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Hey everyone, it's Mikki here. You're listening to Mikkipedia and this week on the podcast, I speak to Dr. Catherine Crofts, all about insulin. When we think about detecting metabolic disease, most of us picture the usual suspects, fasting glucose, HbA1c, maybe even an oral glucose tolerance test. But decades ago, a Chicago pathologist named Dr. Joseph Kraft showed us something extraordinary.

00:30
that insulin often goes haywire long before blood sugar does. Over the course of thousands of glucose tolerance tests, Kraft mapped out insulin responses and revealed a hidden epidemic of what he called diabetes in situ, metabolic disease brewing silently in people who still look normal on paper. Today we know this work matters more than ever. High insulin responses don't just predict type 2 diabetes, they underpin many of the chronic conditions we see across modern life.

00:59
Yet, Kraft's insights were overlooked for years, partly because medicine leaned so heavily on glucose as a marker of disease. And today I'm speaking to Dr. Catherine Crofts, who spent her PhD exploring Kraft's unique database. And we talk all about how this came about. And she's here to unpack what it means for early detection. In this conversation, we explore why Kraft's patterns are so important, how often people have normal glucose but abnormal insulin.

01:27
and whether we might one day use shorter, simpler tests in the clinic. Also, what about if we can actually detect hyperinsulinemia earlier, years before glucose rises, what practical advantage would this give us in protecting long-term health? Catherine is a deep thinker and such an expert in this space. She would be one of New Zealand's foremost experts in insulin, and I loved having this conversation with her. For those of you who don't know Catherine, and to be fair, probably you don't because she is

01:56
behind the scenes doing the work. Dr. Catherine Crofts is a pharmacist, researcher and lecturer based in New Zealand at AUT University with a special interest in the early detection and prevention of metabolic disease. She completed her PhD at Auckland University of Technology where she analyzed the extensive insulin assay data collected by Dr. Joseph Kraft, shedding light on how abnormal insulin responses can precede changes in blood glucose by many years.

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With a background that combines pharmacy practice, clinical research and teaching, Catherine brings a rare blend of practical experience and scientific insight to the conversation around metabolic health and diabetes prevention. Now I have put a link up to LinkedIn for Catherine. She does say she's not that active on social, but just so you can put a face to the name and of course head on over to AUT University website and you can connect up with her there.

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Before we crack on into the interview though, I would like to remind you that the best way to support this podcast, hit the subscribe button on your favourite podcast listing platform. That increases the visibility of Micropedia, and it makes literally thousands of other podcasts out there. So more people get to hear from guests that I have on the show, like Dr. Catherine Crofts. All right team, enjoy the conversation.

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excited for this because I've been wanting to talk to you forever about insulin and I don't know why it took me so long to contact you Catherine so thanks so much for taking the time this afternoon to chat to me. Naki thanks for having me along. So let us kick off like you I feel like you're actually tell me Joseph Kraft which is what your original PhD research is based on is he still with us? No he died in

03:46
2017, he was 94, thereabouts, when he died. I caught up with him in 2014 and spent some time with him and his son, Kevin, in Chicago. And Kevin told me that he reckoned his dad hung on long enough for me to finish my thesis, get it submitted, and to graduate. I did send them a copy of my thesis.

04:16
That is fabulous. Cause it feels like Catherine and you, and of course I want to ask you about how you even sort of came across Joseph Craft's work, but I feel like you sort of took a life of his work and really sort of brought it back to the forefront of how, how a large subsection of people now think about metabolic disease and possibly without you that might not have happened, which is pretty remarkable. is, it is many respects. And you know, I'm now the kaitiaki of that database.

04:46
um It's there for me to protect, to preserve, to use ethically and responsibly to carry on his legacy. And he said a number of times to me that he had passed the baton, he had passed the torch to me to keep his work going. So I do look at his work in different ways, um but that's what we do to our Kamatawe. We take their work.

05:16
respect their legacy, but no one person can do everything. So we build on that. So I'm absolutely building on his legacy. Yeah. And so tell me, how did you even sort of come across his work in the first place? Cause we were at AUT together at the same time when this happened. Of course, I have no idea how that happened. All I knew that there was Catherine Croft who is a pharmacist. And I knew from you from sort of that realm and your interest in low carb high fat. um

05:44
I'm pretty sure that came before your thesis, although I did it not. uh Okay. uh So my master's thesis, I'm going to take you back a little bit. My master's thesis was actually around, so as a pharmacist, my goal is to get people off the pills or better yet, prevent them from starting the meds in the first place. For me, it's just wrong to be telling somebody in the mid thirties,

06:11
they've now got type 2 diabetes, hypertension, cholesterol disease, whatever, and these are the medicines you're going to have to take for the rest of your life. And when people were taking their medicines and things were still progressing, and they'd be telling me they were doing everything in the guidelines, I was either internally going, somebody's being deluded somewhere and I don't know where that is because I don't

06:39
you are, this is happening, or this is a progressive disease, imagine how fast it would be progressing if you weren't doing this. And so those people, I now humbly go, I'm so sorry. We were wrong. Okay, we were wrong. But I was working to the best knowledge of what I had at the time. Then I got involved with these women triathlons. So I'm back at 2004 here. And I joined

07:08
I'm not an athlete. I'm never going to be an athlete, but every now and then I give it a try. I got involved with a bunch of women. We all training for this very, very basic triathlon together. was a woman's only spirit of competition, but not competitive. 300-meter swim, 10K cycle, 3K run or walk. Could be done as an individual or as a team.

07:36
And a lot of people had to train hard in these events to walk three kilometers. And I joined this training group, 12 weeks of training, but the health and vitality in these women, especially some of them, from the beginning of the training program to the end of the training program, it's like chalk and cheese, but they also had this vitality around them and we were all going.

08:04
wow, we did it, what's next? And I carried on doing a few more of these events over the next few years. And you start seeing the people have been at the last event to this event and so forth. And I started talking to more more of these people, they're all women. And they're all telling me about how the event has improved their health. mean, one woman had lost nine zero kilos over three years because of these events.

08:34
So I now wanted to work out what it was about these events that was improving people's health. I'd done my postgraduate diploma, clinical pharmacy. Didn't want to go on and do a master's for the sake of doing a master's, but I wanted to figure this out. So I went and spoke to Skoller Pharmacy in Auckland, because I wanted a local supervisor. And they couldn't really help me. It wasn't really their thing. They told me I should go and talk to Skoller Public Health at Auckland University.

09:02
didn't know anybody about that, wasn't given an introduction. just didn't, yeah, I don't know anything about that. Went on the back burner. Couple of years later, so I'm talking about this to another friend who does triathlons. He said, you should need to go and talk to Grant Schofield about AUT. I spoke to Grant because you know Grant, he had me enrolled a week later. Yeah, it sounds like Grant. Yeah, it does sound like Grant. So my master's thesis though was actually about women, physical activity.

09:32
And what it was about the physical activity had improved their health. It was challenge, it was competition, it was being involved, was social groups. It became identity.

09:44
That was actually my original idea for my PhD thesis. I was actually going to look at different levels of physical activity and how it worked for health because the big thing that came out of my master's thesis was that women were not achieving 30 minutes a day on five or more days of the week. By definition of the time, they were not sufficiently physically active. But mine...

10:11
God, when they were able to go out and exercise, they were racking up the minutes. So they were getting well and truly that 150 minutes of moderate physical activity, which is the reference we now use. But at the time, they were not considered sufficient physically active. So my original PhD was going to be around, does it matter if you're getting 30 minutes a day on five or more days of the week or large chunks?

10:40
of like the weekend warrior type. Absolutely. They were going to be one of the groups I was going look at. think it was going to be the people that go to the gym, team sports, and weekend warriors like the cyclists.

10:57
But in the middle of that, Grant and I forget his PhD student at the time, they come back from Vanuatu. Grant starts talking to me about low-carb.

11:10
I was sort of going, Grant went through the Atkins diet early 2000s, was low carb, it's all non-prudent then. Why are you revisiting this? But what about the, and I sort of went, actually, I don't know enough about the physiology. I don't know enough about the biochemistry to really be to refute this yet. Right, give it to me what it is you're reading. I'll take it away. I'll go and refute it. That book was The Art and Science of Low Carbohydrate Living by Viola Caffini.

11:38
I spent the next three months reading it, going through the references. I was one of those, I was grumpy. I'm going, you're now major cognitive dissonance here. I can't repeat what you're saying, but it goes counter to everything I've been taught. So it took me forever to read that book because I'd hit, you'd be reading through, line of cognitive dissonance, but there was a reference. I would now look at the reference. I would have to...

12:08
probably go back another three references to understand what I was reading and dig out a biochemistry textbook and a physiology textbook. I'm going, if I've been duped, I'm not going to be duped again. And so it kind of all co-developed. And so what was coming out at the time is the thing that I could not reconcile was this thing called insulin resistance. How did insulin resistance mechanistically cause all of these things? Because how did the

12:38
At the time, insulin resistance was basically defined as the body's inability to uptake glucose because we're all thinking that type 2 diabetes is still a disease of insulin deficiency. There's not enough insulin to uptake the elevated glucose. Which is what's causing the insulin resistance. But because I've been duped with so many of the other things, I think it was after I started see of the lipids and I'm sort of going, well,

13:05
That's obviously not true when you look at it. Physiology, what is it about this? And I was determined, um never interrupt somebody who's absolutely hyper-focused on trying to find the answer to a problem. I was absolutely determined to get to the bottom of this. And so I was reading the literature. I was reading the gray literature. I was reading everything I could. I was trying to find this.

13:33
And there was a couple of papers that stood out. There was a 1999 paper, I forget who by, but in the abstract, it talked about the compensatory hyperinsulinemia with insulin resistance. Hang on, what does that mean? And went back and through it, and which made the light bulb start going off going, hang on, we have disease states with hormones where there's a disease of not enough and a disease of too much.

14:04
Thyroid, hypothyroidism, hyperthyroidism. Adrenaline, you can end up with depressive states or you can end up with frantic agitated states. Corticosteroids, Cushing's disease, Addison's disease. Insulin, hang on, what actually is the normal reference interval for insulin? What's a healthy amount of insulin? How much are we giving people?

14:34
We are people with type 2 diabetes. We give them as much as they need. How much is too much? What's going on here? So when I started again going into that sort of stuff and trying to break it down and trying to understand it, the data was coming up short because most of the studies when they had looked at insulin stopped at the two hour mark because that was where we got glucose up to with the oral glucose tolerance tests. And I know we actually need to know what's happening longer than that.

15:03
And I remember trying to plan my PhD budget, $4,000, around trying to do an oral glucose tolerance test, but we're extending it out to four or five hours.

15:16
And I haven't got the money for it. And I'm not going to be able to find the money because this is such a fringe area. Yeah. Nah, I'm granted any money in slush funds at this point. So the next thing was, has somebody done this before? Can I find somebody else's database and have another look at this?

15:38
very difficult to find. And I have not been able to find it since, but I found a bulletin board reference. You know, that was the agent's chap. Chap, bulletin boards. It was a really old one. There was a tiny snippet in there, it's about Joseph Kraft's diabetes epidemic in you. Right, Joseph Kraft, okay. And Google that. And I find his book, Diabetes Epidemic in You, 2008, or ah 2000.

16:06
That one would have been the 2011 and I'm doing this in 2013-ish. And the picture on the back of his book, okay, I don't know when that picture was taken, but it was probably in his 80s or something because you got this really vital looking man. Find his paper, 1975, okay, 50 years ago.

16:31
I don't know how old he was when he was doing this, but if he was a young resident, he's often doing this sort of research, he'll only been his 60s, 70s now. So, I'm mentioning this to Grant says basically, what have you got to lose? Try and get a hold of it. So I emailed the publishers of his book and asked them to pass on my email and they did. This is how I forgot hold of Dr. Krapp. It was a message on a bulletin board.

17:00
But it was also me who was chasing all sorts of rabbits down rabbit holes, ah doing an awful lot of reading because it was grumpy. So in all honesty, serendipity, we found it. It certainly sounds like it, particularly because even 12 years ago, the search functions and just the ability to get anything off the internet, that just wasn't the way it was, even only 12 years ago. But my goodness, Catherine.

17:30
So then can you just sort of describe to us what it was, what was your PhD research? What did you find looking at Joseph Craft's work? And then from there, what does it tell us about how we should think about HbA1c? Okay. There's quite a lot in that. So let's just unpack that slowly. So what my thesis was about was what is this thing called hyperencelemonemia?

17:59
Because we've always been taught that type 2 diabetes was a disease of low insulin. We'd never been taught that there was a disease state around high insulin. But we've got all of these papers that danced around insulin resistance. But when you look at insulin resistance, mean, Raven, the father of metabolic syndrome, where insulin resistance is a big part of metabolic syndrome, because 12 years ago,

18:28
it was a lot about metabolic syndrome. He was the one to say metabolic syndrome is meaningless because it's still a collection of symptoms and you can identify those symptoms with something else. So we're identifying the person's got insulin resistance because of these symptoms. So for me, it was a case of, right, could those symptoms actually then all stem from high insulin? Because if your insulin is high,

18:56
you're more likely to become insulin resistant. And that is like, as I explained to my students, it's like saying you're working in a call center. People have said you need to the radio on music playing to improve productivity, but you're talking. You can't hear the music playing. So you talk louder. Now you can't hear the music. Music gets turned up.

19:23
Talking gets turned up. Something's gonna fail at some point, and we're gonna say it's not working hard enough, and the voices will go first normally. uh It's the same thing. What's happening in the body, and this starts happening 20 years before glucose goes up, is that the glucose can't get into the cells for whatever reason. So the pancreas produces more insulin, gets rid of the glucose.

19:51
But whatever the body system is that's causing glucose levels to not get in cells gets worse. Pancreas produces more insulin. It gets worse, pancreas produces more insulin. Pancreas can only produce so much insulin and it might start failing a little bit, but the body systems are also getting worse. So what we see and measure is the glucose going up. And we say the pancreas is not producing enough insulin.

20:19
Whereas in fact, the pancreas is actually kind of a super producer, but the result is we're seeing high levels of glucose. Because the pancreas basically gets to this point when it cannot produce any more and it starts failing first. Yeah, it's overloaded. You've worn it out. It gets, you know, they can actually measure the fact that it gets bigger and it produces a lot more insulin, but it can only cope so far. You know, it's like having a small engine in the car and you're trying to get it up bigger and bigger and bigger hills.

20:48
That engine ain't gonna work. what did Dr. Craft's work show you, Catherine? So what it showed me was

20:59
a lot. Now, one of the things that most people have trouble understanding about the body, and this includes an awful lot of physicians as well, is that usually when we go for a blood test, when do we tell you to go for a blood test? Something's wrong. No, no, it's not. I'm sorry. I mean, literally time of day. Oh, morning. Fasting. Why do we want people to do that? Because we want you at steady state. We want you your body at rest.

21:30
yet insulin, when it's being released, isn't when the body is at rest. It happens when the body is under load. And the biggest thing that the Kraft database showed me, I've sliced and diced it in a number of ways, one of the big groups I looked at is I pulled out the people with normal glucose. And I analyzed the people with normal glucose.

21:59
And can you define that? Catherine, do you remember what the parameters were? Quick overview of the CRAFT database. Dr. CRAFT sampled as many people as he could in Chicago between the mid 1970s to the early 1990s. He put them all through a four to six hour oral glucose tolerance test with insulin also being collected on a regular basis. So it was two weeks of what he called high carb therapy, 150 grams per day for two weeks.

22:29
In total or? Yeah, a minimum of 150 grams of carbs a That's really low really now. But that was considered high carb at the time. Yeah, funny. And overnight fast. Then the next day it was coming. First lot of blood is taken. Drink 100 grams of glucose or equivalent if you were a child. Then further blood samples taken at 30 minutes, 60 minutes, 120 minutes.

22:57
180 minutes. That's three hours, four, five, six hours, depending on how you're doing and what your physician wanted. Okay. And he got healthy volunteers as well as everybody referred for this test.

23:13
So it was a wide collection of people. ended up with about between 14 and 15,000 people in this test, okay, over those years. So then when I did, and he analyzed the glucose, he analyzed the insulin. And in this book, he just spoke about those two measures. But when I received this CD from him, he said, you'd send me CD, he'd think it had 300 files on it. So I was thinking it had the files for 300 individual tests on it.

23:43
It had 300 files on it. One of those files was a very large database. But the, I know it's a of a tangent, but one of the cool things about this disk when it arrived, the CD, it arrived in DOS format, pre-Windows. I couldn't read it. I had to give it to IT to find me a translation program. Oh, amazing. So IT says, you know, need to keep the disk. Do understand how precious this disk is?

24:13
But when I got home a couple of hours later, they said, yep, we can do this, no problems. Here's the largest file. So I opened it.

24:25
scared the cat. My husband came and running going, what, what's going on? I couldn't talk to him because we also had height, weight data that Kraft never analyzed. Oh, amazing. Yeah. So with the stuff in there that he'd never looked at. Yeah. So what I did was separate it down, look at what we had. And then I brought out the people with normal glucose tolerance. Now I use the World Health Organization

24:54
oral glucose tolerance test guidelines for what was normal glucose tolerance, impaired fasting glucose, diabetes. These days, what would happen is we'd use HbA1c to use those numbers, but we would lump impaired glucose tolerance and impaired fasting glucose in the same group, call it pre-diabetes.

25:24
but it depends on what your fasting glucose is doing and what your two hour glucose is doing. So I looked at the people who consider to have both their fasting and their two hour glucose at World Health Organization levels. I can't remember what those numbers are off the top of my head. I think it's under six at fasting.

25:49
maybe five and a half at fasting and under seven at two hours. Yeah, that sounds about right. And that is millimiles per litre.

25:59
Sorry, forget the milligrams per deciliter off the top of my head. Multiply it by 18. so I just focused on that group. And in Kraft's cohort, depending on what you call impaired insulin, somewhere between 50 and 75 % of people with normal glucose had impaired insulin. And the telling thing was,

26:30
when that glucose peaked. Sorry, the insulin, when did the insulin peak? Because for most people, healthy people, insulin is low at peaks between 30 to 60 minutes, and it is back below baseline at two hours. With people with hyperinsulinemia, the peak wasn't just getting higher,

26:58
So more insulin being produced, it was being delayed to two hours or later. So there was no initial insulin response or it was very low for longer before it started to rise? Pretty much, yeah. And it varies depending on the person. But what it means is when you look at the fasting insulin, you actually can't tell who's in a

27:27
healthy insulin group and who's in an unhealthy insulin group just by looking at their fasting glucose. Fasting insulin. Sorry, fasting insulin. Okay, this is interesting. So, because I've had a number of conversations with people about fasting insulin and some people swear by it in HOMA-IR. That's, you know, that's one of the... I'm very familiar with HOMA-IR, HOMA-2, Macaulay Index and a number of other tests based on fasting insulin.

27:54
That was the rest of my thesis. I looked at a lot of those things in my thesis. Yeah, totally. And the listeners might be familiar with it, but it literally is like a, if you have a HOMA, IR, is it over one? You're insulin resistant is how they do it. But actually what you're saying, it's sort of meaningless. Well, it is and it isn't. Okay. Okay. So this is the challenge. If your insulin is high at fasting, yep, no brainer. You've got hydro-insulinemia.

28:24
So, but it's very labile, isn't it? It can like, if you ate very late at night and went in and get it, or if you didn't eat, then you can change it. I'm going to correct you on that one. Yeah, please do. Because this is what I've heard from other people I've chatted to on the podcast. I don't consider that to be labile. mean, glucose goes up, you eat something, your glucose goes up. Insulin is a reactive hormone. Okay. Its main job.

28:54
is to keep your glucose in very narrow levels. Now you tell me all of the things that can affect your glucose levels. Lack of sleep, stress, exercise, inflammation, autoimmune response, carbohydrate. Right. So your insulin is going to fluctuate with all of those things. But if we just have stress driving to work in the morning, some days it's no stress at all. Yeah. Other days it seems like

29:23
Everybody on the road is out there to hit you. All right. Combine that. Now, if you've got a day where everybody's out there to hit you, your stress levels go up. Your insulin's going to fluctuate to change with that. So your insulin is always reacting to fit what is going on in your day to keep your glucose level.

29:48
Your insulin is reactive. It's always going up and down. And it's worse than that because insulin is released from the pancreas every two to three minute and bursts. It oscillates. It goes up and down. It's always gone up and down. I mean, I've had people come up to me at conferences and I try and be so nice and polite and they sort of tell me, my fasting insulin was, isn't that number fantastic? I smile and say, yeah, absolutely was.

30:17
But inside I'm going, what was it five minutes later? Your insulin can change dramatically in five minutes. People don't know this, Catherine. Doctors don't know this. I spoke to the likes of Dr. Ted Naiman, and you will know that shirtless doctor on X. And he's like, I don't really look at insulin because it changes all the time.

30:46
sort of elucidate what it was about it. And he just sort of talked about the night before, but not, you're saying literally not minute by minute, but almost. oh So there's this saying, so one, somebody has studied this and I've got the name off my top of my head, but I've got the reference. He said, really and truly what you need to be doing, if you want a fasting insulin level and you want it to be accurate, you need to take three levels.

31:14
five-minute intervals, so zero, five, and 10, an average of three of them. But that doesn't completely take into account what's happened over the last three hours. Because you cortisol, know adrenaline, what you've eaten, what you've exercised, it's all going to change things as well. Now somebody else I've spoken to who, his name escapes me, but an experienced physician in this, he does a lot of fasting insulins, but he doesn't do them

31:44
once a year when it's people. He's doing something like once a fortnight and he's tracking trends. If you're taking them that frequently, I can see it working. If you're doing it as a once and done, no, sorry, not actually getting anything. You're not getting anything. So if you want to do a once and done, the time to do it is two hours after the main meal of the day.

32:15
or a normal large typical meal. Because what I found in my research and as I analyzed this and I ran hundreds of calculations manually, because I only just starting to learn about the sophisticated modeling type programs. This was all done through Excel. I ran hundreds of what we call sensitivity and specificity calculations. If I use these parameters, will I get a craft one five pattern?

32:45
or will I get a CRAFT 2, 3, 4 pattern? Okay. And you can explain to us what they are. So a CRAFT 1 pattern is what I would call a healthy insulin pattern. It's uh your insulin's got a low fasting level peaks between 30 to 60 minutes, not too high, back down to an acceptable level at two hours. Okay. So it's two plus three. So it's the sum of the second and the third hour. Nobody would like to do the five hour test. So I wanted to find something simpler.

33:15
Can I work it out? So what I did was decided that, right or wrongly, this is where I did it, that craft one, healthy. Craft two, start saying your insulin's going up, but it might also be slightly later. But your two plus three hour sum is later. Craft three, your insulin is peaking two hours or later. I don't care about the rest of it. Now anything else could be happening, but the peak is two hours or later.

33:45
Craft three. Craft four is you've got a sky high fasting level.

33:54
C.C.R.A.F.T 5, all levels are below 30 international units per mil. Okay. And C.C.R.A.F.T, that was a hypo-insulinemic response. So, your blood sugar would likely be elevated in that instance because… It could be elevated in that instance for a variety of reasons, especially type 1 diabetes, because in C.C.R.A.F.T's database, he did not distinguish between type 1 and type 2.

34:26
So there's limitations to his database. When you understand the limitations, we work with them when we work forwards. So he didn't say in his database who was type 1, who was type 2. I've had to make those inferences. So somebody who's got a very low insulin response and a high glucose response, it's probably type 1. And about 8 % of the database worked out that way, which fits in with the maths.

34:53
that 5 to 10 % of people with diabetes have type 1. Yeah, yeah, makes sense. Totally makes sense. Yeah. So, you know, so it wasn't just an arbitrary thing. I it back to help us in what we expected to see. But people who've been on a low carbohydrate diet for a significant period of time would also have a suppressed insulin response.

35:20
So Kraft's methodology included, if you've got a normal to low glucose response and a low insulin response, it's likely you've been on a low carbohydrate diet. So you need to go and try that two weeks, increase your glucose to 150 grams of glucose a day, come back and we're gonna do this test again. Come back, we're repeating. That's why I've gone with my methodologies for um doing a

35:49
insulin assay, it's a minimum of 150 grams of carbohydrate per day for two weeks before the test. But people have been low-carb-ing. I don't like them doing a craft test because they've got their insulin under control. Do we really want to muck that up? But a suppressed response might be pancreas insufficiency, but it might be also, you haven't eaten enough carbs recently.

36:19
And how would you decipher that? Is it by just talking to the bit like self-report, yeah, I'm low carb or is there other tests that might Self-report is usually a good start. But it's also, if your glucose is high and your insulin is low, I'm going to send you off to the doctor under suspicion of having type 1 diabetes. So if you've got high glucose and a suppressed insulin response, I'm concerned. Okay, that's my health professional hat on, I'm a pharmacist.

36:49
glucose looks pretty good, but your insulin is suppressed. Now I'm suspecting, because I'm suspecting your pancreas is just challenged by the load. So it also can happen that if people have been suppressing their carbohydrates, know, very low carb diets, their pancreas just can't wake up enough in time. And they actually go one of two ways. They've either developed

37:19
peripheral insulin resistance, it's acute physiological insulin resistance, it's normal. The body's just going, yeah, we're hungry. So we're going to divert the glucose into the bits of the body that need it most. Or it's just going to go, whoa, we got glucose, open up. And so I can't tell just from the blood where you fit. So yeah, we'll ask about symptoms, but if you've got high glucose, suppressed insulin.

37:48
I have to refer. So Catherine, like just for the listeners, um well, the first thing, I mean, we've both mentioned it and I'll just say it again that 150 grams of carbs is pretty low considering that back when the National Nutrition Survey done was 2008, 2009, I think that average carbon takes for women were maybe

38:12
I'm going to say 320 and men were 360 or men were 320 and women were 260 or something. So it's 150 just for the listener's perception. It's actually not that high. Oh, it's extremely long. Yeah. this was also, remember America in the early 1970s. Right? If we think about the food that was eaten.

38:40
in the early 1970s was very, different to what we eat today. Yeah, yeah. Right? If we go back to a fresh, plain, simple, whole food diet, it was before the times of, I mean, you know the dates and things better than I do, but when were breakfast cereals really being promoted? Yeah, yeah. No, I hear you. Post the heart attack of that president that then made everything go low fat.

39:10
Was that Eisenhower? Yeah, maybe. You'll be right. I'm not good with names. that, again, though, was the mid-1960s. Yeah, so not too far over. But if you think about the American um dietary guidelines, when were the first ones those come in? That was either the late 1977s? Yeah, yeah, yeah. And then the... This was all done prior to that. So this was when America still had a high fat diet, mostly.

39:39
Right. yeah, then 150 grams of carbs a day was considered high, but that was normal for the time. So that's one of the big things I have to do when I'm interpreting any of the work, because a lot of the work done on insulin was done in the 60s and 70s, some in the 80s. I've got to interpret it with what was social history, what was sociology at the time, what was normal at the time.

40:08
We can't extrapolate craft's work onto modern society. Yeah. And my other, and I guess for the sake of the listener, like, I think one of the questions I asked you, which it's great because you've unpacked it, like, so what does this tell us when we go to the doctor and we get our HbA1c, which is the standard marker of long-term sugar control? So what would you infer from your knowledge?

40:36
Okay, so one of the things I get asked a lot is, should I have an insulin test? And my standard answer is, your HbA1c is greater than 40? No, you do not. You can assume your insulin is high. End of story.

40:52
If your waist is more than half your height, you're gonna see a murincia on the side.

41:00
But yeah, and there's a few other markers like this. mean, if you've had uh two pregnancies with gestational diabetes in each pregnancy, chances are, unfortunately, your insulin is now high. We don't have to test it. If your glucose is more than about nine or 10 at any point in time, your insulin's probably high. So on a CGM.

41:26
if it's after a meal and it's nine or 10, your insulin is probably high. Could be. Yeah. But if we can just add into that, if you've got type 1 diabetes and you're using more than about 50 units of insulin a day, your insulin is high. With type 2 diabetes, it's really hard to tell because we don't know how much your pancreas is naturally making. But if you're using more than 50 units of insulin a day, your insulin is high.

41:56
Don't get a test at this point. There's no point. oh Because most of the tests, as I said, if we don't test you at two hours after your meal, we can't tell what's going on. But the other great tests that I'm recommending people do these days is before your evening meal, test your capillary glucose and your capillary ketones. So a blood, oh a stick.

42:26
Or if you're using the CGMs and can now get the CKMs, continuous ketone meters, you want to know what your ketones are doing. one of the things I've now gone on and done a lot of is looked at the physiology of what insulin does that's not related to glucose.

42:45
And one of the things that we do know is that insulin stops your body from making ketones. Right? It's just not, it's normal body physiology because when your ketone starts getting too high, they actually trigger release of insulin that says stop making ketones. But also if your body's got too much glucose floating around, we've got to get rid of that because that's actually really damaging to your blood supply.

43:13
You how glucose is sticky? You spill the honey, you spill the jam, you spill the soda. It's really sticky and messy to clean up. That's glucose. It's sticky. So you've got a lot of glucose in your blood supply. It sticks to stuff, your proteins, your HbOa1c. That's how we measure it. It's the glucose that's stuck to your hemoglobin. But it's sticking the tiny little capillaries. It sticks the walls together.

43:41
That's how get peripheral vascular disease. That's how we get heart disease. That's how you get erectile dysfunction. So.

43:51
Insulin, we don't want ketones in the body to be available as fuel if your glucose is high. So insulin, when it gets released, it tells the ketone producing part of your liver to stand down. And the other parts of the body that produce ketones stand down. We go offline. We don't need you at the moment. Do that often enough, you have problem making ketones, which is why we get keto flu when you go into ketosis.

44:20
And what happens though is that if you can keep your insulin low enough, you will make your ketones. If you get to the end of the day and your glucose is under control and you've still got 0.3, 0.5 millimiles per litre ketones sitting in your blood, you've kept your insulin under control all day.

44:43
People who don't have any ketones in their blood have got high insulin. Yeah. Okay. And then how does this relate to the tests that we do get done like A1C? And you've mentioned above 40. And for, my, my understanding of it is that 40 is slightly arbitrary. And in fact, if you're up at 37, 38, 39, this isn't good either, but

45:11
What does, yeah, so sort of describe to us what an optimal HbA1c might be, which might also indicate. Say that again. Below 37, according to Ken Tsikaris, quite some years ago, it may have changed. But he said the risk of having a heart attack started increasing if your HbA1c was over 37. So 37 to 38 should be the ideal. This is good.

45:40
but we still don't know what the insulin is doing. And we also have to remember that HbA1c, what it is, is how much glucose has stuck to the hemoglobin over the last 12 weeks. And we use 12 weeks because that's the turnover on an average person of um blood cells. Now, if you've had a of a hemorrhage, blood donation, ah or your body,

46:10
naturally keeps onto its hemoglobin for longer or has a faster turnover, you might not be a 12-week person. So you're quite right. A lot of stuff that happens in medicine is arbitrary. Type 2 diabetes, the cutoff is 50 as long as you're symptomatic. Otherwise, you could have a couple of blood tests at this level. But what really is the difference between 48 and 50?

46:38
It's a spectrum. They put the arbitrary lines on it, basically for hospitals and budgetary reasons. We can't medicalize everything. But for your listeners, if they're concerned...

46:54
There are no medications, no medical treatments that will treat high insulin, especially if your glucose is high. We cannot lower the insulin in somebody by the way, by means of medication, because we can absolutely do that, without causing other major problems.

47:18
Insulin is needed for your nerves to work right, for your bones to work right. It causes all sorts of other signaling around the body. We don't want to upset those things. Yeah, cool. Yeah, because I guess that's the thing, right? Is insulin is essential and it does more than just control glucose. It's, Glucose is not essential to, well, actually glucose is essential to life, but eating glucose is not essential to life. Oh, here's a fun fact for you that you might be really interested in that I discovered fairly recently. Yeah.

47:46
You know how there's debate about the brain needing glucose? The brain absolutely needs glucose. Catch this, it doesn't need it for energy. Okay. Okay. So we have these things in the body called glycoproteins, glycolipids. So glucose or a glucose chain or a byproduct of glucose is stuck to the protein or the fat.

48:15
It does things like bend it into shape. It causes channels. It makes your enzymes work properly. need the 70 % of the proteins in the lipids in the brain have got glucose stuck to them. We need glucose as a building block, structural component for every single cell in the body. But most cells don't need it for energy.

48:44
That's a surprise. Yeah, I thought you'd be interested. Yeah, because of course, when I talk to people about brain and brain energy, I'm like, brain needs glucose for energy, is what I say. And then I'm like, but your body produces glucose. And then if you're not eating carbohydrate, it'll just preferentially deliver it. But, and this is the but, because I often talk to people about brain energy in the context of concussion,

49:13
or traumatic brain injury or cognitive issues. And I'm like, well, that's an issue with glucose metabolism. And so we need to bypass that and use ketones. So what's going on there? But the brain is still using the glucose to repair the structures that have been damaged. go. Yeah. Right? Because all of that stuff in the brain, rapid turnovers for stuff, the brain is constantly breaking things, like the rest of the body, it's constantly breaking things down, building things new.

49:42
Right, there's so many things that rely on glucose. If you're rebuilding things, every cell that's being made needs glucose in it, for structure. And that cell needs energy to make the proteins, to stick the glucose to it, to bend it all into the right place, which is why a lot of the cells actually prefer to use

50:09
aerobic glycolysis over and above oxidative phosphorylation. It's not fit energy. It's just the byproduct of the aerobic glycolysis becomes a building block, like the retina of the eye. Glucose is critical to build components of the retina of the eye. And it happens through aerobic glycolysis. Glucose, through that, the byproduct is an important structural thing.

50:39
So yeah, glucose is critical for the brain, but not for energy. And I think sometimes if we separate out the energy from the structure, people understand a bit more as to what's going on. And then, so okay, so in that instance, this is a bit of a tangent really, how do ketones help, the provision of ketones help when, and make people feel...

51:04
cognitively clearer how I know that obviously ketones work as a signaling molecule reduce inflammation, but I mean, uh yeah, explain that to us. Okay.

51:16
Give me a second to have a think. Right. You've got a house in the middle of nowhere. The house is made of wood. You can have an iron fire, but your fuel is wood. Your house is constantly being damaged. You have to repair your house. You also have to stay warm. You've only got a finite supply of wood.

51:45
And wood is not necessarily the best thing necessary to burn in the fire to keep you warm. So the wood is our glucose. We need it to build the house and to energy to keep us warm. Now imagine the ketones are the coal. When we burn the coal, we get a different amount of heat and actually we might end up with fewer ashes. Now that might not be technically correct. is the analogy. Yeah, yeah, yeah. Right. So it's kind of the same thing in the brain.

52:14
we've got glucose that the brain can use to repair itself for structural components, or it can use it for energy, but there's a finite supply. When we bring the ketones in, the brain can divert all of the glucose back for structural components, and the ketones burn cleaner with less waste product. So you don't have to use up as many

52:44
vitamins, minerals, micronutrients to manage the damage being caused by burning the glucose. And you can funnel all of those things in into clearer thinking, repairing structures faster. Oh, interesting. Yeah. Totally makes sense. um So Catherine, and I know, and I'm looking at the time and I, and obviously we're, well, obvious to me at least is like, this has been such an,

53:11
insightful conversation about insulin. And I've got about 50 other questions, which I'm not going to be asking you today, because I don't want to overwhelm everyone. But I think from a practical perspective, then you mentioned that your waist to height ratio, your triglycerides, was that another one that could? that's definitely I didn't mention that one. That is another good one. You want your triglycerides to be as low as possible, ideally below 1.0 millimoles per liter. Okay, cool.

53:41
That's great. then you also... carbohydrates are the main driver for triglycerides. So it just helps to reflect metabolic health within the body. It's not necessarily a direct market. It's very indirect, but it can definitely be a good one. Yeah. Amazing.

54:05
With that in mind, and of course you mentioned that you can't just shut insulin down with a medication the way you can provide medication for other things. So in your experience, what is the best way to get insulin back under control? You got to get the glucose under control first. Okay. Okay. So, you know, it's, if you can get, so, so there's two things around glucose. One is what we eat and the other is what the liver produces. Okay.

54:35
and the two work together. And the biggest problem with type 2 diabetes is the liver doesn't get the stop making glucose signals. So it's producing a lot of glucose because I'm being told to stand down. So pancreas is producing insulin in response to the amount of glucose around the body. Might not just be to the highs, a low amount that's constantly there.

55:05
is also going to make your body produce a lot of insulin. So if you want to get your insulin down, you've got to get your glucose under control. And there are so many ways to do that that um it's individual preference. There is no one true way on that. Obviously, big part is decreasing the amount of carbohydrates people eat. That's a big one. But intermittent fasting can also do

55:35
a really effective job. mean, if you think about the hummingbird, it drinks nectar. It stops up on the glucose during the day, gets a very, very fatty liver during the day. But overnight, it burns all of that fat out. And so its insulin is actually not a problem because it's a managed system. So fasting is really important. Exercise.

56:05
is really important. The bigger our muscles, the more glucose we can burn. Right, so it's a combination of a variety of things, but it's also making sure we've got all of the micronutrients. We're eating nutrient-dense food because that gives us all of the co-factors for being able to do these things properly, reduce the inflammation. It's about getting decent sleep. It's reducing our stress levels because one poor night, you you get a few nights of bad sleep.

56:35
pushes up your stress, absolutely messes with your insulin the next day. Also drives you to eat the high carbohydrate, low value food from the vending machine at three o'clock in the afternoon. Yeah, and love it even more. Yeah, because it's a dopamine reward and your body's going, I was desperate for this. And it is on a physiological basis. go back 300 years, that wouldn't be around. It would be a huge trend. So there is no one true way there.

57:05
Okay. No, that's awesome and interesting. um I don't know if you've heard of this. Have you heard of the sugar fast diet? The sugar diet? Tell me more. I may have heard of it, but in concept, but not in details. Okay. So it's doing the rounds on X and on Instagram right now. And in fact, I'm about to today and it would be published before this comes out, do a little mini-Micipedia on it, which is just like a little solo 10 minute episode describing it. Essentially people eat. ah

57:35
fruit, fruit juice, honey, maple syrup, sucrose, so table sugar. so they eat, that's all they eat during the day, upwards of five, six, 700 grams of sugar. Then at night, they have lean protein at about 0.5 grams per kg body weight. So less than the RDI and maybe one third of what protein metabolism experts would suggest. And they, and then very little fat, like around 20 or 30 grams of fat.

58:05
And people lose weight on high calories doing this. The mechanism I found this fascinating is potentially an increase in FGF1. So fibroblast growth factor one, 21, 21. And so it increases, it makes our mitochondria super inefficient. And so we burn more energy. Legitimately, this is what, it's a low protein load that does it. Super interesting.

58:35
I can see it working in the short term. Yeah. I can see it making a right mess of people in the long term. Yeah, interesting. There are people out there who only really eat fruit. I believe Steve Jobs was one of them. And I believe he ended up with something like pancreatic cancer and bringing it back to that. But the way, though, I also tell people about appetite and appetite regulation, because this is the other mechanism I can see working for that thing, is

59:05
I'll say to people, if I give you a bowl of sugar and a teaspoon, how much of that bowl of sugar could you eat? I feel sick thinking about it. Not much. Yeah. Most people say, can't eat much because it will make me feel sick. Same bowl, same teaspoon. This time it's just filled with butter. Nothing else, just butter. How much of that bowl could you eat? And I usually say the same thing, maybe a couple of teaspoons and I'm going to start feeling sick.

59:34
Same bowl, flour, but I'm not gonna give you a teaspoon because you'll just choke. Gross. Right. Now, mix that bowl of flour, butter and sugar together. What have you got? Delicious cake mixture that I used to eat when I was about seven or eight and my parents were out. Delicious. Technically you've got cookie dough, cake mixture had the eggs included. It's true. But how much of that bowl could you now eat? Oh, so much. Yeah. I'd be looking for more.

01:00:04
What happens is in the brain, appetite regulation, when you mix sugar and fat together, you override appetite controls. And when you think about the foods that people have challenges with, it's sugar and fat together. Now, can you tell me which is the most common food in nature that has a high amount of sugar?

01:00:34
and a high amount of food in at the same time. Oh, there's none. There is one. Is there one? Yeah. Which, what is it? Milk. I was thinking you were meaning naturally occurring from the ground, but you were just meaning in nature. In nature, milk. The best growth. Why do we want mammalian babies to drink lots of milk? Because we want them to grow. And if baby, for whatever reason,

01:01:02
is struggling with their appetite, by overriding their appetite control, we've overfed them, which can potentially have huge benefits in a baby for keeping the species going, whether it's a baby cow or a baby human or a baby whale. So your sugar diet, you've separated out the sugars from the fats. So there's a number of diets. The rice diet would be one. Ornish diet was one I'm thinking of.

01:01:33
It was super low fat. Is that X-Teen or is that... Dean Ornish. Pardon? It was Dean Ornish. Yeah, and another guy as well. sure. Yeah, yeah. Same thing. Basically the same thing. Essentially those diet extremes that um remove, well, in this instance, protein as well as fat. Yeah. When you've got that much sugar though going, you're going to raise your insulin load.

01:02:02
that's going to cause problems. might be lowered out overnight. can see this diet, as I said, can see this diet working with some people. I can see a lot of other people having major problems with that. Yeah, it's interesting. I mean, and just to finish off, like the diet itself hasn't been studied unsurprisingly, because it's one of these diets, but it's sort of been, the mechanism has been suggested looking at research on uh very low protein diets.

01:02:29
And that's what the increase of the FGF21, the mechanism for that. So that's super interesting. But I would also be looking at who responds and who doesn't respond and what are their factors involved? Because I suspect there is a difference there. Yeah, there is genetic variants in people who express FGF21, oh people who have obesity, I believe are lower as well. Not just that, I would be suspecting

01:02:58
their metabolic status coming into the diet, whether they were good fat burners, good sugar burners, I suspect that might actually also play a part coming in as well. agree actually, because the, and again, this is just social media, and this is you and I just chatting about it, but the people who are doing it are actually already quite lean. You know, like there are the people who are lean getting leaner, not necessarily, and they're exercising, whereas, yeah, which is quite different from someone who's struggling to lose

01:03:26
20 or 30 kilos and was looking for that solution. There's a lot of people out there who are desperate to lose some weight so they can get their knee replaced or their hip replaced or something, but they're too overweight to be safe for surgery. They've been told they've got to lose weight before they have the surgery, but because of their uh inflammation and the damage done to the knees and hips, exercising is really difficult for them.

01:03:56
I would hate to see somebody like that trying that sort of diet. I just can see it go badly wrong. I agree. It was interesting because I was looking at it for the mini-micropedia and I thought, oh, I might just ask Catherine if she's heard of it. I haven't heard of it, but I can correct it. Catherine, so we're to have to finish up there. I really thought that was like a 101, but also like a 401 in terms of insulin. And I will actually...

01:04:23
hopefully get you back on soon to talk about that paper because I'm super interested in that as well. You sent me a whole lot of questions that we could be talking about. It's a whole lot of fun stuff there. I wish we had that. Yeah, amazing. I'd be delighted to come back and have another conversation with That is awesome, Catherine. So I don't know that you're on the internet as much as I am, but I do think you're on X. can... I'm not on X very... Look, my social media dropped off a lot fairly recently.

01:04:52
Yeah, I'm not on social media as much as I used to be. Yeah, okay. But we can find you on ResearchGate. Absolutely. And I'm on LinkedIn. I'm on ResearchGate. I'm on LinkedIn. em Every now and then I do a presentation like this and somebody else puts it up on YouTube. Fantastic. And I'm debating about a sub stack. Oh, you should. You should. Yeah, I'm debating about that, but I've got to find a bit more time. No, I appreciate that. um

01:05:21
Catherine, I will put those links up in the show notes and we will connect to figure out another time for you to come on soon. Thank you so much. This has been really illuminating and also conformational in some ways, but also I love learning stuff and I knew that having you on would allow me to do that as well. So thank you so much for that. Thanks for having me.

01:05:51
Alrighty, hopefully you enjoyed that and literally I think I got two questions in and that's where the conversation had to stop because we were going so in depth. So I've got Catherine on again next week to talk about how this relates to diet, evolution, history and all those really important topics. So Catherine is back with me next week. Until then though guys, you can catch me over on Instagram, threads and X @mikkiwilliden.

01:06:19
Facebook @mikkiwillidennutrition or head to my website mikkiwilliden.com. See you next week. Bye.