What is insulin resistance?

Insulin resistance occurs when a given amount of insulin produces less of its expected effect on the body’s tissues (James et al. 2021; Petersen & Shulman 2018). It is best understood as a metabolic state and a risk factor for type 2 diabetes and other metabolic complications, not a standalone disease.

Insulin resistance is also easy to miss. It usually causes no symptoms, and the pancreas responds by releasing more insulin, which can keep glucose (blood sugar) levels normal even when insulin’s action is substantially reduced (Abdul-Ghani & DeFronzo 2021). As a result, insulin resistance can be present for years before type 2 diabetes develops or standard glucose tests show anything abnormal.

In other words, the first sign is often that the body needs more insulin to do the same job, while blood sugar still looks normal. Researchers are still investigating how insulin resistance begins, what keeps it going, and whether high insulin levels are only a result of insulin resistance or may also help cause it (Abdul-Ghani & DeFronzo 2021).

How insulin resistance works

Insulin is the hormone that tells the body to move glucose out of the bloodstream for storage in cells or for use after eating. Insulin resistance occurs when the same amount of insulin leads to a reduced effect on target tissues (James et al. 2021; Petersen & Shulman 2018).

When insulin action is reduced, the pancreas may compensate by releasing more insulin to do the same work. Sustained elevated insulin levels are called hyperinsulinemia. When compensation is adequate, glucose levels can stay in the normal range for a substantial period, which is why insulin resistance can go unrecognized (Abdul-Ghani & DeFronzo 2021). Whether that extra insulin is purely compensatory or whether it can also feed back and worsen resistance remains unresolved and is discussed in the section of this article on what remains disputed (Abdul-Ghani & DeFronzo 2021; Xing & Chen 2022).

Insulin resistance is not limited to people with obesity. It can occur in lean people and in people with a family history of diabetes and other medical conditions (James et al. 2021; Petersen & Shulman 2018; NIDDK).

Where in the body it happens

Insulin resistance is not a single switch that shuts down glucose uptake or generation at once. Different tissues are affected differently in the same person (James et al. 2021; Petersen & Shulman 2018):

• Skeletal muscle is the largest site of insulin-stimulated glucose disposal. Insulin resistance causes less glucose uptake from the blood into skeletal muscle. This leads to an outsized effect on post-meal glucose handling.
• The liver becomes less responsive to insulin’s signal to suppress glucose production, so it may continue releasing glucose when it should not, even when insulin levels are elevated.
• Adipose (fat) tissue is less regulated in storing nutrients as fat and in suppressing fatty acids from moving into the bloodstream. This leads to more fatty acids circulating to other organs, causing fat buildup in those areas.

The ectopic lipid hypothesis is a well-described pathway that may explain how insulin resistance occurs in some cases (James et al. 2021). Fat accumulating inside tissues such as the liver and skeletal muscle, rather than in fat tissue, can generate lipid-derived signaling molecules that interfere with insulin signaling and weaken insulin’s effects in those tissues (Petersen & Shulman 2018).

Body tissues can differ; two people with the same fasting glucose can have quite different underlying physiology, and a single number rarely tells you which tissue is involved.

Why insulin resistance develops

Currently, no single established universal cause of insulin resistance exists. Contributors described in the research literature include (James et al. 2021; Petersen & Shulman 2018):

• Genetics and family history
• Adipose-tissue dysfunction and fat distribution
• Ectopic lipids in liver and skeletal muscle
• Physical inactivity and reduced muscle use
• Sleep disruption
• Medication effects
• Hormonal and physiological states, including pregnancy
• Aging
• Other metabolic stresses, such as inflammation and illness

More than one contributor may act together in varying degrees in different people; thus the cause of insulin resistance varies considerably in clinical practice (James et al. 2021). Insulin resistance can also occur without obesity.

For further reading, see the dedicated guide on the causes of insulin resistance.

Why insulin resistance usually causes no symptoms

Insulin resistance usually produces no recognizable symptoms. Glucose can remain below prediabetes and diabetes thresholds while insulin secretion compensates; the compensation itself is not something a person feels (NIDDK).

Increased thirst and frequent urination are symptoms of high blood glucose, not early signs of insulin resistance. They appear when glucose spills into the urine, a later development that can progress to diabetes if untreated and is not part of the compensated state (NIDDK).

Two physical findings are associated with insulin resistance: acanthosis nigricans, which is a darkened, velvety skin change often in the neck folds or armpits, and skin tags, also known as acrochordons. A study of these dermatologic findings reported an association with insulin resistance (Barbato et al. 2012). However, the presence of these skin changes is not a definitive diagnosis of insulin resistance.

More details are available in the guide to insulin resistance symptoms.

Normal blood sugar does not rule it out

Normal glucose levels do not indicate that a person does not have insulin resistance. While the pancreas compensates by secreting more insulin, glucose levels can be in the normal range despite weakened insulin action (Abdul-Ghani & DeFronzo 2021).

In cross-sectional studies of young, lean adult offspring of parents with type 2 diabetes and normal glucose levels, investigators identified marked insulin resistance in muscle alongside increased lipid levels inside muscle cells, even though their body weights and glucose levels were normal (Petersen et al. 2004; Morino et al. 2005).

Since the studies focused on selected high-risk participants and were cross-sectional snapshots, the findings cannot be applied to the general population and cannot show who will go on to develop insulin resistance or diabetes. Instead, the studies showed that having normal glucose levels and normal body weight can coexist with substantial insulin resistance.

Why insulin resistance is difficult to measure

Currently, no standardized routine clinical test can diagnose insulin resistance (NIDDK). Instead, doctors do a physical exam, check blood test results, and monitor trends.

Research methods can assess insulin sensitivity directly, but they are labor-intensive procedures used in study settings rather than in ordinary care. Routine clinical practice instead focuses on diagnosing glucose abnormalities using established criteria based on glucose levels and A1C measurements (ADA 2026, Section 2), then evaluating the overall metabolic picture, which includes body weight, blood pressure, lipids, and liver findings.

Research relies on surrogate measures. Fasting insulin and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), a calculation based on fasting glucose and fasting insulin, are widely used in research and sometimes in clinical practice. However, there are some limitations:

• Insulin assay disagreement. Different laboratories and analytical platforms can produce different insulin values for the same sample, because insulin measurement has not been standardized (Rohlfing et al. 2025).
• Biological variability. Insulin resistance markers vary within the same person from one measurement to the next, so a single HOMA-IR value does not accurately portray a person’s degree of insulin resistance (Carobene et al. 2025).
• No universally accepted thresholds. Proposed HOMA-IR cutoffs differ across ethnic populations, and further research is needed to identify the cutoffs (Tahapary et al. 2022).

A fasting insulin or HOMA-IR number is just a piece of the puzzle, not a diagnosis. Its meaning depends on the laboratory, the population reference used, and the rest of the clinical picture. For how these measures are performed and reported, see insulin resistance testing and the HOMA-IR calculator.

What insulin resistance is linked to

Although insulin resistance isn’t typically measured outside of a research setting, it is associated with several conditions:

Prediabetes and type 2 diabetes. These are defined by glucose and A1C criteria, not by insulin action (ADA 2026 Standards of Care). Insulin resistance can be present before either diagnosis applies. Having insulin resistance is not the same as having prediabetes or type 2 diabetes. See our guide to insulin resistance vs. prediabetes vs. type 2 diabetes for more.

Metabolic syndrome. This is a clustering of abdominal adiposity, elevated blood pressure, dyslipidemia, and dysglycemia. Insulin resistance is a major cause of this syndrome and a cardiometabolic risk (Neeland et al. 2024). Its history includes a documented organizational disagreement, covered later in this article.

MASLD and MASH. In 2023, a multisociety Delphi consensus changed the term non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD) (Rinella et al. 2023). MASLD requires the diagnosis of hepatic steatosis plus at least one cardiometabolic risk factor, which focuses on metabolic dysfunction as the cause rather than defining the condition by exclusion of alcohol (Rinella et al. 2023; EASL–EASD–EASO 2024). Also, nonalcoholic steatohepatitis (NASH) was renamed to metabolic dysfunction–associated steatohepatitis (MASH) for a similar reason. Because the diagnostic criteria changed, the prevalence of MASLD and MASH describes differently defined groups and should not be treated as interchangeable with the prevalence of NAFLD and NASH, respectively.

Cardiovascular risk. Insulin resistance is associated with elevated blood pressure and an atherogenic lipid pattern (blood fat abnormalities) that contribute to the metabolic syndrome cluster and increased cardiovascular risk (Neeland et al. 2024).

Polyendocrine metabolic ovarian syndrome (PMOS), formerly called polycystic ovary syndrome (PCOS). The condition was renamed through a multistep global consensus in 2026 because the syndrome affects not only the reproductive system but also the endocrine, metabolic, psychological, and dermatological systems (Teede et al. 2026). International evidence-based guidance recognizes metabolic features, including insulin resistance, as part of the clinical picture and its assessment (Teede et al. 2023).

When insulin resistance is discussed in relation to menopause, visceral fat, cognitive risk, and kidney disease, clinicians follow separate clinical guidelines for these specific conditions.

What has held up, what hasn’t, and what remains disputed

What has held up

Marked insulin resistance can precede detectable glucose intolerance. In cross-sectional studies of young, lean offspring of parents with type 2 diabetes and normal glucose levels, the insulin-resistant offspring group showed approximately 60% lower insulin-stimulated muscle glucose uptake and approximately 80% higher lipids in skeletal muscle cells compared to the response in control participants (Petersen et al. 2004). A companion study in the same selected population reported reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle, which leads to decreased insulin action in skeletal muscle cells (Morino et al. 2005). These studies were completed in a high-risk group; the results do not prospectively predict who develops diabetes, and cannot be extrapolated to the general population.

Ectopic lipid can impair insulin signaling. In healthy, lean participants studied under controlled lipid-infusion conditions, muscle insulin resistance developed within hours and tracked with increased diacylglycerol and PKCθ activation in skeletal muscle cells (Szendroedi et al. 2014). This establishes one possible pathway leading to insulin resistance in humans.

Insulin resistance is tissue-specific. Muscle, liver, and adipose tissue are affected to different degrees, as shown by the different possible pathways (James et al. 2021; Petersen & Shulman 2018).

Insulin resistance usually doesn’t cause symptoms but is a major risk factor for metabolic syndrome and cardiovascular disease (NIDDK).

What hasn’t held up, or hasn’t yet

The carbohydrate-insulin model (CIM) of obesity proposes that diets that produce high insulin secretion drive fat storage and subsequent hunger, making insulin a primary driver of common obesity rather than a consequence (Ludwig et al. 2021). On the other hand, the energy balance model (EBM) argues that obesity results from the effects of the modern food environment on energy intake through brain-mediated appetite regulation, without insulin occupying a primary causal role (Hall et al. 2022).

An independent commentary concluded in 2023 that the debate over the accuracy of the two models is still ongoing (Flier 2023), while a critical review of mechanistic and clinical studies argued that the evidence does not support the CIM as the primary explanation for common obesity (Ashtary-Larky 2026).

In summary, the CIM is an active scientific model that has not been established as the primary explanation for common obesity. Currently, it is neither proven nor debunked.

No standardized routine test diagnoses insulin resistance itself. Surrogate measures, such as HOMA-IR, carry laboratory and biological variability; furthermore, determining cutoffs is difficult because ethnic populations have different HOMA-IR values (NIDDK; Rohlfing et al. 2025; Carobene et al. 2025; Tahapary et al. 2022).

What remains disputed

Which comes first, high insulin levels or insulin resistance? This is the most consequential open question, and each side has compelling evidence.

• The conventional sequence: body tissues respond less well to insulin, so the pancreas compensates by secreting more insulin, leading to higher insulin levels (hyperinsulinemia) (Abdul-Ghani & DeFronzo 2021).
• The alternative sequence: chronically elevated insulin levels, arising from other triggers, may itself contribute to developing or worsening insulin resistance, making high insulin levels a partial cause (Corkey 2012).
• The current state: reviews examining both directions describe feedback that may operate each way, with the initiating sequence not universally resolved (Abdul-Ghani & DeFronzo 2021; Xing & Chen 2022).

This is not a case where “both are true” is a settled compromise. It is an open question, with two models implying different views of how things work and what should be targeted during treatment.

Whether to describe metabolic syndrome as a distinct entity or not is a topic of great interest. In 2005, a joint statement from the American Diabetes Association and the European Association for the Study of Diabetes questioned whether the metabolic syndrome added sufficient explanatory or clinical value beyond its individual components to justify treating it as a distinct syndrome (Kahn et al. 2005).

In contrast, also in 2005, the American Heart Association/National Heart, Lung, and Blood Institute published a scientific statement supporting its diagnosis and clinical use (Grundy et al. 2005). Currently, the term remains widely used and is treated as a recognized clinical entity in current reviews (Neeland et al. 2024).

Is insulin resistance always harmful? One proposed model frames insulin resistance as a physiological defense that protects cells from nutrient overload (Nolan et al. 2015). A more recent review frames insulin resistance and type 2 diabetes as allostatic responses to chronic nutrient excess (Prentki et al. 2026). Both are proposed models under discussion, not consensus.

Measurement of insulin resistance outside research has no settled answer, as described in a previous section.

Lastly, selective hepatic insulin resistance occurs when the liver may resist insulin’s suppression of glucose output while remaining responsive to its stimulation of fat synthesis; this is discussed in mechanistic reviews but is currently not fully resolved (Petersen & Shulman 2018).

Evidence over time

Can insulin resistance improve?

Yes, insulin sensitivity can improve.

Physical activity is one of the best-studied lifestyle approaches. A systematic review and meta-analysis of exercise interventions in adults with overweight or obesity found improvements in insulin resistance measures as well as effects on blood pressure and intrahepatic fat (Battista et al. 2021). The patient populations that were studied were adults with overweight or obesity.

Weight change can improve insulin sensitivity where excess adiposity is contributing. This is just one of many methods that may help certain patient populations.

Sleep may also play a role. In a randomized crossover trial, experimental sleep restriction reduced insulin sensitivity in postmenopausal women (Singh et al. 2023). The trial showed that shorter sleep duration can affect insulin sensitivity, but larger trials are needed to investigate the effect of habitual sleep across the general population.

Dietary change and, in appropriate clinical settings, medication are also part of the picture. Current clinical guidelines on diabetes prevention cover lifestyle intervention and pharmacologic options for people at increased risk (ADA 2026 Standards of Care). The landmark trial underpinning much of this, the Diabetes Prevention Program, compared lifestyle intervention and metformin with placebo and found reduced incidence of type 2 diabetes in high-risk adults (Knowler et al. 2002).

When insulin resistance is improved, there are three outcomes:

1. Improved insulin sensitivity changes how tissues respond to insulin.
2. Prevention or delay of type 2 diabetes changes whether and when a diagnosis of type 2 diabetes may occur.
3. Remission of established type 2 diabetes is an important change that improves an individual’s health.

Evidence for one does not automatically transfer to the others. For more details, see the guide on reversing insulin resistance.

Frequently asked questions

Is insulin resistance a disease or a risk factor?

It is best characterized as a physiological and metabolic state and a risk factor rather than a standalone disease. There are no standardized diagnostic criteria that define who has it, and no routine clinical test that identifies it directly (NIDDK). Formal diagnoses in this area, such as prediabetes and type 2 diabetes, are defined by glucose level and A1C criteria (ADA 2026 Standards of Care). That distinction is why you may be told you have insulin resistance in one setting and receive no diagnosis for it in another.

What’s the difference between insulin resistance and insulin sensitivity?

They are two ends of the same measurement. Insulin sensitivity means your tissues respond strongly to a specific amount of insulin. Insulin resistance means those same tissues respond weakly to that same amount (James et al. 2021; Petersen & Shulman 2018). When one goes up, the other goes down. Different sources use whichever framing suits their point.

How common is insulin resistance?

Currently, no reliable national prevalence estimate for insulin resistance exists, because no standardized routine diagnostic test identifies it (NIDDK). Any figure in scientific literature as the percentage of adults with insulin resistance should be read skeptically.

For context only, the CDC’s National Diabetes Statistics Report estimates the prevalence of prediabetes in the United States as 115.2 million adults aged 18 or older (CDC National Diabetes Statistics Report). This prediabetes figure is defined by fasting glucose and A1C level, not by insulin resistance.

Can a person at a normal weight have insulin resistance?

Yes. In cross-sectional studies of young, lean adults with normal glucose levels who were offspring of parents with type 2 diabetes, researchers documented marked muscle insulin resistance and increased lipids in skeletal muscle cells despite normal body weight and normal glucose levels (Petersen et al. 2004; Morino et al. 2005).

These were selected high-risk participants, so the studies show that insulin resistance can occur without obesity. The studies do not explain how common it is among normal-weight adults in general and were not designed to predict who would later develop diabetes.

Can people with type 1 diabetes have insulin resistance?

Yes. Insulin resistance can coexist with type 1 diabetes and is recognized as clinically relevant in that population (American Diabetes Association; Apostolopoulou et al. 2025). It is a separate phenomenon from the autoimmune destruction of insulin-producing beta cells that causes type 1 diabetes. Type 1 diabetes results from an absolute lack of insulin; insulin resistance, when present alongside it, describes reduced responsiveness to administered insulin (Apostolopoulou et al. 2025).

Does insulin resistance always lead to type 2 diabetes?

No. Insulin resistance increases the amount of insulin the body needs, and glucose can remain well regulated as long as insulin secretion keeps pace (Abdul-Ghani & DeFronzo 2021). Type 2 diabetes develops when insulin secretion becomes insufficient relative to the degree of resistance; it is diagnosed by glucose and A1C criteria (NIDDK; ADA 2026 Standards of Care). Progression is not inevitable and can be reversed through lifestyle changes and more. Insulin sensitivity can also change over time.

Conclusion

Insulin resistance occurs when the insulin signal produces less of its expected effect, affecting muscle, liver, and fat tissue to differing degrees and changing how glucose is used and stored in the body. Insulin resistance may be present even when glucose levels are normal, or no symptoms exist.

No standardized routine test diagnoses insulin resistance. Surrogate measures carry real laboratory and biological uncertainty. Insulin sensitivity can improve, and progression to type 2 diabetes is not inevitable.

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