According to some researchers, the most promising biomarker for heart disease is no longer LDL or HbA1c but an abnormal level of LPIR (Lipoprotein Insulin Resistance Score) identified by Nuclear Magnetic Resonance technology.
During my biology classes in college, I heard about insulin, thinking it was just another hormone. I had no clue it could have a life-changing impact on our health until I faced prediabetes and abdominal obesity in my mid-20s. I noticed something special about this master hormone and investigated it intensely to understand its impact and implications on our healthspan and lifespan.
From a distance, insulin is just a hormone that regulates blood sugar. However, when we examine it closely, we see that this master hormone touches all aspects of our cellular, metabolic, and endocrine health directly or indirectly. I was convinced that it has a significant role in our cells, heart, and brain, affecting our cardiometabolic and neurological health.
Until the early 1990s, I had no idea diabetes was related to atherosclerosis due to inflammasomes like NLRP3, which is the root cause of heart disease and stroke. Then, studying dyslipoproteinemia helped me understand the intricate connections between type 2 diabetes and cardiovascular diseases.
In 1994, I read an eye-opening and visionary paper in the Journal of Atherosclerosis that said atherosclerosis was the most frequent complication of diabetes. Many potential atherogenic factors in diabetes may underlie this problem. One of these is the dyslipoproteinemia group. In diabetes, there are qualitative and quantitative changes in the plasma lipoproteins.
These visionary researchers informed us that based on pathophysiological and epidemiological data, these may be among the many factors that can result in early macrovascular disease. Furthermore, at least one of the dyslipoproteinemias — hypertriglyceridemia — is associated with insulin resistance and, therefore, could aggravate glucose intolerance. Thus, on theoretical grounds, it is reasonable to postulate that treating the dyslipoproteinemias of diabetes would reduce atherosclerotic disease.
Before developing type 2 diabetes, people go through two stages: insulin resistance and elevated blood sugar levels. Insulin resistance means tissues don’t respond well to insulin, so the body makes more insulin. This can lead to pancreatic beta-cell dysfunction, where the cells lose their ability to produce insulin effectively. Over time, this dysfunction can contribute to insulin resistance, more inflammation, and the development of type 2 diabetes, leading to heart disease.
I wrote multiple stories about insulin resistance, hyperglycemia, and hyperlipidemia, looking at them from different angles and providing practical tips to optimize them, especially to lower visceral fat and increase lean muscles. The two critical concepts I introduced were insulin resistance and sensitivity, which determine our metabolic health and might also play a critical role in neurological and mental health.
Why did I write this important story?
After a comprehensive literature review, when I inquired with my cardiologist friend about the previously discussed biomarkers, he, as a preventive cardiologist, emphasized that LPIR now stands out as a significant emerging biomarker for early detection. He elaborated on the reasons behind this and inspired me to write a story about it to inform my readers and approve my draft. The context and nuance are critical as there are many established biomarkers, and LPIR is not intended to replace them but to add extra intelligence for early detection.
I recently watched an eye-opening and educational video presented to the public by Dr Annette Bosworth, MD, on YouTube. As a medical doctor, through her hour-long lecture, she articulates the importance and details of LPIR passionately, how practitioners can use this valuable biomarker to diagnose heart issues earlier, and how they can use it to prevent or treat cardiovascular issues. Dr. Bosworth featured a detailed analysis of Dr. Kevin Forey, MD, on LPIR, which shows it at the top of the chart.
In this story, I aim to spotlight a pivotal and distinctive biomarker known as the Lipoprotein Insulin Resistance Index score (LIPR), which indicates cardiovascular health risks. Indeed, it has emerged as one of the important biomarkers for assessing heart health. I will cover other emerging biomarkers in another story, as it is not possible to include them in this story.
What is a Lipoprotein Insulin Resistance Score Biomarker?
As documented in a 2008 paper, insulin resistance contributes to the pathophysiology of diabetes and is a hallmark of obesity, metabolic syndrome, and many cardiovascular diseases.
Therefore, researchers inform that quantifying insulin sensitivity and resistance in humans and animal models is very important for epidemiological studies, clinical and basic science investigations, and eventual use in clinical practice.
However, researchers identified a better biomarker for heart health. Now, they believe that an abnormal LPIR (Lipoprotein Insulin Resistance) score in the context of heart disease indicates an increased risk for cardiovascular issues. I will cover the details of the literature on Insulin Resistance Dyslipoproteinneia in the next section.
The LPIR score measures lipoprotein particles associated with insulin resistance, a risk factor for heart disease and other metabolic disorders. It assesses the degree of insulin resistance by analyzing lipoprotein subfractions (components) in the blood.
A higher LPIR score suggests a greater degree of insulin resistance. It is associated with an elevated risk of developing heart disease, including conditions like coronary artery disease and myocardial infarction (heart attack). LPIR biomarker is considered valuable for diagnosing heart disease because it comprehensively assesses insulin resistance based on lipoproteins.
Unlike traditional risk factors like cholesterol levels, LPIR leverages insulin resistance measurements to reflect metabolic state accurately. Insulin resistance plays a crucial role in the pathogenesis of heart disease, contributing to atherosclerosis, inflammation, and endothelial dysfunction.
By identifying people with insulin resistance early on, LPIR might allow for targeted interventions like lifestyle modifications or pharmacotherapy, which can mitigate cardiovascular risk and improve patient outcomes. LPIR may offer insights into cardiovascular risk beyond what traditional risk factors provide, making it a valuable tool in preventive cardiology.
Challenges of Testing Insulin Resistance
Since the early 2000s, The American College of Endocrinology Task Force has agreed that it’s important to identify people with insulin resistance linked to health problems. Different ways exist to test how sensitive someone’s body is to insulin.
The glucose disposal rate (GDR) test is considered the best method, but it is mostly used in research because it’s complex and requires special equipment. Other tests also exist, like the insulin suppression test and the minimal model analysis, but they are not common in clinics because they involve intravenous injections and monitoring.
Some simpler tests, like the homeostasis model assessment of insulin resistance (HOMA-IR), can be done with fasting blood samples, but they also have limitations, such as needing repeat testing and not being standardized for insulin measurement.
Early signs of insulin resistance often show up in changes to lipid (fat) and lipoprotein (fat-protein) metabolism, like higher levels of triglycerides (TGs) and lower levels of high-density lipoprotein cholesterol (HDL-C), even before someone is diagnosed with diabetes or prediabetes.
Early researchers like Dr McLaughlin and colleagues have suggested using the ratio of TGs to HDL-C as a simple way to identify insulin-resistant overweight and obese patients instead of using glucose and insulin measurements.
More advanced methods, such as nuclear magnetic resonance (NMR) spectroscopy, provide a detailed look at lipoprotein abnormalities linked to insulin resistance. I introduce NMR in a separate section below.
In particular, insulin-resistant patients tend to have higher levels of large, very-low-density lipoprotein particles (VLDL-P) and small, low-density lipoprotein particles (LDL-P), along with lower levels of large HDL particles (HDL-P).
Additionally, the average size of VLDL particles is usually larger, while the average sizes of LDL and HDL particles are smaller in people with insulin resistance or prediabetes.
Summary of Promising Insights from the Prominent Literature on LPIR
In 2002, MESA (Multi-Ethnic Study of Atherosclerosis) was a large ongoing research project involving 6,814 men and women aged 45 to 84 years who showed no signs of clinical cardiovascular disease. The study aimed to understand the prevalence of risk factors for the development and progression of hidden cardiovascular disease in a diverse group of people.
For this specific investigation, plasma samples from 4,972 MESA participants were analyzed. These participants had provided consent, had baseline plasma samples available, and did not have diabetes when the study began. Using standardized methods and materials, lipid, insulin, and glucose levels were measured at a central laboratory.
Analysis of different groups within the MESA study showed consistent correlations between LPIR and HOMA-IR, regardless of gender. European Americans exhibited the strongest connection between LPIR and HOMA-IR, followed by African Americans, Chinese Americans, and Hispanic Americans.
In 2014, three PhDs and an MD wrote an outstanding paper based on MESA study. These researchers said that as insulin resistance occurs before type 2 diabetes, the LPIR score might predict it, regardless of glucose levels and BMI, offering a practical way to gauge cardiometabolic risks.
In this study, researchers found that insulin resistance, measured by the LPIR score, was strongly linked to early heart disease, more so than about 50 other biomarkers they examined. The LPIR score estimates insulin resistance using nuclear magnetic resonance and predicts the likelihood of developing diabetes.
Interestingly, the LPIR score showed a stronger connection to heart disease in younger women up to age 75 compared to other commonly used measures like A1c or cholesterol levels.
This suggests that insulin resistance and its related changes in cholesterol may play a role in diabetes and heart disease risk. However, more research is needed to understand this link fully.
They said that while a history of diabetes significantly increased the risk of early heart disease, metabolic syndrome was also associated with heart disease, although to a lesser extent. Unlike metabolic syndrome, the LPIR score requires specialized lab testing, making it a newer and less widely available biomarker.
In addition, researchers highlighted that the LPIR score has the potential to alert patients about their risk of developing diabetes before reaching the prediabetic stage, allowing time for lifestyle changes to prevent or delay the onset of the disease.
In 2016, researchers in JAMA reported that statins decrease levels of low-density lipoprotein (LDL) and triglycerides and cardiovascular events but increase the risk of a diagnosis of type 2 diabetes mellitus (T2DM). The risk factors associated with incident T2DM are incompletely characterized.
To investigate the association of lipoprotein subclasses and size and a novel lipoprotein insulin resistance (LPIR) score (a composite of 6 lipoprotein measures) with incident T2DM among individuals randomized to a high-intensity statin or placebo.
Size and concentration of lipids, apolipoproteins, and lipoproteins at baseline (11,918 patients with evaluable plasma samples) and 12 months after randomization (9180 patients). The LPIR score, a correlate of insulin resistance, was calculated as a weighted combination of the size and concentrations of LDL, very low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) particles.
They concluded that among placebo- and rosuvastatin-allocated individuals in JUPITER (a placebo-controlled randomized clinical trial), the LPIR score is positively associated with incident type 2 diabetes after adjusting for traditional risk factors. The LPIR score has the potential to serve as part of a broader clinical approach to identify additional cases at risk.
A 2017 study published in the Journal of Clinical Lipidology examined 25,925 nondiabetic women aged 45 years or older. They measured LPIR by nuclear magnetic resonance spectroscopy as a weighted score of very low-density lipoprotein, low-density lipoprotein, and HDL particle sizes and their subset concentrations.
They concluded that in middle-aged or older healthy women followed prospectively for over 20 years, LPIR was robustly associated with incident type 2 diabetes, including among those with an optimal clinical metabolic profile. LPIR improved risk classification and may guide early and targeted prevention strategies.
Frontiers published an exciting peer-reviewed paper titled “Association between lipoprotein(a) and insulin resistance in Chinese adults: results from the China health and nutrition survey” on October 2023.
Lipoprotein(a) is a well-established risk factor for cardiovascular diseases. However, the relationship between Lp(a) and insulin resistance (IR) remains controversial. The current study aimed to investigate the association between Lp(a) concentrations and IR in Chinese adults.
The paper concluded that Lipoprotein(a) concentrations are inversely associated with insulin resistance in Chinese adult males, but the association in women needs further study. In Chinese adults, Lipoprotein(a) interacts with gender in insulin resistance.
How is the LPIR Score tested and determined?
The LPIR (Lipoprotein Insulin Resistance) score is determined through specialized laboratory testing using nuclear magnetic resonance (NMR) spectroscopy, which analyzes lipoprotein subfractions in blood samples to assess insulin resistance.
MDPI’s Nutrients also published an interesting paper titled “A New Era with the NMR Metabolomics Assessment.” Metabolomics is a promising source of new molecular markers, standing out in the research of biomarkers in NMR approaches.
This process involves collecting a blood sample from the patient, conducting NMR spectroscopy analysis, calculating the LPIR score based on the lipoprotein component profiles, interpreting the score to assess insulin resistance status, and making clinical decisions accordingly.
Scientists call this process Insulin Resistance Dyslipoproteinneia. Lipoprotein subfractions in this process includes measurement of VDLD-p size, large VLDL concentration, HDL-p size, large HDL-p concentration, LDL-p size, and small LDL concentration. P stands for particles.
Healthcare providers, like physicians, cardiologists, endocrinologists, or metabolic health specialists, order and interpret the LPIR score to assess a patient’s risk for diabetes and cardiovascular disease.
The timing of the test may vary based on individual patient factors and clinical indications. It is used to evaluate insulin resistance risks for cardiometabolic disorders.
What is Nuclear Magnetic Resonance, and why is it important?
Nuclear Magnetic Resonance (NMR) spectroscopy is a powerful analytical technique for studying the structure and properties of molecules at the atomic level. I came across this technology in the early 1980s when studying Informatics.
It is a useful tool for molecular biologists interested in biological macromolecules' structure, dynamics, and interactions. It is widely used in chemistry, biochemistry, and medicine to elucidate molecular structures, identify compounds, and study chemical reactions.
This unique technology relies on the interaction between the magnetic properties of atomic nuclei within a molecule and an external magnetic field. When subjected to radiofrequency radiation in a magnetic field, the atomic nuclei absorb energy and transition between energy states.
NMR spectroscopy measures the resulting electromagnetic signals emitted as the nuclei return to their original states, providing detailed information about the chemical environment, connectivity, and dynamics of atoms within a molecule.
This 2021 paper in Frontiers about NMR documented that personalized medicine must combine innovative tools to measure, integrate, and model data. Towards this goal, clinical metabolomics appears to be ideally suited to obtain relevant information.
These researchers mentioned that the metabolomics signature brings crucial insight to stratify patients according to their responses to a pathology and/or a treatment, to provide prognostic and diagnostic biomarkers, and to improve therapeutic outcomes.
Conclusions and Takeaways for Preventive Cardiology
Understanding the complex relationship between insulin resistance, lipoproteins, and cardiovascular health reveals the significance of an emerging biomarker, the Lipoprotein Insulin Resistance (LPIR) score, in predicting heart disease and stroke risk.
Understanding the valuable role of the LPIR score as a biomarker for heart disease risk surpasses traditional indicators because it enables early detection of cardiovascular risk by measuring lipoprotein particles associated with insulin resistance and facilitates personalized risk assessment through specialized laboratory testing.
This approach may allow for timely intervention, reduce the burden of cardiovascular diseases, and improve patient outcomes by promoting proactive lifestyle modifications. So, through pioneering research and clinical studies, experts illuminate the pivotal role of LPIR as a valuable indicator of cardiovascular health compared to traditional markers like LDL or HbA1c.
The scientific and clinical journey continues with advancements in testing methodologies, such as nuclear magnetic resonance spectroscopy, which offers precise insights into lipoprotein components and insulin resistance.
As we understand and welcome these insights, patients, scientists, and medical practitioners can be empowered with a transformative tool to assess, prevent, and manage cardiovascular risks, heralding a new era in preventive cardiology and personalized healthcare.
Given our current understanding, insulin resistance plays a pivotal role in the development of type II diabetes, increasing the risk of cardiovascular complications. Hence, engaging in conversations about LPIR scores with healthcare professionals like family physicians, cardiologists, or endocrinologists is a wise choice. They can proactively integrate this valuable information into preventive strategies, potentially mitigating the risks associated with these conditions.
As you may know, intermittent fasting is one of the best tools for defeating insulin resistance, lowering lipids, and reducing chronic inflammation. However, recently, the American Heart Association sent a press release saying this practice can increase heart disease risk by 91% based on a premature study. I address this important public health issue in an article to inform my readers on NewsBreak.
Perfect Storm in a Teacup: Can Intermittent Fasting Increase Heart Disease Risk by 91%?
Thank you for reading my perspectives. I wish you a healthy and happy life.
If you found this story helpful, you may also check out my other articles on NewsBreak. As a postdoctoral researcher and executive consultant, I write about important life lessons based on my decades of research and experience in cognitive, metabolic, and mental health.