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Kathleen Wyne Part 2, Detecting Adult Onset Type 1 Diabetes

In part 2 of this Exclusive Interview, Kathleen Wyne talks with Diabetes in Control Medical Editor Joy Pape during the AACE 2018 convention in Boston, MA about proving type 1 in an adult who was previously misdiagnosed.

Kathleen Wyne MD, PhD, FACE, MACP, FNLA is an endocrinologist and Director of the OSU Adult Type 1 Diabetes Program at The Ohio State University.


Transcript of this video segment:

Pape: So, you say that you’re going to prove to them that they have type 1. How do you do that?

Wyne: That’s actually a very good question because most people think you diagnose type 1 by doing a C-peptide and if the C-peptide is undetectable, then by definition, they have type 1. That’s not true. First of all, someone who has had type 2 for many years could have an undetectable C-peptide. Second of all, any time you measure C-peptide, it must have a simultaneous glucose. You need a context. So, this person who is an adult onset type 1, may have a C-peptide that’s reported in the normal range. But if the simultaneous glucose is 410, then it’s inappropriately low which is not what you would see in a newly diagnosed type 2 where it would be inappropriately high. So, first of all, your C-peptide needs to be in a context. Second of all, that alone may not convince you it’s type 1. But what you do is you go ahead, and you draw the antibodies. We now have five antibodies that we use to characterize type 1 diabetes. Not everybody has all five antibodies. Everybody knows the GAD65 antibody, they know the ICA antibody. There’s also IA-2, ZnT8, which is the newest one and stands for Zinc Transporter 8, and there’s also the Insulin Autoantibodies. So, we measure all five of those in all of our newly diagnosed type 1s or suspected type 1s, using them to confirm the diagnosis. There will be an occasional person who is negative for all of those antibodies, so, we believe there are still more antibodies to be found.

There’s a couple papers in the literature describing a new antibody called, Tetraspanin-7, not commercially available. So far, data suggests some minor antibody, but again, for those antibody-negative people, there’s hope that there are more antibodies coming.

Now when we look at these five antibodies, as I mentioned, not everybody has all five, but I’ve very often, in my adult-onset type 1s, found that their GAD65 negative, ICA negative, so if you had only done the two classic antibodies, you would have said, “Oh you’re type 2, you’re not type 1.” But, they come up positive for IA-2 and ZnT8.

Pape: Very interesting. So, I have a question to ask and I have heard in the literature and what people tell me; When you do the C-peptide and the antibodies, should it be fasting or non-fasting?

Wyne: So, the antibodies do not need to be fasting. Ideally, to be clean, you would want to do the C-peptide in a fasting situation. Here’s the reason why I do it fasting: I’m actually doing the C-peptide, not to make the diagnosis, but in case I need it to qualify them for an insulin pump. To qualify for an insulin pump, the C-peptide must be drawn with a glucose below 225 mg/dl. So, that’s why I am drawing at fasting. I’m hoping that I’ll catch those two, and generally if insurance requires it, it just has to be drawn within six months prior to the application. What that is also telling you is I’m pushing my newly diagnosed patients to pump and CGM as early as possible. This raises the next questions of: Should we be doing that with the newly diagnosed type 1s because many of the adult-onset type 1s have a prolonged honeymoon – they may honeymoon for five years, whereas in the childhood-onset, the classic honeymoon is one to two years. So, maybe they don’t need insulin at first. Maybe they don’t need to go to a pump, but I want that option as early as possible. So, if I am going to measure the C-peptide, I’m going to do it fasting, so it serves that other purpose if I need it.

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