Blood Sugar's Role in the Brain - with Dr. Melissa Schilling | The Empowering Neurologist EP. 21

Hello, I'm Dr. David Perlmutter, and welcome to The Empowering Neurologist. I was recently reading the Journal of Alzheimer's Disease, and I came upon a very interesting study that relates Alzheimer's risk to some of the things that go on with type 2 diabetes, specifically the mechanisms that are involved in insulin and another chemical called Amylin. And I looked up the author of the study, Professor Melissa Schilling, and I was very surprised at what I found. Dr. Schilling is a professor of management and organizations at NYU, New York University Stern School of Business. She teaches courses in strategic management, corporate strategy, technology, and innovation management. And before NYU, she was an assistant professor at Boston University. And she has taught strategy and innovation courses at Siemens Corporation, IBM, the Kauffman Foundation Entrepreneurship Fellows Program, and she is widely recognized as a global expert in innovation and strategy in various high-tech industry applications. Her research in innovation and strategy have earned her awards including the National Science Foundation's Career Award and Best Paper in Management Science and Organizational Science for 2007. She is widely published in a variety of very well-respected management journals, and she did receive her Bachelor of Science in Business Administration from the University of Colorado at Boulder and received her Doctor of Philosophy in Strategic Management from the University of Washington. So again, you know, the real question is, what did I just say that would qualify this individual to write such a compelling paper relating Alzheimer's to diabetes? I think you're going to get the answer to that. I'm really looking forward to this interview, so here we go. Well, hello, Professor Schilling.

Hi, thank you for having me.

Well, let me— I explained in the intro that I read this really exciting article in the Journal of Alzheimer's Disease that talks about Who knew this relationship between diabetes and Alzheimer's, both in terms of risk, but also mechanistically, which I thought was really super cool. And, you know, truthfully, I expected that would have been coming from a physiology laboratory or a clinical laboratory somewhere. And look what I found. I found you that— who had written that article. And I explored a little bit. So I want you to tell us why you got an interest in Alzheimer's. I know there was a family thing. We'll talk about that.

Right.

But what's a nice girl like you doing in Alzheimer's research?

Well, about 3 years ago, I got really interested in neurodegenerative diseases. I had a— first of all, my grandmother died of Alzheimer's, but I also had a good friend who had advanced multiple sclerosis. At the time, I had no idea what the relationships were between any of these diseases, so I started following Alzheimer's, multiple sclerosis, Parkinson's, Huntington's, and ataxia. I just wanted to learn anything I could about them in case I found something I thought would help her. Okay. But I became interested. I started— it became a hobby. I was an obsessive reader. I read all the articles that came across my desk, and I had Google Alerts set up, so I was reading everything. And then at some point, I started understanding some things, and I started seeing a pattern in the— on the hypotheses that were being made between diabetes and Alzheimer's, and it became a puzzle I had to solve. And that's how I got into it.

So, you know, I would just say for our viewers that getting a paper published in the Journal of Alzheimer's Disease is not an easy task. And this is a very highly respected peer-reviewed journal with researchers and clinicians. So, you know, you got your foot in the door because you did such great work. And then, you know, when you take a step back and realize what you did, it was basically an area of comfort for you. It was data analysis, wasn't it?

Right, right. So I wanted to solve this problem, and I knew there was— I figured there was a solution out there. So I was tracking leads down across all different kinds of journals, and I was looking at the data very closely, and I was trying to figure out why some papers would come to different conclusions than others. So I would check the samples very closely. I would call up the researchers when I had questions. I even figured out which labs they were getting their enzymes from, and I ended up unraveling some riddles that explained what was happening.

You found a fairly constant theme amongst most of the papers that you researched. Tell us about that theme.

If you read— I read about thousands of articles across biochemistry, Alzheimer's, diabetes, some neurology journals. The bulk of the evidence suggests that one of the main causes of Alzheimer's is hyperinsulinemia, which people— it's also called prediabetes. It's when you have elevated insulin in your system, but you may or may not have been diagnosed with diabetes already.

Basically, what you're saying is, for whatever reason, insulin is elevated, which we know is something that happens when a diet favors sugar and carbohydrates.

Right.

Your body secretes a lot of insulin to deal with the sugar, and as such, the insulin levels can creep up. Years ago, 2013, in Grain Brain, that was one of the most important laboratory studies I recommended was a fasting insulin level, to a lot of criticism, I might add, and an A1c level, I might add. That said, so you discovered then that a recurrent theme seems to be that the insulin level is elevated. Why would that be a bad thing?

Okay, so it's pretty interesting. There's an enzyme in your body that we call insulin-degrading enzyme, and we call it insulin-degrading enzyme because the first thing we knew it degraded was insulin. It turns out that enzyme breaks down a bunch of other amyloidogenic proteins, so it also breaks down amyloid beta, which is the protein that forms plaques in Alzheimer's. binds to alpha-synuclein and helps chaperone that out of the brain. That's the protein that's at the basis of Parkinson's. Now, if you— but the main thing it does is breaks down insulin. It has preferential attachment for insulin. So if you have hyperinsulinemia and you have high levels of insulin all the time, what's going to happen is you're going to occupy that enzyme. It's called competitive inhibition. The enzyme ends up being so busy trying to break down the insulin that it neglects its duties of breaking down amyloid plaque or alpha-synuclein.

So, in the Alzheimer's brain, we see this collection of this plaque that people have been actually targeting with experimental drugs called amyloid plaque that builds up. One of the jobs of this insulin-degrading enzyme is to get rid of that plaque.

Right.

And if your insulin level is elevated, then it's not going to get to work full-time because it's going to be busy dealing with your insulin. So, what would the answer then be if I wanted to protect myself? Okay.

You've got to treat the hyperinsulinemia. You've got to change your diet, change your exercise level. Exercise will help you regulate your insulin levels better. Some people even need to go on metformin, and I don't think it's a coincidence that they've now discovered that metformin seems to slow down the progression of Alzheimer's and for some people even reverses their symptoms. So there's a clinical trial undergoing right now about using metformin to treat Alzheimer's. I think it's basically because it's affecting the hyperinsulinemia.

Well, that said, we also know that metformin does affect the dynamics of mitochondrial function through AMP kinase. There, there are a lot of factors there. But, you know, I always go back to the original study published in the New England Journal of Medicine when looking at prediabetics. One group had lifestyle modification, diet and lifestyle and exercise. The other group was put on metformin, and the mortality risk was doubled in the metformin group compared to the lifestyle. group, although both had similar outcomes in terms of whether they did or did not develop diabetes. You also called our attention to a very interesting relationship, another protein that is produced right along with insulin called amylin.

Yeah.

A-M-Y-L-I-N. Can you walk us through that science a little bit?

Yeah. I have to tell you, this was a really interesting part of the research. Amylin is co-secreted with insulin, and it helps regulate the rate at which your stomach empties and and glucagon, so it's very, very important in how you deal with food and sugar and those things. So amylin's co-secreted with insulin. When you have hyperinsulinemia, you almost always have hyperamylinemia also, meaning that you have elevated amylin. Now the really interesting part was that I found papers that were saying amylin has this protective effect on the brain. These people had administered amylin to mice that had been engineered to get Alzheimer's, because mice don't naturally get Alzheimer's, but you can engineer them to get Alzheimer's. They administered amylin, and they thought they saw positive effects. They also thought they might have seen some short-term positive effects in humans. There was another study that did a postmortem of people who had died of Alzheimer's and looked at their brains. That study found plaques of amylin. It found big clumps of amylin on the brain co-located with clumps of amyloid beta. And that study came to the conclusion that amylin might be one of the proteins that's implicated in Alzheimer's. So that study concluded that amylin was really bad for you. And this, of course, made me really intrigued. How could 2 studies come to such radically different conclusions? But then it became really simple. When you looked at the studies that administered amylin to mice and even amylin to humans, They were using a synthetic amylin called pramlintide. Now, pramlintide is very similar to mouse amylin. It has 3 proline substitutions that keep it from being amyloidogenic. In other words, it doesn't clump up. The amylin they were giving the mice and giving the people was not human amylin. The people that were being studied who had amylin plaques, that was, of course, human amylin.

Interesting. Let me take a step back. Here you create this kind of a stir. I mean, there have been many people over the years who've been talking about this relationship to diabetes, and therefore, let's not pull any punches, the relationship to lifestyle choices. Right. Because, not to be rude, but we, we sort of choose whether we're going to be a type 2 diabetic or not. I mean, we do see the occasional patient who has been on a very strict diet, but nonetheless, through genetic issues or microbiome issues, they become a type 2 diabetic. But by and large, no pun intended, People become diabetic type two because of their dietary and lifestyle exercise choices. So that said, with this profound relationship, then it's I think it's fair to draw the conclusion that what you're really talking about here is an Alzheimer's prevention protocol program based upon lifestyle modification.

Yeah.

When you wrote your article and it got It was picked up in various news services. How was the response? What sort of response did you get?

The response has been pretty great. I've done a lot of interviews. There have been short rewrites of the article for a layperson audience. It's interesting, though, because I did hear from a few researchers who were maybe a little threatened by the results. One of the reasons is that if you believe hyperinsulinemia is at the core of Alzheimer's, and there's lots of evidence to suggest that it is, it may account for 40% of Alzheimer's cases, then giving people who are at risk of this additional insulin would probably be a really bad thing, right? Yes. Because it's going to put fuel on the fire and just make it worse. You get insulin resistance from having too much insulin, and when you have insulin resistance, you get too much insulin. It's a self-reinforcing effect. Too much insulin, then you get insulin resistance. Insulin resistance, too much insulin. Adding more insulin into the mix there just makes the disease worse. Now there's a team of people who are looking at using inhaled insulin, like intranasal insulin, to treat dementia. I think that's incredibly risky given the association that we can see between hyperinsulinemia and dementia.

Well, I think it's fair to say that there are individuals and corporate entities that have a huge interest in perpetuating the notion that diabetes is a situation of live your life however you want, and we'll just keep ratcheting up the medications. We'll start with metformin, we'll add in insulin even if you're type 2.

Right.

Which we used to call non-insulin-dependent diabetes, but now they're using insulin for it. How did that all happen? And, you know, basically what I'm saying is you're up against pharmaceutical interests who want to have people continue to develop this disease, now 26 million Americans,

Absolutely.

But what you're saying is it's not a free ride, that yeah, you can take your drugs and maybe keep your blood sugar under control, and— but if you don't eat right, if you don't change your diet, you're still at risk. Your insulin levels are going to go up until they ultimately don't, and you're increasing your risk according to your research for a disease, Alzheimer's, for which we have no meaningful treatment as you and I have this conversation right now. So, I think the pushback that you're seeing is industry-related. I've experienced it over the years as I've recommended lower-carb, lower-sugar, more-fat diets, and it's okay. You know, we take a deep breath and we try to light the candle and not curse the darkness, but you got to curse the darkness a little bit sometimes.

Can I say something about this? One of the biggest, longest epidemiological studies of Alzheimer's found that diabetics were twice as likely to get Alzheimer's, and they were 5 times as likely to get Alzheimer's if they were diabetic and being treated with insulin, right? We've had plenty of information on this. For some reason, Alzheimer's patients are not routinely tested for glucose tolerance. They're not given an A1c test. That's not part of the protocol.

Well, there's a direct correlation between A1c and degree of hippocampal atrophy. And further, you know, I really like the study from the New England Journal of Medicine from September 2013 that looked at individuals in terms of a very sophisticated blood test called fasting blood sugar, and then followed them for 6.7 years, 2,300 individuals, and found a very linear correlation between blood sugar levels and risk for dementia.

Yeah.

Even at blood sugar levels of 130. 5, where your doctor is going to give you a pat on the back and say, hey, everything's great, you're not diabetic, with that word yet in the background just hanging there. So I think we should redefine not what should we consider to be a normal blood sugar or a normal fasting insulin or A1c, but what is optimal. Right. And now with research like you've just published, I think this is the information people really need, that, you know, a blood sugar of 100, an A1c of 5.8, An insulin level of 12, these are not satisfactory anymore because we know these things are associated with Alzheimer's risk. Does it mean you'll get it? No. Does it mean you're at increased risk? I absolutely believe it. I mean, you made that very, very clear.

Yeah. You know, the last 4 years of my grandmother's life, when she didn't know me at all, the only thing she would eat was Ensure. So we would just give her cans of Ensure, you know, all day long. And in retrospect, that's the last thing in the world I would do for someone who was in cognitive decline. I mean, we were probably— we were giving her so much sugar between the glucose and the lactose. I feel really bad about it.

And it's such a great product because it's low fat. How much sense does that make? But look what the FDA did just this week. They finally reassessed the notion of not being able to call Nuts and salmon, healthy foods, because they had such fat. Now they're going to take a step back and realize that fat is back, and avocados. These are good foods for the body, for the brain. Now that we're eating fat calories again, we're allowed to get rid of the carbs and get rid of the sugar. Who knew?

Yeah. Now, you're really invested in your health, and so you know a lot about nutrition. I'm pretty invested in my health, so I'm paying attention to nutrition. I think there's an awful lot of people that have no idea what pasta is doing to their body. They don't understand that that's sugar. They don't have a way to understand that. We need an easy way. I think we actually need an easy way to have food labeling that indicates how this product is going to impact your insulin levels in your body.

I know. In fact, you were quoted in one news report as lobbying for glycemic index to be on the food label. Maybe explain to our viewers what that means and why you think it's important.

Yeah. I actually don't think it's enough, but I think it's a start. The glycemic index measures how quickly a food will raise your blood sugar. If you actually had glycemic load on the package, it would take into account also the serving size and the quantity of sugar in the product. I did petition the FDA to add that to food packaging, but it's also true that fructose raises your insulin as well. It's probable that lactose and sucrose all raise your insulin, so I don't know what the measure is. I think we need a better measure.

The fructose story is certainly— Interesting and confounding, not specifically through the insulin mechanism, because I think that the effect on insulin is certainly less profound, but I think more in terms of its changes to the microbiome, its effect on the liver, non-alcoholic fatty liver disease, and ultimately, you know, the detrimental downstream effects from that. And of course, we do also recognize that a lot of people are getting their fructose from high fructose corn syrup, you know, that brings to our attention the spraying of glyphosate and the genetic modification of the very food that we eat. But it's so— it really is terrific just to hear that you are, you know, sounding this clarion call and have stepped forward and from your background, which I think is really, really terrific. I mean, to me, one of the top researchers in the world in terms of the microbiome is an astrophysicist named Dr. Larry Smarr. Why? Because he can look at data and understand what to do with data. And you've, you've really done the same thing. And I think you've done a lot of good here. I think, you know, for years to come, people are going to look back at your work and really, you know, really call attention to it. So I want to thank you for the work that you've done and also for sharing your wisdom with us today. This has been terrific.

Oh, thank you for having me. And thank you for getting the word out.

Great. Well, we'll talk soon, and again, thanks for being part of the show.

Thank you. Bye.

Well, that was a very interesting and exciting interview. Professor Schilling has done some incredible work, and I'm really happy that we got to explore what motivated her to carry out this investigation. And, you know, basically, she is extremely well qualified to look at previous research and statistics and come up with these ideas being published in one of the most well-respected Alzheimer's journals that there is. So what an exciting interview. I'm glad you had a chance to join us. I'm Dr. David Perlmutter. Goodbye.