Series 2 Episode 7. Jean Claude Katte. Type 1 Diabetes in Africa: different in so many ways.

Dr Jean Claude Katte explains how in Sub Saharan Africa diagnosis, treatment and monitoring of Type 1 diabetes in children and young adults is so much harder than in Europe.  He discusses with Maggie and Andrew his own exciting research that has shown that around 60% of African children with diabetes do not have the typical autoimmune Type 1 diabetes seen in over 90% of children with diabetes in Europe. Jean Claude aims to do more research to discover what causes this new cause of severe young-onset diabetes in Sub Saharan Africa.

Transcript

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This is One in Six Billion, a podcast about diabetes and genes with me, Maggie Shepherd, and me, Andrew Hattesley. I believe the journey of a thousand miles always starts with the first step and I believe that first step was made during my PhD.

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So welcome back to the One in Six Billion podcast. Today's episode is carrying on looking at type 1 diabetes, but the subject today is type 1 diabetes in Africa. So we're delighted today to be joined by Jean -Claude Catté. I wonder if you could introduce yourself to our listeners. First of all, thank you for inviting me to join this wonderful podcast. My name is Jean -Claude Catté. I'm a medical doctor.

a primary care physician. And I've been working in diabetes research for the past five to seven years. And I also now serve as one of the postdoctoral research fellows at the University of Exeter. Welcome, John Claude. And really, it would be interesting to hear how you came into diabetes research. What was your journey? I think there are two main things that have marked my journey into

diabetes research from hindsight. The first was a particular mentor back in the days when I was in the medical school. So I was in the third year of medical training at the faculty of medicine and biomedical sciences at the University of Yawanda 1, which was the lone medical school at the time. And so we had a lecture on

what we semiology in French. I think that should be like clinical science and symptoms if there is an Anglo -Saxon equivalent. And Professor Eugene Sabui was taking us into endocrine physiology and the lecture was just so wonderful. And it was his charisma and the way he explained things caught my attention. And so during clinical years, I decided to

do my medicine clinical rotation at the diabetes unit. And of course, I then met Professor Jean -Claude Bagnier, which we know it's a phenomenal mentor as well. And so those two people actually motivated or stirred that journey into diabetes research. And as I said on hindsight, I think growing up knowing that

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My dad died of diabetes, may have played a role in that. My dad passed away while I was just two years old. And I know he died of diabetes complications. So I think consciously or unconsciously that may have motivated the route into diabetes research. Wow. And I remember the first time we met was when you applied for a post.

funded by the National Health Global Support for Research. And you came and took one of the three posts to come and do a PhD in Exeter, but you were doing the research work out in Africa, both in Cameroon and Uganda predominantly. Yes, that in itself was quite interesting because I always wanted to do diabetes research. And I worked in a number of

projects for my mentors back home in diabetes research. And I was looking forward obviously to doing a PhD because obviously if you want to be a researcher, you should get a terminal degree. But there was no specific PhD training at the time that was interesting for me. And at one point I got so frustrated that I was willing to take any offer on the table. And so

I was actually preparing to go to South Africa for a PhD training at the time when the opening for Exeter came out and I applied and I was successful. So that was in 2018 and that's how I came to join the team in Exeter. I just wonder if it might be easiest for our listeners if you could imagine yourself as a parent of a

child who develops diabetes in that setting where you were working as a general doctor and talking about the challenges that there are of being in that situation in Africa rather than Europe. Yes. So normally we would tend to see children who come into the hospital very slim, probably as a result of the fact that they had

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symptoms and signs of diabetes for several months to years in some cases. And they would present really late, very lean. In some cases, they would show up in an emergency situation with a very pattern diabetes complications like ketosis. And I think one of the other things that have marked my journey looking back was that

some of the cases, especially in the semi -urban towns, were really coming from the rural villages as well. And so these people that would generally not have access to insulin, for example. And so the weight and burden of the disease is quite heavy on them already when they show up to the hospital. We've had cases where some of these kids show up already having a cataract or diabetes.

diabetic retinopathy, which is a complication of the eye and all the neurological complications from high blood sugar, for example. And so the general picture is that they would usually present late and most at times with complications. And can you tell us a little bit about access to insulin for these patients with type 1 diabetes? So with regards to access to insulin,

I think there has been a phenomenal improvement, I would say, within the last two decades. Prior to, let me say 2010, it was quite difficult for parents, know, having children with diabetes to get insulin, because insulin was only present in pharmacies and it's expensive.

the simplest form of insulin, human insulin, would cost about 10 pounds in the pharmacies. And so in 2010, the Change in Diabetes in Children program, which I think it's funded by NovoLodisk and many other partners, started across a number of low and middle income countries, including Cameroon. So these children now have access to insulin through this program. But

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They are provided with insulin until the turn, for example, 25 years, or in some cases, 30 years, and then they have to fend for insulin for themselves. So insulin access is still really a challenge. I mean, that's a remarkable thing, because obviously in the UK, then there are lots of problems with type 1 diabetes, but at least the NHS will always provide your insulin and all your blood glucose monitoring strips.

When you say it would be 10 pounds for insulin, how does that compare with, the average annual salary in Cameroon? The average or basic average salary in Cameroon, it's I would say around 40 to 50 pounds. So that's so you can just imagine the challenge for families. And I remember

Professor Jean -Claude Bainier would usually tell a story of one of his patients several years back where they had a diabetes child in the family. And the parents were usually very sad, you know, because of the burden of the disease. And then several years, you know, after many years of following up, he saw one of the parents one day in town and the parent looked a bit happier, if I could say.

And when he asked the question that, you're looking much better than when I would see you in the hospital. And the response was the child with diabetes passed away. So you can get that picture where at times having a child with diabetes with type one diabetes in particular, where they have to fend for insulin can really, really lay a huge burden on families. Well, that's terrible to hear, isn't it?

And in terms of monitoring kit as well, we know in the UK individuals with type 1 diabetes now are getting sensors and access to pumps. But tell us about blood glucose monitoring in Africa for those with type 1 diabetes. When I see what is available for children and other young people in terms of access to monitoring and treatment here in the UK, and I

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compared to what is available to similar kids back in Cameroon or to some other African countries. It's like night and day. Here in the UK, in the NHS, for example, kids are now provided with continuous glucose monitoring devices. But that is like, it's going to be a wild dream for some of these kids at the moment.

back in Cameroon, for example, because just getting access to simple glucose meters can be very challenging for some families, not all families, but at least for the majority of families. some of these kids through the SEDIC program, Changing Diabetes in Children program, are provided also with a glucose meters and with monitoring strips.

We know that these devices don't last forever, for example. And if something goes wrong with that device, some of these families cannot even find it possible to replace these glucose meters in order to get strips to continue monitoring. So it's very challenging. It's completely like night and day. So how does that feel for you as a doctor?

when you've got a new patient coming in with type 1 diabetes and you know all the challenges that they're going to be facing? I think that is where we need to be imaginative, I would say. We would usually have access to strips in the clinics and at times some of these children would rather come to the clinic to get their blood sugar tested, maybe because of, you know, they currently don't have strips at home.

And if you are a doctor, would probably, if strips are limited, then you would, okay, instead of monitoring, maybe three times or four times in a day. So you would probably monitor in the morning on a particular day, monitor in the afternoon on another day, in the evening on another day, so that we have like a wide overall picture of what is happening within a week. So those are some of the strategies we use.

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And for now they are working. They may not be the best strategists, but I think that's what's available. And for some of the kids that are really deprived and really young, they are provided with monitoring strips a minimum of four times per day, just in terms of managing access and inequalities and deprivation carefully.

So what you're describing is a situation which is now much easier for children to remain alive with type 1 diabetes. And actually there have been significant improvements during this time. But in some ways, it reminds me a bit of when we spoke to Jean and Jill, who've had diabetes for over 50 years. And it's really talking to them about what it was like maybe 30 years ago. So we've got a long way to go to

bring everybody in the world to an equal level and the first steps are made, considerable more effort is needed. That's true, Andrew. Really considerable efforts have already been made. I think we should all agree on that with regards to what's happening with some of these insulin provision schemes in partnership with different ministries of health back in Sub -Saharan Africa.

In terms of what has happened recently, like I'll take the case of one of the studies I conducted during my PhD, just looking at mortality over a period of five years in Cameroon, we found a mortality incidence rate of about 33 per thousand person years. Obviously, if you compare that to European standards, that's unheard of.

because some of the countries, for example, in the UK, there are about one per thousand. But if we look back 40 years ago, and some of the very first epidemiological data from Africa were showing that about 80 % of children who are diagnosed with type 1 diabetes die within the first year of diabetes diagnosis. So, from the 90s to where we are now in 2020,

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I believe they've been tremendous improvement. But I think with regards to where we want to be in the future, there's still a lot to be done. You were talking about your PhD and the increased mortality or death rate of those with type 1 diabetes. What kind of things were those individuals dying from? So when we looked at the data at the time, some of the reported causes of death were obviously

things like diabetes, ketoacidosis, which of course we know it's a very major complication. But also we saw other things like hypoglycemia, infections, obviously we are talking about African infections. And there were very few cases of chronic kidney disease because now these kids are surviving long enough to develop this chronic metabolic complications of diabetes.

So in terms of the big three, are diabetes, ketoacidosis, hypoglycemia and infections. So the first two would effectively be either too little insulin or too much insulin. so it's still a problem of insulin regulation. Exactly. Okay. So one of the exciting things you did in your research was to not only study in Cameroon, but also to go

Uganda where I think there were similar problems. One of the questions you were looking at is, is type 1 diabetes in Africa the same disease as we see in Europe? I wondered if you could give an outline of what you found. So we went into some of the clinics. These clinics are usually based in either public

government hospitals or in some private or missionary hospitals. And so we took every kid and let's say family household who were willing to participate in the study. And so at the end we had a mixture of those with newly onset diabetes and those who had had diabetes for a number of years.

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Were you looking at any particular age groups or what was the criteria for people to be able to join the study?

Our study was really open and so we had children as young as four years, but we had a particular limit in terms of age of onset of diabetes, which was 30 years because we wanted to focus on a seemingly young and young adult age range. So these were people diagnosed under 30 who were being

treated as type 1 diabetes with insulin. And what kind of numbers were you able to study in Cameroon and Uganda? In total, in Cameroon, we were able to recruit slightly above 300 from two main clinics. But these two main clinics, would say, would serve as hubs covering about

seven different regions in Cameroon, we were unable to access the northern regions of the country. And in Uganda, we recruited mainly around Kampala and also in the western region of Uganda in an area, I think the main town there, it's called Massaka, which is really quite rural in order to have a good picture of what is happening in an urban center like Kampala, but also in

the rural parts of the country. Now, I believe this is the interesting bit in terms of some of the results we got. So first of all, we found that a number of these children and young adults who present with type 1 diabetes do actually have classical type 1 diabetes. And what I mean by classical, I mean what has been described

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in the textbooks, which is what we would normally find, for example, in the UK or in the US in developed settings. So these were children and young adults who were diagnosed with diabetes around an age of about 13 to 15 years. They're quite lean. And obviously they've got markers showing autoimmune destruction of their pancreas. And they also had

a genetic picture which is linked to what we see in the textbooks of what we know type 1 diabetes to be. Interestingly enough, this proportion of people or individuals who had classical type 1 diabetes was just about 30 to 40%, which was contrary to what we were thinking. And now on the other hand,

there's this other group of children and young people who look completely opposite to these individuals with true classical type 1 diabetes. And in what way are they different, JC? So, clinically, when the presenter, when we looked at their clinical picture, for example,

they were diagnosed at the same age as the children with type 1 diabetes. So around 13 to 15 years, they are lean as well. So for a doctor, and it will be difficult for a doctor to differentiate which of these children have got true type 1 diabetes or this atypical form of diabetes. And the interesting findings came when we started looking at their immune profile and also

at their genetic profile. So we found that about 60 to 70 % of these children and young adults from Cameroon and Uganda never had the autoimmune markers, which we know is associated with type 1 diabetes. And their genetic picture as well was completely different from what we would expect.

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in children with type 1 diabetes. Why I think and why we think as a group that they do not have type 1 diabetes is first and foremost linked to the fact that they don't have immune markers for type 1 diabetes, but more importantly, their genetic profile seems not to be associated with the classical HLA, for example.

the human leukocyte antigen pattern for type 1 diabetes, which we know is strongly associated to some of the loci around DR3 and DR4. And we used a particular tool, developed the ANX, et cetera, by Richard Oram, which, if I'm not mistaken, was a previous guest on the podcast called the Type 1 Diabetes Genetic Risk Score.

which gives us an indication of the genetic profile of people who have type 1 diabetes or not. And so this atypical group of children had a very low type 1 diabetes genetic risk score, which is an indication of the fact that they don't have that natural predisposition genes for type 1 diabetes. And so based on those two findings, we think

something is happening in this particular group of children and young adults, which probably might be coming from the environment or a mixture of both genetic and environmental components. So if I understand correctly, you're saying these patients don't have the typical autoimmune type 1 diabetes where the immune system turns on yourself and destroys the beta cells that produce insulin.

But despite that, they're still slim. They still are not making much insulin at all. So they're not like type 2 diabetes. So the big question is, what is causing their diabetes? Because that's not something we find in the UK at all. Yes. So I was going to come back to the question on type 2 diabetes. Because what we know is that if you've got type 2 diabetes, you still make your own insulin.

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And so even when young children develop type two diabetes, what we now call young onset type two diabetes, there is a classical picture where they are heavy in terms of size and BMI, but in this kids, for example, they were all really very lean. And as Andrew mentioned, they still had insulin requirements that were quite high, meaning they were still supposed to be treated with insulin.

their beta cell function was quite low. And so we think it's not type two diabetes. And even when we've looked at other genetic methods of trying to distinguish between type one diabetes and type two diabetes, we still see that these kids don't have type two diabetes. And so that brings us to the question, if it's not type one diabetes, and if it's not type two diabetes,

which are the major causes of diabetes, what then is causing or driving diabetes in this proportion of about 60 to 70%. And we ended up looking into whether they had a single point spelling mutations, know, what obviously called monogenic diabetes, whether this is present in this atypical group of children.

And we found that monogenic diabetes was present just around 2%, which is not different from what you would normally see, for example, here in the UK. So meaning monogenic diabetes is not contributing to this proportion of children who have this atypical form of diabetes. Now to the question, what is driving diabetes? The answer is I don't know, but it's what I think I would want to find in the future.

So just to clarify, this large group of patients, the 60 to 70 % that seem a bit different, you were able to show that they were insulin deficient. You'd measured C -peptide and showed that their C -peptide levels were relatively low, and therefore they were generally insulin requiring. Is that right? Correct. So C -peptide levels really low. And although it was just really slightly higher,

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than those who had classical type 1 diabetes. Just really an indication showing that those who really had classical type 1 diabetes have the same picture of classical type 1 diabetes in the UK because it's a severe disease. But we are also seeing that in this group there are high levels of insulin deficiency, meaning something aggressive should also be happening at that pancreatic level.

And at the moment, we don't know what is happening, but I believe it's going to be a long journey, but also an interesting journey to discovering what is happening to this group of children with this atypical form of diabetes. And has this atypical type of diabetes been described anywhere else in the world before, or is this a new type that you're the first person to describe it in Africa?

I think the been pointers to these atypical forms of diabetes. And we all know that African populations and minority ethnic populations would usually have varying forms and presentations of diabetes. But I think what is interesting in the work I was able to accomplish in my PhD was that this was in a very specific group of children.

who we thought all had type 1 diabetes. And as we said, they were all on insulin. And when we looked back at studies published previously from Africa, we saw that just a very few number of studies that have used both clinical tools, immunological tools, and genetic tools to describe type 1 diabetes. And the novelty

in my study was that I was able to combine all these tools and to show that a particular group of children who would think just have antibody negative type 1 diabetes have a completely different form of diabetes, which is not antibody negative type 1 diabetes. You're very modest, John -Claude. I think...

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Your contribution is massive. As you say, previous studies had said there's less antibodies in type 1 diabetes. There's less genetic susceptibility that we normally see in Europe. But what you pointed out was that really there were two groups. There were groups that had exactly the same number of antibodies and exactly the same amount of genetic susceptibility as the Europeans and then another group who had none. So it wasn't just a mild group.

overall, was two different groups, which really opens this exciting question of it being a different disease. And I think if anybody is going to find out what that is, I would back you 100 % to do this in the rest of your career. But I agree with you, it may be a long journey to find out what this new cause is. So Jean -Claude, what are your next steps? I think, Andrew said it all, it's going to be an interesting and long journey. And I think I'm committed.

to giving myself time to learn, to continue to learn diabetes research, which I find quite interesting and revealing probably based on what I said previously around the passing of my dad with diabetes. But I believe the journey of a thousand miles always starts with the first step. And I believe that first step was made during my PhD and I hope to continue making further steps.

into trying to decipher what is causing diabetes in this group of young children. But as a whole, just really studying diabetes in young people, which I believe is a specific group that is not always talked about. It's underfunded, it's under research, but I believe some of the interesting insights around diabetes in the next decade or so would probably come.

from studying young people with diabetes from Africa. Thank you very much, Jean -Claude, for a fascinating episode. It's been fantastic listening to you. And we really look forward to hearing about those future steps as you take them, which I'm sure you will. So thank you so much for joining us, Jean -Claude. I think it's been amazing to hear your story, to hear more details about diabetes in Africa, and to hear about the wonderful work that you're doing, which I'm sure will make a massive difference to those.

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patients that you and other colleagues look after in Africa. So thank you. Thank you very much, Andrew. Thank you very much, Maggie, for having me on the podcast. And I would end by saying that the work that I do would not be possible if not with the help of colleagues working back home in Cameroon and in Uganda. And also the patients themselves, or I would say the people living with diabetes, but also including their parents, would take our time.

bring these kids to the clinics and also to care for them back at home.

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I was really struck by the stories of how different type 1 diabetes is in sub -Saharan Africa. It's hard enough for families and parents who trying to cope with children and young adults with type 1 diabetes in the UK with all the support they have. But to imagine yourself in a situation where there isn't even a primary care doctor to go and visit to make the diagnosis and then just the resources to treat.

and monitor diabetes is so difficult. Yes, I think as a healthcare professional working in the UK, it's really hard to imagine the challenges that are faced in Africa. I think Jean -Claude described those really clearly to us and really powerfully. And I think sometimes it's tempting to think when there's a massive care need that really should we not be doing research in that situation.

I think actually in many ways when there's a care need, becomes even more important to understand the disease, especially as John Claude is suggesting, it's going to be different. Yes, it really highlights health inequalities across the world, not only in terms of care and access to facilities and something as basic as insulin, but also it highlights the importance of the need to do research within those populations. Yeah.

And I think the reason you need to do research is because it removes that assumption that everything's going to be the same. But we've learned everything we can in Europe and now we just apply that. And I think the great thing about the National Institute of Health Research and their global health program is their emphasis is really on identifying people like John Claude to train them as researchers.

So it's not researchers coming from England with their preconceived ideas. It's actually researchers developed within the countries themselves. And he's a fantastic example of that. Yes, absolutely. I'm in admiration of the work that Jean -Claude's done. And I found it really moving to hear his story and interest in diabetes had been inspired by his father. Yes, just hearing that makes you stop and think, doesn't it?

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The personal reasons for entering into a particular area can be quite strong, but that's obviously the strongest. I think the work that Jean -Claude's done has been amazing and it's really opened my eyes up to what it's like to have type 1 diabetes in Africa, but also the finding that he's got this big group of patients who are not what we considered to be the typical type 1 patient. And I'm really fascinated to see his future work and what he goes on to find out.

Yes, we see him developing as a scientist and a researcher kind of on a day -by -day basis and he'll go to that big question and ask, is it infection that's causing it? Is it toxins in the environment that are causing it? What is the difference and why is it occurring in sub -Saharan Africa but not Europe? And I would really back him to come up with an answer. So I hope you really enjoyed this episode.

and please join us again in two weeks' time.

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