Insulin resistance is a common metabolic dysfunction that may contribute to various health challenges, such as type 2 diabetes, cardiovascular disease, and obesity. Recent studies show that at least 25% of adults in the United States who don’t have diabetes may experience insulin resistance.
Insulin resistance occurs when cells do not respond effectively to insulin. This can lead to increased insulin production, resulting in consistently high insulin levels. This article will discuss how insulin resistance develops and its potential impacts on the body.
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What is Insulin Resistance?
Insulin is a hormone released by the pancreas in response to a rise in blood glucose. When carbohydrates are consumed and metabolism begins, blood glucose rises, signaling the body to release insulin. Insulin functions in two ways: to help manage blood glucose levels and to act as a signaling molecule for different cells.
Insulin resistance indicates a disruption of metabolism occurring when cells do not respond effectively to insulin. In turn, the pancreas releases more insulin to overcome this reduced response. Over time, blood glucose may remain consistently elevated, which can contribute to the development of type 2 diabetes mellitus. A chronically elevated insulin level may support inflammation and disease progression.
Causes of Insulin Resistance
Lifestyle Factors:
Lifestyle factors play a significant role in the development of insulin resistance.
- Diets high in processed foods, including added sugars, refined carbohydrates, and processed meats, can lead to increased pancreatic insulin secretion and a proinflammatory state, which may increase the risk of insulin resistance.
- Physical inactivity is a risk factor for developing insulin resistance.
- Weight gain leading to obesity may independently increase the risk of insulin resistance.
Genetic Factors:
In addition to lifestyle factors, genetic predispositions can also increase the risk of insulin resistance. Variations in genes coding for insulin signaling or other genetic factors affecting lipid metabolism, mitochondrial activity, and inflammatory mediators are genetic factors that can increase the risk of insulin resistance.
Examples of genetic markers that may increase the risk for insulin resistance include these:
- PTB1
- LEPR
- RETN
- SLC2A4
Hormonal Imbalances:
Imbalances of neuroendocrine hormones can significantly increase insulin resistance. Dysregulated glucagon-like peptide-1, glucose-dependent insulinotropic peptide (GIP), ghrelin, peptide YY, and others can affect insulin release from the pancreas.
Hormone imbalances in conditions like polycystic ovarian syndrome (PCOS) may lead to elevated insulin levels and decreased activity of insulin on organs, further increasing the risk of weight gain and type 2 diabetes mellitus.
Mechanisms of Insulin Resistance
Understanding insulin resistance requires a biochemical explanation of actions at the cellular level.
Excess accumulation of adipose tissue is a significant risk factor for developing insulin resistance. Adipose tissue (particularly visceral or abdominal fat) secretes pro-inflammatory cytokines and adipokines, which may disrupt insulin signaling pathways, thus promoting insulin resistance. In addition, elevated levels of free fatty acids in obesity may further exacerbate insulin resistance by interfering with insulin action in the peripheral tissues.

Finally, insulin is a pro-inflammatory hormone, and obesity is a pro-inflammatory state. Both are associated with energy storage rather than energy burning, representing a continuous cycle of weight gain and metabolic dysfunction.
Effects of Insulin Resistance on the Body
Insulin resistance may increase the risk of developing diseases of metabolic dysfunction and is a core component of metabolic syndrome, which is a constellation of several adverse metabolic conditions:
- Central obesity
- Low high-density lipoprotein levels
- Elevated triglycerides
- Hypertension
- Impaired glucose metabolism
Metabolic syndrome is a state of chronic inflammation, which may increase the risk of the development of inflammatory-mediated diseases, such as cardiovascular disease and type 2 diabetes. Type 2 diabetes mellitus can lead to end-organ complications, such as chronic kidney disease, neuropathy, and vision problems.
Insulin resistance may increase the risk of atherosclerosis and endothelial dysfunction, raising the risk of hyperlipidemia, coronary artery disease, stroke, and peripheral artery disease. Obesity also contributes to systemic inflammation, which may independently increase cardiovascular risk.
Insulin resistance may promote the storage of glucose as fat in the liver and the formation of triglycerides, which can contribute to the development of non-alcoholic fatty liver disease (NAFLD). As NAFLD progresses, it may result in increased liver inflammation, fibrosis, and, ultimately, cirrhosis.
Diagnosing Insulin Resistance
Insulin resistance develops gradually and exists on a spectrum. Therefore, diagnosing it requires assessing various biomarkers related to glucose metabolism.
Serum insulin levels should be tested in a fasting state and also after eating a carbohydrate-containing meal. A fasting blood glucose and an oral glucose tolerance test should be performed alongside insulin levels as an integrated test like HOMA-IR to understand how insulin levels correspond with serum glucose levels. Elevated fasting glucose levels (>100 mg/dL) may indicate impaired fasting glucose and suggest underlying insulin resistance when correlated with insulin levels.
The hemoglobin A1c (HbA1c) test measures the average blood glucose levels over the life of the hemoglobin molecule, which is generally about three months. Higher HbA1c levels (>5.7%) may indicate chronically impaired glucose metabolism.
Physical findings of insulin resistance may include the development of skin tags in areas like the axilla or neck. Acanthosis nigricans, which are dark, velvety appearing areas on the back of the neck, is a common presentation of insulin resistance. Central obesity (adipose tissue heavily located in the abdomen) is commonly associated with insulin resistance.
Managing and Supporting Insulin Sensitivity
Lifestyle Modifications to Support Insulin Sensitivity
Lifestyle interventions are integral in supporting insulin sensitivity and managing obesity, providing effective strategies for promoting metabolic health and reducing the risk of associated complications.
Diet is one of the most significant drivers of insulin sensitivity and requires balancing energy intake with optimal macronutrient composition.
- Focusing on a diet of whole, nutrient-dense foods while minimizing refined sugars and processed foods may help regulate blood glucose and support a healthy weight.
- Prioritizing healthy fats, like omega-3 fatty acids, may help reduce inflammation.
- Emphasizing high-fiber foods like fruits, vegetables, legumes, and whole grains may help control insulin release and promote insulin sensitivity.
Regular physical activity supports overall metabolic health, including insulin sensitivity.
- Cardiovascular exercise may enhance insulin sensitivity by increasing glucose uptake and utilization in muscles. It also helps promote a healthy weight by increasing energy expenditure and promoting fat oxidation.
- Strength training, including weight lifting and bodyweight exercise, may improve insulin sensitivity by increasing muscle mass and glucose uptake into muscles. Strength training helps increase and preserve lean body mass, which supports long-term weight management by increasing resting energy expenditure.
Medications and Other Treatments
Several medical treatments and surgical interventions can be considered when lifestyle modifications do not sufficiently support insulin sensitivity.
- Metformin is a commonly used medication for type 2 diabetes, often prescribed to enhance insulin sensitivity and reduce hepatic gluconeogenesis. Metformin may also help support a healthy weight by reducing appetite and aiding in mild weight loss.
- Glucagon-like-peptide-1 receptor agonists (GLP-1 RA), including liraglutide, semaglutide, and the dual agonist tripeptide, may improve insulin secretion and slow gastric emptying, leading to better glycemic control and clinically significant weight loss.
- Other medications used for diabetes include sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, thiazolidinediones, sulfonylureas, alpha-glucosidase inhibitors, and others.
In cases of severe obesity or when lifestyle interventions and pharmacotherapy are insufficient, bariatric surgery may provide an option for long-term weight management and improved metabolic health. Bariatric surgical techniques like sleeve gastrectomy and Roux-en-Y gastric bypass can lead to substantial weight loss and may help manage conditions like obesity, type 2 diabetes, hypertension, and dyslipidemia.
Bariatric surgery and the loss of notable amounts of excess fatty tissue may lead to hormonal changes that support insulin sensitivity, leading to sustainable weight management and metabolic health benefits.
Monitoring and Prevention Strategies
Early identification of insulin resistance is important to help delay the onset of type 2 diabetes, cardiovascular disease, and other metabolic dysregulations. It also allows for treatment with lifestyle interventions first.
Preventing insulin resistance starts with preventing obesity and optimizing healthy lifestyles, including nutrition, regular physical activity, stress management, and adequate sleep. This requires a multifaceted approach focused on patient education and implementing healthy individual lifestyle choices.
Using personalized approaches may provide effective patient-centered care to improve overall health outcomes.
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Key Takeaways
- Insulin resistance is a common metabolic disruption that may increase the risk of other health challenges, like obesity, type 2 diabetes mellitus, and cardiovascular disease.
- Modifications to diet, physical activity, and, in some cases, medications can help support insulin sensitivity.
- In cases of severe obesity, insulin sensitivity may be supported by bariatric surgery.
- A personalized approach to holistic health may help reduce the risk of insulin resistance.