Dr. Jennifer Luis ND

Unraveling Insulin Resistance: A Comprehensive Guide

Person pinching their stomach with one hand

Introduction to Insulin Resistance

A reduction in the ability of tissues to respond to insulin appropriately defines the medical condition of insulin resistance. Insulin is an important hormone responsible for the regulation of blood glucose levels and in the case of insulin resistance, glucose levels can eventually increase to the point of hyperglycemia and type 2 diabetes. Insulin resistance (IR) is under-diagnosed and missed in traditional screening blood tests; only the progression of dysfunction caused by long-term IR is observed when blood sugar levels rise above baseline.

Recognizing the signs of IR can help result in testing and diagnosing this condition. Weight gain or inability to lose weight is a hallmark sign of IR and can be accompanied by fatigue, hair loss, sugar cravings, irregular cycles, infertility and sleep disruption. These symptoms can overlap with hypothyroidism and low iron thus blood testing with an insulin tolerance test is the ideal way to diagnose IR.

Insulin resistance can be considered the first stage of insulin and blood sugar imbalance that can eventually lead to diabetes. It is reversible and often best treated with diet and lifestyle changes to yield permanent results. Sometimes supplements may be useful in difficult or stubborn cases with success. IR can lead to diabetes, cardiovascular disease, obesity, infertility and cognition diseases of the elderly such as Alzheimer’s disease.

Physiology of Insulin and Insulin Resistance

Insulin and its role in the body

Insulin is produced by the pancreas in islet cells. The biggest role of insulin is to help regulate the body’s supply of energy. This is achieved by control of glucose transport to insulin-dependent tissues such as fat (adipose), muscle and the liver. If there is not enough sugar supply readily available, adipose tissue will initiate fat breakdown to be used as energy which will accelerate insulin secretion. This cycle of insulin and glucose is vital for energy and metabolic function in every human.

The liver is the primary target for insulin to control metabolic nutrient balance. The creation and breakdown of stored sugars (glycogen) and influence on triglycerides is initiated by insulin. In the condition of IR or progression to hyperinsulinemia, individuals can store away fat and lose muscle mass resulting in weight gain and loss of strength. Growing evidence shows the relationship with insulin and glucose uptake in the brain and spinal cord to provide energy and allow for memory processing and cognition. It is suggested that impaired signaling and response to insulin may contribute to Alzheimer’s disease.

Once glucose has been transported out of the bloodstream and into the cells, it enters the mitochondria. Often referred to as the powerhouse of the cell, the mitochondria uses water and glucose to produce ATP, the cellular energy source of life. ATP enables biochemical reactions to take place in all organs and tissues of the body. If glucose is not transported efficiently, many medical conditions and disease processes can result. Glucose in elevated concentration is inflammatory to blood vessels which in the long-term can lead to cardiovascular disease, kidney disease and blindness.

Development of insulin resistance

Tissues that are insulin-dependent can become resistant. Normally insulin would signal cell membrane proteins to allow glucose into cells and out of the blood stream or surrounding tissue fluid. Insulin resistance is due to the impaired ability of this signaling pathway and can result in less glucose entering muscle cells. This can lead to less muscle growth, often people with IR notice difficulties with gaining muscle mass yet increasing weight and abdominal circumference.

Contributing factors of IR involve genetic predisposition, poor diet, high stress, lack of exercise and muscle strengthening. Diets high in sugar and carbohydrates may require more insulin secretion to properly balance blood sugar. Over prolonged periods of time and paired with other factors such as genetics, this can lead to insulin resistance and diabetes.

The hormone cortisol is associated with stress management and response. Stress can be from an emotional situation, physical situation such as repetitive, high-intensity exercise and from a physiological standpoint such as chronic inflammation from a disease or medical condition. Continuous, long-term cortisol elevation can affect insulin and glucose balance and may be one of several factors to cause the development of IR.

Insulin resistance can begin with mild changes to glucose sensitivity. Symptoms may not be obvious initially and sometimes do not progress if a healthy diet and lifestyle is followed. Early signs can be a change in the ability to lose weight, where in previous attempts weight loss was achieved with diet and exercise and it now no longer works. Abdominal weight gain is classically associated with insulin resistance or glucose elevation. As time progresses, cells can get further resistant to insulin thus the pancreas secretes higher amounts of insulin to compensate. This can result in energy changes, fatigue after eating carbohydrate-rich meals and sometimes changes to sleep patterns such as insomnia or waking up hungry.

Causes and Risk Factors

Genetics and family history

Advancements in medical genetics have helped to identify different genes that contribute to a higher risk of diabetes. Genetic testing and family history of those with diabetes in the family may also be at a higher risk of developing insulin resistance. Genetics is only half of the equation when it comes to development of good sugar or insulin dysregulation. Lifestyle factors can have a strong influence, especially in those with genetic predisposition.

Lifestyle factors

Poor diet has been attributed to an increased risk in the development of both diabetes and cardiovascular disease. High refined sugar and carbohydrate-rich diets may accelerate the development of insulin resistance and lead to the next stage of hyperglycemia. Ideal diets to lower the risk of IR include the Mediterranean diet which has been well studied and concluded to have a statistically significant positive impact on lowering both diabetes and cardiovascular disease risks.

Maintaining a healthy amount of physical exercise on a regular basis has also been proven to reduce risk and can be used to lower blood glucose and insulin levels. Focusing on building muscles during workouts will push the body to make more insulin-dependent receptors which works to lower or reverse insulin resistance. Weight training and using the body as resistance in exercises such as pilates, yoga and functional patterns will help build muscle mass.

Sleep is an important part of body recovery, including the re-balancing of hormones. Sleeping can be considered a fasting state which helps the body to take a break from the constant release of insulin due to eating. The hormone cortisol should be low in the evening to enable deep sleep, using healthy sleep hygiene routines will improve recovery.

Other medical conditions

There are multiple medical conditions that increase the risk for insulin resistance or can be caused or associated with IR. Obesity, both caused by IR and can cause IR, allows for increased fat tissues and less muscle mass to promote insulin sensitization. Along with multiple other diseases correlated with obesity, insulin resistance can quickly develop into hyperglycemia and diabetes.

Polycystic Ovarian Syndrome (PCOS) is a common female condition that can be derived or associated with IR. PCOS is a spectrum of a disorder that can present as very mild or severe. The hallmark symptoms include obesity, acne, hair loss, hair gain in unwanted locations and irregular cycles. PCOS is most often correlated with insulin resistance that can develop into full diabetes. Treating PCOS with IR and diabetic protocols may significantly improve PCOS symptoms.

Metabolic syndrome is a conglomerate condition that can include hyperglycaemia, obesity, elevated cholesterol. One way metabolic syndrome can sometimes be identified early is testing insulin levels and initiating lifestyle, diet and supplement protocols to initiate weight loss and insulin sensitization.

Symptoms and Diagnosis


Early signs that you might have developed insulin resistance can begin with difficulties losing weight or unexplained weight gain. Eating right and exercising in ways that have allowed for weight loss in the past are no longer working. Some notice this happening during or after stressful periods of time while others can’t correlate it to stress. Increasing hunger or thirst and difficulties with blood sugar balance resulting in “hangry” feelings of irritability or nausea, headaches and fatigue when too much time has passed between eating can be hallmarks or IR. Strong cravings for sugar or carbohydrate-rich foods can make it challenging to stick to healthy food choices.

As IR progresses, energy levels can drop along with waking in the night or insomnia. Physical symptoms sometimes are evident on the skin. Skin tags, usually developing in a patch or darkened, non-raised  areas of skin can be the results of insulin resistance. Hair loss and growth of hair on unwanted areas of the body can signal hormonal imbalances as a result of insulin. Even hypothyroid-like symptoms can result such as weight gain, cold body temperature, irregular periods, fatigue, headaches, depression and anxiety.

Complications involving long-term untreated insulin resistance pertain to the development of more serious conditions such as diabetes, heart disease, kidney disease, blindness, cancer and Alzheimers. These diseases may be prevented if IR is detected early and reversed with diet, lifestyle, supplementation and sometimes prescriptions.


Unfortunately, insulin resistance is not usually diagnosed until it has progressed to the next stage of development such as hyperglycemia, diabetes or high lipid profiles with blood work. The best test, for the earliest detection is the insulin tolerance test. This is performed at a laboratory and 3 samples of blood are tested over a 2 hour time frame. Similar to the glucose tolerance test that many pregnant women will undergo as part of pregnancy screening, the insulin tolerance test evaluates both insulin and glucose at baseline, 1 hour after sugar consumption and 2 hours after sugar consumption. Comparing blood values between both insulin and glucose at each of the 3 times will lead to a clear ability of the body to control blood glucose with appropriate levels of insulin. This test is the best way to identify IR, yet it is rarely ordered.

A simple fasting insulin level and comparative glucose level will diagnose a majority of IR cases however those that struggle to control levels after eating only can have normal fasting insulin levels. Other helpful blood tests to round out an evaluation include a full lipid panel with attention to triglyceride levels and HbA1c. Hemoglobin A1C is a useful test to examine how well your blood glucose has been controlled over a 3-month span of time. This accounts for an average as opposed to a single day blood sugar control level and is useful to evaluate treatments as well as diagnose.

More advanced testing is available as part of the Adrenal Stress Index  saliva test. Cortisol levels can play a big role in the production of insulin and risks of IR. This comprehensive test measures cortisol at 4 times in a day, insulin fasting and insulin challenge (2 hours after sugar consumption) and other adrenal health indices such as DHEA, immune IgA, 17 OH- progesterone, and gluten antibodies. This is a specialty test that can be ordered by your naturopathic physician.

Treatment and Management

Lifestyle changes

Sometimes the hardest part to wellness is breaking daily routines and patterns. Intermittent fasting helps many people with insulin resistance lower the amount of blood insulin at fasting or after a meal. Fasting is most commonly followed by the 8/16 rule. During a 24 hour period, 16 straight hours are fasting where no calories are consumed. Regular caloric intake resumes after 16 hours and lasts for 8 hours. The 8/16 routine isn’t ideal for everyone and can be modified to a longer eating window for an individualized approach. Intermittent fasting should be discussed with a health professional to ensure no contraindications exist. Along with intermittent fasting, eating a lower carbohydrate diet that focuses on vegetables, healthy oils and protein will speed up the insulin/glucose balance.

Building muscle mass is one of the other approaches to help insulin-dependent cells become re-sensitized to insulin’s signaling. Glut-4 receptors are insulin-dependent and have been shown to increase in numbers with regular exercise. Using weights or body mass resistance can lead to improved insulin levels.The stress hormone cortisol plays a role with glucose and insulin balance. In cases of prolonged stress, insulin resistance may develop. Cortisol levels can be tested using a 4-point saliva test. One laboratory will use the saliva samples provided and report both fasting and challenged insulin along with cortisol and other adrenal-derived or related markers. This report can help to determine the unique interrelationship between stress and insulin which leads to developing strategies and treatment plans.


Conventional treatment of insulin resistance focuses on weight loss. Usually, the wait and see approach is taken and until diabetes is officially diagnosed, no prescriptions are provided. Diabetic drugs can work to improve glucose’s response to insulin and the most popular first choice drug is Metformin. This drug has been around for a long time and has helped to lower blood sugar levels of diabetics and can be used for insulin resistance. Digestive side effects are common, making it difficult for some people to tolerate the therapeutic dose required for efficacy. An alternative prescription drug family is the thiazolidinediones which have a different mechanism of action that is mainly focused on fat tissues. A common side effect is weight gain which is not desirable for people with diabetes.

Another drug family that can be used to improve insulin production by blocking an enzyme that causes limitations of production. This is often used alongside diet and exercise, but side effects of headaches and nausea have been reported. The newer drugs to help with glucose balance are of the GLP-1 family such as Semaglutide (Ozempic). These medications are used to treat diabetes and obesity.

On the supplemental side of insulin resistance, there are several natural agents that can be used either one at a time or in combination. Berberine, NAC, alpha lipoic acid and inositol help to improve IR and can often be better tolerated than medications. To determine the best natural supplement for you, a Naturopathic Physician takes into account your full history, family history and lab work.

Monitoring and follow-up

Beginning with a detailed appointment including a full health history will help to determine which labs to run. Often the insulin tolerance test along with other metabolic hormones such as a thyroid panel, renal stress index and Vitamin D will provide clear answers. If insulin resistance is uncovered, full treatment plans including diet, lifestyle and supplementation is provided. After 3 months, a re-test is useful to determine the biological progress that has been made. Ultimately there are obvious signs such as weight loss, improved mood, hair regrowth, energy and improved sleep patterns that can also be tracked within a few weeks.

Treatment plans may be modified if required at any time. Some cases of insulin resistance are more stubborn and may require changing or increasing supplements or switching to a prescription medication. This should be discussed after 1 month or sooner if side effects or lack of progress have been noted. Otherwise, every 3 months is a great time to check in, do new blood work and review progress.

Prevention Strategies

Preventing insulin resistance comes down to leading a healthy lifestyle. Regular exercise and physical activity will help insulin receptors remain sensitive to signaling and keep healthy and balanced levels. Working towards a balanced diet that focuses on non-starchy vegetables, healthy oils such as olive and avocado oils, nuts, seeds and fish along with protein is ideal. Avoiding snacks throughout the day but rather eating distinct meals gives the body a break from constantly adjusting blood glucose levels and can ultimately improve insulin balance.

Maintaining a healthy weight keeps balance between muscles and fat. This will also work towards preventing insulin resistance in the long run. Sometimes the first signs of IR can be weight gain without a clear reason. If you suspect a hormone imbalance, speak to your Naturopathic Physician to have your insulin tested.

Concerned About Insulin Resistance?

Insulin resistance can be caught early if tested as part of routine, baseline testing. This is not a common practice but can be discussed with your Naturopathic Physician and ordered through conventional laboratories. Early treatment often results in reversal of insulin resistance which also means prevention of hyperglycemia and diabetes.

Long-term management of insulin resistance is possible and becomes routine quickly. Working with a Naturopathic Physician will ensure that the best treatment plan is developed for you and is modified as health and life circumstances change. The first step is making an appointment to review your current health symptoms and full health history. The right tests for you can be ordered and used to help determine the best way to achieve optimal health.