Metabolism is how your body manages fuel and energy -- how it acquires, transports, converts, burns, and stores fuel to generate energy and perform work. This process is exquisitely regulated by genes, hormones, enzymes, and biochemical pathways - continuously adapting to your lifestyle. These hidden, automatic adjustments help your body to maintain metabolic balance and health.

In this foundational article, I introduce the first three of the 8 key pillars of metabolic health. Together, these 8 pillars define your metabolic profile. They determine where you currently fall on the Metabolism Spectrum: optimal balance (green), early metabolic imbalance (yellow), pre-disease (orange), or overt disease (red).

For each pillar, I briefly describe what it represents, why it matters, and how it can be tested. The three pillars covered here are glucose tolerance, lipid transport, and insulin sensitivity. The remaining five pillars will be introduced in later posts.

As a bonus, below I provide some INSIDER information, tips, and MetaHacks™ that you won't find elsewhere.

Pillar 1: Glucose Tolerance

Some of the food we digest is broken down into glucose, a simple carbohydrate that serves as a central fuel source. Inside cells, glucose is converted into ATP, the biochemical form of energy that powers motion and work. Although the body can also generate ATP from fats and proteins, it cannot function without glucose.

Several tissues have a particularly high reliance on glucose, including the brain, immune cells, red blood cells, the eye, the inner portion of the kidney (renal medulla), and the insulin-secreting beta cells of the pancreas. During prolonged fasting, the liver helps meet these demands by producing glucose from alternative fuels.

Glucose tolerance refers to the body’s ability to manage dietary carbohydrates. In modern environments with abundant energy-dense foods, carbohydrate intake can exceed our immediate needs. The body can compensate in the short term, but chronic overload gradually damages these regulatory systems.

When compensation fails, glucose intolerance develops. Also known as impaired glucose tolerance (IGT), it is a defining feature of prediabetes and diabetes. In the Metabolism Spectrum, IGT first appears in the Orange Zone.

Glucose tolerance can be measured using fasting glucose (snapshot), hemoglobin A1c (2 month average), or continuous glucose monitoring (daily fluctuations). Each provides useful information but reflects different time scales of glucose control.

The most definitive test of glucose tolerance is the oral glucose tolerance test (OGTT), which functions as a metabolic stress test. After an overnight fast, blood glucose is measured at different time points after consuming a standardized glucose drink. Diagnostic ranges for the 2 Hr glucose reading are shown in the figure. Though not shown, the yellow zone of the Metabolism Spectrum also has normal glucose tolerance (2 Hr glucose < 140 mg/dL).

Although the OGTT is not as practical as hemoglobin A1c and not commonly used in routine clinical care, it is widely used in pregnancy. Also, it is valuable tool for proactive metabolic assessment in health-motivated individuals and high-performing athletes. More about that in future posts.

Pillar 2: Lipid Transport

Lipids are fats and oils -- energy-dense hydrocarbon fuel analogous to the gasoline in your car. Triglycerides, the primary storage form of lipids, are broken down by the body into fatty acids and oxidized in mitochondria to support ATP production.

Skeletal muscle and heart muscle are major consumers of fatty acids, particularly during rest, fasting, and low-to-moderate intensity activity. During high-intensity activity, muscle relies more on glucose. This ability to switch fuels is a hallmark of metabolic flexibility – similar to a hybrid car, but even more sophisticated.

Because blood is mostly water and lipids do not dissolve in it, they are transported in ball-shaped particles called lipoproteins. Each lipoprotein has a lipid-rich core surrounded by a detergent-like surface containing phospholipids and apolipoproteins. The proteins stabilize the particle and direct it to specific tissues.

Some lipoprotein particles, such as LDL and HDL, are rich in cholesterol (yellow core in figure). Others, including VLDL and chylomicrons, are rich in triglycerides (green core) and deliver fat to tissues for energy use or storage.

Lipids and lipoproteins are essential for health but become harmful when they accumulate where they do not belong. For example, excess cholesterol in artery walls drives atherosclerosis, clogging the arteries and leading to heart attacks and strokes. Another example is excess triglycerides in the liver leading to fatty liver disease and its complications.

Testing for lipid transport is typically performed using a standard lipid panel. Advanced lipid testing and mixed-meal challenge tests provide deeper insights into lipid handling and clearance. We'll cover lipid testing in future posts.

Pillar 3: Insulin Sensitivity

Insulin is a hormone and master regulator of metabolism. It is secreted into the bloodstream by pancreatic beta cells in response to rising blood glucose. Insulin signals cells and tissues to take up glucose and lipids from the blood into cells to meet energy demands. In other words, insulin tells cells to "open the gate" to let glucose and lipids in.

When your metabolism is balanced, tissues are insulin sensitive. This means only a small amount (a low concentration) of blood insulin is needed to maintain healthy blood glucose and lipid levels. This scenario is shown on the left side of the figure.

Skeletal muscle is the body’s largest consumer of both glucose and fatty acids. Muscle is the primary tissue that clears these nutrients from the blood. It follows that our muscles play a big role in determining insulin sensitivity. Our liver and adipose tissue (fat stores) play major roles as well.

When nutrient intake chronically exceeds energy needs, our muscle, liver, and adipose tissue cells reduce their responsiveness to insulin to protect themselves from nutrient overload. This initially adaptive response is known as insulin resistance, depicted on the right side of the figure. In this scenario, a large amount of blood insulin (higher concentration) is needed to tell cells to take up glucose and lipids, out of the bloodstream and into tissues.

Note: Insulin sensitivity and insulin resistance are opposite but interchangeable terms for the same phenomenon: low insulin sensitivity means high insulin resistance, and vice versa.

In early insulin resistance, pancreatic beta cells compensate by secreting more insulin into the blood, a state called compensatory hyperinsulinemia. (Hyper means high, emia refers to blood.) Initially, this compensation is beneficial, keeping blood glucose and lipids in the normal range. However, the short-term benefit can lead to long-term harm. Chronic insulin resistance and hyperinsulinemia slowly damage beta cells, blood vessels, and vital organs, leading to chronic diseases like type 2 diabetes, cardiovascular diseases, liver and kidney diseases.

Blood testing for insulin sensitivity is not straightforward, as direct measurements are too invasive and expensive for routine use. Even so, several surrogate biomarkers can be used. This requires care and attention to the various nuances and limitations of these markers. But fear not - we're here to guide you in the proper use and interpretation of insulin sensitivity tests!

Fasting insulin is the concentration of insulin in your blood after an 8-12 hour overnight fast. Alone or combined with glucose or triglycerides, fasting insulin provides insights into insulin sensitivity when you're not eating. Metabolism during sleep in an overnight fast is managed mostly by the liver, when muscle and adipose tissue are metabolically quiet. For this reason, fasting insulin is primarily a measure of liver insulin sensitivity.

A fasting insulin test also detects hyperinsulinemia, which has its own metabolic importance beyond insulin sensitivity. More about that in Part II.

In contrast to fasting insulin, measurements of insulin after an oral glucose drink offers a broader view by assessing whole body insulin sensitivity. The glucose drink stimulates insulin activity in muscle and adipose tissue, as well as liver. This test is called an expanded OGTT.

In addition to whole body insulin sensitivity, the expanded OGTT provides important measures of pancreatic insulin secretion and beta-cell function. These measures are highly valuable for metabolic health and diabetes prevention.

Although the expanded OGTT test is well established and validated in the medical and scientific literature, it is rarely used in the clinic. This has mostly to do practical issues, mostly time, as the test takes about 2.5 hours. However, we see this as a gaping hole in metabolic health promotion and diabetes prevention strategies. It is a missed opportunity to detect insulin resistance and track beta cell function in order to rescue your cells and restore balance as early as possible.

For these reasons, our advanced test panels (Zenova Aligned™ and Aventra Ascending™) strategically incorporate the expanded OGTT to provide you with a valuable, highly informative assessment of your metabolic health status. Early detection is everything...it is a game changer!

INSIDER MetaHack™ (my term for a biohack focusing on metabolism):

Early compensated insulin resistance accompanied by normal blood glucose and lipids is called Early Metabolic Imbalance (EMI). It's a term you've probably never heard before. Most doctors and healthcare providers -- even those taking a preventive proactive approach -- may not be aware of EMI either. There are some scattered reports of this phenomenon in the vast medical literature if you know where to look, as it comes under different names.

We have a unique perspective. Over the past decade, my medical research team has been characterizing EMI by analyzing data from the U.S. population. We coined the term Early Metabolic Imbalance, partly because EMI includes more than just early insulin resistance. Our research on EMI is the scientific inspiration for the Metabolism Spectrum concept, which depicts EMI as the Yellow Zone. Some our published work is referenced at the bottom of this article.

In conventional clinical testing, EMI is elusive and overlooked. It has no symptoms, and the clinical signs are usually missed. Conventional surrogate markers for insulin resistance, such as glucose, A1c, triglycerides, and HDL, are normal in those with EMI. They fail to detect EMI because the body is compensating for it, covering it up. While glucose and lipid markers can detect insulin resistance in its later stages (Orange and Red Zones), they are not reliable measures of early insulin resistance or EMI (Yellow Zone).

Why is testing for EMI important? Four reasons:

1) EMI is prevalent (common) in the population. It represents approximately 10% of the U.S., over 30 million people! Though it can occur at any age, most individuals with EMI are young -- teenagers and young adults.

2) EMI is a risk factor for chronic disease. Late teens and young adults with EMI have double the risk for midlife diabetes and cardiovascular disease, even after accounting for other known risk factors.

3) EMI represents the earliest zone for detecting this increased risk for future chronic disease. It's the first warning sign!

4) EMI is the best opportunity to prevent prediabetes and type 2 diabetes, as well as metabolic syndrome and cardiovascular disease. It's easy to reverse EMI without medications, as no significant cell and tissue damage has been done yet.

Because of the critical importance of early detection and prevention, our Zenova MetabolicBalance™ and Aventra PeakPerformance™ panels offer a range of testing options for insulin sensitivity. Some panels include tests for fasting insulin and derived indices, while others offer expanded OGTT testing. In addition, our panels are designed to pick up the other underlying components of EMI: oxidative stress, hypoxia, impaired oxidative metabolism, and chronic low-grade inflammation. More about these conditions in Part II.

If you haven't had a blood test in the last six or more months, we recommend starting with either Zenova Grounded or Aventra BaseCamp. Each panel is a carefully designed starting point to keep costs low and avoid over-testing. But unlike conventional screening panels, our starting panels include markers of EMI! They measure the key pillars of your metabolism.

If the initial panel suggests evidence of EMI, we would then recommend an advanced panel including an expanded OGTT to get a broader and deeper look at insulin sensitivity and the state of your beta cells. This is how you detect and fix the problem before serious damage is done.

Looking to the near future... T2YourHealth will soon introduce cutting-edge T2 testing to screen for metabolic health and EMI. Our research team accidentally discovered that plasma and serum water T2, measured using portable magnetic resonance, detect EMI with high sensitivity and show promise for use in community settings. More about that in future posts.

Take-Home Message

The first three pillars of metabolic health are glucose tolerance, lipid transport, and insulin sensitivity. If you've received conventional test panels during doctor or clinic visits, you've likely been tested for 2 of the 3: glucose and lipids. However, you've probably not received a test that detects early insulin resistance or EMI.

Early detection of EMI (decreased insulin sensitivity) provides the best opportunity to restore metabolic balance and protect pancreatic beta cells, arteries, and vital organs. Detecting EMI is a game-changer!

How do you know if you have EMI? Get tested - Know Your Zone. See Zenova Grounded or Aventra BaseCamp. If you have questions, feel free to reach out: david.cistola@t2yourhealth.com.

INSIDERS -- We are just getting started! The topics introduced here will be addressed again in future posts. You've got this!!

© 2025 Dr. David P. Cistola/T2YourHealth LLC. All rights reserved.

Source for OGTT diagram: modified version of shutterstock.com - 2375292627

Peer-reviewed Publications:

1) Cistola DP, Dwivedi AK. (2025) Plasma and Serum Water T2 are Strong Predictors of Cardiometabolic Health: Implications for Point-Of-Care Screening. Circulation 151(Suppl_1), P3004. https://www.ahajournals.org/doi/10.1161/cir.151.suppl_1.P3004. American Heart Association, Epidemiology & Prevention | Lifestyle & Cardiometabolic Health Scientific Sessions; 2025 March; New Orleans, Louisiana, USA. Lippincott Williams & Wilkins.

2) Delgado R, Dwivedi AK, Cistola DP. (2024) Early Metabolic Imbalance is an Independent Risk Factor for Incident Metabolic Syndrome: A Retrospective Cohort Study. American Journal for Preventative Cardiology 19(S), 100832. https://doi.org/10.1016/j.ajpc.2024.100832 and https://doi.org/10.1016/j.ajpc.2024.100898, Elsevier. ASPC Annual Congress on CVD Prevention; 2024 August; Salt Lake City, Utah, USA. Elsevier.

3) Malize N, Dwivedi AK, Cistola DP. (2024) Early Metabolic Imbalance is a Risk Factor for Incident Pre-Diabetes: CARDIA 30-year Follow-Up. (2024) American Journal of Preventative Cardiology 19(S), 100835. https://doi.org/10.1016/j.ajpc.2024.100835 and https://doi.org/10.1016/j.ajpc.2024.100898, Elsevier. ASPC Annual Congress on CVD Prevention; 2024 August; Salt Lake City, Utah, USA.

4) Park C, Campbell EB, Dwivedi AK, Cistola DP. Triglyceride-to-high-density-lipoprotein ratio has limited diagnostic accuracy for detecting early insulin resistance. (2024) American Journal of Preventative Cardiology 19(S), 100764. https://doi.org/10.1016/j.ajpc.2024.100764 and https://doi.org/10.1016/j.ajpc.2024.100898, Elsevier. ASPC Annual Congress on CVD Prevention; 2024 August; Salt Lake City, Utah, USA.

5) Cistola DP, Dwivedi AK. (2023) EMI Not Just BMI: Unveiling Hidden Diabetes Risk Among Apparently Healthy U.S. Young Adults. Metabolism 142(S), 155469, Elsevier; https://doi.org/10.1016/j.metabol.2023.155469. 20th Annual World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease (WCIRDC); 2022 December; Los Angeles, California, USA.

6) Cistola DP, Dwivedi AK. Early Metabolic Imbalance in Young Adults is a Hidden Risk Factor for Midlife Cardiovascular Disease: CARDIA 35-year Follow Up. (2023) Circulation 147, AP336, Lippincott, Williams & Wilkins; https://www.ahajournals.org/doi/10.1161/circ.147.suppl_1.P336. American Heart Association Scientific Sessions: Epidemiology & Prevention, Lifestyle & Cardiometabolic Health; 2023 March; Boston, Massachusetts, USA.

7) Cistola DP, Patel V, Deodhar S, Mishra I, Robinson MD, Dwivedi AK. Whole Blood T2P Links Hemoglobin Status to Cardiometabolic Health. (2023) American Journal for Preventative Cardiology 15S, 100576. https://doi.org/10.1016/j.ajpc.2023.100576, Elsevier. ASPC 2023 Congress on CVD Prevention; 2023 July 21; Arlington, Texas, USA.

8) Cistola DP, Dwivedi AK. (2022) Compensatory Hyperinsulinemia is a Hidden Risk Factor for Type 2 Diabetes: CARDIA 30-year Follow Up. Metabolism 128(S), 155061, S3919th Annual World Congress on Insulin Resistance Diabetes & Cardiovascular Disease (WCIRDC); 2021 December; Los Angeles, CA, USA. Elsevier. http://dx.doi.org/10.1016/j.metabol.2021.155061.

9) Mishra I, Jones C, Patel V, Deodhar S, Cistola DP. (2018) Early detection of metabolic dysregulation using water T(2) analysis of biobanked samples. Diabetes Metab Syndr Obes. 2018;11:807-818. doi: 10.2147/DMSO.S180655. eCollection 2018. PubMed PMID: 30538517; PubMed Central PMCID: PMC6260129.

10) Robinson MD, Mishra I, Deodhar S, Patel V, Gordon KV, Vintimilla R, Brown K, Johnson L, O'Bryant S, Cistola DP. (2017) Water T(2) as an early, global and practical biomarker for metabolic syndrome: an observational cross-sectional study. Journal of Translational Medicine 2017 Dec 19;15(1):258. doi: 10.1186/s12967-017-1359-5. PubMed PMID: 29258604; PubMed Central PMCID: PMC5738216.