shown that these screening programs can result in clinically significant levels of stress or anxiety for kids and caregivers alike. Parents will also often attempt to change their kids’ diets or increase their monitoring of their kids’ health, perhaps unnecessarily.

Profit and Loss

In reality, it will likely be the insurance companies that decide where to draw the line. The most important question, sad as it sounds, is whether or not testing children for type 1 diabetes risk is cost-effective.

Early research into this question tended to say that no, broad screening efforts are not economically worthwhile. A 2015 study concluded that screening would have to cost $1 or less in order to be viable (it’s a lot higher)—anything more would cost too much to justify the health improvements.

That study, however, looked only at the impact of reduced incidence of DKA, and not at the other benefits for patients. The University of Colorado’s Dr. R. Brett McQueen argued to the Scientific Sessions audience that this early study fell short of the mark, because screening is likely to offer many benefits beyond just DKA avoidance.

Dr. McQueen presented his own study, which assumed that screening would result in lifelong health improvements for patients with new-onset type 1 diabetes, such as improved A1c. While McQueen’s work confirmed that DKA avoidance alone was not enough to justify the high cost of most screening programs, those other benefits may tip the scales. Even an extremely modest improvement in glycemic control can make a big difference over the years, leading to many fewer diabetic complications and expensive interventions. And that’s before we even consider teplizumab, the potentially groundbreaking therapy that can delay onset for years.

The cost of screening is certainly substantial – Colorado’s ASK screening program ended up spending about $4,700 per case detected, a number that could be even higher when implemented elsewhere. But DKA and diabetes complications—think retinopathy and kidney disease—are pretty expensive too.

This type of math requires some guesswork. McQueen stated that if we want a rigorous accounting of how cost-effective early screening is likely to be, we’ll need about 30 years of follow-up data. Of course, we don’t have the luxury to sit back and wait for generations—“we need to make these decisions now.”

Conclusion

Today there is virtually no screening for type 1 diabetes risk factors in mainstream medical practice. There are many children (millions worldwide) that are at an enhanced risk of developing type 1 diabetes, and would stand to benefit from diabetes awareness and education.

Screening (and follow-up education) can have a significant positive effect. Risk screening has been shown to dramatically reduce the incidence of DKA, and is likely to improve diabetes management and reduce stress and anxiety. And the recent development of teplizumab, a drug that can delay the onset of the disease, may make early screening even more efficacious.

The most accurate screening would combine genetic testing at birth with antibody testing in early childhood, either once at age 3-4, or twice, at ages 2-3, and again at 5-7. But even a single test, either of genetics or autoantibodies, can provide significant predictive value.

Screening for type 1 diabetes risk could become a routine element of childhood checkups—if doctors and insurers can be convinced that it’s worth the effort, time, and money.

Source: diabetesdaily.com

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Source: diabetesdaily.com

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