Series 2 episode 9. Nick Thomas. Type 1 diabetes in the older adult

Dr Nick Thomas talks about Type 1 diabetes in the older adult. In an iconoclastic study he showed most cases of Type 1 diabetes occur in adults rather than children. In older adults it is very hard to recognise as 98-99% of people with diabetes have Type 2 diabetes. Older adults with Type 1 diabetes have just as rapid a decline in their own insulin and need all the expert care offered to children. 

Transcript

 (00:04.078)

This is One in Six Billion, a podcast about diabetes and genes with me, Maggie Shepherd, and me, Andrew Hattesley. Something we found previously was that people thought type 1 diabetes couldn't develop in adults, so they didn't even think about the diagnosis.

 (00:26.478)

Welcome back to the One in Six Billion podcast. Today is another episode about type 1 diabetes, and we're going to talk about type 1 diabetes in the older adult. And we're really delighted to have Dr Nick Thomas with us to help us talk about his research in this area. So thanks for joining us, Nick. Could you introduce yourself to our listeners? So thank you so much for having me. I'm Nick. I'm a diabetes doctor in Exeter and also a lecturer at the university.

Right. So we're talking about type 1 diabetes in older adults. And I think for many of our listeners, they'll be surprised that it even exists because we always think of type 1 diabetes as a disease of children rather than adults. So how common is it? So certainly when I first started medical school, it was always said to be a disease of children and maybe young adults.

But some work I did in 2015 showed that actually over half of type 1 diabetes develops in adulthood. So it's far more common than we previously thought. So if it's about half the cases, why are we still thinking it's a childhood disease? So if you develop diabetes as a child, essentially you've got type 1 diabetes to prove otherwise. But as people get older, we see this dramatic increase in the prevalence of

type 2 diabetes. So it's much, much harder to then pick out the cases of type 1 diabetes. And as we've heard previously, misclassification in adults is common. And so it's hard then to really understand how common type 1 diabetes in adults is. And I think your research, showed that individuals can develop type 1 diabetes at any age of life. Could you tell us a bit more about that? So the work that I

did went up to 60, but certainly in my clinic, have individuals who've been diagnosed even older than that, even some into their nineties with type 1 diabetes. So certainly it can develop at any age. So we've got a problem in that most people have type 2 diabetes. You've got to try and pick out these rare cases from them. And most cases of diabetes will be dealt with by general practice. So for them, it's

 (02:43.374)

a difficult thing because they don't have a lot of experience of type 1 diabetes and so to try and pick it out is hard. Does that mean there's quite often diagnostic problems in this age group? Yeah, really common. I think that's a really good point because it is so difficult and I think that's a key point is that it's a challenge rather than we talk about misclassification but that's not because clinicians are getting things necessarily

wrong, it's just that it's really difficult because of this prevalence of type 2 diabetes. And what we've shown is that in both directions, actually, people thought to have type 1 diabetes in adulthood actually many years down the line have lots of insulin suggesting they've actually got type 2 diabetes. And then equally, people thought to initially have type 2 diabetes, but who rapidly progress, who actually turn out to have type 1 diabetes. And it's just really difficult because you're trying to unpick

a very small proportion of type 1 from a massive proportion of type 2. We're talking about 1 to 2 % type 1 diabetes when people are developing diabetes in their 50s, 60s. So as you mentioned, Nick, obviously in adults, the most common diagnosis is type 2 diabetes. So how can we pick out the adults who actually have type 1 diabetes? So I think it's really tricky. And the first thing I'd always say is to have an awareness of it.

be type 1 diabetes. That's something we found previously was that people thought type 1 diabetes couldn't develop in adults and certainly older adults, so they didn't even think about the diagnosis. I think the next thing to say is certainly to have a suspicion when people are slimmer, although still the vast majority of slim people will have type 2 diabetes. People who have very high glucose, particularly

they present with ketoacidosis, so severely unwell, again have a suspicion, but the majority again of people who have those very high glucoses or DKA will still have type 2 diabetes. And then the other key thing is people who progress rapidly or fail on their kind of traditional type 2 therapies, and by progress I mean require insulin, so they're

 (05:01.23)

glucose is high despite the fact that they're having all these type two treatments and therefore to have that thought that actually this might not be type two, we might be dealing with type one here. And once you've got that thought in your head that it might be type one, what test would you do? So what we've shown is that the most important thing is to measure markers of the autoimmune process. So islet autoantibodies and we've heard about these and

various different episodes. But if you've got an individual who either you think has got type 1 diabetes or who rapidly progresses to insulin, so requires insulin within three years of diagnosis, an autoantibody in that context that's positive is highly, highly suggestive that patient has type 1 diabetes. If you've got individuals who are antibody negative, but you still think, I think they might still have type 1 diabetes,

then the key thing is to measure the hormone that's important, which is insulin, which we can do with a test called C -peptide. Now, that may still be higher than established type 1 diabetes a few years after diagnosis, but certainly at three years plus after diagnosis, we'd expect patients with type 1 to have a very low C -peptide, suggesting or indicative of the fact that they've got severe insulin deficiency. So this C -peptide,

test is the one that tells you about your own insulin because C -peptide is present from the insulin used to create but not present on the insulin that you take as injection. So you're using it in people on insulin treatment to see how much of their own insulin made. And this is really because the key marker of type 1 diabetes is ultimately that they do not have insulin and the insulin making cells have been destroyed. Absolutely. So their pancreases, their

beta cells that producing insulin have been destroyed by the autoimmune process, so they're not producing any of their own insulin. And so an absence of measured insulin from themselves suggests that actually, yes, they do have type 1 diabetes. And we wouldn't expect that in type 2 diabetes. Even many years after diagnosis, we expect them still to be producing some insulin that we can measure. Now in the past, there's been lots of discussion about LADA, or latent autoimmune diabetes of adults.

 (07:28.846)

So would you like to comment about that? So L 'Azère or type 1 .5 diabetes has often been described as this halfway house between type 1 and type 2 diabetes developing in adults. And just to explain how it's defined, it's defined as individuals who are slow to progress to insulin and by that they take at least six months after diagnosis to go to insulin. And then they're found to have

a marker of autoimmunity, so one positive autoantibody. And typically that's an antibody called GAD. Now, as we've looked into this further, we know that in the general population, individuals who never developed diabetes can still have occasionally markers of the immune system. again, they can be positive for GAD. And what we suspect is that actually this halfway house, this Larderor,

type 1 .5 diabetes actually reflects a mixture of type 1 diabetes and also type 2 diabetes that happens to have a positive auto antibody or a positive GAD, but that we don't think is necessarily driving the actual cause of their diabetes. So what you're saying is that they used to think it was an intermediate form and it was defined because you took people that look

as if they had type 2 diabetes and then they had an antibody. And what you're really picked up is that in some people that antibody test is not really a real positive. It's actually just a statistical chance. And in other people, it's a sign of underlying type 1 diabetes. So if half the people have got a statistical chance and the other have true type 1 diabetes, then half the group will go to no insulin and the other group will carry on making insulin. And so if you put the two together,

you'll find something halfway. But in truth, it's not a halfway condition. You either have one or the other. Absolutely. I've always thought about it in terms of we learn about how to mix colors in early childhood. And if you've got lots of red balls and you mix them with lots of blue balls, then generally things will look purple. That doesn't mean that all those balls are purple. It just means you've got a mixture of the two colors. And the same thing is what I think is going on with LADA. We've got

 (09:53.358)

red balls are type 1 diabetes that are rapidly progressive and losing their insulin and then our blue balls that have got type 2 diabetes who aren't progressive and therefore if you mix them all together you get this kind of intermediate looking purple diabetes for wants for better description. If we go back to our older adult and we're now confident that they've got type 1 diabetes how does that change the treatment that they would have compared to if they're thought to have type 2 diabetes? So

It's a really good question. So these individuals at diagnosis are producing very little insulin and ultimately we're expecting them to produce no insulin at all. So just as you would with a child or a young adult, they need insulin replacement and we're gonna try and replace that insulin to match what their body would have been producing had they not developed type 1 diabetes. So they're gonna need regular insulin injections across a day.

including varying how much insulin they need with their meals to try and keep their blood glucose in as normal range as we can. So are there particular challenges in treating type 1 diabetes in these older adults? So generally patients, once they've got the right diagnosis, do really, really well. But remember, I've said that this disease can develop at any age and of course,

individuals get older, there are other things that are going on in their lives that might make it harder to learn new skills. And let's not forget, this is really difficult when it comes to trying to replace insulin to match what the body would have been producing, as well as trying to balance that with other conditions and other treatments. So I think there are specific challenges to these older age groups in terms of thinking about how we treat the disease.

were bringing in insulin treatment. assume that really the drugs that they were getting them for type 2 diabetes are doing nothing if there isn't their own insulin for them to work on. therefore you need to stop all of those treatments. they may suddenly be moving to an effective treatment whilst before they were taking a lot of ineffective therapy. And you're right, there's this kind of

 (12:13.44)

challenge of needing to know their blood glucose. And we actually heard from Jill and Jean, who weren't diagnosed later, but they had diabetes from young adults. But they were saying how much they have benefited from having a glucose sensor and not needing to prick their finger to know about their blood glucose. And presumably, that's critical information in trying to get this balance between just the right amount of insulin to make sure the glucose isn't too high or too low.

Yeah, absolutely. Essentially, I think a key point is that we've shown that this disease is really the same, essentially irrespective of whether it's developed in childhood or young adulthood or older adulthood. So we manage it and test blood sugars in exactly the same way. So these individuals need the same tools to be able to manage their diabetes and are going to need the same treatments. It's just that they develop the disease a bit later on in their life.

So Nick, what you're really saying is this is not an intermediate type of diabetes at all, but this is absolutely the same and just as severe as the type 1 that we would see in childhood. Absolutely. And we've shown that the rate of loss of insulin from adults with type 1 diabetes is very, similar to what we see in children. And indeed, that's what drives the difficulties that patients have when they aren't classified.

correctly at diagnosis because they're rapidly losing insulin. So they're not going to respond to tablet treatments that work on insulin they don't have. And so they need insulin replacement and they need it rapidly and they need it in such a way to match what their body would have been producing had they not developed the disease. Nick, I think in your PhD, you set up a study comparing younger people with old people really to see

how much their insulin changed. And you had to try and do that during COVID, which must have been a real challenge. Yeah, that was fun. One of the curve balls you don't expect. It's hard enough, I think, trying to do a PhD at the best of times, but trying to do a multi -centre in -person study during lockdown certainly put a few years on me, let's say. But very much that was trying to look and see the rate of loss of insulin.

 (14:36.546)

between older adults and younger adults. And in some data that we've already got, we've shown it's very similar. And we're just waiting for those final results that have been very delayed by COVID to come through for that study. So Nick, can you tell us anything about the decline in C -peptide in these patients over time? So in children, we know that from diagnosis, they will lose around half of how much insulin they're producing around every year.

Now in adults, it's slightly slower than that. And we expect them to lose half of how much insulin they're producing in around 1 .2 years or 1 .3 years. So it's slightly slower, but still far more similar than it is different. So do you think clinically it's useful in these adult patients who develop type 1 diabetes to have a baseline C -peptide done at diagnosis? So then you can follow that up over the next 12 months or so?

So I think it's certainly in something I do in my practice, good to keep an eye on the C -peptide. What I tend to do is every year where I'm not sure measure a C -peptide to get an idea of how quickly an individual is losing their insulin. And ultimately it's that C -peptide as a marker of insulin that really dictates what treatment these patients need. And it's that absence of insulin that means they absolutely need insulin replacement.

That's a very interesting point, you're saying it. think one of the things I've seen over my time as a consultant looking after people with type 1 diabetes is close to diagnosis. They're making a lot of their insulin. It's a lot easier. And then you see other healthcare professionals saying, they're not doing as well as they were and maybe they're not working as hard as they used to, but it's not that at all. It's just that they're no longer making so much insulin. And so you can start to say that you're going to need more and it's going to get more difficult.

because as there's less of your own, it will be more variable. Not just their healthcare providers, I think the patients themselves I often find say, I've gone from finding this relatively straightforward, it's been a big thing in my life to have this diagnosis, but then I've got on top of it and suddenly I'm just not doing as well as I was. So I always try and warn my patients around the second or third time I see them that this is going to happen. This is not a reflection of them, it's just,

 (17:01.772)

biology of their disease, that they are rapidly going to lose their insulin and things will get more tricky as they've got less of their own insulin and they're having to work harder with giving insulin to try and match what the body was doing. think one of the great things that Angus Jones has done is really make sure that C -peptide is something that is measured in those early days because it really helps to know who starts up high and who...

there's not very little from the beginning because it does say what progress is going to happen from that point. Well, we also all work as hormone doctors, endocrinologists, and we spend our time measuring the key hormones of those diseases. So if we talk about thyroid disease, we measure thyroid hormone. So it's almost a bit strange in diabetes that we actually measure the outcome, which is glucose, rather than the hormone itself, which is insulin. And we have this

excellent surrogates. As you say, Dr. Jones has pushed to make it more readily available. That is the key hormone in type 1 diabetes. So it makes sense to me that we should measure it. if we think about our elderly patient as they progress through life, so they're stable on their treatment, what are their risks of complications compared to say, a young adult or a child?

So I think that's a really interesting question. It's hard to answer as we've only recently really appreciated how common type 1 diabetes developing in adults is. And it's hard to therefore pick out from type 2 diabetes and really know that this is truly type 1. Kind of instinctively, you'd have to say, well, they develop the disease much later. So if you're developing it in your 30s or 40s as opposed to age 5, that's

25, 35 years less that your body's gonna be exposed to a higher blood glucose. But still, as we've talked about already, it's a rapidly progressive disease and we know that complications can develop within 10 years of diagnosis if blood glucose is really high. So it really is still key that these individuals manage their blood glucose really well to try and avoid those future complications. But I think it's a really key area to really understand

 (19:23.982)

again, differences that may be occurring in terms of complications in those developing type 1 later in life. And while we're talking about complications, there's the other issue of low blood glucose or hypoglycemia. So how much of an issue is that in older adults with type 1 diabetes? So again, of course, hypoglycemia is a direct consequence of insulin treatment. So it's the fact that

managing type 1 diabetes is really hard and occasionally patients are going to give slightly more insulin than they needed or they're going to exercise a bit more than they thought and their blood glucose is going to go low. And that really again is a function of them not producing any of their own insulin and we've already said that's the same scenario for those that are developing it in later life. Obviously the consequences of that hyperglycemia can be different when patients are older

in terms of falls and loss of consciousness can have real impacts in terms of thinking about breaking bones, fractures and other consequences. So we may as doctors and healthcare professionals want to balance how much and how aggressively we're treating as patients get older. But certainly, they're still at very high risk of low blood sugars, hypoglycemia. And in terms of recognising the symptoms of hypoglycemia, is that more of an issue in the very elderly?

It's a really good point that as individuals get older and we know that as people get older, they don't always recognize symptoms of hypoglycemia quite as well. They've got other health conditions that may mask the symptoms of hypoglycemia. So it certainly is very tricky managing type 1 diabetes in patients as they get older. And really that is both in those that developed it later in life, but also people as we thankfully increasingly seeing

living with type 1 diabetes for a long, time, as we've heard from previous guests. And type 1 can get more challenging as we're managing it later in life. So just to finish up with Nick, just to ask you, do you think that the older adult, when they're diagnosed with type 1 diabetes, is able to live well with it with all these challenges? So once patients have the right diagnosis, they're on the right treatment, i .e. insulin,

 (21:47.95)

They do really, really well and have a good quality of life. That's a great positive note to end on, Nick. Thank you very much for joining us. Thank you so much for having me. Yeah, thanks so much, Nick, for all the work that you're doing in this area, which is really important in highlighting that type 1 diabetes can develop at any age.

 (22:13.486)

So was really good to have Nick on the podcast. And for me, the real take home message was that type 1 diabetes can occur at any age. And if it occurs in the older adult, it's the same disease as when it occurs in children and young adults. And this is really important for health care professionals to be aware of, isn't it? To just think, actually, could this be type 1 diabetes, whatever age the patient presents her? Yes.

Just being prepared to change your diagnosis, I think one of the problems as healthcare professionals is we quite often get fixed and we write at the top of the page, this is type two diabetes and we're not prepared to scrub it out and start again. I think one of the things that's important is when there's any question for people to say diabetes, not sure what type it is, rather than forcing it into a category. It really is a big change that type one diabetes.

is occurring later and it isn't this mild form of diabetes that was known as LADA. It's actually real type 1 diabetes and needs all the care and attention that type 1 diabetes needs at other ages. We hope you've enjoyed hearing about type 1 diabetes in older adults. Please join us again in two weeks time.

 (23:37.134)

So if you'd like to keep up to date with further episodes, please subscribe on your podcast platform. Please tell your friends about the podcast. We'd like it to be spread as far as we can.