Diabetes Scientist Reveals What They Don’t Teach in Medical School…

So we're stuck with current standard of care, which is leaving greater than 99% with poor glycemic control. Lower insulin doses can improve safety in patients with type 1.

Unbelievable rates of obesity leading to what some people call double diabetes.

You improve your blood sugar while reducing your insulin dose by 43%, if I recall correctly.

If you have to choose between glycemic control and insulin, the very low carbohydrate diet is the most evidence-based or most studied strategy in the management of type 2 diabetes. That's remarkable. It's true. You should do something now. Don't wait.

And it is possible.

Just find resources along the way.

All right. We're back with Dr. Andrew Koutnik. If you didn't see part 1 of this interview, he gave impressive disclosures about his personal journey with type 1 diabetes that I thought were very insightful, whether or not you have type 1 diabetes. But just to review who we're talking to, this is Dr. Andrew Koutnik, a scientist and a patient with type 1 diabetes who does work with Harvard, Johns Hopkins, NASA, the Department of Defense. Really a stellar guy who is genuinely fueled by a mission to to make metabolic health mainstream and particularly passionate about type 1 diabetes care. So that's what we're going to be talking about today, discussing the broader literature, broader context, and what insights we can gain from that. So I'll just kick it off with our first question. What is the single biggest mistake and misconception when it comes to treating and managing type 1 diabetes?

That the discovery of insulin back in 1921 that won the Nobel Prize meant that we could do whatever we wanted, eat whatever we wanted, and get the same outcomes as our peers who didn't have type 1 diabetes. That has led to a false interpretation of this disease and ultimate recommendations back in the 1925s that ultimately led to guidelines in 1971 that have, I think, led patients down the wrong course., and arguably a suboptimal course, uh, along the way.

So I now want to define the scope of the problem. You shared a paper with me that was published in The Lancet in 2021 that 8.4 million people were living with type 1 diabetes in 2021, but that by 2040 that number might more than double over— so 107% growth, which is pretty alarming, the rate at which type 1 diabetes is increasing in prevalence And you shared another paper that blood sugar control in type 1 diabetes is getting worse, not better, despite advancements in technology like pumps and CGMs. So what's going on? Why is type 1 diabetes becoming more common, and why is blood sugar control getting worse despite advances in care?

One common trigger of this is what we understand right now revolving what actually causes diagnosis of type 1 diabetes. So there's a number of prior studies that immune triggers, so different forms of things that ultimately trigger the immune system and change them, can ultimately be causes of new diagnosis for type 1 diabetes. And every year we're exposed to these. We've had a big one that everyone's aware of a few years back. And so this is, this is one of the common described triggers. However, this is an autoimmune disease that people arguably get triggered and offended when you even think that it's a lifestyle-based diagnosis because every time you get type 1 diabetes, you go, you know, let's go to your family's house for Thanksgiving, and they're like, okay, so yeah, you're not allowed to eat this food. You're not— you know, is— aren't you supposed— aren't you thin? Like, why are you thin and have diabetes? You know, because of the confusion and confounding belief in the general public of diabetes as just type 2, or everything that is type 2 diabetes. So people in the type 1 community often get very upset and say, well, this is not a lifestyle disease. However, Nick We now have data that says that obesity rates are explaining up to 25% of all of these new diagnoses with type 1 diabetes, something that never used to— type 1 diabetes.

Okay.

Type 1 diabetes. And by the way, the rates of obesity in type 1 diabetes, a disease that used to be plagued by underweight or at worst normal body weight, Uh, we now see the same rates of obesity as those in the general population. This isn't a slow climb, Nick. This is an exponential rise in the rates of obesity in type 1. And so yes, we actually see that lifestyle factors are clearly associative of the disease now. And so even type 1 diabetes, an autoimmune disease that was believed to never have a lifestyle, uh, component, at least for a trigger, is now known to have risk related to lifestyle. And that's just one of the key things that we're starting to appreciate, but it just illustrates a broader picture that poor health is leading to triggers in, in a whole health diseases, not even just type 1, but even type 1 diabetes.

I have a lot of reactions and questions to that, but I do want to double-click on the idea that obesity is contributing to type 1 diabetes because I can personally attest, like most physicians probably don't know that. And there's a heuristic that, yeah, somebody presenting with type 1 diabetes will tend to be underweight. That's what you see in textbooks. That's what you learn. You learn it's early onset diabetes occurs mostly in children and they tend to be skinny because they're peeing out glucose and not processing sugar. So my assumption is that there's also maybe an uptick in the proportion of cases that are diagnosed later on in life. Is that accurate?

That's also accurate. So one of the, the another layers of why people— the incidence is also going, or let's say prevalence, this more accurate term, uh, of why type 1 diabetes is going up is because while the peak age of diagnosis is in childhood, 10 to 14 years of age, the average age of diagnosis is in the 30s. This is a disease that was called juvenile diabetes because it was only believed to happen in children. However, you can actually look back to the 1920s prior to the discovery of insulin and find examples of adults being diagnosed with type 1 diabetes at slower onset. Now, even 100 years later, today we have people who have type 1 diabetes who are often misdiagnosed for type 2 diabetes just because they see elevated levels of blood sugar in advanced age and assume, oh, you have type 2 diabetes. And oftentimes the lifestyle interventions and drugs that are given to people with type 2 diabetes also help control glucose in adults with type 1, which often have slower onset. And these adults with type 1 often have more residual beta cell function, where these drugs and lifestyle interventions actually allow for the retaining endogenous metabolism that's still intact with insulin to be optimized further. And so as a result, we do have a high level of misdiagnosis in type 1 diabetes that are now, through more awareness, being diagnosed as type 1 and what we call LADA, so a form of type 1 diabetes diagnosed in, in later in age, in adulthood. So that is also a contributor.

Okay, next question is the— even the way it's named, type 1, type 2, they sound mutually exclusive, but based on the way you're speaking, it seems like that might not be the case. Can you have type 1 and type 2 diabetes?

Based on what we understand are the metabolic problems of type 2 diabetes, yes, because type 1 and type 2 diabetes are distinct things diagnosed in distinct ways. However, type 1— patients with type 1 diabetes match in many critical ways that I'll outline. Number 1, type 1 diabetes have high and variable glucose levels. So do patients with type 2. In fact, average HbA1c and CGM values and fluctuations in type 1 and type 2 are actually much more similar, obviously, than, than, than they would be to people without this disease. Beyond glycemic control, patients with type 2 diabetes are historically known to have insulin resistance because that's, that's what defines the disease. Actually, DeFranzo, back in the 1980s, discovered that when you clamp patients using this advanced technique called insulin, uh, euglycemic insulin clamps, they discovered that patients with type 2 diabetes have an inability to bring in glucose levels with higher and higher insulin load compared to the general population. So now we're defining type 2 as insulin resistant. But what people ignore is in that same exact study, they had patients with type 1 diabetes and patients with type 1 diabetes younger in age, lower in body weight, without high adiposity in the intra-abdominal region, visceral fat, or high lipids or high amino acid and dis— and all these other forms of dysfunctional metabolism had the same level of insulin resistance. Not just high insulin, but high insulin plus resistance, just like type 2. So type 1 and type 2 are actually very similar. They both have high and variable glucose levels, but also almost ubiquitously in meta-analysis show insulin resistance compared to those without type 1 diabetes. But I think what you're asking, Nick, is can they have the phenotype of type 2 in type 1? And that means obesity. And yes, we actually see that patients— and actually also in a Lancet article illustrated that about 60% of the population with type 1 diabetes as of a year ago, actually 2 years ago, had the same rates of obesity as the general population. That is incredibly concerning because this is a disease, Nick, that already got 11 to 18 years in shortened life expectancy, already had increased risk for all-ten leading cause of death. We see atherosclerotic progression signals of this within 3 years of diagnosis— actually within 4 years of diagnosis in kids. We see brain damage related to dysglycemia within 4 years, so impaired neurological development in children on MRI scans in association with poor glycemic control. That the damage happens fast, Nick. But now You take all of that and you stack all the problems that obesity has on top of that, further complicating the issue. And so it's a huge issue here, Nick. And we also know in that same Lancet article, they actually looked at what, what are the recommendations given to patients. Nick, less than half of patients are told about nutrition. Uh, less than half of patients are even told about exercise. Uh, it's— or around half actually are told about exercise. Um, And the only nutrition they actually surveyed was should you eat low-fat, high-carb diets, because that was perceived to be healthy even as of 2 years ago, even for this disease. And so, yeah, we have unbelievable rates of obesity now leading to what some people call double diabetes, uh, in type 1, which is arguably way worse than just having type 2 diabetes or obesity alone. You have type 1 diabetes, which already had even lower life expectancy than type 2, and now you're taking all the problems of type 2 that type 1s didn't have and stacking that. Into the already complicated nature of type 1.

That's terrifying. Um, I'll actually disclose the reason I was asking the question is I was— I want to get to iatrogenic, um, hyperinsulinemia and injecting. But before I ask my question on that, because you were talking about the information that patients get or don't get, you shared another paper with me. It was a national study done in Canada where they looked at how much education dietitians got on prescribing low-carb diets. And the— this was a knowledge bomb for me, which was 75.6% of dietitians had little to no education on the clinical utilization of low carbohydrate diets. I just need your reaction to that because I read that. I'm like, holy crap.

Yeah, that was one of the most— yeah, unfortunately, yes. And it's, it's, it's— that number was shocking to me. I mean, it's an objective number. They actually looked at healthcare clinics at multiple sites. But it's very real. And it, it was higher than I expected because dietitians are an entire healthcare field around expertise in nutrition, and they lacked expertise in one of the most powerful therapeutic nutritional strategies that we know of, uh, for many diseases, particularly obesity and diabetes, both forms. And I say both forms, there is gestational, but I'm— we're talking type 1 and type 2 here. And so It's extremely alarming. In fact, that same study, Nick, also talked about how healthcare professionals, uh, dietitians don't even feel supported by their healthcare team to implement these strategies. It's a complex problem. And to bring some data to this, we've done a very large analysis, uh, that we're about to submit. And when you look at these low-carb, particularly very low-carbohydrate ketogenic diets, half of the reports from a systematic review of, of over 5,000 articles, and I've read all of them, actually, uh, legitimately all of them. And what you see is that on the low, very low carbohydrate end, uh, defined as less than 50 grams per day, technically in the ketogenic diet kind of definition as well, that over half of those reports, 17, showed that patients were doing these approaches with little or no healthcare support. Okay, so this illustrates— and I've had clinicians reach out to me and say, how do we do this? The problem is that we don't have guidelines that are institutionally backed to do these strategies despite record levels of patients doing this, which is why we know that entire professions like dietitians and beyond— Nick, by the way, endocrinologists, primary care— they don't have any guidance on how to do these strategies despite record levels of patients doing them and has led to a clear and evidence-based disconnect between patients and healthcare providers where they feel unsupported by their healthcare team. And unfortunately, the healthcare team isn't just not wanting to support them— sometimes that is the case because they feel a diet can be harmful due to misinformation— but also because those healthcare professionals don't have the resources. And that is an institutional problem.

We will get to that. I do want to call back, as it's just like shouting in my mind, to part 1 of our conversation where we're talking about your medical case report and the opening line, which was that less than 1% or fewer than 1% of patients with type 1 diabetes achieve normal glycemia. And yet you've been achieving it for like at least 12 years on a low-carb ketogenic diet. And then I asked you, do you think this is achievable for everyone? You said 100% yes. So I I want to emphasize that healthcare practitioners are not educated in how to use this tool that you and others like you have used successfully to achieve normal glycemia, and the effects are that 99+% of people can't achieve normal blood sugar levels even though it should be physiologically possible for anyone. Anything I misstated there?

It's all accurate, Nick, unfortunately.

All right. Now, I want to then return to iatrogenic hyperinsulinemia. So, to kind of just give a high-level overview, iatrogenic means harm caused by a medical treatment. And as we reviewed in type 1, you need to inject yourself with insulin, take a syringe, stab yourself, put it in, which is a different route of delivery than the body normally does. Usually your pancreas releases insulin via your portal vein, it goes to the liver, gets processed there. So why is iatrogenic hyperinsulinemia a problem?

Underappreciated problem, Nick, as well. Uh, I actually didn't know of it until I started studying metabolic health in great detail specific to type 1 diabetes, even having been in the metabolic space arguably for a decade and a half in the research world. This is a phenomenon where there's artificial elevations of insulin in the peripheral vasculature, which is distinct from the vasculature that feeds the liver, or the— they call hepatic portal vein. Now, when you eat food, uh, let's say someone were to go to a donut shop and eat a donut, you know, highly unrecommended, but let's just say they did it. And they ate this donut and they had elevations in glucose levels from the breakdown of the, the, you know, polysaccharide or polysaccharides into smaller and smaller components, ultimately individual glucose molecules. Immediately goes into circulation, and what happens? Well, the body takes that and releases insulin from pre-stored granules. Granules. So they already produce insulin, they're just storing them, waiting, waiting for that elevation in glucose in the beta cell.. And once they see the signal, the beta cell releases the signal, that insulin goes immediately into the liver vein. Why is that? Well, the body built this brilliant, beautiful system that when you obtain glucose, the first place you wanna store it is the one tissue that can save your life if your blood sugar got too low, because if you have low blood sugar, it can be fatal. And so it stores it in the liver. Well, the liver contains all the functional machinery to release glucose in low glucose or low insulin environments. Let's say a fast for multiple days on end. So it's life-saving and protective, but it goes there first, arguably well over 50%, up to 66% in a normal physiologic environment where you have insulin being produced. It would go to the liver, and the remaining 33% would end up in the periphery for muscle, fat tissue, and, and beyond. However, if in the context of type 1 diabetes because you're artificially injecting it into the peripheral tissues. I can't take a giant needle and stab it into my liver, like, uh, won't end well, Nick. And so we're stuck having to inject in the fat and muscle tissue. So on the back of my arm here, if your audience is watching, you'll see an insulin pod. That insulin pod is attached to the back of my arm. An insulin pod releases insulin into my fat tissue. What happens next? The fat tissue through blood flow that's reaching that peripheral tissue site, will absorb that insulin into the bloodstream. Now it becomes active. Now it becomes actually implicative on glucose levels. But there's this time delay between the periphery and, and to the blood, which has therapeutic implications. But to your actual point here, that elevation in the periphery, that we have discovered in and of itself causes insulin resistance. So high levels of insulin periphery, just like in type 2 diabetes, which is artificial due to the route of administration— type 1 causes the same level of peripheral insulin and the same level of insulin resistance in both populations. In fact, you can see insulin resistance in normal healthy individuals. So say we took Nick, we threw him into a clinical metabolic ward, and 48 to 72 hours after infusing insulin into his peripheral tissues, he's going to see the same level of insulin resistance that a patient with type 1 diabetes would see or type 2 diabetes would see. And we believe that's due to a number of mechanisms. But the, the long story short on this is that we do see insulin resistance due to route of administration, and it has major implications for cardiovascular health in patients with type 1 diabetes.

I want to take the long story short and maybe make it a little bit longer, because the question I genuinely had, not just for my audience but for my own education, was what are the mechanisms by which physi— you told me, um, off air that basically higher levels of exogenous insulin administration yields, you know, proportionally higher levels of insulin resistance. How does that work?

So we believe it works through kind of 3 main factors. Number 1 is the higher saturation of insulin at various tissues. Just like in many other tissues, when you have a high level of molecule that constantly touches a tissue, that we believe that, that you're downregulating key receptors that allow for that molecule to have an effect. The same philosophy of if you take coffee every morning and all of a sudden you have a dulled effect due to reduction in the amount of available receptors or some counter-regulatory mechanism to normalize your homeostasis. Same thing is believed to be happening in the peripheral tissues in type 1 diabetes, this downregulation of insulin receptors at key tissues like the muscle over time with higher levels. That's number one. Number two is we believe the pathway is disrupted both in animal models and actually in humans. Where we know that higher levels of insulin in the periphery can often be linked to these disruptions in the cells, let's say in the muscle cell or fat cells, of key molecules related to signal transduction of insulin. What does that mean? It means that when you have an insulin molecule bound to the receptor, it has to go through a process to actually have an effect. Well, some of those molecules called IRS-1 hexokinase and others are known to be dysfunctional in the context of things like type 2 diabetes. We know it's dysfunctional in specific populations. Like when I was at Sansum Diabetes Research Institute, we were studying, uh, Hispanic population because we know that there's a high risk of genetic alterations in some of these key intracellular insulin pathway molecules that disrupt phosphorylation and other key components of how you actually induce an insulin effect in the cell.

So kind of just to pause and let you get to the third one, but We are getting into the weeds here, which is usually, yeah, what I'm a culprit of. But just to summarize, basically you're saying, look, insulin, one of its functions is to get glucose to sink into body tissues, including the muscle, which is a great sink. So one thing that happens is the glucose receptors on the muscle tissue, they start to go away. So you're not sinking glucose. So then your glucose can actually get even higher, which is a problem. But also in order to trigger these adaptations, insulin binds to receptor and then you get a signaling pathway inside the cell. So I'm kind of doing things with my hand here. If this is the membrane, here's the insulin, binds receptor signaling pathway. The signaling pathway is getting cut off, at least to some extent. There's a bottleneck. So you have dysfunctional insulin signaling in the cell, and then the thing that's supposed to trigger is also getting downregulated, so you can't sink glucose. Those are 1 and 2, correct?

Correct. And the, the last layer to this, Nick, is that, you know, we believe that there's even— this is contextual to both type 1 and type 2— some degree of beta cell dysfunction, right? So if you have we know that high and variable insulin levels, but also hyperglycemia as well, can, can actually change beta cell function. We know that both high glucose and variable glucose and high levels of insulin can induce insulin resistance. And so we believe there's this other layer of the problem which is at the pancreatic level. Now, at Type 1, that's a little different, right? You already don't have that function inherently present, and so insulin resistance is, is usually tied those three things. But in type 1, the main things we think are actually happening is that it's, it's this downregulation receptor and then this dysfunction at the cellular level, um, that we know are often coupled with things like inflammation. Uh, you know, higher levels of inflammation with higher insulin load is often linked to— there's studies back to when I was doing my PhD, you could look 40 years back, 30, 40 years back, and actually look at how things like inflammatory cytokines directly disrupt phosphorylation, of the insulin receptor. And so we know that there's these interactions with other factors as well, but that's kind of trying to give a 30,000-foot view of how we think this insulin resistance is happening, not just in type 1 but actually outside of type 1 also.

Yeah, that's awesome. Um, really quickly, you had also mentioned to me, and some of this is in the newsletter that I, I did on you in particular recently, but that lower insulin doses can improve safety in patients with type 1. And you explained it nice and concisely and really clearly. Can you explain why You actually improve safety with lower insulin.

Anyone with type 1 diabetes will immediately learn quickly how complex metabolism is, particularly how variable and complex insulin sensitivity and resistance is within the day. Okay, like within the day itself. So let's say that you are about to eat, let's say, a standard highly recommended high carbohydrate whole foods meal. Okay, I'm being a little sarcastic here because I don't think that's actually what you should recommend for people with type 1 diabetes, Let's say you were to do that, okay? That high carbohydrate meal will ultimately cause glucose levels to elevate. You will know you will need a proportional level of exogenous insulin to regulate that insulin load, right? So to some degree, you would see changes in insulin load as well. And what is that change in insulin load actually doing? Well, it's going to lower blood sugar levels. But let's say in type 1 diabetes, that altered insulin level is now confounded by exercise. Let's say you go outside, it's hot outside, you go and exercise, you have increased heart rate, uh, all of a sudden you have this increased vasodilation, you have increased blood flow to peripheral tissues. Just so happens that you injected into peripheral tissue. Now that increased blood flow is going to pull that insulin into the bloodstream so much faster, Nick. And as a result, when it gets in faster, plus the altered insulin sensitivity of exercise, now you have this powerful additive and arguably synthetic or synergistic effect on how potent that insulin is going to be at every single meal or any single moment. So let's say you injected, you know, 5 units of insulin, Nick, which is actually not uncommon for like, let's say, a standard high carb meal, 5, 10 units of insulin for someone who's normal and healthy, quotes around it, in type 1 diabetes. Well, now you exercise or you're more physically active because all of a sudden you had to go run an errand or move outside because someone knocked at the door and you're starting to move more and et cetera, that 5 or 10 units of insulin can now act like 10 to 20 units because of the amplification of the speed of the insulin getting to the circulation, but also because exercise has a potent impact on insulin sensitivity. Imagine, Nick, that for some people, 1 unit of insulin can drop blood sugar levels 100 milligrams per deciliter. So imagine you're taking 5 units or 10 units of insulin and taking it to 10 to 20. The delta between the original dose and now this amplified dose due to sometimes predictable and sometimes unpredictable factors means a massive delta of the, the overall insulin impact of that dose. But let's say, Nick, you did a low-carb meal instead of a high-carb meal, and the amount of insulin you now require for that meal is somewhere between 1 to 2 units. Well, now that 1 to 2 units, due to unexplained factors, is acting like 2 or 4 units. Well, the delta, instead of it being 5 to 10 fold higher, is now 1 to 2 higher. And the implications of that on blood sugar control and safety are massive.

So just to kind of summarize, maybe with a goofy analogy, people might think for someone with type 1 diabetes, you see an apple. Apples are variable in size, but let's just imagine, let's make it easy that all apples are the same size. Okay, now you know the carb count in the apple. You can match it with a dose of insulin for your body, which you figured out. What you're saying is there's all these other variables, exercise is just one example, but that toggle how the carbs and the insulin interact in your body. So it's almost like if you're not paying attention to all of these, which is impossible, you're taking your carb and then you have a roulette wheel with every meal and you just spin it and there's a multiplier on the roulette wheel. And every time you're going to get some multiplication. It can be anywhere from say 1 to 10, right? That's going to have a dramatic impact on your body because if you overdose, quote unquote, you could go into severe hypos and end up in the hospital. So what you're saying is lower doses of insulin reduce the noise. So you're reducing the multiplying factor. So like, you know, if a 10 times impact could be very dangerous, you'll never roll a 10 on the roulette wheel. It gives you security against that. That's basically what you're saying, right?

I've never heard anyone explain it like that, Nick, but it's brilliant. It's so accurate. It's, it's because roulette wheel illustrates the danger and the variability and uncertainty, and that's real. It's very, very real, which is why patients often preference towards hyperglycemia and live there. The average blood sugar control for someone with type 1 diabetes, uh, on the average is 180 milligrams per deciliter with a fluctuation above and below the mean of 120 milligrams per deciliter unit. They avoid normal control because of these— if you have higher insulin dosages often associated with higher levels of glycemically impactful foods like carbohydrates, that means higher variability, and it also means you're at high risk. So what's more damaging right now, Nick? Hyperglycemia or a potentially fatal hypoglycemic event right now?

Hypo.

Exactly.

Yeah, you don't want to die right now.

Yes. And so often not just the patient will preference that, but also the physician will recommend that because, God forbid, you're, you're risking going low all the time, and that's, that's life-threatening. And so patients live in hyperglycemia all the time, and hence why the complications and risk are as high as they are. But of course it doesn't have to be that way. But the interaction between insulin variability, insulin dose and the complex nature of daily lifestyle variability on those factors is why, and one of the key reasons why, arguably not the number one reason why, choosing a nutritional strategy and lifestyle that minimizes the insulin dose can be a profound safety tool in the management of type 1 diabetes.

So just to emphasize this, putting it in the context of your story, which we reviewed in our prior episode, we didn't get to this, you improved your HbA1c by not following ADA recommendations and going keto, kind of almost against standard advice, you not only improved your blood sugar, but you improved your blood sugar while reducing your insulin dose by 43%, if I recall correctly. So that is a double whammy for better health. I just— you can react to that, you cannot react to that. That is almost just— you can refute me, but I think that's a fact and an underappreciated one, that you're having this added benefit of not having chronically high insulin levels.

It is the most underappreciated aspect of type 1 diabetes. Before, in this conversation and in part 1, we discussed how the rates of body weight have exploded to— the rates of obesity with elevated body weight have exploded in type 1 diabetes. The reason that's happened, Nick, is because we have studies, some of the most expensive long-term 30-year trials over 1,000 patients with type 1 diabetes illustrated that giving more insulin just to get slightly better glycemic control— not normal glycemic control, far from it, but just even slightly better— dramatically reduced cardiovascular disease risk, risk for all 10 leading causes of death, uh, particularly microvascular disease. So diseases of the eye, diseases of the kidney, diseases of the nerves. We saw it dramatically improved it despite higher insulin load, showing the predominant number— what prominent nature or priority nature of glycemic control in type 1 diabetes over other risk factors. However, Nick, these high insulin load, which are ubiquitously associated with insulin resistance in type 1 diabetes, is contributing as well. Which is why if you look at data on risk in type 1 diabetes in this large trial and you see the, the curve, it goes down, it goes down precipitously as you get closer to glycemic control. But the hazard ratio never goes to zero, Nick, or never goes to 1, which means an illustration of a neutral impact on risk related to not having disease. It never goes to 1, it stays around 2. Why is it staying around 2? Well, I speculate because of insulin resistance. If you don't ever normalize insulin levels back into normal range, you will never reduce that risk on overall cardiovascular disease. And this was a study looking at cardiovascular risk and mortality. And so it's an undeniable fact outside of type 1 diabetes that insulin resistance complicates the disease. In type 1 diabetes, it's inherent you have insulin resistance for most patients unless you control insulin dose. And an effective therapeutic strategy is one that not only arguably normalizes, or at least dramatically improves, glycemic control, but also dramatically reduces the insulin load. Because it's not just, hey, here's, here's my insulin, I want to use less medication. Well, yeah, there's a cost factor there too, but it's also because that every dose you give in type 1 has much more impact, multifold more impact on your overall metabolic health because it's, it's going to the peripheral tissues and leading to a much more powerful response on insulin resistance. Which is also why when patients are given fat in non-diabetes scenarios they often don't see much of a change in insulin. But in type 1 diabetes, they see a direct dose-dependent impact on insulin needs because we know that things like fat at high levels can alter sensitivity, not to, let's say, liver, but more so to muscle. This is why the nuance in metabolism is so particularly important and why type 1 diabetes can teach you quite a bit about how metabolism works.

So simply put, in summarizing, the standard line is eat carbs like a normal person, cover with insulin. And you're saying if you have to choose between glycemic control and insulin, glycemic control is most important, but you don't, to pardon the, the saying, you can have your cake and eat it too. You can have good glycemic control and low insulin doses via maybe a non-standard approach, in this case therapeutic carbohydrate restriction, a ketogenic diet for type 1 diabetes. With that said, I want to get to my like kind of last line of questions, which is about guidelines. What can you tell us about guidelines and national dietary recommendations for patients with type 1? Are they evidence-based? What's the evidence? Are they appropriate?

So the most recent dietary guidelines around nutrition and diabetes in general come from the American Diabetes Association Diabetes Care. Most recent one was 2019 by Everett et al. And what you see in there is that they describe that the very low carbohydrate diet is the most evidence-based most studied strategy in the management of type 2 diabetes. That's remarkable. It's true. It reduces HbA1c, it reduces body weight, it leads to other powerful changes along the way. Guess how much they talked about type 1 diabetes in that article, Nick?

How much?

Zero times about how nutrition impacts type 1 diabetes, even though type 1 diabetes, I would contend, and I would be up for a debate at any time, is is arguably the one disease where nutrition affects it more than any other scenario, where what you eat directly impacts medication dose at every meal of every single day. And even outside those meals, you're chronically managing how nutrition interacts with metabolism. And so in this case, there was zero reference to nutrition in this, in this guideline paper. I have worked with endocrinologists who do ketogenic diets themselves, because it clearly improves glycemic control for many patients. And we know that there's emerging evidence on observational analysis of over 300 patients from Harvard, where you're from, Nick, showing that you can achieve normal glycemic control if you do particular approaches, at least survey-based data, observational in nature. But I'm also a lived example of this as well, so I, I don't sit here and refute that that's possible. Obviously I know it's possible, I live it. And so when you consider those things, you would think, wow, patients are doing this at record rates. We're seeing emergent evidence that it could be extremely powerful. In fact, Nick, it was standard of care for over 200 years, over 2 centuries ago. It was standard of care for not just type 2 diabetes but type 1 diabetes. This is not a new thing. This isn't a lack of, of clinical, uh, awareness that this, this can work, or there is now because we've lost generations of scientists and clinicians who've done this approach decades, or not just decades, but centuries prior. But those guidelines lack any, any description of type 1 diabetes. In fact, I spoke to many of the leading institutes and alarmed them of the high rates of use of this, the clear disconnect that it has led to between clinicians and patients. Patients are often doing this rogue, and that there needs to be guidelines to address this. In fact, it was mentioned in an American Diabetes Association webinar, that I was invited to present on nutrition. And so this is not an unknown thing, it is a known thing. But the problem is that due to a lack of resources in federal nutritional funding and support, we don't have the same volume of studies looking at long-term randomized controlled trials in type 1 diabetes nutrition. That's lacking. And so as a result, they have specific criteria for guidelines. It isn't what's the weight of the evidence, it is are there long-term randomized controlled trials, and we're going to discuss those and that's it. And so as a result, we're not able— or institutional bodies who make the guidelines for how clinicians have to practice, if they go outside of that they're in danger for their licenses— don't provide guidance on type 1 diabetes despite me raising the alarm bell for 4 to 5 years. And so as a result, we wrote guidance on this for those individuals. I had so many people Uh, and not just obviously for myself, I'm a patient and a researcher studying this disease, but we had endocrinologists, we had dietitians, a whole team of people was reviewed by over 11 individuals, often with lived experience with type 1 diabetes in the healthcare field, actually treating patients, uh, to provide guidance on what to do nutritionally for patients who are doing this approach, just to give some type of guidance for healthcare professionals at all on what to do. But yes, they failed. And Nick, I wanna add something very important. The American Academy of Pediatrics, the leading body in pediatric medicine, giving guidelines around what kid— what pediatric— pediatricians and what kids should do, uh, for management of disease, talked about type 1 diabetes. And they actually did talk about it, and it did address it, and they recommended against it. So what they instead recommended is an approach that standard of care reliably increases, uh, neuroanatomical dysfunction, reliably leads to neurological impairment through developmental ages reliably leads to dysglycemia and also almost near immediate brain damage, early signs of atherosclerotic progression. And all of this is happening in kids. And so impaired growth—

I'm gonna pause you for a sec because what I just heard from you was what the American Academy of Pediatrics is basically saying is, hey, our way sucks, but we have RCTs on it, so do it.

No, they didn't even do that, Nick. What they said is, hey, there's these hypothetical review studies that described the potential risks of doing these diets without citing any primary literature whatsoever and recommended against it. So they didn't cite any of the studies that actually directly assessed it. They just cited review studies that did not— they cited zero primary literature on type 1 diabetes and very low carbohydrate diet to justify the claims that they should be not only extremely cautious but potentially recommending against this approach. And children with type 1 diabetes. And keep in mind, Nick, what kids are experiencing right now on average is impaired growth, reduced IQs, neuroanatomical changes, and early signs of atherosclerotic progression with standard of care approaches. And here we have is a, is a nutritional strategy that's been around for 200 years as standard of care. There's emerging evidence that allows for normal glycemic control, the primary risk for everything I described, and they're recommending against it without citing a single form of primary evidence. This is not me picking a fight, Nick, or trying to be controversial. This just me telling you facts and that we should do better for our patients, for healthcare providers to give them better guidance. Because yes, parents are actually called for, called on by healthcare teams for doing this approach as, as basically they're called family services on parents. This has been cited before. This has actually happened. Parents have had to go to court to justify a nutritional strategy they're giving the kids for better glycemic control. That's shameful.

So what you said with respect to the term emerging evidence, We're referring to is things that, like, aren't the, quote, gold standard randomized controlled trial. And I think this is really important for everybody to understand what Andrew said earlier about how guidelines are structured. You need a certain type of evidence, but that evidence doesn't always exist yet because we haven't done the trials. There can be several reasons for this. Sometimes certain trials are not plausible. So for example, I can't really do a randomized controlled trial on diet for Alzheimer's disease because you need to do it for like 30 years and you Can't really. You definitely can't do a— say, oh, people like, oh, you want a double-blind randomized control trial. You can't even double-blind, you know, a study on diet. So there are practical limitations, and then there are— sorry, there are like, yeah, the practical limitations. Then there are economic and financial structures that preclude our ability to do certain studies. So in the metabolic health space, this is commonly a problem, which means there's an absence of the type of evidence that one would need in order to recommend a certain approach. So there can be this huge division between what actually works best and what might be supported by like physiologic logic and even like uncontrolled trials. So take your, your, your case report. You are a case where you achieved, you know, the, the top 1% in glycemic control while reducing insulin for over a decade. It was 10 years in the report. You're probably now at 12 years. If, correct me if I'm wrong, but let's say we had that study multiplied by 10,000. Let's say we took 10,000 patients and prospectively observed them on a ketogenic diet and intention to treat, let's say, so like all starting it, all achieved perfect glycemic control. That still wouldn't be an RCT, so it couldn't be ranked in the guidelines as high-quality evidence or sufficiently high quality to recommend it as standard of care. Am I overstepping or is that actually accurate?

That's, that's accurate, Nick. And it, it's also really important to highlight that when describing risk, it's very different, right? So, uh, keep in mind, medicine, in medicine, the, ethos is first do no harm, despite the absence of doing greater good. And, and that's— it doesn't mean that first do no harm is not a good ethos. It's a brilliant ethos. It's simple. It makes sense. It shows the, the need to, to first help the patient. But the problem is that that also applies to these guidelines. It's risk mitigation. Uh, we can't recommend this because we don't have the gold standard evidence, but yet we can't evaluate other evidence to illustrate that this could be a therapeutic strategy that, you know, there, there might be hypothetical risk, but the potential good is so profound. So oftentimes it's first do no harm despite the potential to do great good.

Yeah, I think I, I don't like the term first do no harm because it's, it's a nice virtue signal, but it doesn't actually mean anything because in clinical medicine it's always a cost-benefit analysis. If it's first do no harm, You wouldn't give patients with cancer chemotherapy. Chemotherapy harms. Might also kill the cancer and save their life, but it does harm. So first, you know, harm isn't actually that valuable a statement. It's always a cost-benefit analysis. Um, I, I do want to double-click and ask you— I said it, but I want to hear from you— what financial and economic or other incentive structures preclude the widespread adoption of low-carbohydrate and ketogenic diets for patients with type 1 diabetes? Well, the one—

the biggest one is what we just described, which is I don't think anyone's trying to prevent anyone from doing these diets to get better outcomes. I think the reality is that we're not distributing resources to understanding at the same level that is required to get guidelines what's actually happening with these diets. And so it's a, you know, you have pharma companies who are on the track to make hundreds of millions, maybe billions of dollars off therapeutic interventions. And so they will fund trials at will using gold standard evidence to get FDA approval. But where is that incentive in nutrition? We don't have that same approach. Like, where, where is that? The federal government would have to provide those incentives for, uh, the kind of industry community to have the same level of interest to do nutritional-based approaches as they do for pharma because of the financial benefit for doing that work. So they need to incentivize that as well. We don't have those same incentives, uh, there. Beyond that, there's a clear when you go to the— when you change your diet, Nick, it can have powerful medicinal and therapeutic impacts. But you're essentially saying, I'm going to the grocery store, and it could be a neutral cost. You literally are flipping what you're doing when you already— you have to buy food. I mean, you can't go forever without eating something, so you have to go to the grocery store, you have to get food, and you're essentially flipping what you're choosing there And so it can be a near-neutral impact, but there are massive, massive costs related to devices, medicines, technologies, which cost the average patient with type 1 diabetes around $18,000 per year. So food is, is essentially a swap on a financial cost and also can, in this case, the one— the nutrition strategy we're talking about, this ketogenic diet strategy, can lower medicinal costs because you're using less insulin. Often we're often using cheaper forms of insulin also for those who are doing these approaches. And so you're, you're reducing that layer of cost. And so who's there to promote this? Who's here to— I mean, as you said in the very first part of this interview, uh, in part 1, who, who are the advocates for making change? Well, everyone's an advocate if they're making money. But, you know, in the industry, like, they're all about advocating for that. If you go to the American Diabetes Association meeting, uh, like plastered over everything, you can't miss it. Uh, frankly, you go pee and they'll put a TV in front of your face that says, here's the new drug by Eli Lilly and Novo Nordisk. And I'm a fan of these drugs, by the way. I wouldn't be alive speaking to you, Nick, if those companies didn't produce the insulins that I currently take. This is just me illustrating that where, where's the money to put a placard that says, hey, look, this nutritional strategy can help you too? It's just not the same thing. Awareness is, is built by, uh, honestly, financial components. You know, you can't, you can't work for free forever. You have to— it costs money to market. The American Diabetes Association meeting wouldn't happen without sponsors. And so it's an awareness component. Uh, it's also both from an industry perspective, but, you know, also all the way to like where people communicate science is, is highly influenced by who's paying for that science communication to happen in the first place.

So just to emphasize what Andrew and I are saying here, and I, I think we are on the same page about this, we're not saying anybody's evil or out to get patients with type 1 or patients with diabetes in general. We're just saying you need an incentive structure in order to motivate the research that will make low-carb keto diets, which might work the best for type 1 diabetes, better than standard of care, make them standard of care. There isn't the incentive structure. So research isn't done, it can't be recommended as standard of care, so we're stuck with current standard of care, which is leaving greater than 99% with poor glycemic control and probably overmedicated in terms of iatrogenic hyperinsulinemia. That's the state we're in. My final primary question, um, you mentioned in part 1 that in 2013 when you started a ketogenic diet, you went to your doctor's office. And they were shocked by your A1C of 5.5%. They said they'd never seen anything like it. Turns out they were the president of the American Diabetes Association at the time. If you could now speak to the president of the ADA for 30 seconds, like get the next 30 seconds of airtime, you have a message to speak straight to them, what do you tell them?

We need to look at the weight of the evidence for what could be a profound therapeutic strategy in type 1 diabetes that no medicinal and technological strategy has ever had the potential of reliably achieving and bring guidelines that allow for the weight of the evidence to be discussed and guidance to be provided to not just help the patient but to guide healthcare practitioners who are and went through decades of education to help patients. They're not here to hurt patients, they're here to help patients, and we're failing both of them right now. And we need to do something about that immediately. And by the way, it might be helpful if you also fund research that gives us better answers and context and nuance on how to optimize these strategies.

All right. That's an excellent answer. For everybody knows, I didn't prime Andrew. That was a, that was a hot seat answer. Um, well, thank you for, uh, spreading your wisdom and knowledge with my audience. We're gonna link your website, andrewkutnick.com, in the video notes along with all your socials. Um, any final words, call to action, things I should have asked that I didn't, that you want to speak to?

Yeah, you don't have to accept the outcomes that you're expected to get in type 1 diabetes. That's ridiculous. You, you can do better, and it often requires, uh, obtaining resources, looking for evidence-based information, and charting a course for yourself. Sometimes, uh, even if it means you're an N-of-1 and going outside the norm, uh, you don't have to accept anything other than thriving, and 100% achievable, and I hope that all patients realize that and feel empowered to do something about their situation, not to sit back and hope that quote unquote a cure is going to come and fix their problem, which is what unfortunately is often marketed to gather support in many ways, which is we've yet to see. And so you should do something now. Don't wait. And it is possible. Just, just find the right resources along the way.

I love that. I should let that be the last comment, but I actually have one more thing to say, which is I've been admiring for both parts of our interview, the artwork on the wall, "I love you, Dad" and "Dada." And I just have to say with medical conditions like this, it's like, it's not just affecting you, it's affecting your loved ones, your ability to be a parent. I have to give you a moment to speak to that.

Man, Nick, I, um, sorry. Yeah, man, um, yeah, it isn't just about me, Nick. It's also about, um, my wife who slept with me in the same bed since, you know, for for quite some time now. We've been together for over a decade, and she used to wake up every single night, and, and still does sometimes because of the pattern, uh, related to it, uh, because I, I would, uh, alarms would go off and she would have to check it. And, um, it doesn't— yeah, it doesn't just affect you. I want to be around for the rest of my life. I want to live a full life. I want to live a healthy life for my kids. I want to show them example. My sons are at infinitely higher risk than everyone else is for getting type 1 diabetes because I have it. And I hope to be an example for them that you, you, you're not just going to get this diagnosis and be stuck with this, um, what feels like for many people debilitating and overwhelming, but you can be not just as healthy as your friends, but healthier. You can achieve amazing things. The insights you will have from this condition, if you choose for them to be, can be some of the most powerful insights on your own personal health journey. You will have access to two of the most important molecules, not just at a single snapshot, but 24/7 for the rest of your life. And it can empower a health journey that can give you more information objectively on how to improve your health than any other disease, any other condition can. And in that way, it can be the ultimate asset. Which hopefully can help others. So it's, it's, it's super personal for me because I've met parents who will do anything to take the disease away from their children and want to do everything to empower their children. And that's why I, I speak about this, Nick, because I, uh, it's not helping my career to speak about this. I could promise you that. I'm doing this because I believe it's important and I believe that we can do something to dramatically improve outcomes in this disease. And I refuse to sit back and not say anything about it when we can do something.

I have goosebumps. Um, sorry for springing that on you. I'll cut the end if you want me to, but that was awesome. All right. Thank you for joining us. I'm sure there'll be a round 2 at some point in time. Bye.

Appreciate it, Nick.

Thank you.