HOMA-IR and fasting insulin

Have fasting insulin and fasting glucose drawn with your yearly bloods, in the same lab each time, and treat a HOMA-IR of about 2 or more as worth acting on. A lower value is reassurance, not a number to push down.

What it is

Fasting insulin is the amount of insulin in your blood after an overnight fast. As tissues become insulin-resistant, the pancreas compensates by pushing out more, so fasting insulin can rise while fasting glucose still looks normal.

HOMA-IR (homeostasis model assessment of insulin resistance) combines the two fasting values into one number: fasting glucose in mmol/L × fasting insulin in μIU/mL, divided by 22.5. Higher means more resistant. A common pattern in apparently healthy 40-somethings is a fasting glucose of 5.3 mmol/L (95 mg/dL), which counts as normal, alongside a fasting insulin of about 110 pmol/L (18 μIU/mL), well above the range seen in lean, healthy adults. That works out at a HOMA-IR of about 4.2.

Conventional reference ranges count a fasting insulin below about 150 pmol/L (25 μIU/mL) and a HOMA-IR below 2.5 as normal.

Why it can warn earlier than glucose

The standard diabetes screens, fasting glucose and HbA1c (a three-month average of blood sugar), are late signals. In a study of 6,538 British civil servants, insulin sensitivity fell steeply over the five years before a diabetes diagnosis, the pancreas briefly pushed out more insulin to compensate, and the sharp rise in fasting glucose began only about three years out.^[1] So fasting insulin and HOMA-IR probably pick up insulin resistance before glucose or HbA1c become abnormal; that rests on cohort data rather than on trials showing that testing improves outcomes.

Why the "optimal" targets don't hold up

No "optimal" HOMA-IR or fasting insulin has been tested against outcomes, and the targets sold online fail even a simple check against healthy people.

• Healthy people sit higher than the targets. In 21,684 lean adults with normal glucose and lipids, used to set one laboratory's reference interval (mostly women, aged 20–60, one assay), the median fasting insulin was about 40 pmol/L (6.5 μIU/mL) and the median HOMA-IR about 1.3 in both sexes, with 95% of values between 0.39 and 2.86.^[2] A target below 1.0 would put most of that healthy group above target.
• The outcome data point at the high end. Among 5,511 US adults without diabetes, the quarter with a HOMA-IR above 2.8 had about 64% higher mortality from any cause than the quarter at 1.4 or below (hazard ratio 1.64), a link seen only in people with a body mass index below about 25.^[3] This is an observational association, not proof that lowering the score extends life.
• Cut-offs depend on how they are set. In one Spanish population, the cut-off for insulin resistance sat near 2 (1.85–2.05) when tied to metabolic-syndrome risk, and at 3.46 on a purely percentile basis.^[4]

Taken together, a HOMA-IR of about 2 or more is worth acting on: that is roughly where metabolic-syndrome risk starts to climb, while the mortality study above found its extra deaths in the top quarter, above about 2.8. Pushing a lower value down further has no outcome evidence behind it and can mislead.

One lab, one trend

Insulin immunoassays are not standardised between laboratories, and the differences between methods are worst at low concentrations, exactly where healthy values sit.^[5] A fasting insulin from one lab cannot be read against a cut-off from another. Track your own trend in the same lab rather than treating a single value as a universal line.

Insulin resistance and low-grade inflammation also travel together; see hs-CRP.

What to do

1. Draw both values fasting, in the morning, once a year, alongside HbA1c, as part of the midlife lab panel.
2. Keep the same lab, so that a change reflects you rather than the assay.
3. Calculate HOMA-IR (glucose in mmol/L × insulin in μIU/mL ÷ 22.5). About 2 or more is worth acting on; below that, take it as reassurance.
4. Ignore targets below 1.0. In a large group of lean, healthy adults, most scored above 1.0.

Further reading

• Tabák AG et al. Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study. Lancet 2009.^[6]
• Schrank Y et al. Proposal for fasting insulin and HOMA-IR reference intervals based on an extensive Brazilian laboratory database. Arch Endocrinol Metab 2024.^[7]
• Ausk KJ et al. Insulin resistance predicts mortality in nondiabetic individuals in the U.S. Diabetes Care 2010.^[8]
• Rohlfing C et al. The current status of serum insulin measurements and the need for standardization. Clin Chem Lab Med 2025.^[9]