Insulin Resistance, Metabolic Health, and the Biomarkers Your Doctor Isn’t Testing

Standard metabolic testing checks glucose and A1c — markers that can look normal for years while insulin resistance builds underneath. The WHOOP Metabolic Health Panel looks at 78 biomarkers that cover insulin dynamics, thyroid function, adipose signaling, and the mineral cofactors that drive metabolic function, alongside the foundational health data that puts them in context. Dial deeper into what’s driving your energy, weight, and blood sugar.

More than a third of US adults meet the criteria for metabolic syndrome (a cluster of conditions including elevated blood sugar, abnormal cholesterol, high blood pressure, and excess abdominal fat) and prevalence continues to rise.

Metabolic dysfunction doesn’t require being overweight. Some lean adults are classified as metabolically unhealthy despite having a normal BMI, a pattern researchers call the TOFI phenotype: Thin Outside, Fat Inside. These individuals carry visceral fat around their organs while looking healthy by most external measures. Their standard labs often look healthy, too.

Based on aggregated, de-identified data from approximately 16,000 WHOOP Advanced Labs members (a group that skews younger, more active, and more health-conscious than the general population) approximately 22% showed markers consistent with insulin resistance.

Why fasting glucose and A1c aren’t enough

Glucose is often the last domino to fall in the metabolic cascade. Insulin rises first, sometimes years to decades before glucose or A1c ever moves outside the normal range.

This progression unfolds in approximate stages:

Stage 1 (approximately years 1-10+): Cells become less responsive to insulin. The pancreas compensates by producing more of it. Fasting glucose stays normal. A1c stays normal. Standard labs see nothing wrong.

Stage 2 (approximately years 5-15+): The pancreas starts to strain under the constant demand. Beta cell function begins to decline. Glucose creeps upward, but often stays within the reference range.

Stage 3 (approximately years 10-20+): Beta cells can no longer compensate. Fasting glucose crosses the threshold. A1c flags prediabetes or diabetes. The standard lab finally catches up.

Note: these timelines are approximate and vary between individuals. This is a conceptual model of how insulin resistance can progress, not a fixed clinical timeline.

The WHOOP Metabolic Health Panel can detect dysfunction at Stage 1. Standard testing waits until Stage 3.

The markers that detect dysfunction early

The Metabolic Health Panel includes biomarkers that work across different timescales. That distinction matters: some markers reflect what happened in the last 24 hours, others summarize the last few weeks, and others reveal patterns building over months or years. Together, they create a picture that no single test can provide.

Right now: 1,5-Anhydroglucitol (1,5-AG)

1,5-AG is a compound that drops within 24 hours of a glucose spike above roughly 180 mg/dL. It provides a shorter-term view of glycemic control than A1c.

This matters because of what A1c misses. In clinical research, changes in A1c were not correlated with CGM glucose variability, while 1,5-AG was. Patients with “well-controlled” diabetes (near-normal A1c) who had high glucose variability looked identical to patients with genuinely stable glucose, by A1c. 1,5-AG separated them.

If you’re eating meals that spike your blood sugar past roughly 180 mg/dL and it returns to normal before your next fasting test, 1,5-AG catches it. A1c and fasting glucose don’t.

This month: Fructosamine

Fructosamine reflects average blood sugar over the preceding two to three weeks. That fills a specific gap: fasting glucose tells you about one morning. A1c averages over eight to twelve weeks. Fructosamine covers the middle ground.

It’s also unaffected by hemoglobin variants, anemia, or red blood cell lifespan, conditions that can throw off A1c readings. For anyone whose A1c might not be reliable, fructosamine can provide a cleaner signal.

This quarter: A1c and eAG

A1c and its companion metric, estimated average glucose (eAG), give you the broadest view, average glycemic control over the past two to three months. They’re useful as a baseline. But they’re best interpreted alongside the markers that capture the variability and short-term shifts that A1c averages away.

Years: HOMA-IR and C-Peptide

HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) is a calculated index that quantifies insulin resistance. Research in Diabetes Care established HOMA-IR as an independent predictor of cardiovascular disease in diabetes, and prospective studies have shown elevated HOMA-IR is associated with significantly increased risk of developing type 2 diabetes, even when A1c is normal.

HOMA-IR catches the years-long buildup of metabolic dysfunction that glucose testing can miss.

C-Peptide complements HOMA-IR by revealing how hard your pancreas is working. It’s released in a 1:1 ratio with insulin from pancreatic beta cells, but with a much longer half-life (20-30 minutes compared to insulin’s 3-5 minutes), making it a more stable measurement. C-Peptide also bypasses liver clearance (the liver metabolizes roughly half of all insulin on first pass) so it’s a more accurate reflection of actual pancreatic output.

High C-Peptide with normal glucose means your pancreas is compensating. The engine is running hot even though the speedometer reads fine.

How metabolic markers affect fitness and body composition

Leptin and Adiponectin: what your fat tissue is telling you

Not all fat tissue behaves the same way. Two hormones secreted by fat cells (leptin and adiponectin) signal whether your adipose tissue is functioning normally or driving metabolic dysfunction.

Leptin rises with increasing fat mass and promotes inflammation. Adiponectin decreases with increasing fat mass and works against inflammation while improving insulin sensitivity. In metabolic dysfunction, leptin climbs while adiponectin falls.

The ratio between them captures aspects of metabolic risk that complement measures like HOMA-IR. Research has proposed cutoffs: a ratio above 1.0 indicates normal adipose function, 0.5-1.0 indicates moderate increased risk, and below 0.5 indicates severe cardiometabolic risk. The ratio can detect adipose tissue dysfunction before it shows up as metabolic syndrome on standard labs, and it also tracks improvement, making it useful for monitoring whether interventions are working.

Free T3 and Free T4: energy regulation beyond TSH

Standard thyroid screening tests TSH (thyroid-stimulating hormone) and sometimes total T4. That catches most overt thyroid disease. But TSH can read normal while the active thyroid hormones are off.

T4 is the precursor thyroid hormone. It has to be converted into T3, the active form that actually regulates your metabolic rate, energy, and cognition. Among patients on thyroid medication with “normal” TSH, 15.2% have Free T3 levels below the normal range. Their screening test says everything is fine, but the hormone responsible for driving metabolism is deficient.

Free T3 and Free T4 testing can help identify differences in thyroid hormone production and conversion that may not be fully captured by TSH alone.

GGT: the early metabolic stress signal

Gamma-Glutamyl Transferase (GGT) is traditionally associated with liver function. But in the Framingham Heart Study, GGT independently predicted metabolic syndrome, cardiovascular disease, and death. It can rise before standard liver enzymes flag anything abnormal, making it an early signal of oxidative stress and metabolic strain.

Uric acid

Elevated uric acid is associated with oxidative stress, endothelial dysfunction, and impaired insulin sensitivity. It sits at the intersection of metabolic and cardiovascular risk, and higher levels are associated with increased risk of developing type 2 diabetes. When interpreted alongside other metabolic markers, uric acid helps distinguish temporary lifestyle effects (dehydration, high-purine diet) from sustained metabolic patterns.

The building blocks: minerals that drive metabolic function

Many of the markers above don’t exist in isolation. Mineral deficiencies affect thyroid conversion, insulin sensitivity, immune function, and energy metabolism. When cofactors are depleted, other biomarkers look worse than the underlying biology requires, and supplementing the right mineral can shift the picture.

Magnesium is one of the most common deficiencies in Western countries. A large share of Americans consume less than the Estimated Average Requirement, and 10-30% are subclinically deficient. Magnesium serves as a cofactor for enzymes in glucose metabolism and acts as a second messenger for insulin. Deficiency may contribute to insulin resistance directly, not just result from it. For active adults, strenuous exercise increases magnesium losses through sweat and urine, potentially raising requirements by 10-20%.

Zinc intake is inadequate in a meaningful share of US adults, and athletes face a paradox: they often have lower serum zinc despite higher dietary intake, because exercise increases losses through sweat and urine. Zinc deficiency in active individuals can present as fatigue, decreased endurance, and impaired recovery.

Selenium is a key thyroid mineral. The thyroid contains the highest selenium concentration per gram of any organ, and selenium-dependent enzymes are responsible for converting inactive T4 into active T3. In a study of 6,152 participants, thyroid disease prevalence was 30.5% in low-selenium areas compared to 18.0% in adequate-selenium areas. If your Free T3 is low, selenium status is one of the first things to check.

Iodine deficiency is re-emerging. In the US, a significant share of the US population has urinary iodine concentration below adequate levels, indicating deficiency. Iodine is the raw material for T3 and T4 production; without it, the thyroid’s ability to synthesize hormones is impaired, regardless of how well the rest of the system is functioning.

Copper supports thyroid function from the other direction; deficiency reduces circulating T4 and T3 concentrations and impairs the peripheral conversion of T4 to T3. It’s frequently underrecognized as a contributor to fatigue and metabolic disruption.

Phosphorus is the energy currency mineral. It’s critical for ATP generation (the molecule that powers every cellular process), cell signaling, bone mineralization, and acid-base balance. Deficiency impairs cell metabolism at the most basic level.

The Metabolic Health Panel tests all six of these minerals alongside your insulin, thyroid, and adipose markers, so you can see whether a mineral gap is contributing to what the other numbers show.

What the WHOOP Metabolic Health Panel includes

The Metabolic Health Panel tests 78 biomarkers, including 18 markers unique to this panel — markers you won’t find on a standard annual physical or a general health screening. Those unique markers include:

• Insulin and glucose dynamics: C-Peptide, 1,5-AG, Fructosamine, HOMA2-IR, eAG
• Body composition hormones: Leptin, Adiponectin, Leptin/Adiponectin Ratio
• Minerals: Zinc, Selenium, Iodine, Copper, Magnesium, Phosphorus
• Thyroid detail: Free T3, Free T4
• Early metabolic stress: GGT, Uric Acid
• Nutrients: Vitamin B12, Folate

The remaining biomarkers cover the metabolic foundation, including fasting glucose, insulin, and HbA1c (the glycemic baseline that C-Peptide, 1,5-AG, and fructosamine deepen), TSH (the thyroid screen that Free T3/T4 extend), ALT, AST, and ALP (the liver baseline that GGT builds on), hsCRP (the inflammation context for interpreting adipokines), plus standard lipid panel, CBC, iron studies, and Vitamin D. You get the baseline covered and the depth added in one test.

Every result is reviewed by a licensed clinician. The panel’s biomarker selection was developed with WHOOP’s Medical Advisory Board, and all testing is exclusively powered by Quest® Diagnostics. No subscription or baseline test required. FSA/HSA eligible. Schedule a test at 2,000+ Quest® locations nationwide, right in the WHOOP app.

Frequently asked questions

What is insulin resistance and how is it detected? Insulin resistance occurs when your cells become less responsive to insulin, forcing your pancreas to produce more of it to keep blood sugar in range. It’s detected through markers like HOMA-IR (which quantifies resistance), C-Peptide (which measures pancreatic output), and fasting insulin. Standard panels test only glucose and A1c, which can stay normal for years to decades while insulin resistance builds. By the time glucose rises, the dysfunction has been present for a long time.

What’s the difference between A1c and 1,5-AG? A1c reflects your average blood sugar over the past 2-3 months. 1,5-AG detects glucose spikes above roughly 180 mg/dL within the past 1-2 weeks. Two people can have the same A1c but very different glucose patterns, one stable, one spiking after every meal. 1,5-AG separates them. It’s especially useful for people whose A1c looks normal but who suspect post-meal glucose variability.

What does the Leptin/Adiponectin ratio tell you? Leptin rises with increasing fat mass and promotes inflammation. Adiponectin decreases with increasing fat mass and improves insulin sensitivity. Their ratio captures aspects of metabolic risk that complement traditional markers. A high ratio suggests your fat tissue may be driving metabolic dysfunction. The ratio also tracks improvement, making it useful for monitoring whether interventions are working.

Why are minerals included in a metabolic health panel? Minerals like magnesium, zinc, selenium, iodine, and copper serve as cofactors for the enzymes that drive thyroid function, insulin sensitivity, and energy metabolism. When they’re depleted, other biomarkers look worse than the underlying biology warrants, and supplementing the right mineral can shift the picture. About 50% of Americans consume less than the recommended amount of magnesium alone.

Want to understand what standard bloodwork misses across all five health domains? Read: What Your Doctor’s Bloodwork Misses.

WHOOP Advanced Labs includes Specialized Panels, the Comprehensive Health Panel for ongoing longitudinal tracking, and free blood work uploads. Choose the path that fits you. Explore Advanced Labs.

This data is not diagnostic and does not identify individuals; individual results vary.