The Metabolic Domino Effect

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Issue #27: January 19, 2026

⚠️ Insulin Resistance: The Silent Metabolic Slow Creep

Most people think insulin resistance is a “diabetes thing.” It’s not. It’s the upstream metabolic dysfunction that quietly fuels the Four Horsemen Peter Attia talks about — cardiovascular disease, cancer, Alzheimer’s, and metabolic disease. Different diseases, same origin story: metabolic dysfunction. And metabolic dysfunction almost always starts with insulin resistance.

Here’s the part that should make you pause: multiple NHANES datasets suggest roughly 7 in 10 adults in the U.S. are metabolically unhealthy — using markers like triglycerides, waist circumference, fasting glucose, blood pressure, and HDL. Many clinicians and researchers (Casey Means among them) consider these patterns early warnings of insulin resistance.

Yet most of these people walk around with “normal” labs, completely unaware their metabolism is losing flexibility year after year.

If you care about living longer and better, you need to understand this — in plain English, not in biochem diagrams.

🧬 What Insulin Resistance Actually Is (In Plain English)

When you eat carbs, your body breaks them down into glucose — basically sugar your cells use for fuel. That glucose enters your bloodstream. Too much glucose floating around for too long is damaging, so your pancreas releases insulin, a hormone that moves glucose out of the blood and into your cells.

Think of insulin as a bouncer at a club: glucose wants in, insulin gets it through the door.

Now here’s the problem: if your diet is heavy in ultra-processed foods, you snack constantly, you don’t move much, you sleep poorly, and you’re stressed — your cells start ignoring insulin’s signals. They stop letting glucose in easily.

So your body does the only thing it knows: it makes more insulin.

Over time, insulin rises to keep blood sugar looking “normal.” This is the silent phase. Your glucose looks fine. Your HbA1c looks fine. You get gold stars from your doctor — while the underlying machinery is already compensating.

That compensatory state is insulin resistance: when the “bouncer” needs more muscle to get the same job done.

🧪 Why Most People Never Know They Have It

Here’s the wild part: standard bloodwork rarely checks insulin. It only measures:

• Glucose = sugar in your blood right now

• HbA1c = your 3-month average of blood sugar

These are lagging indicators. They don’t move until insulin resistance has been present for years.

Meanwhile the hormone that breaks first — insulin — is totally absent from routine panels. As Casey Means often notes, this means we diagnose metabolic dysfunction only once it becomes disease.

This is why millions of people are insulin resistant while carrying “normal” labs.

📊 Understanding the Numbers (Without the Jargon)

Let’s decode the key labs in human language:

Fasting Insulin (µIU/mL)

Functional medicine and metabolic researchers generally view:

• Optimal metabolic health: ~2–5

• Early compensation: ~5–8

• Borderline: ~8–15

• Likely insulin resistant: >15 (context matters)

These are functional/optimal ranges — not the broad “normal” reference ranges based on the average U.S. population (which is largely metabolically unhealthy).

For context, my fasting insulin is 2.3. That didn’t happen by accident — it reflects years of prioritizing protein, strength training, and metabolic health. The only reason I know this number is because I tested it — it’s not on standard labs.

HOMA-IR

A formula using glucose + insulin to estimate insulin resistance:

• Optimal: <1.0

• Borderline: 1–2

• Elevated: >2

Glucose vs. HbA1C vs. Insulin

A cheat sheet:

✔ Glucose = today
✔ HbA1c = last ~3 months
✔ Insulin = how hard your body is working behind the scenes

One more nuance: some endocrinologists argue mild insulin resistance is adaptive (e.g., during puberty, pregnancy, aging). Fair point. My take: adaptive doesn’t equal benign. If something is pushing you toward the Four Horsemen over decades, it’s worth addressing early.

🔥 Why Insulin Resistance Actually Matters

Chronically elevated insulin drives:

• inflammation

• fat storage, especially around organs

• adipose tissue dysfunction

• oxidative stress

• mitochondrial damage

• vascular injury

• brain aging

• hormonal dysregulation

This is why insulin resistance shows up in heart disease, Alzheimer’s, cancer, and metabolic disease — it’s the common thread.

🌸 Women, PCOS & Insulin

PCOS (polycystic ovary syndrome) affects ~10% of women, and many assume it’s purely a reproductive condition. But roughly 50–70% of women with PCOS are insulin resistant, even if they’re not overweight.

Simple version:

➡️ High insulin → ovaries produce more androgens (like testosterone) → disrupted cycles, cystic acne, fertility issues, stubborn belly fat.

Many women get put on birth control or metformin without anyone addressing the metabolic root.

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🧠 What Drives Insulin Resistance (Option A Depth)

It’s not just “carbs bad.” Other big levers:

Ultra-processed foods: fast spikes, no fiber
Sedentary lifestyle: muscle is a glucose sink — if you don’t use it, you lose it
Chronic cortisol: stress hormones raise glucose + impair insulin signaling
Poor sleep: one bad night worsens glucose tolerance
Circadian mismatch: late-night eating = worse glycemic response

Metabolism is holistic. Food matters, but so does movement, stress, and sleep.

🏋️‍♂️ How to Improve Insulin Sensitivity

Tier 1 — Foundation

• Minimize ultra-processed carbs

• Eat protein forward (0.7–1g/lb lean mass)

• Whole foods with fiber

• Walk after meals (10–20 min)

• Strength train 2–4x/week (muscle = metabolic insurance)

• Zone 2 cardio

• Earlier dinner

Tier 2 — Lifestyle

• Prioritize sleep (7–9 hours)

• Morning sunlight

• Stress modulation (breathwork, sauna, cold immersion, nature)

Tier 3 — Supplements (With Realistic Expectations)

• Berberine: insulin sensitizer, often compared to metformin in studies; can cause GI issues & may interact with meds — talk to a clinician first

• ALA

• Magnesium

• Chromium

• Myo-inositol: especially helpful for PCOS

But let’s be clear: you can’t supplement your way out of a bad diet or sedentary lifestyle.

🩺 Test, Don’t Guess (The CTA)

Supplements and lifestyle changes are great, but they’re useless if you don’t know your baseline.

Here’s how to check insulin resistance upstream:

✔ Ask your doctor for fasting insulin 
✔ Use Function Health
✔ Work with a functional medicine clinician who tests upstream

This is one of the highest-ROI blood tests you can run for longevity.

Until next week. Stay vital.

-Jordan Slotopolsky

📚 Sources & Further Reading

• Peter Attia, MD — Outlive, podcasts on metabolic disease

• Casey Means, MD — metabolic flexibility + upstream diagnostics

• Calley Means — healthcare incentives & metabolic burden

• Benjamin Bikman, PhD — insulin resistance research

• Pradip Jamnadas, MD — fasting & metabolic education

• NHANES data on metabolic health

• ADA & AACE diagnostic guidelines

• Trials on berberine, inositol, and ALA

• TG:HDL ratio as metabolic predictor