Why is type 2 diabetes so widespread?

In today’s episode, we’re talking about a disease so widespread that it touches nearly every family in some way: type 2 diabetes. It’s not just a health issue, it's a rapidly expanding crisis. And many people don’t know that they have it. 

Prof. Naveed Sattar joins us to shed light on preventing, treating, and potentially reversing type 2 diabetes. 

Naveed is a medical doctor and professor of metabolic medicine at the Institute of Cardiovascular & Medical Sciences at the University of Glasgow. He’s one of the world’s top 1% most cited clinical scientists, and he’s worked on many clinical trials of lifestyle changes and drugs to prevent and manage diabetes.

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Episode transcripts are available here.

Transcript

[00:00:00] Jonathan Wolf: I'm your host Jonathan Wolf, founder and CEO of ZOE. Today we're tackling a silent killer that's claiming more of us every year. It's a disease so widespread that it touches nearly every family in some way: type 2 diabetes. This is not just a health issue, it's a rapidly expanding crisis, and many people don't even know they have it.

In the U.S. alone, 100 million people have prediabetes. And over 37 million grapple with type 2 diabetes. Globally, the last 30 years have seen a four-fold increase in the number of people living with this condition. And this isn't just about high blood sugar. This is a serious chronic disease that can rob you of your vision, your limbs, and even your life.

But there is hope. Professor Naveed Sattar joins us today to tell us how to prevent, treat, and even reverse type 2 diabetes. Naveed is a medical doctor and professor of metabolic medicine at the Institute of Cardiovascular and Medical Sciences at the University of Glasgow in Scotland. He's one of the world's top 1% most cited clinical scientists and has worked on many clinical trials of lifestyle changes and drugs to prevent and manage diabetes.

Naveed has also been a member of ZOE's scientific advisory board and an important contributor to ZOE's science in this area.

Naveed, really lovely to see you again. Thank you for joining me today.

[00:01:42] Naveed Sattar: Pleasure, Jonathan.

[00:01:43] Jonathan Wolf: So we have this tradition on the show that we always start with a quick-fire round of questions from our listeners. And the rules are really simple. You can say yes or no, or if you absolutely have to, you can have a one sentence to answer it. It's specially designed to be really hard for professors.

Are you willing to give it a go? 

[00:02:03] Naveed Sattar: Yeah, absolutely.

[00:02:06] Jonathan Wolf: Alright, are there millions of people around the world who don't know they are living with type 2 diabetes?

[00:02:12] Naveed Sattar: Yes.

[00:02:13] Jonathan Wolf: Does type 2 diabetes significantly increase my risk of other diseases like heart disease and cancer?

[00:02:21] Naveed Sattar: Yes.

[00:02:22] Jonathan Wolf: Is it true that almost 100 million Americans have prediabetes?

[00:02:28] Naveed Sattar: That seems a high number. It's possible. I think it's probably slightly overestimated, in my opinion.

[00:02:34] Jonathan Wolf: Okay, let's go and dig into that. That is a quote from the CDC, so I'm intrigued to go into that. If the food I eat leads to big blood sugar spikes day after day after day, can this significantly increase my risk of type 2 diabetes?

[00:02:50] Naveed Sattar: Probably yes, but it would generally tend to do so through weight gain.

[00:02:56] Jonathan Wolf: Are women better at controlling their blood sugar than men?

[00:02:59] Naveed Sattar: Women have a lower risk of type 2 diabetes than men for reasons linked to where they store body fat.

[00:03:06] Jonathan Wolf: I think we definitely want to talk about that. And then finally, last question, and you definitely can have a sentence or two for this one, Naveed. What's the biggest myth about type 2 diabetes that you come across as an expert in this area?

[00:03:19] Naveed Sattar: Certainly my patients’ biggest myth, often when I tell them that they may have type 2 or are at risk, is that they don't eat much sugar. 

Type 2 diabetes predominantly is a disease in most people, of excess weight to a level in themselves that leads to too much fat in the wrong places, including within the liver.

[00:03:40] Jonathan Wolf: Got it. And so they're saying, hey, but I don't eat loads of sugar, so how can I have type 2 diabetes? And the answer is they still do.

[00:03:46] Naveed Sattar: They still do, and it's predominantly, people can put on excess weight for a number of reasons, not necessarily just high sugar, but also, obviously, lots of fat.

[00:03:55] Jonathan Wolf: Well look, let's start to dive into all of this and you know, just to start with, I think many listeners to this podcast know I have a personal interest in blood sugar because my own blood sugar control is actually really quite poor. But I actually didn't know this was happening inside me at all until I wore a continuous glucose monitor when I took part in the very first ZOE Predict clinical trial, which is about five or six years ago.

And it was a complete eye-opener for me, understanding that my blood sugar would often be very high for hours after I ate certain foods and was quite high even when I woke up in the morning fasting. Because I didn't feel anything, I had no idea about this. So, you know, I'm really fascinated in this topic.

Now, before I get carried away though and jump to all the things that I'd love to discuss about what I could do to improve my blood sugar control. Can we just start right at the beginning and maybe just start with like, what is blood sugar and why does it matter?

[00:04:51] Naveed Sattar: Well, sugar is one of the fuels, one of the key fuels that many body cells require for making energy and for conducting their normal functions. So, particularly, of course, the brain is dependent upon fuel for it to function, and it's its source of fuel for it to work, for the cells to work, as well as requiring oxygen.

It's also, when we are sick, the body is very good at preserving, trying to preserve sugar for your immune cells, the cells that fight off infection or help repair tissues. And again, they require lots of fuel for that, for those mechanisms to fight off infection or repair tissues. And therefore, when you are sick, it makes sense the body tries to preserve the sugar more for those cells.

But it's required, sugar is required for all body cells. basically for them to function normally.

[00:05:45] Jonathan Wolf: And one of the things I think that people often mention when they talk about diabetes, you often hear this word insulin. What is insulin and why does it ever come up in a discussion around blood sugar and diabetes?

[00:05:55] Naveed Sattar: So insulin is a hormone. So if I've just eaten a banana and my body is breaking down that banana, putting its breakdown products, one of which is sugar, into my blood. But I don't want it to be my blood for very long, I want to be able to store that energy in various tissues.

Insulin is a bit like a key that opens up some of my cells to take in that sugar and store it when I don't need it. This also stops my own body making sugar when I don't need it. So I've just had a lot of sugar, hopefully my insulin started to go up, put the sugar in the right places, and it's also probably signalling to my liver, stop, you don't need to make any more sugar because there's already lots coming in.

So it's like a master regulator of keeping sugar levels within the right levels in the blood, putting it in the places where you need it to store for future needs, and also helping you liberate it when you need it. 

And that actually happens when the insulin levels go right down. So that perhaps when you're sleeping and you're not having sugar in your body, your sugar levels, your insulin is low down and the liver keeps making sugar sufficient to feed all the cells in your brain, etc. for normal bodily function. So insulin is a master regulator in all of us for our sugar levels.

[00:07:13] Jonathan Wolf: And thank you Naveed, that's really, really clear, I think. So you've got this sort of insulin keeping things level. I guess the obvious question is, why doesn't our body just let all the sugar hang around in our blood, you know, like the fridge, you just keep putting more stuff in it, and then, you know, my brain or whatever else could take the sugar out when they want it.

Why can't I just let it get higher and higher?

[00:07:35] Naveed Sattar: Yeah, I know that's a brilliant question. If you think about sugar, if you spill sugar, particularly in the context of water, it becomes very sticky. When sugar levels become very high in the blood It starts to stick to lots of our bodily proteins and changes their function and makes them abnormal.

So for example, some of the damage that happens in the eye is because the sugar at very high levels starts to stick. So lots of proteins are relevant to aspects of our eye function and disrupt it and you lead to what's known as retinopathy, a damage to the eyes. The same thing happens in the kidneys, the same things happens to some of the bodily parts, proteins that are relevant to nerve function.

So sugar levels when they're high, effectively disrupt lots of raw materials and proteins in our body and disrupts, therefore, lots of normal functions and causes damage.

[00:08:25] Jonathan Wolf: I think that's both very clear and it's quite scary, this analogy with like the sugar on the table sticky, I can see that that's not what you want sort of coursing through your blood.

[00:08:36] Naveed Sattar: It's a process partly called glycation, and effectively it changes the structure of your molecules from what's normal to abnormal, and then that means it's almost, if I think about it, if you're building a house and you start to make bricks and they're the wrong shape, that building is going to be disrupted and will potentially, not have the same level of integrity and will be disrupted and fall apart.

That's effectively what's happening inside your eyes, your kidneys, your nerve cells. If your sugar levels are high, you're changing the structure of protein. So they no longer do what's healthy and you, you're building up tissues in an abnormal way that leads to disease.

[00:09:14] Jonathan Wolf: Thank you so much, Naveed. I think that's both a bit scary, but also really clear. Could you explain, then, What happens when someone gets prediabetes or type 2 diabetes? What does that actually mean?

[00:09:28] Naveed Sattar: So this is a question that's often happened. Now, people living with prediabetes do have a higher risk of obviously developing diabetes. They don't inevitably develop diabetes. So the term prediabetes doesn't mean that it's always inevitable. People who have prediabetes, some stay in that level for years.

Others can actually go back to normal levels of sugar or diet, because if they prove their lifestyle. But if you do have prediabetes, your risk of developing diabetes is clearly higher. Your risk of heart disease is about double compared to people who have normal sugar, you know, sugar levels don't have prediabetes or healthy levels of glucose.

[00:10:05] Jonathan Wolf: I just want to make sure I got that. You're saying that if you have prediabetes, your risk of heart disease is actually double the level if you don't have prediabetes.

[00:10:13] Naveed Sattar: Roughly speaking, but here's the rub. At the level of prediabetes, that risk is not necessarily caused by sugar levels, because they're not at the level of diabetes. What it is caused by, is the processes that have led you to develop prediabetes in the first place. So, for example, for me to develop prediabetes, I would probably need to put another four or five kilograms of weight on.

That excess weight will also mean my blood pressure will go up. It will also mean my blood fats and my cholesterol levels will be disrupted. So then I will have higher weight, higher blood pressure, more abnormal, toxic levels of lipids and possibly also other changes. And those are the things that cause my higher risk for heart disease.

They will also, in a sense, they're stressing my sugar levels. I'm able to keep them still within the non-diabetes range, but they're being stressed because I've put fat in the wrong places in my body.

[00:11:12] Jonathan Wolf: And Naveed, I just want to make sure that we all understand what prediabetes and diabetes is. And then I'd love to understand more the way these are linked. So what does it mean for someone to have prediabetes or type 2 diabetes? And how is that linked to their blood sugar that we were talking about a minute ago?

[00:11:30] Naveed Sattar: So let me explain it in the terms of a hemoglobin A1c level, which is a common test that we use that gives us an average sugar level for an individual over three months. So, our normal hemoglobin A1c in the U.K., it doesn't really matter about the units, is 41 millimoles per mol or under.

Hopefully, you and I sitting here have got levels of, I don't know, somewhere between 32 and 41, okay? prediabetes within U.K. and other, you know, in Europe is between 42 and 47. Diabetes is when you get to 48 and above. 

In America, prediabetes criteria is a bit wider than we use in the U.K. It's from 39 to 47, which is probably why the category perhaps of 100 million. I don't think it's quite as high as that. There's always some interpretation based on CDC data that they have to extrapolate and base, just a few caveats. But nevertheless, that's what it is. In older hemoglobin A1 terms, the levels we had in our mind was diabetes is at 6.5%. We use the percentage. Prediabetes is from 6 to 6.4 in the UK or from 5.7 to 6.4 in the US. 

And effectively that's hemoglobin A1c and it's capturing your average sugar levels, your average exposure to sugar levels for three months. So it's a very good stable measure that we measure in the clinic all the time. Increasingly is used to diagnose diabetes or diagnose prediabetes.

[00:13:04] Jonathan Wolf: And I've heard doctors often refer to this as HbA1c, is that right?

[00:13:06] Naveed Sattar: HbA1c. Hemoglobin and A1c.

[00:13:08] Jonathan Wolf: And so the way I understand, I just want to make sure I'm playing it back right, the way I understand it is, your blood sugar is changing all the time, so you ate that banana right now and your blood sugar is probably starting to, like, shoot up, then you'll put in the insulin you described and it'll come back down. And this HbA1c is sort of like this average measure of your blood sugar, sort of like something on the tank on the car that's just telling you, like, what the average is over months, rather than this thing that's changing all the time. Is that…?

[00:13:36] Naveed Sattar: That's perfectly correct. So if I'm able to, after my banana, keep my sugar levels from going too high and keep them within the normal range, and every time I eat food, if I keep it relatively within the normal range, my HbA1c will stay within the normal range because on average my sugar levels are high. I've been kept normal.

[00:13:57] Jonathan Wolf: Amazing. And so, to make sure that I just want to make sure that I've got this, you're sort of saying, we all have a level of sugar that we would normally have in our blood, we can measure it with this HbA1c, and if somebody's been diagnosed as listening to this with prediabetes or type 2 diabetes, this is higher than it should be. And this is the concern and we'll then talk a bit more about what it means and what you might be able to do about it.

[00:14:26] Naveed Sattar: That’s broadly correct and I mean, and the reason I think clearly we can measure sugar levels, they can also give us an indication, you know, particularly when you're fasting, you know, we think the sugar level should be below 7 millimoles per liter, so we can do it in fasting. 

The move in, certainly in the U.K. and also in the U.S. and many other countries in the world to diagnose diabetes, they've increasingly started using HbA1c because of its stability, because it doesn't need to be done fasting, because it can also be measured when people have infections or admitted to hospital.

Because none of those things are going to change on average for 3 months. So it's a very good aggregated marker. Now it's not perfect all the time. There are some circumstances like people who have very severe anemia. Or they have a certain different type of hemoglobin, so-called hemoglobinopathy.

You know, we have to be slightly careful, but that's a very, very small percentage of the population. So therefore, for the vast majority of circumstances, HbA1c is a very good aggregated measure of sugar exposure that your body has been exposed to and gives us an indication of whether you have prediabetes, diabetes, or an abnormal range.

[00:15:38] Jonathan Wolf: So I think the obvious follow-on question is, it's why has there been this enormous explosion in people with diabetes and prediabetes? The team was sharing, again, some of these stats and apparently, there's a sort of fourfold increase in the number of people with diabetes around the world, to like hundreds and hundreds of millions of people.

I know that when we look at our own data of people doing the ZOE study, of whose there's hundreds of thousands, you see there's lots of people whose levels are far, far lower than the levels you're describing, of people with diabetes. 

So clearly, you know, there's a big shift, I guess, from where I think about my children. I don't know what their HbA1c is, but I'm pretty confident it's a long way below these levels, right? They aren't there. 

So what's, what's going on? What is causing what I think we could sort of describe as an epidemic of type 2 diabetes with all the scary implications you're describing, and why is it so much more common now, even than when I was a child growing up?

[00:16:40] Naveed Sattar: Okay, so I think it's obviously a brilliant question. I'm sure many listeners can work out some of the major causes. And one of them, of course, is rising levels of weight and waist girths in society. 

Because as you put on more weight, as people put on more weight and as average body mass index levels or whatever waist circumference levels have risen in the communities, that means more people have got to the point where they can no longer store fat peripherally. And that excess fat gets deposited into some of the key organs in the body that are exquisitely sensitive to too much fat and are relevant to how well you either make or store sugar.

And if you put too much fat in some of these organs, you will disrupt their ability to control sugar levels. So for example, too much fat in the liver means that it will continue to make excess sugar in excess of the body's needs when you don't need it. 

Too much fat in muscles means that your body will not take up the sugar in response to insulin as well as it normally would do if your fat levels in the muscles were less. That's a simple example. So weight gain is one of them. 

Another key factor is actually linked to success in part. Another risk factor for diabetes is actually living longer, older. So as life expectancies have gone up and more and more people are living longer, we get more diabetes. And part of that reason happens is this, in my simple mind, there's three things that determine diabetes risk. The weight you reach, how much fat you put in your organs, your muscle mass, because that's your engine to burn up sugar, and how well your pancreas works. 

Now two of those three things, probably all three things, change with age. As we age, our muscle mass goes down, our pancreas becomes less, which is the organ that makes insulin, becomes less plastic as it were i.e. its capacity to make more insulin to keep the sugar levels down becomes less over time. And also, with age, we tend to put on more weight in our stomachs, and we tend to lose fat from our peripheries and our arms and legs and our, you know, and peripheral regions. 

So with people living longer, we're also increasing the likelihood of diabetes. And that's not just in high-income countries. If you think about all the millions of people, billions in fact, in low-income countries, as they've improved their hygiene gradually and, you know, industrialization, people are no longer dying in their 30s and 40s, they're living to their 40s and 50s. So they're able to develop diabetes in the 50s and 60s when they didn't, because they died with infection or something else.

So there's multiple reasons, but, so weight gain, increased life expectancy are probably the two major ones.

[00:19:26] Jonathan Wolf: And so, Naveed, I just want to unpack that and make sure that I've understood it and our listeners have understood it fully. 

So maybe to start with the first one, I think you said something really interesting, which is, it's about rising levels of weight in particular places. So it's not just generically whether someone has put on weight. You're saying it's about the fact that that weight is actually being stored, and so that fat is actually being stored inside crucial organs in our body, and that that is really what starts to trigger the diabetes. Did I understand that right?

[00:20:00] Naveed Sattar: So yes, that's so-called ectopic fat. Fat where it normally isn't supposed to be in any sort of high level. So as an example, all of our liver fat levels should be below 5%. Ideally, usually, if you look at the normal range, under 2%. 

But when the liver accumulates more fat because your body has been unable to store the fat in other areas because your weight's got to such a level, the body is looking for other places to store that excess fat. One of which then tends to be the liver. As the liver fat levels go up, that disrupts the liver's ability to regulate sugar levels normally, and the liver actually starts to make excess sugar beyond the body's needs, which then keeps the sugar levels high. So that's one of the examples, so ectopic fat, it's not the only cause. 

Some people also have shall we say, pancreases which make insulin, but which are unable to make as much insulin as perhaps a healthy individual. So that even when they're not very overweight, their pancreas’s ability to make insulin, becomes diminished with age very quickly and then it's a pancreatic-driven type 2 diabetes.

But even there, you know, genetically, if you can't make as much insulin as the other person, it's still usually weight gain that's the trigger for diabetes. And people then tend to have to put on less weight to get that diabetes. So there's an interaction between how well your pancreas can make insulin.

How much fat you put in the wrong organs, and how good is your muscle mass.

[00:21:32] Jonathan Wolf: I'm so sorry, Naveed, before we jump on, because I think the weight in your organs affecting the way that they work, that makes sense, and you're describing the pancreas as one of those examples, it's so important, it's making the insulin. 

Could you just explain the muscle mass for a minute? Why does the muscle mass have any impact on diabetes?

[00:21:52] Naveed Sattar: Muscle mass is often it's a measure of how active you are. So activity, plus you know, as an example, my muscle mass used to be not so good. It's actually probably a bit better now I've got a dog and I cycle and so on.

[00:22:08] Jonathan Wolf: Congratulations.

[00:22:10] Naveed Sattar: Yeah, well, you know, and my HDL has gone up, and I can see it, I can see it as a biomarker. It's gone up, you know, really almost doubled.

[00:22:16] Jonathan Wolf: Which is a good thing.

[00:22:18] Naveed Sattar: Which is a very good thing because I do have a family history, so I think my pancreas, probably genetically being South Asian in family history, it's got a lower reserve to keep making insulin to the levels I need to overcome any resistance in my tissues, as it were.

So by building up muscle and being more active, I have, an engine that burns sugar more. So that means I've got an engine that can burn sugar. That means that sugar is not going to stay as high if that makes sense. Also will burn fat as well.

[00:22:53] Jonathan Wolf: So by having more muscles, it's actually going to pull the sugar out of my blood, it's going to burn it up. So that's like, it's improving everything. And if I don't have that, I'm more likely to store it in my liver and my pancreas and all this sort of thing.

[00:23:06] Naveed Sattar: It’s a bit like a car. It's like having a very efficient engine and a bigger engine for the amount of fuel. If you overpack the car with fuel, you know, too much oil, the oil will disrupt the engine and if you've got, if you keep the engine clean and bigger, it may be easier to cope with more oil. It's that, you know, that kind of simple analogy.

[00:23:24] Jonathan Wolf: And can I follow up on the point about the differences between people? Because I'm really interested in that. And you were just talking about being South Asian heritage. And I'd love to understand a bit more about that. 

But the other thing I was interested in is sort of difference between men and women, because I know that when we've had other conversations to do with other risk factors we've had this conversation about women particularly before menopause, sort of storing fat in different places. And is there a difference between men and women in terms of their risks of diabetes as well? 

So I'm really curious about, for people listening, how these things might be different depending on who they are.

[00:24:01] Naveed Sattar: Yeah, well let's explain all those risks in the prism of where you store the fat. So women generally have a much greater subcutaneous…, so they're able to store fat peripherally, thighs, legs, and obviously, the shape of women is such that they have other stores of fat, shall we say.

So, women generally in a sense, have a greater storage capacity for fat in the peripheral area. That means they have to put on more weight overall before that fat starts to seep into the liver.

[00:24:36] Jonathan Wolf: And peripheral, just to make sure, basically, because for anybody who's not seen the video where Naveed is helping to indicate, you're basically saying everywhere that's not sort of in my torso and around my belly, that women can store a lot more fat there.

[00:24:47] Naveed Sattar: And part of the reason women have to store more fat is partly because women have children. They have to feed the children, they have to breastfeed, they have to supply nutrients to the child. 

You know, one of the things that happens in pregnancy is the placenta can suck lots of nutrients from mum. So if mum doesn't have enough fat storage, they can't often get pregnant. You see that in athletes.

[00:25:10] Jonathan Wolf: So we're talking about evolution over millions of years, not necessarily, doesn't mean you as a person listening to this have to get pregnant, but the point is, that's how our bodies have evolved.

[00:25:21] Naveed Sattar: Yeah, that's exactly right. So, if you compare men and women in terms of how much fat they have in their liver, even in healthy levels, men tend to have higher levels of fat within their liver compared to women. 

And also men, when they generally put on weight, it usually is accompanied by their waist circumference going up straight away because they tend to store it, you know, they're all closer already to the threshold of fat going into the wrong places. So with a little weight gain, men's fat usually goes into the wrong places. 

Women, however, generally can put more fat in, in peripheral regions into the thighs and other areas before it goes into the more harmful places like the liver and muscle as it were. So, that explains why men in every ethnic group are at higher risk of diabetes than women for type 2 diabetes.

It probably also explains in part why men are at higher risk of heart disease than women in all ethnicities by and large.

And with that same prism, if you compare you and I, Jonathan, you're sitting there, you know, you're, Caucasian or white. I'm South Asian. We know that South Asians on average have 10% on average lower muscle mass and carry more fat mass already.  And we also have higher levels of liver fat even when we're healthy. So me, compared to you, I've got higher liver fat, so I'm closer to where I'm going to put too much fat in my liver, sufficient to develop diabetes than you are. You are closer than the average age-comparable woman. 

So that explains the men versus women risk. It also explains the whites versus non-whites. And every non-white individual compared to whites are at higher diabetes risk. One of the reasons is where people put their fat. 

It's not the only other reason. Black people, I think there's another mechanism we don't fully understand. It's maybe to do with how well your pancreas can make insulin. But certainly for South Asians, our body makeup is such that we are, for less weight gain, we will start putting fat into the wrong places and therefore we will develop diabetes at lower average weight gains than whites.

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And these are quite big differences you're describing, aren't they, Navi? Because I feel like in general, when you talk to a lot of scientists, then it feels like often they've ended up coming to the conclusion that even genetics in general, never mind ethnic differences, are sort of ending up being quite small versus environment. 

But here you're talking about quite important differences, it sounds like, in terms of risk factors based on your ethnicity. Is that, did I understand?

[00:27:56] Naveed Sattar: Yeah, no, you're correct. So, roughly speaking, South Asians risk for diabetes, comparing age by age and, you know, sex by sex. Somewhere between two to four-fold higher risk of type 2 diabetes.

[00:28:08] Jonathan Wolf: Two to four times higher. So that is an enormous difference in risk.

[00:28:12] Naveed Sattar: And even within the South Asian groups, there is a gradient of risk. So, the highest groups in the big countries is actually in Bangladesh. Then it's Pakistan, then it's India. 

And a nice, potential explanation for why Bangladeshis, compared to Pakistanis, is height and early growth. Because height is a proxy for how much muscle you have. Bangladeshis tend to be shorter than Pakistanis, who tend to be shorter than Indians, on average.

[00:29:43] Jonathan Wolf: It's, it's fascinating. The one thing I would say is, of course, these are just averages, and so you can have this huge… Because, I mean, and listeners will have heard this, I don't want to bore them, but, I actually have quite a lot of fat stored around my belly in terrible places. And very little anywhere else, which I had no idea of until as part of that first ZOE clinical study, I actually had a DEXA scan.

And I remember the face, I remember the look on the nurse doing it, who was like really surprised. And the answer was, I'm, apparently what's, I think it's called like a toffee or something like this and it turns out that I have fat nicely stored around my liver and elsewhere. And I remember Tim explaining to me that this was really bad news.

And so of course, you know, there are these ethnic differences, but there's obviously also very big personal variation, which is why some person, I guess, is much more at risk of diabetes than something else.

[00:29:40] Naveed Sattar: I mean, and there may be various genes at play as well, and you know, the question I would ask if you were one of my patients, Jonathan, is do you have a family history of type 2 diabetes? Your BMI is obviously not high, it's pretty good and it may not be that actually this is a BMI factor, clearly because you're not, you know, you're clearly not heavy.

It may be that you've got a specific gene that doesn't allow you to export liver fat out of your liver into your circulation. I don't know. But that's something for you to interrogate. It's, but by and large…

[00:30:11] Jonathan Wolf: I'm going be following this up in detail after this call, Naveed, but I'm conscious that I need to move on because I don't want to, I know you have limited time before you had to be back in clinic. I'd love to talk for a minute before we talk about what we do. Like what are the symptoms?

So let's say that somebody's listening to this and they're like, oh, I wonder if I do have diabetes, what are the symptoms that I'm going to be experiencing that are going to answer that question for me.

[00:30:37] Naveed Sattar: So most individuals who have type 2 diabetes who move into the sugar levels going high, generally have very vague symptoms and some lots are completely asymptomatic because that change has been so gradual that they haven't…

[00:30:52] Jonathan Wolf: So asymptomatic means they're not aware of any symptoms at all.

[00:30:54] Naveed Sattar: Yeah the symptoms come generally when the sugar levels go really high at that point. When the sugar goes very high, the kidney's ability to reabsorb that sugar gets diminished and you push more sugar out into your urine. 

Sugar cannot go out on its own, it has to carry water with it, so you tend to pee a lot, pee more during the day, pee more during the night, so called polyuria. You may then get more Infections, because you've got higher sugar levels as well. You tend to feel tired and fatigued. Partly because if you're starting to pee out sugar, your body's efficiency in how it uses the sugar for optimal function is diminished.

So you're fatigued. So fatigue, more infections, passing out more urine, other kind of major symptoms.

[00:31:45] Jonathan Wolf: And it sounds like those symptoms you're describing, they aren't when you first… It's not like when you get a cold or something. You don't get these symptoms when you first get prediabetes or even diabetes. This is like when it's already lived with it.

[00:31:57] Naveed Sattar: Yeah, exactly. You know, the sugar levels are going up relatively slowly and so most people generally, maybe they have some vague feeling of, I don't have as much energy as I used to, I'm sleeping a bit more erratically, I'm just, you know, just vague symptoms and some may not.

It depends how fast that sugar level is rising. It depends over what period it's rising. It depends what age you are. We know that younger people develop diabetes as sugar levels rise faster than older people. 

Also, excess weight is a much bigger factor in younger people who develop diabetes than older people. So there's lots of different dimensions. 

The thing I would say, we did a study of 100 Asian men and, and, and, and white men. Of those 100 Asians, 13 had diabetes and didn't know about it. Okay. Didn't know they had diabetes.

[00:32:44] Jonathan Wolf: So you had a hundred Asians that you studied. None of them thought they had diabetes.

[00:32:48] Naveed Sattar: None of them knew they had. And 13, one in ten…

[00:32:52] Jonathan Wolf: 13% turned out... So that's huge. 13% had this and they had no idea that they had this serious disease.

[00:32:58] Naveed Sattar: Exactly. Yeah. Yeah.

[00:33:00] Jonathan Wolf: So that's, I think everybody listening to this is now going to be a little bit scared if they haven't spoken to somebody. Is it alright, if you think you have some concerns, so maybe I think you're describing some of the reasons, like you think maybe you have put on more weight around your tummy and —

[00:33:13] Naveed Sattar: Well, it's more than that Jonathan. Yeah, so the things you should do, tere are simple scores you can look up, you know, what is my risk for diabetes high, low or medium, you know.  

And you can do that, there’s the diabetes UK risk score which you can get online. There's the Leicester diabetes score. There's what's known as QDiabetes online. And the risk scores capture your age, your family history of diabetes, your ethnicity, whether you're a male or female, and generally your weight, and a few other things. And they will give you an idea. 

And it, it may be that when you put that risk score, it comes up, and for the vast majority, it's going to be actually low. In which case, don't worry about it. It's very unlikely you have diabetes. If it comes up medium or high, then at that point, you might want to reach out to your GP and say, Look, I've done this score. Could you potentially do my HbA1c test? I would like to know, and just get an MOT as it were. And that's what…

[00:34:07] Jonathan Wolf: So just to, just to make sure that makes sense to everybody not in the U.K. listening, who may not know what an MOT is. What you're saying is, firstly there's a score, and we will put a link in the show notes for anyone listening to this who can find the right way to score this for their country, which basically gives you an indication of your likelihood of risk.

And what you're saying, I think, is if that risk is medium or high, then don't feel bad about going and speaking to your doctor, your physician, and that there is this very, is it a very difficult test to do to then find out this HbA1c?

[00:34:40] Naveed Sattar: No, it's effectively, it's a blood test that the GP, you know, or the healthcare professional can take, or a phlebotomist can take any time of the day. 

And it costs about in British terms, 1 to 2 pounds. You know, it's not very expensive, probably a bit more expensive in the U.S. and some other places. So it's not very expensive.

[00:35:04] Jonathan Wolf: The tests are always a lot more expensive in the U.S., yes, but we won't go and discuss that right now.

[00:35:08] Naveed Sattar: That's a completely different, but anyway, it's relatively easy. It's done, you know, get the result within a day, and it comes up with the hemoglobin A1 test. 

[00:35:16] Jonathan Wolf: And you wouldn't be, because I think sometimes people say, oh, you know, if you're not really sick, you shouldn't, you know, are you just like creating all these people worrying for no reason?

[00:35:26] Naveed Sattar: The vast majority of listeners when they do this test, the risk will come up as low. Okay, the vast majority, and then they're reassured. Doesn't mean to say they can, you know, they still have to, everyone has to try and live the best life they can, and an enjoyable life in a way as well.

But as an example, somebody like myself, I have a family history of diabetes, so I have a risk factor. I'm also getting older, you know, that in itself isn't a risk factor, but because I have a family history and I'm South Asian, then if I do my diabetes risk score, it comes up as something like 15% chance over the next 10 years. So it's a 1 in 6 or 7 chance that I would.

And I have had a hemoglobin A1 test done and it came back as it's actually okay, but it's getting close to the prediabetes range, which fits with my family history. The reason I've kept it down is because I've kept my muscle mass up. You know, my father and my mother both developed diabetes in their forties and fifties.

[00:36:25] Jonathan Wolf: You know what, that is a brilliant transition point, because I'd love to talk about, so what do you do to avoid getting hopefully diabetes, prediabetes in the first place. And it sounds, Naveed, that you're literally living this yourself so I'm fascinated. And you mentioned, I wasn't sure, was getting the dog part of this solution.

But tell me, I think you've painted a pretty clear picture that you would really like to avoid this because of all the serious implications. 

So if someone's listening to this and they're saying they want to make the right actions. Could you talk through, I think, based on your own research, but also I think fascinating to hear what you're doing yourself as an expert.

[00:37:04] Naveed Sattar: I mean, it's not even my research. I think it's based on the kind of global evidence that we know from all the randomized trials, all the various studies around the world. 

You know, the evidence base is the following, is that if you want to reduce your risk of diabetes, the key aspects are keeping as a healthy weight as you possibly can. So, you know, diet makes a big sense and probably all the listeners here are well-tuned to that and keeping relatively physically active. Aand those are the two major things. We cannot stop aging. 

The one thing I would also say, and I think I've hinted at this, Jonathan, I'm now 56. if I can delay developing diabetes till I'm 75, I'm far less worried because if my sugar levels start to escape high level, then I don't have many more years for that sugar to cause damage. High sugars immediately do not cause damage. It takes about, you know, five to 10 to 15 years.

And also the older you become to get diabetes, the slower your sugar will elevate, because it's less linked to weight gain. The younger you develop diabetes, it's more toxic, it's a more toxic disease, because sugar levels rise faster, you tend to have to need more weight. The reason you tend to need to have more weight to trigger diabetes, is because when you're young, you tend to have a bigger muscle because you're young. And your pancreas is healthier because you're young. 

So in other words to overcome your better buffering capacity because you're younger, you need to stress the system more by putting more fat in the wrong places, but that comes with all the other risk factors that means your risk is much higher.

[00:38:42] Jonathan Wolf: So you're saying, if I can hold it off till I'm 75, then at that point maybe you could start to eat chocolate croissant all day.

[00:38:52] Naveed Sattar: I wouldn't necessarily say that but I know that the diabetes then is you know is not likely to…

[00:38:58] Jonathan Wolf: But you're less worried about the diabetes.

[00:38:59] Naveed Sattar: it's not going to massively impair my life expectancy, if at all. It's not going to lead me to have raging eye or kidney disease or nerve disease, if at all. 

So if you're in your 40s and 50s and you're in prediabetes, some small sustainable lifestyle changes, that means that you either stay the same weight, put on a bit of muscle mass. Or else lose three or four kilograms and sustain that and able to keep healthy with a little bit of activity to stop you putting on weight, means that you will probably delay developing diabetes for five, you know, three, four or five or up to ten years. And some people can delay it for a long time or even revert back to normal sugar levels.

So it's effectively improving your muscle mass, cutting your weight, ectopic fat, sufficient to de-stress your glucose control mechanisms.

[00:39:58] Jonathan Wolf: And Naveed, I'd love to talk about what you've done yourself and you touched on it maybe briefly, but I'd love to understand, it sounds like this is a real live risk for you. You described the fact that like both your parents developed it when they were very young, and it sounds like this is really on your, and it just reminds me a little bit of Tim when he's making his own changes for his health.

Like, it sounds like this is live for you. How does it affect what you do?

[00:40:21] Naveed Sattar: You know, I'm obviously fortunate to live, you know, in an area where there's an ability to do more physical activity. I think the dog wasn't an effort necessarily to keep my diabetes away. The side product of the dog is that I've increased my walking much more than I ever did before and I enjoy it.

I've now cycled to work for the last 10 years and I love it. So I've almost changed my own identity and who I am by becoming more physically active and in finding things that I physic, that I really enjoy. The side product of that is my muscle mass. I can feel it has gone up. 

I probably reduced a little bit of excess fat within my liver. 25 years ago, I was a bit heavier. And one of my signals for diabetes was incredibly high. And then, you know, and it's come right down. because effectively it built more muscle, got rid of some of that fat mass. And some of those changes have been very gradual. 

Equally, I've also made some dietary changes as well. Cutting out some of the refined sugars, increasing the variety of the foods I eat, more fiber-rich, you know, retrain my palate to have different tastes, which takes a bit of time to get used to. Would you believe I even enjoy shredded wheat now, you know? I love shredded wheat, but that's taken me a few weeks to get used to that taste and texture, but I love it. Okay, I add two or three grapes on it for a little bit of sweetness, but that's fine. 

Again, so in a sense, I've been on this gradual step by step by step journey to eating a better quality fuel, having a better quality activity that's in a sense stop me putting fat in the wrong places, keep my engine better, to stop me pushing into diabetes in my 40s or 50s.

And hopefully I can keep doing that by staying active. Even if I get diabetes in my late 60s, I'm not worried about it because I could undergo a weight loss intervention. I could go undergo metformin. There's some better drugs coming forward as well.

[00:42:16] Jonathan Wolf: For someone who's listening to this, who already has, you know, type 2 diabetes, or maybe they've been told they have prediabetes,  is it possible to actually reverse some of this? Can you actually lower the blood sugars that you were, were talking about?

[00:42:32] Naveed Sattar: Yeah, absolutely. So in every individual, we all have a different slope between weight gain and the hemoglobin, the HbA1c level. So In a sense, there's almost a straight line between each of us, and my line is steeper than yours, Jonathan, because of my family history. So for a smaller amount of weight gain, my HbA1c will elevate because I'll put fat in the wrong places.

So we've shown in the DiRECT trial that if you have a person who's developed diabetes from the last three to four years, if they lose 10 kilograms. About 46% after one year, or 33% after two years, no longer have diabetes. Because they've got rid of fat, the liver fat comes right down, then the liver responds far better to insulin, the liver makes less sugar, your sugar normalises. 

So, there's a straight line between how much weight people lose, and how well their HbA1c improves, by and large. And it works the other way as well, there's a straight line between how much weight you put on, Just that slope of that line is different for different individuals based on whether you're male or female, South Asian or white, and whatever age you're at and so on and so on.

[00:43:46] Jonathan Wolf: And so that does mean, wherever you are, there is something you can do and it's not just about taking drugs.

[00:43:52] Naveed Sattar: Absolutely. So I had a patient this morning in the clinic who has diabetes who'd undergone surgery for weight loss. They'd lost a lot of weight, their sugar levels had plummeted. They're still within the diabetes range, and the thing I discussed with them was, and they were starting to worry about mobility, was can you actually now increase your muscle mass?

And they had lost seven stone because of surgery. But they could do some resistance exercise, a bit more physical activity to improve the mobility. So, to improve the engine side of it. 

So everyone listening can do something, but what they need to do is find something that they can sustain or enjoy to reinvent a new version of themselves that they enjoy and they can sustain for better health as well.

Whether that's dietary, physical, better sleep, all the things that you've discussed in ZOE in various podcasts. Better sleep gives you better appetite, allows you to control your appetite better, more, you know, de-stress, maybe more physical activity, all those things. And try and do it in a way that are either small steps that you can get to slightly better health to keep some of these diseases away and also to increase the life expectancy of healthy life, as it were, and contract unhealthy life for later years.

[00:45:10] Jonathan Wolf: Which I think everyone listening to this podcast is interested in. 

Can I ask one final question before we then get to the summary?  there are some new drugs that have been in the news, like Ozempic, and there's been a lot of discussion. We're really lucky to speak to somebody who's one of the world's experts on diabetes. What's your view about this?

[00:45:30] Naveed Sattar: So in some respects, I wish we didn't need to have those tools, you know, because I wish we could change the environment, make it easier for people to live easier lives. Because it's not easy changing your diet. It's not easy becoming more physically active. 

We talked about it and we have to overcome weight stigma. We have to talk about helping people navigate the environment that they live in.

[00:45:52] Jonathan Wolf: If you're surrounded by awful food,

[00:45:54] Naveed Sattar: It's very hard. Yeah, it's almost impossible. I don't want people to think that I think it's easy. It's not easy. You know, some of the changes that we've all had to make, we've had to work at them. But even then, for a lot of people, willpower is not enough. The environment that we live in is not enough. So I wish we did. 

Having said all of that, there's millions of people living with obesity and chronic diseases. These drugs are good, powerful tools that will help people control their appetite, lose quite a considerable amount of weight, and therefore reduce the risk of a number of chronic diseases. 

Not only diabetes, but more recently, you reduce the risk of heart attacks or strokes, improve symptoms and heart failure, reduce the risk of kidney disease. improve the quality of life. 

So I'm glad they're there. They're expensive, we don't have great availability. So we need to work out in all healthcare systems, how do we get them to the people who need them the most to get the maximum benefit for those individuals and society?

And that's a big ask. And hopefully over the next 10 years, we'll have more of those tools. The prices will come down. They'll be proven to be long-term safe and the benefits outweigh any potential risks.

[00:47:01] Jonathan Wolf: But it sounds like you are expecting to be prescribing these to some people.

[00:47:07] Naveed Sattar: I've already prescribed them in some people, because we have to. But we need to do both prevention and treatment. We can't do just one.

[00:47:13] Jonathan Wolf: And that is a whole other podcast that I would like to get you back for.

[00:47:16] Naveed Sattar: Indeed it is.

[00:47:17] Jonathan Wolf: Naveed, I would love to do a wrap-up and for you to make sure whether I've got this right before you shoot off to see another patient if that's alright. 

So I think we started by talking about why would you worry about blood sugar at all, and you gave this brilliant analogy of spilling sugar on the table and getting it wet, and that that's this sticky mess, and you do not want that in your blood vessels. And what happens is if you lose this control over your blood sugar because, for example, you're starting to get all this fat in your liver and your pancreas and all the rest of it, actually you're getting this stickiness in these little blood vessels, and this is, damaging your, your eyes and your nerves, and it doesn't sound good. So it's very clear that we don't want that. 

And then the question is, well, why is this happening? Because it's now happening where there's a hundred million people with prediabetes, according to CDC in the U.S. and, you know, this big increase. 

And you're saying the biggest reason is we're starting to get, number one, that we're getting fat stored in our organs in a way that is really bad for them and didn't really happen in the past. And you particularly talked about it being in your liver and in your pancreas. 

And that interestingly, one of the reasons why we see so much variation between the risks of diabetes is that different people have very different likelihood to store excess weight in those places.

And so you describe that, for example, women before menopause are lower risk for diabetes because they tend to store their weight in almost anywhere other than the liver. But interestingly, as a man, you're saying almost the first place that I'm going to store this excess weight. And in my case, in particular, that's obviously very true, is like right in the liver.

And then it starts to cause all of these problems that interesting there are big ethnic differences and I think you described that anyone who isn't caucasian actually has significantly higher risk. And then there's further differences between ethnicity. That there's some online tools to look at this and we will share those links in the show notes so you can understand your own risk which are averages.

Because I think what we always see with ZOE is there's a lot of personal variation. But this is a free first step and then if it looks high you you should go to your doctor and check.

And then I think we talked about the fact that I think one of the things that's quite scary about this is that many people feel no symptoms. So you can have diabetes for a long time and this damage is starting to happen and you just don't even realize. Which is again a reason to really believe in preventive health care.

And then we talked about what to do. And I think the main answer is for many people listening to this is do what Naveed has done. So firstly, get a dog. Secondly, cycle to work. so basically find ways to be more physically active, you're saying, because it increases your muscles compared to just this very non-moving way we tend to be.

And try and figure out how to control your weight. Which, you know, is a topic we talk about a lot on other podcasts and we know is hard. But fundamentally, if your weight is just going up year after year after year, then you've got this, this problem. So physically active, healthy weight, so the right healthy diet.

[00:50:20] Naveed Sattar: And a lot of people need support on that. Obviously, yeah. Carry on Jonathan, sorry.

[00:50:24] Jonathan Wolf: Absolutely and part of what we talk, obviously a lot on the podcast is, is about this. And of course we want people ultimately to decide they'd like to try the personalized program that's really focused for them, which, which we talk about. 

And then I thought one thing you said that was really interesting is in your minds eye actually, what you want to do is delay diabetes in your perspective. If you got diabetes when you're 75, you're actually not too stressed about it, because it takes quite a long time for there to be damage to you. So it's not like having a heart attack when you get diabetes. It's more like a risk. And so you're saying, you want to push that out, because actually if maybe you're quite high risk, if you could push it out till 75, you're going to be okay. 

And then the final thing you said, which I thought was really positive, is you can reverse diabetes, right? It's not like having cancer or a heart attack. It's not a one-way street. Actually, by removing this fat out of your liver, you can actually get to the point where you don't have diabetes or prediabetes.

And I thought that was a beautiful, positive way to wrap it up.

[00:51:27] Naveed Sattar: Perfect, that's a fantastic summary, Jonathan. Yeah.

[00:51:30] Jonathan Wolf: Naveed, thank you so much. I know that we jumped over a lot of this very big topic, and I know you're doing a lot of research in these areas. I hope that I can tempt you back in the future and we can continue.

[00:51:42] Naveed Sattar: Delighted, yeah absolutely. Particularly whatever the feedback to try and unpick some of the other… Because obviously it's hard to go into very specifics. There are some variations in various things, but I've given you the broad picture for the vast majority of people in terms of type 2.

[00:51:57] Jonathan Wolf: We would love to do that. And we'll talk a lot more about the diet side of it as well of course, this being ZOE. Naveed, thank you so, so much for taking the time.

[00:52:04] Naveed Sattar: Pleasure.

[00:52:07] Jonathan Wolf: Thank you, Naveed, for joining me on ZOE Science & Nutrition today. It's been fascinating to learn so much about blood sugar, how type 2 diabetes impacts our health, and how we can prevent and even reverse it.

If you want to hear more insights from the podcast, you can download our free guide with our 10 most impactful findings by going to zoe.com/podcast.

And if, after this conversation, you want to understand your own blood sugar levels in more detail, and how they respond to the food that you eat, as I have done myself, then you can learn more about becoming a ZOE member and getting personalized advice about how to eat the best foods to reduce your blood sugar spikes.

You can also get 10% off your membership, again, by going to zoe.com/podcast. As always, I'm your host, Jonathan Wolf. ZOE Science & Nutrition is produced by Yella Hewings-Martin, Richard Willan, and Tilly Fulford. See you next time.