Identifying Individuals at High Risk for T1D


Justin M. Gregory, MD, MSC, reviews the risk factors of T1D, highlighting a family history of T1D and antibody screening.

Steve Edelman, MD: What are the key factors and criteria that help identify high-risk patients for type 1 diabetes? Please mention family history and genetics. Schafer [Boeder] touched on that a little in his first answer, but we can expand a little. I hope I’m not stealing your thunder that of all the people who get screened for type 1, 80% do not have a family history. I did not. You did not. I don’t know about you.

Egils K. Bogdanovics, MD: No.

Justin M. Gregory, MD, MSC: What are the key factors? We’ve already talked a little about family history. Dr [Linda] DiMeglio talked about having a history of first-degree family members and some of the risk associated with that. When I’m in clinic and the question comes up, I say that in the United States, the population risk of getting type 1 diabetes is between 1 in 250 and 1 in 500. If your father [has it], the risk is between 1 in 10 and 1 in 20. If your mother has type 1, your risk is between 1 in 20 and 1 in 40. If your sibling has it, it’s between 1 in 20 and 1 in 40. I try to say [to patients] that their relative risk, compared with the population, may be in the neighborhood of 10-fold higher, but their absolute risk is still low. You don’t need to needlessly worry about this. If you do anything, lead toward antibody screening. I encourage my patients to move in that direction for the reasons we’ve talked about. We know that once you get to 2 or more antibodies, it’s probably a matter of time before you progress to what we talked about earlier, having stage III type 1 diabetes. Those are some of the key factors.

Why is it that people with a family history of type 1 are at an increased risk? It has to do with several genes, but the largest genetic contribution comes from the HLA genes [to determine] what your HLA genotype is. Sometimes it seems like alphabet soup to say that the DR3 or DR4 HLA genotype confers increased risk, but suffice to say that certain HLA haplotypes increase the statistical likelihood that your immune system is going to mistakenly identify antigen as something it wants to take out. The key word is likelihood. Your likelihood of having autoimmune insulitis is higher; that’s not the whole story. In fact, most patients who have those high-risk haplotypes don’t go on to develop type 1 diabetes.

Steve Edelman, MD: How come we don’t use haplotype and gene analysis for screening patients with type 1 diabetes? Because all we’re going to talk about is the official autoantibody. Any idea on that? Or is cost too much?

Justin M. Gregory, MD, MSC: Cost is an important component. Until this point, especially with the big contributions that TrialNet has made to identifying these patients, we’ve had to think about scarcity. There are scarce resources. Until this point, we’ve said we’re going to use antibody screening because it’s more cost effective. Will that change in the future as we get better at genetic sequencing? There’s a good chance that it will.

Steve Edelman, MD: With a drop of blood, you can find all your relatives you don’t know.

Egils K. Bogdanovics, MD: I forget which DR4 it is, but it’s protective. If you have it, you definitely will not develop type 1 diabetes, and that’s great.

Steve Edelman, MD: That would be good.

Transcript edited for clarity

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