Dr. Johnson, a nephrologist at the University of Colorado, explains how sugar raises uric acid, which drives hypertension, kidney disease, and metabolic syndrome. He covers the five markers of metabolic syndrome, why kidneys show damage early, and why GLP1 drugs work for weight loss but cause side effects and weight regain when you stop.
GLP1 agonists (e.g., Ozempic) — noted benefits: substantial weight loss (examples: ~20–50 lb reported); drawbacks: GI side effects, high cost, weight regain after stopping
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Thank you so much for being here today with us, Dr. Johnson. My name is Dr. Ana Najafi. I am a pharmacist by training. My background is in pharmacology. I, I'm really excited to sit down with you here today and learn about you, your practice philosophy, your thoughts on metabolic syndrome, what you've seen over your many years of practice. So I thought we could start off with, if you wouldn't mind introducing yourself, giving a little background into your career journey, how you came to become kind of specialized in this metabolic syndrome area and that kind of thing.
Sure. So I'm a professor of medicine and that means that I both a clinician and a research scientist and I've been, I'm currently at the University of Colorado and I also have a part time position right now with a company called RX Sugar that is marketing allulose, which looks a bit like fructose, which is an area that I have a lot of research expertise in. So I'm a, you know, I've been doing research for a very long time, pretty much all my career. And I started off, you know, getting boards in internal medicine, nephrology and infectious diseases. And I'm officially a nephrologist, which is a kidney specialist. And but the kidneys are, are also very important in blood pressure. And so I started studying what causes hypertension. I've always been interested in the big questions and so I was curious, you know, if we could figure out what causes primary hypertension or which is, you know, afflicts a third of the population. And I worked on that for a long time and we, I think we did get answers. And then from there we started looking at this relationship of uric acid with blood pressure and kidney disease. And we found that uric acid actually was more important than just in blood pressure and kidney disease, but that it was central to how sugar can cause obesity and metabolic syndrome. And so that took me into the world of sugar and nutrition and metabolic disease. And since about, for about 20 years I've been studying sugar and I'm kind of an expert on the mechanisms by which sugar, you know, causes biologic changes in people. My talk today is going to really link, you know, talk a lot about our research on sugar and its role in metabolic disease and also in dementia.
Wonderful. Well, we're excited to hear more about it. So what, what would you say is your definition on metabolic syndrome and how it comes about?
Well, historically, metabolic syndrome was viewed as a syndrome of, where you had to have three out of five different criteria you know, which included abdominal obesity or waist circumference. You had to have a high, you kind of on the high side of blood pressure. You had to have evidence for insulin resistance or impaired fasting glucose, elevated triglycerides and a low HDL cholesterol. But really, people think of metabolic syndrome is the classic overweight pre diabetic individual that makes up about one quarter of, of our adult population. And my work really tried to identify what the cause of metabolic syndrome is and what the consequences of it are and how, you know, and how to prevent it and so forth. So that's really the focus of my research.
And what would you say after, you know, your many years of research? Is there one central cause of Metabolic syndrome? Is there, you know, is sugar the culprit? What do you think about that?
There may be one major cause, and our work certainly suggests that. And it suggests that a lot of different, quote, causes may all work through one central pathway. And I'm going to be presenting on that at this meeting or at this talk that I'm going to give. But it's, you know, it's certainly a controversial area. And so, you know, I expect to hear some controversy on this. And we, you know, but, but I do think that, that there could be a central pathway. And recently we just published a paper where we linked all the major obesity hypothesis through this one central pathway. So.
Well, we're excited to hear more about it. And what would you say is your, you know, practice philosophy as it relates to treating patients with metabolic syndrome? If somebody comes into your office and you suspect that they may have it, how do you go about treatment?
Well, you have to look at it from several angles. So there is this dietary lifestyle approach, which is always a good place to start, but you also want to look at the consequences of what's going on in terms of, you know, whether or not they're actually becoming, you know, diabetic or they're developing hypertension and so forth. And so we have to control those problems too, even if they're driven primarily by lifestyle and diet. Obviously, diet is the first place we start, but we have to look at the whole picture. And there are medications, these GLP1 agonists are very expensive, but they can be very valuable tools at helping a person to lose weight.
Right? No, exactly. And those are, you know, definitely gaining popularity in the coming months. And I have some questions for you about that. But you mentioned uric acid. Are there any other key biomarkers you look at in your patients that kind of signal that you know, there's a problem on the horizon and somebody may be developing metabolic syndrome.
Yeah, I mean, blood glucose is a very fasting glucose. Fasting insulin, hemoglobin A1, C C reactive protein. You know, there's quite a few serum osmolality, serum sodium. I, I look at a lot of different features and they all can provide important information to me. Microalbuminuria are evidence of early kidney disease, endothelial dysfunction. You know, there's a lot of ways to look at it because this is a syndrome that has multiple effects. So triglycerides are often very high. Fasting triglycerides. Yeah. There's a whole large panel of tests you can look at.
Right. And from a nephrology perspective, you know, when do you see that metabolic syndrome starts having an effect on the kidneys? And what effect do you see, you know, on those kinds of patients?
Well, metabolic syndrome is associated with very early evidence of kidney disease in a very significant percentage. So it's part, actually, it's sort of part of the syndrome. And maybe I'll just point that out in my talk, since you're bringing it up. But yes, it occurs early in metabolic syndrome. Chronic kidney disease correlates. The highest percentage of patients with chronic kidney disease actually are people with metabolic syndrome. And then when it progresses to diabetes and hypertension, those are two of the most common causes of kidney failure or end stage kidney disease. But this whole syndrome begins early on.
Yeah, right. And everything is linked, you know, with the rein and angiotensin system and you start to see the diabetes bleeding over into the kidneys. So I guess my last question for you before we get into your talk today is over the last year or so, there's been a really growing popularity. You know, people are asking me, I'm sure they're asking you about Ozempic and GLP1 agonists and you know, their thoughts on using, you know, this drug that was intended for diabetes for, you know, prevention of metabolic syndrome and weight loss and various other things. So what are your thoughts and do you think that there is a place in therapy for GLP1 agonists?
I do think that they can really help people. There's been some dramatic num percent of weight loss that can occur when people are losing, can lose 20 to 40, 50 pounds on a GLP1 agonist. But they're also associated with lots of side effects. Impaired emptying of the stomach can lead to bloating, gas burping, you know, a lot of GI side effects. It's also very expensive. And when you stop it, it tends to re. Your problems tend to recur. So you can lose weight, but as soon as you stop it, it seems like weight, the regaining of weight is very common. So it's not really a, a perfect solution in any way and a lot of people can't tolerate it and it's a huge cost to the government. But in select patients, I think it can really be helpful. You know, it can help bring down the weight enough so that a person can have a transplant, for example, or if they really have suffering a lot from severe morbid obesity, you might be able to avoid bariatric surgery and help people. You know, it certainly can help even people with modest obesity or mild obesity if they're trying to lose weight. So there's a lot of good things about it, but it definitely is not the perfect treatment.
Right, right. It definitely can help, you know, kickstart some weight loss, like you said, for patients that are undergoing a transplant and need to lose weight. But it doesn't seem like it's a long term solution to the problem. Would you agree with that?
Yeah, I think the expense is very high. And you know, so, you know, there are other alternatives that people are looking at. One of the reasons I joined Rx sugar is because their sugar allulose actually stimulates GLIP one naturally. And so it might be an alternative approach to a GLP1 agonist. It'd be nicer to eat a chocolate and lose weight than it would be too inject yourself.
Right, right, exactly. And, you know, which patients would you say, you know, that you look at and you, you think, you know, this patient is not a good candidate for a GLP1 agonist. Is there anyone in particular that you know that sticks out?
Yeah, I mean, if a person has a lot of GI problems, GI distress, it may not be the ideal drug because of its very high frequency of exacerbating GI complaints. So some people get a thing called gastroparesis, especially diabetics, where they can't empty their stomach very well. And you know, my suspicion is that a Glip1 Agonist would, would probably make that worse. So, you know, I. But yeah, I mean, it's one of those things where you kind of discuss with each patient.
Right. It's definitely a cost benefit analysis. Yeah, exactly. Well, great. I really appreciate you sitting down with me, Dr. Johnson. We're really excited to hear more from you. This was definitely a great teaser into your talk today and I know that our listeners will definitely benefit and learn a lot from what you have to say.
