Delaying the Onset of Type 1 Diabetes Through Early Intervention - Episode 7
Linda A. DiMeglio, MD, reviews screening options for patients with a family history of T1D, highlighting TrialNet.
Steve Edelman, MD: Linda, let’s talk about some practical issues. In a clinical setting, what are the best studies that you’d conduct in someone who has a family history of diabetes, so you can pick up type 1 diabetes at the earlier stages?
Linda A. DiMeglio, MD: I’d go with antibody screening. Through TrialNet, we start by screening 2 antibodies and then move forward. In clinical practice, the guidance is more to do the panel you can get in front of you. We’ll do antibody screening, and if there’s a single autoantibody through TrialNet, we confirm it. If there are multiple autoantibodies, and we know in the lab that we send it to that it’s a valid test, then we move forward to do a glucose tolerance test and A1C [glycated hemoglobin so we can] stage the diabetes at that point. TrialNet screening is available online, so anybody can access it, get a test kit sent to them, or go to a center to do it. For patients who don’t want to go through TrialNet, there’s screening available through various labs. In those settings, the lab accuracy may not be exactly what you’re expecting. The recommendation is to get the antibodies. If they’re positive, repeat them, ideally on a second blood sample in a new lab and confirm it in that way. A single autoantibody, especially if it’s a low-titer autoantibody, may not confirm.
Schafer Boeder, MD: I was going to ask you specifically about titers and if that would change your approach. Compare positive but barely positive vs through-the-roof, off-the-chart positive.
Linda A. DiMeglio, MD: The recommendation, which isn’t a formal—we’re working on formal guidance around this—is repeat it if it’s high. If it’s high, not only is it more likely to confirm but also you’re more likely to progress with the diabetes, depending on the antibody. Later we’ll into which antibodies are important.
Steve Edelman, MD: Linda, you talked a little about TrialNet, which is the best organization. It has done all the work and been a conglomerate of all type 1 trials. What about other ways to screen? You can put your drop of blood on a card, but where would you send patients to get information on screening?
Linda A. DiMeglio, MD: The JDRF had a T1Detect program for a while. T1Detect was offering, through enabled biosciences, direct-to-consumer antibody testing. That stopped. It was around $35, but that was stopped. Patients can still go to physicians to get that done, but it has to be ordered through a physician office. JDRF has good information on its T1Detect website. TrialNet has good information about that. What Schafer said was correct: rescreening is something that has to be answered, and it may also depend on the caliber of the lab that’s doing the screening. Within TrialNet, we decided not to rescreen relatives for a while. We’re reconsidering whether we may offer a second screen to older patients. I’ve heard individuals argue that you should do it at 2, 6, 10 years for children, but there aren’t great data. This winter, there will be consensus monitoring guidelines coming out to talk more about how to do that. Although I’ve been part of that working group, we haven’t solidified what that will look like. That initiative has also been sponsored by JDRF so we know what the next best steps are.
The only thing I wanted to add in this space is that, like the panelists here, a lot of patients with type 1 diabetes are Caucasian, and a lot of the studies that we’ve done have been done in non-Hispanic White individuals around family history and risk. Individuals who are in non-White populations may have a different likelihood of risk based on antibody profiles and may be more likely in some situations to be single-antibody positive when they’re diagnosed with stage III diabetes. That’s something else that we need to learn more about, and a research gap is how diabetes progresses in populations who aren’t White.
Steve Edelman, MD: I used to say that type 1 diabetes is a White man’s disease, but the data clearly show that in some of these non-White ethnic groups, the rate of increase of type 1 diabetes is increasing dramatically. That’s not true anymore. Have you had your children tested?
Egils K. Bogdanovics, MD: Yes, I had my children tested as part of the DPT-1 [Diabetes Prevention Trial of Type 1 Diabetes].
Steve Edelman, MD: They had that positive device.
Egils K. Bogdanovics, MD: Yes. Do you ever give a form to family members to screen all the other children, to give it to their doctor?
Linda A. DiMeglio, MD: We’re a TrialNet center, so we do it through TrialNet. We have posters up and materials, and we refer patients there to encourage them to get screened because it’s free, it’s confidential, and even if they don’t want to enter a research trial, they can still be screened in that way. That’s where I refer them.
Steve Edelman, MD: It’s a strange situation because my patients all have diabetes, and of them have type 1 [diabetes]. But you’re not asking them for the test.
Linda A. DiMeglio, MD: Yes.
Steve Edelman, MD: The first step is to tell them that there’s a therapy that can delay the onset of type 1 [diabetes]. The first step is getting your children screened for antibodies. Is that something you’d be interested in? I won’t give the details of the study, which we’ll get into. Did I interrupt you, Egils?
Egils K. Bogdanovics, MD: I have them all scan the QR [quick response] code for TrialNet. I say, “Have all your friends and family do this.” We’re not going to get to the general population yet, but at least they’re family members.
Linda A. DiMeglio, MD: For endocrinologists, there’s talk about whether you should screen other patients in your clinics who have other autoimmune diseases, particularly with multiple patients with autoimmune diseases in the family. There’s not a great consensus there. I’m curious to hear what the panel is doing. I don’t do a lot of general endocrinology to see patients who have other family members. They may have thyroid disease, Addison disease, or something else. They’re interested in getting their children screened or in screening for diabetes themselves. That’s another population, and with the approval of immunomodulatory agents, you can finally do it. I always think about population screening. You don’t want to screen until you have a therapy. In that sense, it’s something you know you’re going to do. For so long, we’ve talked about this area around prevention of DKA [diabetic ketoacidosis], but now we have like other options.
Steve Edelman, MD: Well said.
Transcript edited for clarity