What is insulin resistance, and why is it so often missed?

What's actually happening in the body with insulin resistance?

In insulin resistance, the body’s cells respond less to insulin, the pancreas compensates by making more of it, and that excess insulin quietly changes how the body stores fat and handles inflammation. Insulin is the hormone made by the pancreas (the organ behind your stomach) that helps move sugar from your bloodstream into cells where it can be used for energy. In insulin resistance, cells stop responding well to that signal. To compensate, the pancreas produces more insulin to push sugar into cells anyway.

Elevated insulin has its own consequences. It promotes fat storage. It inhibits fat release. It contributes to inflammation. And eventually, the pancreas can't keep up with demand, blood sugar rises, and the diagnosis becomes prediabetes or type 2 diabetes.

How common is insulin resistance, and who has it?

Roughly 4 in 10 nondiabetic US adults have insulin resistance [PMID: 40364246], and it is most common with age, abdominal weight and a family history of diabetes, though many people with none of those have it too. Insulin resistance is far more common than most people realize. The age-standardized prevalence in nondiabetic US adults rose from 24.8% in 1999-2000 to 38.4% in 2017-2018, with hyperinsulinemia (elevated fasting insulin) now affecting roughly 41% of nondiabetic adults [PMID: 40364246]. The trajectory has been upward across all sociodemographic groups for decades.

It's more common with age, with abdominal weight, with family history of diabetes, and in certain ethnic groups (particularly Black, Hispanic, South Asian, and Native American populations). But it's also present in many people who don't fit any of those profiles.

What does the progression look like?

The progression runs from rising insulin with normal glucose, to glucose spikes after meals, to a creeping fasting glucose that earns the label prediabetes, and eventually to type 2 diabetes, usually over many years. Insulin resistance progresses through recognizable stages, but slowly. Insulin starts rising while glucose stays normal. That phase can last 10 years or more. Then post-meal glucose starts spiking. Then fasting glucose creeps up, and the diagnosis becomes prediabetes (HbA1c 5.7 to 6.4% or fasting glucose 100 to 125 mg/dL) [Source: ADA 2024 Standards of Care, Classification and Diagnosis of Diabetes]. Eventually, if untreated, type 2 diabetes.

The earlier in this progression you catch it, the more reversible it is.

What labs actually pick it up early?

Fasting insulin, HOMA-IR, the triglyceride-to-HDL ratio and the patterns on a continuous glucose monitor pick up insulin resistance years before fasting glucose and HbA1c change. Several labs catch insulin resistance years before standard glucose testing would:

• Fasting insulin. This is the marker that changes first, often years before anything else. Most labs report a wide reference range (something like 2 to 25 µU/mL), but values around 10 or above are considered elevated in the research [PMID: 40364246]. Many precision physicians want this number on the lower end, not just inside the range
• HOMA-IR. A simple calculation that combines fasting insulin and fasting glucose into a single insulin sensitivity score. The lower, the better. Most insurance-based panels don't include this; you usually have to ask
• Triglyceride-to-HDL ratio. A useful clue from any standard lipid panel. Triglycerides are a type of blood fat; HDL is the so-called "good" cholesterol. When the ratio is elevated, insulin resistance is often the reason
• Continuous glucose monitor (CGM). A small wearable that shows exactly how blood sugar responds to food, sleep, exercise, and stress. Now available without a prescription [Source: FDA 510(k) clearance K234070, Dexcom Stelo 2024]. The patterns it reveals are often more informative than any single fasting blood draw
• Fasting glucose and HbA1c. These show up on most physicals. Fasting glucose is your blood sugar after an overnight fast; HbA1c is a 3-month average of your blood sugar. Both shift late in the progression. By the time they're abnormal, insulin resistance has been going on for years

What does insulin resistance actually look like?

Insulin resistance tends to look like weight that settles on the midsection, energy crashes after meals, sugar cravings, dark velvety skin patches or skin tags, irregular cycles in women, and liver enzymes that drift up without explanation. Things that often accompany insulin resistance:

• Weight that creeps onto the midsection and won't come off
• Energy crashes after meals
• Sugar cravings
• Dark velvety patches of skin around the neck or armpits (a finding called acanthosis nigricans, often a visible sign of insulin resistance)
• Skin tags
• Irregular cycles or fertility issues in women
• Elevated liver enzymes on routine bloodwork that go unexplained
• Difficulty losing weight even with significant effort

Why does insulin resistance matter beyond weight?

Insulin resistance is the upstream driver of much of what shortens healthspan, the years of healthy, functional life. Type 2 diabetes is the obvious endpoint, but it's also a major contributor to cardiovascular disease, fatty liver, PCOS (polycystic ovary syndrome, a hormonal and metabolic condition affecting many women), certain cancers, and Alzheimer's disease. Researchers now sometimes refer to Alzheimer's as "type 3 diabetes" because brain insulin signaling looks similar to what happens in the body [PMID: 35269827].

Catching insulin resistance early changes a lot of long-term trajectories at once.

What actually reverses insulin resistance?

Strength training, fewer refined carbohydrates, consistent sleep, a regular eating window, a few well-studied nutrients and, when appropriate, medication are what consistently improve insulin sensitivity. It's one of the most reversible chronic conditions in medicine when caught early. The interventions that consistently work:

• Strength training. Muscle is where most of the body's glucose ends up after a meal. Building muscle increases your capacity to handle carbohydrates and improves insulin sensitivity directly [PMID: 16394814], even when the muscle gain is modest. This is one of the highest-leverage things you can do
• Reducing refined carbohydrates and ultra-processed foods. Less work for the insulin system, more stable energy
• Sleep. Even a few nights of poor sleep can measurably worsen insulin sensitivity in healthy people. Chronic poor sleep is a slow drag on metabolism
• Time-restricted eating. Eating in a consistent window, often somewhere between 8 and 12 hours, gives the insulin system a daily rest
• Specific nutrients with research support. Magnesium, berberine (a plant compound used in traditional medicine), inositol (a vitamin-like compound, especially helpful for PCOS-related insulin resistance), and a few others
• Medications when appropriate. Metformin is the long-standing first-line option [Source: ADA 2024 Standards of Care]. GLP-1 medications work on a different mechanism and have changed what's possible for many patients with significant insulin resistance

What's the connection to PCOS?

Insulin resistance is the underlying driver of most cases of PCOS. The visible PCOS symptoms (acne, hirsutism meaning unwanted facial or body hair, weight resistance, irregular cycles) are largely downstream of insulin resistance. PCOS affects somewhere between 6 and 22% of women of reproductive age depending on which diagnostic criteria are used.

Treating the insulin resistance often resolves the visible PCOS features by addressing the upstream metabolic driver. This is why PCOS isn't just a reproductive condition; it's a metabolic condition with reproductive manifestations.

Can I work out HOMA-IR from my own numbers?

Yes, provided the report shows fasting glucose and fasting insulin drawn at the same visit. HOMA-IR, the homeostatic model assessment of insulin resistance, is simply those two numbers multiplied together and scaled by a fixed constant, and the higher the result, the more insulin the body is using to hold glucose in range while fasting.

The index was published in 1985 by a group who modelled the feedback loop between fasting glucose and fasting insulin and checked their estimate against the research gold standard, the insulin clamp, with which it correlated closely [PMID: 3899825]. The same paper reported a coefficient of variation of about 31% for the insulin resistance estimate [PMID: 3899825], which is the honest caveat: two draws a week apart can give noticeably different scores, and insulin assays differ between laboratories, so a single HOMA-IR is a reasonable estimate rather than a precise measurement.

What the number is: a fasting snapshot of how hard the liver and the pancreas are working to keep glucose steady overnight. What it is not: a measure of what happens after meals, which is where insulin resistance often shows first, and it is unreliable in anyone whose pancreas is no longer keeping up. There is no single agreed cutoff; different populations have used different lines, which is why many precision physicians read HOMA-IR alongside fasting insulin itself, the triglyceride-to-HDL ratio and, when the picture is unclear, glucose and insulin measured after a sugar load.

The useful reading is the trend across draws, held against weight, waist, sleep and the rest of the panel. A physician who follows the number over time can tell whether a plan is working long before glucose or HbA1c would say so.

What kind of doctor works up insulin resistance?

An internal medicine physician or a primary care physician works up insulin resistance, and an endocrinologist, a physician who specializes in hormones and metabolism, is brought in when the picture is complicated: diabetes that has become hard to control, a question of another endocrine disorder, or a severe or unusual presentation.

The workup is mostly history and ordinary blood draws. The history covers the weight trajectory and where the weight sits, family history of diabetes, sleep and snoring, energy after meals, cycle regularity in women, and every medication, since several classes raise insulin resistance. The examination notes waist size, blood pressure and skin changes such as dark velvety patches or skin tags. The labs are fasting glucose and fasting insulin (with HOMA-IR calculated from them), HbA1c, a lipid panel read for the triglyceride-to-HDL ratio, ApoB, liver enzymes, uric acid and hs-CRP, with thyroid and sex hormone panels when the history points that way. Some physicians add a short run on a continuous glucose sensor, now sold over the counter, to see how glucose behaves around real meals and nights.

What matters as much as which tests are ordered is what happens with the results. The physician doing this work typically reads fasting insulin against the low end of the range rather than the top, decides which finding would actually change the plan, sets the order in which sleep, muscle, food and medication get addressed, and coordinates with the primary care physician, an endocrinologist or an OB-GYN when one is already involved. Because the workup runs on history and standard labs, it is well suited to care by video, with the blood drawn at a local laboratory.

What does the triglyceride-to-HDL ratio tell you?

The triglyceride-to-HDL ratio, triglycerides divided by HDL cholesterol from an ordinary lipid panel, is a quick proxy for insulin resistance: when insulin is chronically high, the liver packages more triglyceride into the bloodstream and HDL tends to fall, so the ratio rises.

In a study of overweight, nondiabetic adults who had their insulin sensitivity measured directly, a ratio above 3.0 (in the units US laboratories report) was among the most useful simple markers for picking out those who were insulin resistant, though it caught roughly two in three of them and flagged about one in three who were not [PMID: 14623617]. That is the right way to hold the number: a clue that is easy to get and worth acting on, not a diagnosis.

The ratio also performs differently across populations. In a study of overweight African American adults whose insulin sensitivity was measured directly, neither fasting triglycerides nor the ratio tracked insulin resistance, and the usual lipid cut points identified only 17% of those who were insulin resistant, so in that group a normal ratio is less reassuring and fasting insulin carries more weight [PMID: 15983289].

In practice the ratio earns its keep in two situations: an old lipid panel sitting in a patient portal from years ago, which can show when the pattern started, and a normal fasting glucose paired with a high ratio, which is the classic early signature that fasting insulin then confirms. A physician reads it with the triglyceride number itself, ApoB and the liver enzymes, since the same high-insulin state that raises the ratio tends to raise them too.

What does a prediabetes result actually change?

A prediabetes result changes the timeline and the plan more than the biology: the process behind it has usually been running for years, and the label marks the point where glucose can no longer hide it. What it does change is the urgency, the breadth of the workup, and how success gets measured.

The strongest reason for optimism is trial data. In the Diabetes Prevention Program, adults with elevated fasting and post-meal glucose who joined a structured lifestyle program aimed at modest weight loss and regular activity had 58% fewer new cases of diabetes over roughly three years than those given a placebo [PMID: 11832527]. Progression is common without action and far from inevitable with it.

What a physician does with the result is widen the lens. Prediabetes rarely travels alone: the same insulin resistance raises triglycerides and ApoB, pushes fat into the liver, and often sits next to untreated sleep apnea, high blood pressure or, in women, PCOS, so the next step is usually a fuller panel (fasting insulin, a lipid panel with ApoB, liver enzymes, uric acid) and a sleep history rather than a repeat of the same glucose test. The result also resets the follow-up rhythm: glucose and HbA1c get rechecked on a schedule, and the plan is judged on whether fasting insulin, waist size, triglycerides and liver enzymes move, not on the A1c alone.

The label itself is a range on two tests, and where a person sits inside it matters less than the direction of travel. A reading that has crept up over three physicals says something different from one that appeared after a year of poor sleep and a new medication, and that context, not the number, is what decides whether the right response is food, sleep and strength training alone or a glucose-lowering medication alongside them.

Why is fasting glucose highest in the morning?

Fasting glucose is often the highest reading of the day because of the dawn phenomenon: in the last hours of sleep the body releases cortisol, growth hormone and adrenaline to prepare for waking, and those hormones tell the liver to release stored glucose. In someone whose liver still answers to insulin, a small rise in insulin keeps the number flat; when the liver has become insulin resistant, the morning output goes unchecked and the fasting value drifts up.

This is why a morning fasting glucose is really a liver number, not a food number. It says little about last night’s dinner and a lot about how well insulin is restraining the liver overnight. A late or large evening meal, alcohol, a short or broken night’s sleep and a stressful drive to the laboratory all push it higher; an evening walk or a strength session the day before tends to pull it down.

The pattern is easy to see on a continuous glucose sensor, which shows whether glucose ran flat all night and rose before waking, the classic dawn shape, or climbed steadily through the night, which points elsewhere. For someone taking glucose-lowering medication, high morning readings are a question for the clinician managing that treatment, since the treatment itself shapes the overnight curve. For everyone else, a morning number that stands above an otherwise normal day is one of the earlier signatures of a liver that is losing its sensitivity to insulin, and fasting insulin drawn at the same time usually explains it.

Are skin tags and dark patches on the neck related to insulin?

Often, yes. The dark, velvety thickening of skin in the folds of the neck, armpits and groin is called acanthosis nigricans, and both it and clusters of small skin tags are associated with high circulating insulin: insulin at high levels stimulates growth receptors on skin cells, and the skin in the body’s folds responds by thickening and darkening [PMID: 15186199].

Neither finding is a diagnosis. Plenty of people with insulin resistance have clear skin, and skin tags in particular are common with age and friction alone. The findings are a prompt for a fasting insulin and the rest of the metabolic panel, not a verdict. In one case-control study, adults with two or more skin tags had higher measures of insulin resistance, fasting glucose and blood pressure than matched controls [PMID: 24761238], and the darkening of acanthosis nigricans tends to fade as insulin levels fall [PMID: 15186199].

A physician looking at these changes also rules out the other causes. Acanthosis nigricans runs in some families, is more visible on darker skin, appears with PCOS, and can be triggered by certain medications and rarer hormone disorders. Darkening that appears abruptly, spreads widely, or shows up on the palms or lips, especially in an older adult, is a different entity that can signal an internal cancer and warrants prompt medical evaluation.

The deeper picture

Insulin resistance is rarely the only thing happening when it's present. It interacts with thyroid function, with cortisol (the body's main stress hormone), with sex hormones, with sleep, with inflammation. The lab numbers tell part of the story; how to act on them depends on the whole picture, and on the specific person.

The challenge with insulin resistance is that the standard screening focuses on glucose, which changes years after insulin resistance has started. The labs that catch it early are inexpensive, but most patients have to ask for them specifically. Extend's standard workup includes them as part of comprehensive metabolic assessment.