Insulin Resistance (part 1)- what it is and how to test for it

 If you have ever been told you might be “insulin resistant,” or you’ve found yourself wondering why your body no longer responds the way it once did, you are very much not alone.

Insulin resistance is a term that comes up frequently in conversations about weight, blood sugar, and metabolic health, yet it is often poorly explained. My aim here is to walk you through what insulin resistance actually is, how it develops over time, and why testing for it can feel confusing.

This is not about something suddenly “going wrong.” It is about understanding how an extraordinarily adaptive system responds to modern pressures.

What insulin is actually doing in the body

Your body keeps blood glucose within an astonishingly narrow range. At any given moment, there are only about four grams of glucose circulating in the bloodstream — roughly a teaspoon — yet this balance is maintained continuously, day and night.

Insulin is the hormone that makes this possible. After you eat, insulin is released to help move glucose out of the bloodstream and into cells — particularly muscle, liver, and fat cells — where it can be used for energy or stored for later. In metabolically healthy states, this system is tightly regulated and remarkably efficient.

But insulin does more than manage blood sugar. It is an anabolic hormone that supports growth, tissue repair, and energy storage. It influences fat metabolism, protein synthesis, and even signalling in the brain. When insulin is not working as effectively as it should, the effects extend far beyond glucose alone.

What insulin resistance actually means

Insulin resistance occurs when the body’s cells become less responsive to insulin’s signal. Glucose does not move into cells as efficiently, so the pancreas compensates by producing more insulin to achieve the same result.

A helpful analogy is caffeine tolerance. The first coffee works beautifully. Over time, you need more caffeine to feel the same effect. The caffeine hasn’t stopped working — your sensitivity to it has changed. Insulin resistance works in much the same way. Higher and higher insulin levels are required to keep blood glucose stable, and this compensation can continue quietly for many years.

Importantly, insulin resistance exists on a spectrum. It often precedes measurable disease by 10–15 years, long before someone is diagnosed with type 2 diabetes or metabolic syndrome.

How insulin resistance develops over time

There is no single cause of insulin resistance. It develops through the interaction of multiple biological processes influenced by genetics, lifestyle, and environment.

One of the central mechanisms involves fat accumulating in places it does not belong — particularly within muscle and liver cells. When fatty acids overflow into these tissues, they interfere with insulin signalling at a cellular level, a process known as ectopic fat accumulation.

At the same time, enlarged fat cells can become inflamed. These cells release inflammatory cytokines (inflammation signals) such as TNF-α, which further disrupt insulin signalling pathways. This creates a compounding loop: inflammation worsens insulin resistance, and insulin resistance promotes further inflammation.

Mitochondrial function also plays a critical role. Mitochondria are responsible for energy production and fat oxidation. When their function is impaired — something observed even in young, lean individuals with insulin resistance — fats are less effectively used for energy and instead accumulate within cells, further impairing insulin action.

A note on fat oxidation: Fat oxidation is the process where your body breaks down stored or circulating fat and uses it as fuel to make energy. It happens mainly in the mitochondria of your cells and is especially active at rest, during low-to-moderate intensity movement, and overnight when insulin levels are lower. When fat oxidation is working well, your body can flexibly switch between burning fat and carbohydrate depending on what it needs — a key marker of good metabolic health.

While excess body weight increases risk, insulin resistance can develop independently of body size. Research consistently shows that people can appear lean yet still be insulin resistant due to genetic susceptibility, inflammation, mitochondrial dysfunction, or environmental exposures.

Why insulin resistance often goes unnoticed

One of the reasons insulin resistance is so often missed is that the body is exceptionally good at compensating. Blood glucose can remain completely normal for years while insulin levels quietly rise behind the scenes.

This is why insulin resistance is often described as a hidden metabolic state. By the time fasting glucose or HbA1c (a blood marker commonly tested by your GP to look for diabetes) levels rise, the underlying process has usually been present for a long time.

During this prolonged compensatory phase, insulin resistance may already be contributing to changes in blood lipids, blood pressure, uric acid levels, blood vessel function, and inflammatory markers — all before a formal diagnosis appears.

Patterns that can be linked to insulin resistance

Insulin resistance does not present with a single symptom profile. Some women feel nothing at all in the early stages. Others notice more subtle patterns emerging gradually.

Common associations include increased central fat storage, particularly around the abdomen; difficulty maintaining stable energy levels; post-meal fatigue; stronger hunger signals; and increased cravings for quick-energy foods.

Biochemically, insulin resistance is often linked with raised triglycerides, lower HDL cholesterol (both found in your cholesterol blood panel), rising blood pressure, and low-grade inflammation — all reflections of the body working harder to maintain metabolic balance.

It is important to emphasise that these patterns do not represent failure. They represent adaptation.

What insulin resistance testing is really measuring

If insulin resistance has come up in relation to your health, testing can feel confusing. Some women are told their blood sugars are “normal,” yet insulin resistance is still suspected. Others are told results are “borderline” without a clear explanation of what that means.

The key distinction is this: insulin resistance is not primarily about how high glucose goes. It is about how much insulin the body must produce to keep glucose within a healthy range.

In an insulin-sensitive state, relatively small amounts of insulin are enough to manage glucose effectively. In an insulin-resistant state, the same glucose control requires larger and often more prolonged insulin responses.

The underlying question testing is trying to answer is therefore simple, but profound:

How hard does the pancreas have to work (how much insulin is being produced) to maintain glucose balance?

The gold standard: the hyperinsulinaemic–euglycaemic clamp

In research settings, the most accurate way to measure insulin resistance is the hyperinsulinaemic–euglycaemic clamp.

In this test, insulin is infused at a fixed rate while glucose is infused simultaneously to keep blood glucose perfectly stable. If someone is insulin sensitive, only a small amount of glucose is needed to maintain that balance. If someone is insulin resistant, far more glucose must be infused to counteract insulin’s reduced effectiveness.

What the clamp measures is how much glucose is required to balance a given amount of insulin — a direct reflection of insulin efficiency.

The reason this test is not used in routine clinical practice is practical rather than scientific. It is invasive, expensive, time-intensive, and requires specialised facilities.

Why everyday clinical testing is indirect

Because insulin sensitivity cannot be measured directly in routine care, clinicians rely on surrogate markers — tests that reflect insulin demand or its downstream metabolic effects rather than insulin resistance itself.

No single test tells the full story. Understanding what each test represents is far more useful than categorising results as simply “normal” or “abnormal.”

Fasting insulin and HOMA-IR

HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) is calculated using fasting glucose and fasting insulin- a simple blood test you can get at your blood lab. Fasting ideally only water for 12 hours prior to the blood test.

If fasting glucose is normal but fasting insulin is elevated, insulin is already working harder than it should to maintain baseline glucose balance. If both glucose and insulin are elevated, insulin resistance is more advanced and pancreatic compensation may be under increasing strain.

HOMA-IR reflects basal insulin demand and can detect early insulin resistance before glucose rises. Its limitation is that it provides only a resting snapshot and does not show how the body responds to a glucose challenge.

Oral glucose tolerance testing with insulin

An OGTT with insulin and glucose is a test where you drink a measured glucose solution and have blood samples taken over time to see how well your body handles sugar and how much insulin it needs to keep blood glucose in a healthy range. Usually this is a fasting test at the blood lab, then a sugar drink, and then a test at 1 hour and another at 2hours to see how your body is dealing with the big sugar load.

When insulin is measured alongside glucose during an oral glucose tolerance test, the picture becomes far more informative.

Two women may have identical glucose curves within the “normal” range, yet one may require a large and prolonged insulin surge to achieve that result. That hidden effort is insulin resistance — and it is invisible if insulin is not measured.

This approach is particularly valuable for identifying insulin resistance years before fasting glucose or HbA1c become abnormal.

Continuous glucose monitoring: useful context, not diagnosis

A CGM (continuous glucose monitor) is a small wearable sensor that continuously tracks glucose levels day and night, giving real-time insight into how food, movement, sleep, and stress influence your blood sugar. It’s simple to apply at home — the sensor is gently stamped onto the skin, where a tiny filament sits just under the surface to measure glucose in the interstitial fluid, which closely reflects blood glucose levels. The sensor then sends this data to an app on your phone, displaying easy-to-read graphs that show how your glucose changes across the day in response to everyday life.

Continuous glucose monitors measure glucose patterns over time but do not measure insulin.

They can reveal post-meal glucose excursions and delayed clearance, but they cannot tell us how much insulin was required to produce those patterns. Two people can show very similar CGM traces while one is producing significantly more insulin than the other.

CGMs are therefore best understood as a window into glucose behaviour, not insulin efficiency. However we know that big sugar spikes contribute to inflammation and insulin resistance; therefore, they can be a great tool for learning how your body responds to food, exercise, stress and sleep.

Other metabolic clues across routine blood tests

Insulin resistance often leaves subtle fingerprints long before blood sugar rises.

Mild elevations in ALT or GGT (liver function blood tests) can reflect liver insulin resistance and early metabolic fatty liver, even in women who drink little alcohol and do not consider themselves overweight.

Lipid patterns (cholesterol blood testing) commonly include elevated triglycerides and lower HDL cholesterol due to altered fat handling. Some clinicians use the triglyceride-to-HDL ratio as a rough surrogate marker; ratios above ~1.1 (mmol/L) are increasingly associated with insulin resistance when glucose remains normal, though this must always be interpreted in context.

Uric acid (another blood test) can also rise as insulin reduces kidney excretion, making it an under-recognised metabolic signal.

When insulin levels stay high for long periods, it can raise blood pressure by causing the body to hold onto salt, stimulating the nervous system, and affecting how blood vessels relax and tighten. Ongoing low-grade inflammation in the body — often seen on blood tests like CRP — can also disrupt how insulin works, making these problems more likely.

Why normal glucose does not always mean normal metabolism

One of the most misunderstood aspects of insulin resistance is this:

You can have normal glucose because insulin resistance is already present.

For many years, the pancreas compensates by producing more insulin, keeping glucose within normal ranges. This compensatory phase can last a decade or more. By the time type 2 diabetes is diagnosed, insulin resistance has usually been present for a very long time.

This is not a failure of testing. It is a reflection of how adaptable the human metabolic system truly is.

Pulling the picture together

Insulin resistance is best identified through patterns rather than single numbers.

Glucose shows the outcome.
Insulin shows the effort.
Liver enzymes, lipids, uric acid, blood pressure, and inflammation show where that effort is beginning to strain the system.

Understanding this framework allows results to be interpreted with clarity and reassurance — and sets the stage for meaningful, supportive intervention.

In the next article, we will explore how insulin resistance can be addressed and supported, working with the body rather than against it.

 Dr Taisia Cech

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