New Program in North Carolina Uses Genetic Testing to Screen Newborns for T1D

A few years ago, my niece shared that she’d decided to join a type 1 diabetes (T1D) screening program to be better informed about her risk and to show support for me in my lifelong journey with the condition. As her “Tia with T1D”, her gesture got me thinking about what it would be like if she had screened positive and how crucial early detection for this condition may be.

Newborn Screening for T1D Risks on the Horizon: Early Check Program

As those of us with T1D can attest, pinning down those unique T1D risk factors that led to our diagnosis can be varied and challenging. Surprisingly, over 85% of those with T1D don’t have a known family history of the condition, which is typically the most telling risk factor.

However, in North Carolina, there’s a groundbreaking research program called Early Check that aims to screen newborns for a variety of conditions, including T1D, regardless of known risks. Unlike traditional newborn screening (NBS) programs, which have existed since the 1960s as part of public health programs and currently focus on screening approximately 63 rare genetic conditions, Early Check uses two healthcare resources not traditionally used in T1D care; advanced genetic testing for genes associated with serious health issues, including T1D, and genetic counselors. Genetic counselors are healthcare professionals with specialized training in both genetics and the art of counseling patients on what those genetic results may mean for them practically.

Most of the current T1D screening relies on family history and a blood test to see if any T1D-related antibodies are present. The Early Check Screening Program, though, takes a broader view of T1D screening by using genetic data and evaluating a large range of newborns, including those with no known family history of T1D. If, and when, T1D-antibodies present in the body, new treatments such as Tzield/teplizumab, may be used to potentially delay T1D onset, but in general can’t stop it completely in the majority of people. Earlier screening across a broader audience will enable high-risk individuals to be watched and, as necessary, treated once antibodies and symptoms present.

The Genetic Basis of Type 1 Diabetes

For T1D risk, understanding the genetics is key. While only 1% of T1D cases appear to be monogenic  in nature, meaning the presentation is based exclusively on the DNA sequences that we inherit from our parents (genes), the remaining 99% of cases are due to autoimmune triggers that come from a 50/50 mix of both genetic variation and environment. Recent research has found more than 70 areas along the human DNA, called loci, which may contribute to the onset of T1D. This makes predicting the genetic sources of classic T1D difficult. Scientists at Early Check are working on a way to use this DNA research to predict more accurately who may develop T1D based on their genetics.

Using a mathematical formula derived from research, coupled with the genetic test results, Early Check generates a genetic risk score (GRS) for each tested newborn. This score enables the assignment of risk levels—low, moderate, or high—based simply on genetic test results.

A low-risk result means <2% chance of developing T1D over a lifetime while moderate and high-risk results indicate 2-5% and 5-10%, respectively. Newborns screened as medium or high risk are followed up by the Early Check team of genetic counselors to collect more risk information, such as family history, and to provide further testing and care, as necessary. Earlier detection means we can possibly do something about T1D onset even before clinical signs are present.

Genetic Risk Assessment for T1D: Opportunities and Challenges

Although the use of genetic markers are exciting steps forward in T1D screening, there are some limitations to keep in mind:

• High or medium-risk results do not guarantee that the individual will develop T1D. Global risk scores do not include environmental considerations which are presumed to account for 50% of T1D onset factors.
• Knowing there is only a 5-10% risk may not be appreciated by everyone. The highest resulting risk level, a 5-10% chance of developing T1D, still suggests that 90-95% of the time, T1D is not likely to manifest. We already know that, absent genetic testing, having a first-degree relative with T1D typically poses similar odds for individuals (6% if a father has T1D, 4% if the mother developed T1D before she was 25, 1% if the mother developed T1D after she turned 25; 10-25% if both parents have T1D).
• There is still no cure for T1D. Though we may be able to screen for it with improving accuracy and treat it, cures are not yet available.
• Screening test results are not conclusive. Further or repeat testing may be needed to rule out a false positive result. Alternatively, though a low chance, false negatives could lead patients to believe they are risk free for T1D when they are not.
• Genetic testing will reveal identifiable information about the patient that is sensitive. Some families may not be comfortable testing in this manner. Before any genetic testing is performed, families should meet with genetic counselors or other healthcare professionals to better understand these specific risks and what could happen with the genetic information after testing is completed.
• Scoring does not apply to those rare T1D cases that are exclusively genetic since their diabetes may be caused by other unique factors.
• The Early Check program is only open to newborns born in North Carolina.

Future Directions in Genetic Screening for T1D

Led by genetic counselors, noted earlier as clinical professionals with specific expertise in genetics, the Early Check program represents a significant advancement in how the medical community can apply genetic knowledge to T1D care. While researchers are still assessing the effectiveness of the Early Check program, it holds promise for improving T1D screening and early prevention.

The last five years of medical research in T1D have brought an unprecedented awareness to the genetics of the condition which continues to grow. It’s interesting to think what this could mean for patients and providers alike as we move forward, especially with newborn screening.

By finding T1D risk factors early on, we can strive for better outcomes and explore innovative ways to address T1D in the future. Perhaps that ever-evasive cure is closer than we know, making accurate early detection more important than ever.[i]

Additional Resources:

I Screen You Screen…Why Everyone Should Be Screened for T1D

References:

• [i] https://www.cdc.gov/diabetes/basics/risk-factors.html#:~:text=Type%201%20Diabetes,-Type%201%20diabetes&text=Known%20risk%20factors%20include%3A,%2C%20teens%2C%20or%20young%20adults.
• https://devwebsite.earlycheck.org/type-1-diabetes-frequently-asked-questions/
• https://diabetes.org/about-diabetes/genetics-diabetes
• Sharp, S. A., Rich, S. S., Wood, A. R., Jones, S. E., Beaumont, R. N., Harrison, J. W., Schneider, D. A., Locke, J. M., Tyrrell, J., Weedon, M. N., Hagopian, W. A., & Oram, R. A. (2019). Development and Standardization of an Improved Type 1 Diabetes Genetic Risk Score for Use in Newborn Screening and Incident Diagnosis. Diabetes care, 42(2), 200–207. https://doi.org/10.2337/dc18-1785
• Luckett, A. M., Weedon, M. N., Hawkes, G., Leslie, R. D., Oram, R. A., & Grant, S. F. A. (2023). Utility of genetic risk scores in type 1 diabetes. Diabetology, 66(9), 1589–1600. https://doi.org/10.1007/s00125-023-05955-y