Insulin Resistance 101
Most 'normal' people already have it
Insulin resistance — cells responding poorly to insulin, requiring more of it to push glucose out of the blood — is the silent precursor to type 2 diabetes. The surprise: in population studies, ~88% of American adults show at least one marker of metabolic dysfunction. Most of them feel fine.
The progression: decades silent, then sudden
Insulin resistance develops silently over 10–20 years. During that time fasting glucose and HbA1c can still look 'normal' because the pancreas compensates by producing MORE insulin. Fasting insulin rises first — long before glucose. That's why fasting insulin is the under-appreciated early marker.
HOMA-IR — the DIY insulin-resistance score
HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) = (fasting glucose × fasting insulin) / 405. Optimal: under 1.0. Above 2.0 suggests insulin resistance. Above 3.0 is severe. You can calculate this from any basic lab panel that includes fasting insulin — which most standard panels SKIP. Ask for it.
Rank by how early each marker flags insulin resistance
From earliest-warning to last-to-move.
This step is interactive — open the Thier app to try it.
Where the resistance starts: ectopic fat
Insulin resistance doesn't start in the pancreas — it starts in the **liver and skeletal muscle**, where excess fat accumulates *inside* the cells (not around them). This **ectopic lipid** disrupts insulin signalling pathways (IRS-1 phosphorylation, GLUT4 translocation). Lean people who store fat in their liver or muscle ("TOFI" — thin outside, fat inside) can be more insulin-resistant than overweight people whose fat is purely subcutaneous. Where you store it matters more than how much you have.
Counter-intuitive: a high-fat meal raises glucose tomorrow
Conventional wisdom: "fat doesn't spike glucose." Reality: a single high-saturated-fat meal can **measurably reduce insulin sensitivity for 12–24 hours afterward**, raising the glucose spike of your *next* meal — even one with the same carbohydrate content. The mechanism is acute lipid accumulation in muscle cells transiently blocking insulin signalling. CGM users see this as the "second-meal effect" running in reverse: yesterday's dinner is influencing today's breakfast.
Reversibility: the DiRECT trial
Type 2 diabetes was treated as a one-way trip until the 2018 **DiRECT trial** (Lancet) put 306 patients on a 12-week 800-cal liquid diet. **46% achieved diabetes remission at 12 months — 86% if they lost ≥15 kg.** No drugs, no surgery. The mechanism: rapidly clearing ectopic fat from liver and pancreas restored beta-cell function. This rewrote the textbook: T2D is reversible up to a point, and the earlier you intervene, the steeper your odds.
Estimate your HOMA-IR cutoff
What HOMA-IR value typically indicates clear insulin resistance?
This step is interactive — open the Thier app to try it.
Key Takeaway
Insulin resistance is the under-diagnosed precursor to type 2 diabetes and to most of its damage. The driver is ectopic fat in liver and muscle, not body weight per se. Fasting insulin moves first; HbA1c moves last. Most importantly: it's reversible — the DiRECT trial showed near-half remission with sustained weight loss. The 'my glucose is normal' reassurance misses a 10–20 year window during which the problem is fully fixable.