The Insulin Resistance Revolution: The Key to Preventing Chronic Conditions

The Insulin Resistance Revolution: The Key to Preventing Chronic Conditions (PODCAST TRANSCRIPT)

[00:00:00] Welcome to Healthier World with Quest Diagnostics. Our goal is to prompt action from Insight as we keep you up to date on current clinical and diagnostic topics in cardiovascular, metabolic, endocrine, and wellness medicine.

[00:00:24] Metabolic dysfunction is the root cause of many cardio-metabolic conditions that burden the healthcare system. this episode will address insulin resistance, a syndrome that underlies metabolic dysfunction and discuss how we can use laboratory tools to catch risk early, which may allow us to prevent and reverse the onset of chronic illness. I'm Dr. Maeson Latsko, a researcher by training with a passion for learning, and today we have guest speaker, the one and only Kenneth French, a clinical consultant and an absolute wealth of knowledge. With many years of clinical experience in the field, Talking us through insulin resistance. A topic that he speaks about day in and day out. So Kenneth, we're so excited to have you on the podcast today. There's just so much we could talk about with this particular subject and I'm looking forward to hearing your perspective.

[00:01:13] Thanks for having me, Mason. Looking forward to our discussion.

[00:01:14] So Kenneth let's jump into the reason why we're so passionate about this topic. And the last few decades, obesity rates have skyrocketed creating major healthcare crisis. And those rates are not expected to decline anytime soon. The prevalence of obesity is expected to soar to 50% by 2030. Let's review for the audience, the link between obesity, metabolic, dysfunction, and insulin resistance.

[00:01:39] Well, this particular subject that we're going to be talking about today is actually my favorite subject, in my career. 25 years and, laboratory diagnostics. Um, this is probably the most important discussion and topic of our time. you mentioned 50 percent of people will be obese by year 2030. just to give some color to that number of people who will have morbid obesity will be one in four So we're not, we're not backing out of this. and, in healthcare, we see some of the bad fruit of what obesity can drive when it leads to kidney disease, liver disease, heart disease.

[00:02:15] But what's the link? I mean, obesity in of itself is not the link. The link is what's driving the obesity. and that is this condition called insulin resistance which affects more individuals metabolically than any other condition.

[00:02:27] And, and if you go back and you think, well, is insulin resistance a new concept or a new idea? No, it's not. In fact, all the way back in 2000, the National Collateral Education Program, adult treatment panel, three guidelines came out and said explicitly for the first time, it sort of made a splash into the public space and into the clinical space in particular of a condition called metabolic syndrome. And that was a series of Different traits that if you add up enough of them, we could diagnose someone with metabolic syndrome. That was the first attempt at identifying the root cause for a lot of the issues, in particular obesity, which is insulin resistance.

[00:03:03] Yeah, I think the way that you're describing it really helps to exemplify how chronic disease Is a continuum. it's not just a dichotomous split Where one day you have a disease, whereas the day before you didn't. We know that this is a long road To the development of something like diabetes, starting with insulin resistance. So we know that these syndromes are part of a collection of risk factors that indicate insulin resistance, but Let's talk about the trajectory from insulin resistance, All the way to chronic illness like pre-diabetes and diabetes.

[00:03:33] Yeah, we know what healthy looks like, and we know what people who have type 2 diabetes looks like, right? But what's before pre diabetes? A healthy person? The answer to that is no. what's before prediabetes is the state of insulin resistance, and that's in and of itself actually is where the problem lies. During the insulin resistant years, the body is exposed to more and more glucose, therefore the body is putting out more and more insulin, and Our own cells and our own,organ systems are not responding to the insulin

[00:04:05] and so the provider doesn't see that they have a patient with insulin resistance that's driving a lot of issues you see liver enzymes, begin to go up, you see kidney dysfunction, you begin to see a dyslipidemia, triglycerides are going up, HDL is dropping, you see they're adding a little bit of extra weight compared to last year, their blood pressure may be going up, all of these things are symptoms of insulin resistance So excess insulin is what's keeping the glucose and A1C under control until a certain critical point where those cells become very fatigued after working so hard for so long, and then you start seeing metabolic dysfunction, And now we see the glucose and now we see the A1C climb . Well, that could be 5, 8, 10 years that we live with that insulin resistance hiding the problem. And it's not until later that we actually see the issue manifest in the glucose or an A1C.

[00:05:01] And the easiest question to ask is you have insulin resistance? Because if you do, and you manage the insulin resistance then you're managing all the comorbidities associated with it.

[00:05:10] Absolutely. So let's go ahead and summarize what we're talking about so far, because I know this can be a dense topic. So let's take, uh, an example of a healthy individual. That person eats something, their blood sugar or blood glucose goes up. And in response to that increase in glucose, that person then releases insulin to help control their glucose and bring it back down to basal levels. [00:05:32] If a person consistently has high levels of glucose, their body will continue to have to release more and more insulin in order to respond to that glucose over time, their cells become less responsive to the signal of insulin And become insulin resistant. And this state of insulin resistance can occur for years before an increase in A1C and glucose. And at a certain A1C cut point for example, seven or six, four. That's when people actually get diagnosed with pre-diabetes or diabetes. . So catching this earlier is always better. Right? So say we have a provider listening in today who says great. I measure an insulin, I always take an insulin on my patient to assess the state of insulin resistance. Is that enough?

[00:06:17] Yeah. what's interesting about this whole space. is a lot of clinicians don't realize that, insulin has never been a standardized test. When you have a test that's not standardized, this essentially means you could have three different laboratories run the quote unquote same test and you literally get three different results. So that's very problematic. Then number two, is, insulin does not exist in one form in the blood. and , because it can exist in many different forms, you need to have a technique that is powerful enough to discriminate those different forms. Antibody assays, like most insulin measurements, unfortunately, do not do that.

[00:06:54] So historically we haven't had a very good means by which to determine who's at risk

[00:07:00] For, insulin resistance.

[00:07:01] the

[00:07:02] Euglycemic clamp, even the insulin suppression testing. These are techniques that are very laborious. they require hooking the patient up to multiple different lines and and infusing or ingesting certain quantities of glucose and infusing certain quantities of insulin.

[00:07:16] And so it's, it's just not practical from a commercial perspective.

[00:07:19] So, this is where the strength of, the technology, liquid chromatography, tandem mass spec comes into play. to measure insulin

[00:07:26] Now we can, you know, we can actually use this assay with high degree of accuracy, reproducibility and precision. It can be standardized. And now we have a real way, if you will, a gold standard way of measuring something that historically has had problems with Antibody assays, because antibodies can bind to various stages of insulin, and there's no standardization

[00:07:50] Yeah. Those are all really great points.

[00:07:52] So liquid chromatography, tandem, mass spectrometry really brings that specificity, as you mentioned, and you and I both know quest diagnostics put a lot of effort. Into identifying a quick and easy way to measure insulin resistance., because spoiler alert, we can do better than just insulin by itself. So what tools do we have to measure insulin resistance

[00:08:12] Well, that's actually the task of what Quest Diagnostics did when they set out to look for a way to measure insulin resistance in patients with quote, unquote, A1C, but they have peripheral vascular insulin resistance. So Quest Diagnostics connected with Stanford University, Dr. Gerald Reven's laboratory, who coined the phrase many years ago called Syndrome X, which we now know as Metabolic Syndrome. His laboratory uses the euglycemic clamp method, the insulin suppression method. And so we,collaborated with his laboratory to see are there certain markers we can look at in the blood.

To measure that we can get as close to this gold standard method for finding insulin resistance, but we can do this In a commercial environment using the tube of blood and the good news is the answer is yes, we found it by using liquid chromatography tandem mass spat And measuring specifically the intact insulin and the C peptide, simultaneously, we will use those two values in a formula to generate what we call now the insulin resistance panel or score, a score between one and a hundred.

[00:09:17] So it's, it's not enough to identify, Oh, you likely have insulin resistance. To what degree, to what extent do you have insulin resistance? The irofinalis score was designed to not only identify who has insulin resistance, but also to give some degree or, or scale of where you land on insulin. in this case, a scale of one to a hundred.

[00:09:37] So this tool, this insulin resistance panel with score. Or I R score. it's a predictive tool, like you said, and it takes C-peptide and intact insulin together to tell you the likelihood of being insulin resistant. And it also helps you to find the degree to which a person has insulin resistance. So a person with an insulin resistance score between one and 33 suggests that a person has normal insulin sensitivity. 33 to 66 suggests that an individual has four times greater odds of having insulin resistance compared to somebody with low risk. And a score above 66, suggest that an individual is 15 times more likely to have insulin resistance compared to somebody with low risk. One of the key things that I hear from providers a lot is what should we do about it? Can you walk us through your answer to that question?

[00:10:27] Yeah Um, 5. 5 percent A1C and their fasting blood glucose, let's say for example, is 85 milligrams per deciliter. Well, on the reference ranges, those are perfectly normal. But if that same patient had the insulin resistance panel with score performed on them and their score came back, 66, now we've identified issue. We recognize that this individual has risk. And usually when you see that positive our panelist score, you're gonna see other issues like we talked about earlier. It could be dyslipidemia, could be weight gain. It could be blood pressure issues. It could be things that are changing over time that weren't present last year.

[00:11:02] Now, all of a sudden they are. Well, here's the good news. If we initiate the strategy of managing the insulin resistance the same way we would treat somebody with metabolic syndrome and we bring them back up for follow up, we hope to see the score going from a higher number like 66 to 45 to hopefully 14. But what's interesting is the glucose in A1c may not change at all. So the patient or the provider would think there was any benefit if they were trying to track the patient's A1C or glucose. But when they look at the insulin resistance panel or score and see that that value went from 66 to 14, they know they had a positive impact.

[00:11:38] And then they can look at the dyslipidemia and say, is this resolving itself or has it resolved itself? The answer is yes. Excellent. Do we see a reduction in liver enzymes or do we see increase in kidney function? Are we seeing some weight loss? Is the blood pressure coming under control all because now we're actually identifying the cause for all of those, which is insulin resistant, and that's a measurable number that we can document on day one and track over time.

[00:12:02] Yeah, absolutely. I think that's a great summary for providers for when they're thinking about what do we do about an elevated insulin resistance panel with score And from the patient perspective, check out our podcast with Patty, Biyanki a certified dietician. Who provides some context behind actionable tips to address insulin resistance? So you've hinted at the idea, Kenneth that fixing insulin resistance can improve other systems. like. Liver enzymes and kidney function. Let's dive into that a little deeper. Let's say we bring down the insulin resistance score from 66 to 14. What other things might we expect to see an improvement on?

[00:12:41] Oh, wow. The profound effects of insulin resistance on the kidney, on the liver, on, uh, blood pressure, weight, even neurological issues, . Insulin resistance has a huge play in all of those conditions. So, a classic example is, is what, what's the common dyslipidemia that we see in someone with insulin resistance? Well, these are probably people who were going to start forming a dyslipidemia. Where they're able be is going to be significantly higher than their LDL cholesterol, meaning their LDL cholesterol is not predicting the risk, but they're able be is, and it's likely the insulin resistance is driving this.And when you you solve the insulin resistance problem, most likely you're going to solve the ApoB problem. Another example is, most providers know it as non alcoholic fatty liver disease. It's now called metabolic dysfunction associated steatotic liver disease. While that's a mouthful, what I like about it is it's telling you the reason or what's causing the non folate fatty liver disease. It's metabolic in origin. Even the insulin resistance panel was scored, was used in patients without diabetes to see if it can predict the likelihood that certain individuals have non folate fatty liver disease or metabolic dysfunctions, steatotic liver disease.

[00:13:59] And what was remarkable is in quote unquote, normal, healthy subjects, the IR panel was scored, the score was 31 or greater, or the intact insulin for that individual was 10. 5 or greater. That patient had a, 80 percent positive predictive value for non alcoholic fatty liver disease So what this is showing is is not only does insulin resistance have the ability in the case to predict who is potentially on the trajectory towards type 2 diabetes, but it can also help us understand who likely has non alcoholic fatty liver disease and otherwise healthy individuals. the link is, is inescapable.

[00:14:37] Yeah, because all these disease states are so intertwined. chronic kidney disease. dysglycemia increased lipids as well as non-alcoholic fatty liver disease and even endocrine disorders. It makes a lot of sense that the insulin resistance panel with score can be so predictive of an individual at risk for multiple chronic diseases.  So, I know we've touched on a lot today and I really appreciate your insights.Let's put a nice bow on our conversation by listing out some key takeaways from today's conversation.

[00:15:08] , I think, what's interesting is when you look at the, the CVD mortality, you know, we, we talk about diabetes and, obesity that are increasing rather rapidly, in the last,20 years, especially in the last 10, even the CVD mortality in both men and women's going up.

[00:15:26] why are these things happening? the easiest thing to do is to evaluate, does a person have insulin resistance or not? . And then I would think number two is it's totally treatable. It's just not a new phenomenon. Everything we brought to bear and everything we understand about metabolic syndrome, we can apply to patients with positive insulin resistance panel and score values.

[00:15:48] And then number three, imagine the consequences of solving the insulin resistance problem for our population. When you solve insulin resistance before it hits prediabetes and diabetes, that means you've diverted those patients from that condition. But not only have you done that, you've also reduced the burden of kidney disease.

[00:16:08] You've also reduced the leading organ system disease, which is non alcoholic fatty liver disease, affects one in three people. You're reducing that burden. You're reducing the hypertension crisis for a lot of individuals where it's driven by the insulin resistance. You're reducing the obesity epidemic.

[00:16:23] You're seeing improvements in certain neurological and major depressive disorders where insulin resistance is a big play. all because we're addressing the root calls. And in most of these, insulin resistance is the reason, and it's so treatable and it's reversible.

[00:16:38] Well, Kenneth, it's always a pleasure to have you on and chat with you and learn from you. So thanks for joining us today and discussing insulin resistance.

[00:16:48] Thanks for having me. Look forward to the next one.

[00:16:51] That's a wrap on this episode of Healthier World with Quest Diagnostics. Please follow us on your favorite podcast app, and be sure to check out Quest Diagnostics Clinical Education Center for more resources, including educational webinars and research publications. Thank you for joining us today as we work to create a healthier world, one life at a time.

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