Demystifying Insulin Resistance

It is no exaggeration to say that the United States is facing an epidemic of poor metabolic health. Poor metabolic health is a condition characterized by poor blood sugar control, and often means weakened immune functioning and weight issues. A 2021 study found that 40% of American adults aged 18 to 44 are Insulin resistant, with many unaware of their condition [1]. As a society, we are failing to control this epidemic, as numbers continue to rise. 

What is Insulin Resistance?

Insulin Resistance is a metabolic condition where cells in our muscle, fat, liver, and brain become less responsive to Insulin. Insulin is a hormone made in the pancreas that is responsible for regulating blood sugar levels by facilitating the entry of glucose (sugar) into our cells, where it is used for energy. When cells resist the effects of Insulin, glucose accumulates in the bloodstream, leading to elevated blood sugar levels. Over time, this can progress to Type 2 Diabetes and other health complications, such as heart disease, hypertension, PCOS, fatty liver disease, non-alcoholic fatty liver disease, Alzheimer’s disease, and certain types of cancer [1]. Shockingly, or maybe not so shockingly, 8 out of the 10 current leading causes of death in the US are related to poor metabolic health. Understanding Insulin Resistance is crucial for managing and preventing these associated conditions.

What Causes Insulin Resistance?

We know that when cells become resistant to Insulin, blood sugar becomes chronically elevated, which can cause Type 2 Diabetes and a host of other health conditions. But what causes cells to stop responding to Insulin in the first place? The truth is that scientists continue to debate what the #1 culprit could be, but a consensus has formed that the main contributors to Insulin Resistance include:

• Excess Caloric Intake + Obesity

• One of the primary drivers of Insulin Resistance is excess caloric intake, particularly from diets high in refined carbohydrates and unhealthy fats. Consuming more calories than the body needs leads to weight gain, especially around the abdomen. This visceral fat releases pro-inflammatory cytokines, which interfere with Insulin signaling pathways in cells.

• Mitochondrial Dysfunction 

• Mitochondria, the powerhouses of the cell, play a crucial role in energy metabolism. Mitochondrial dysfunction, which can be caused by oxidative stress, poor diet, exposure to pollutants + toxins, nutrient deficiencies, viral / bacterial infections, and excess consumption of trans fats + alcohol, can lead to inefficient energy utilization and contribute to Insulin Resistance.

• Sedentary Lifestyle

• A sedentary lifestyle reduces the muscle’s ability to efficiently utilize glucose. Regular physical activity, especially muscle-building activity, helps improve Insulin sensitivity by increasing glucose uptake in muscle cells. Without exercise, muscles become less responsive to Insulin.

• Chronic Inflammation

• Chronic low-grade inflammation can also disrupt Insulin signaling. Inflammatory cytokines released by fat tissue and immune cells interfere with the insulin receptors on cells, making it harder for Insulin to facilitate glucose entry.

• Hormonal Imbalances 

• Certain hormonal imbalances, such as chronically elevated Cortisol and imbalanced Estrogen to Progesterone ratios, have been associated with Insulin Resistance (more on this in the section “Insulin’s Interactions with Other Hormones”).

• Genetics

• Certain genes may increase your likelihood for developing Insulin Resistance, but diet and lifestyle will always influence the expression of these genes.

• Gut Microbiota Imbalances

• New research suggests that an imbalance in gut microbiota (dysbiosis) can affect metabolic health and contribute to Insulin Resistance. In fact, one study found that excess levels of Firmicutes in the gut led to an increased absorption of 150 calories per day [2]. A healthy gut microbiome plays a vital role in maintaining Insulin sensitivity.

• Stress + Poor Sleep

• Chronic stress and sleep deprivation increase Cortisol and decrease the effectiveness of Insulin, making it harder for cells to absorb glucose.

• Certain Medications

• Long-term use of certain medications, such as steroids, statins, beta-blockers, immunosuppressants, hormonal birth control, and antipsychotics have been shown to contribute to the development of Insulin Resistance through various mechanisms.

Symptoms of Insulin Resistance

Insulin Resistance often develops gradually over the course of many years and can be difficult to detect in its early stages. However, there are several signs and symptoms that may indicate Insulin Resistance.

External Indicators:

• Increased weight gain, especially around the abdominal region

• Acanthosis nigricans (dark, velvety patches of skin, typically found on the neck, armpits, groin, and knuckles)

• Skin tags, often found in similar areas as acanthosis nigricans

Internal Indicators:

• Increased fatigue

• Increased thirst

• Frequent urination

• Constant hunger

• Cravings for carbohydrates

• Difficulty concentrating / brain fog

Insulin’s Interactions with Other Hormones

Insulin is one of many hormones in the Endocrine System that work in harmony to keep your body in balance. When other hormones are out of balance, such as Cortisol, Leptin, Estrogen and Progesterone, then Insulin is often also affected, which can lead to a variety of negative effects on metabolic health.

For example, chronic stress and / or poor sleep can lead to elevated Cortisol levels, which will raise blood sugar levels and prompt the pancreas to release more Insulin, eventually leading to Insulin Resistance [3]. It is important to keep in mind that elevated Cortisol is not always caused by the usual factors such as stress at work or relationship problems. The body may identify other things such as overexercising, malnourishment, nutrient deficiencies, depression, addiction, or recent surgeries / illnesses as “stressful”, thereby increasing Cortisol levels.

Leptin is another key hormone related to energy balance and appetite. Leptin is a hormone produced by adipose (fat) tissue, which under normal circumstances signals the brain to “stop eating” and suppresses appetite. As the body becomes resistant to Insulin, the pancreas produces more Insulin to compensate. High levels of Insulin (hyperinsulinemia) can interfere with Leptin signaling, creating a vicious cycle of increased appetite and further metabolic dysfunction. 

Sex hormones such as Estrogen and Progesterone are also closely intertwined with Insulin and play significant roles in maintaining overall metabolic health [4]. 

Estrogen levels may impact Insulin via:

1. Improving glucose uptake in muscle and fat cells, thereby improving Insulin sensitivity. For this reason, menopausal and perimenopausal women, as well as women with low Estrogen levels, should pay close attention to their metabolic health and look out for early signs of Insulin Resistance. 

2. Regulating fat distribution within the body. Estrogen influences distribution of fat within the body, promoting the storage of fat in subcutaneous tissues (under the skin - the “safe” fat) rather than in visceral tissues (around internal organs - the “unsafe” fat). Visceral fat is more closely associated with Insulin Resistance and metabolic disorders.

3. Lowering overall inflammation. Certain types of Estrogen, especially Estradiol (E2), have anti-inflammatory effects in the body. Therefore, keeping overall inflammation low is crucial in preventing Insulin Resistance. 

Progesterone may impact Insulin via:

1. Counterbalancing Estrogen. Elevated levels of Progesterone can actually reduce Insulin sensitivity. During times of higher Progesterone, such as the luteal phase of the menstrual cycle and pregnancy, women often experience a decrease in Insulin sensitivity. This may explain the slight increase in weight many women experience during the luteal phase. 

2. Affecting glucose metabolism. Progesterone plays a role in promoting gluconeogenesis (the production of glucose in the liver), which means elevated Progesterone can increase blood glucose levels. 

How to Know If You Are Insulin Resistant

If you suspect you may have poor metabolic health, or if you have any of the symptoms of Insulin Resistance, it is highly encouraged that you speak with a medical professional and get a full metabolic health panel. The labs we recommend running include:

• Fasting Blood Glucose

• Hemoglobin A1c (HbA1c)

• Fasting Insulin

• Lipid Profile (Total Cholesterol, HDL, LDL, Triglycerides, Homocysteine, LDL + HDL Particle Number / Size)

• C-Peptide

Functional Test Kits We Recommend:

• GI MAP

• DUTCH Complete

It’s important to recognize that reference ranges for some of these markers can differ: holistic practitioners often aim for optimal ranges, while traditional practitioners might use conventional reference ranges. By focusing on optimal reference ranges, it's possible to identify Insulin Resistance in its early stages, before any irreversible damage occurs.

If you don’t have immediate access to a full blood panel, or if you’re interested in obtaining a more complete picture of how your blood sugar levels fluctuate day-to-day, investing in a Continuous Glucose Monitor (CGM) is another option. A CGM is a medical device that tracks blood sugar levels in real time throughout the day and night. It involves inserting a small sensor under the skin, typically on the abdomen or arm. This sensor measures interstitial glucose levels (the glucose present in the fluid between cells) every few minutes. 

The advantage of using a CGM lies in its ability to provide real-time monitoring of glucose levels, enabling immediate comprehension and trend analysis of how different foods or activities impact glucose levels. It’s important to note that there can be significant variation from person to person in how glucose levels respond to various factors. At DLW, we recommend the CGM by Veri (use code VSM-DRLANAWELLNESS for $30 off).

Treating Insulin Resistance Holistically

Conventional treatment plans for Insulin Resistance are proving inadequate, as deaths from metabolic diseases continue to rise. The standard Western approach often relies on generic, outdated dietary advice and places excessive emphasis on medications that can have harmful side effects. It also tends to wildly undervalue lifestyle modifications and natural supplement options, often delaying intervention until patients develop full-blown Type 2 Diabetes, when stepping in at the early stages of development continues to prove to have the best outcomes. Additionally, conventional treatments rarely adopt a whole-body approach to Insulin Resistance, neglecting to check for hormonal or gastrointestinal imbalances or to identify the root causes of chronic inflammation. Although Insulin Resistance can be an alarming diagnosis, the encouraging news is that it is often reversible through dietary and lifestyle changes, especially when detected early.

Dietary Recommendations 

• Modify your carbohydrate quantity + quality. Studies have consistently shown that low-carb diets outperform high-carb diets for improving metabolic function [5]. Individuals with Insulin Resistance may consider obtaining no more than 15% of their daily calories from carbohydrates. It is also important to note that not all carbohydrates are created equally. Highly processed carbohydrates in the form of white bread, pasta, rice, fruit juice, and cane sugar will cause a much greater blood sugar spike than complex carbohydrates like sweet potatoes, legumes (beans, lentils), and whole fruit. 

• Eat a whole-foods based diet; avoid processed foods + additives. Processed or packaged foods should be avoided for a number of reasons. Processed foods often contain additives, preservatives, and oils that promote inflammation in the body which can fuel Insulin Resistance. Additionally, processed foods typically lack the fiber and nutrients which slow blood sugar spikes. And finally, processed foods are engineered to promote overconsumption and bypass satiety (fullness) signals, which encourages excess caloric consumption [6]. 

• Increase dietary protein. Increasing dietary protein to 20-30% of total caloric intake can be a powerful tool in preventing and reversing Insulin Resistance. Including a substantial source of protein (25-40g) with each meal slows blood sugar spikes, and moderate-to-high protein diets increase satiety and preserve muscle mass. Organic, pasture-raised animal products (chicken, turkey, beef, lamb, eggs, yogurt, cottage cheese, etc.), wild-caught fish, and legumes (beans, lentils, chickpeas) are good blood-sugar friendly sources of protein.

• Increase dietary fiber, antioxidant rich vegetables, and low-sugar fruits. Adequate dietary fiber protects against Insulin Resistance in multiple ways. Fiber slows down the digestion of carbohydrates and prevents rapid blood sugar spikes. Additionally, high-fiber meals increase satiety and prevent the urge to overeat. Acting as a prebiotic, fiber nourishes beneficial bacteria in the gastrointestinal tract. Fiber is also fermented in the gut into short-chain fatty acids, known as Butyrate, Acetate, and Propionate, which possess anti-inflammatory and blood sugar-regulating properties. Vegetables and low-sugar fruits (berries, avocado, grapefruit, citrus, etc.) are also rich in antioxidants which protect against oxidative stress.

• Avoid inflammatory fats (seed oils / trans fats). Trans fats, which are found in partially hydrogenated oils, margarine, shortening, fried foods, and many pre-packaged foods, are a type of unsaturated fat that have been chemically altered to stay solid at room temperature. Trans fats have been shown to induce oxidative damage in the body, increase inflammation, and impair mitochondrial functioning, all of which can contribute to Insulin Resistance [7]. Industrially processed seed oils (such as canola oil, sunflower oil, grapeseed oil, soybean oil, etc.) go through high-heat and chemical processing methods that create trans fats. For this reason, it is always best to choose cold pressed, unrefined oils such as extra virgin olive oil, avocado oil, or coconut oil.

• Avoid high fructose corn syrup at all costs!! Fructose is a type of sugar that, unlike glucose, is primarily metabolized in the liver, and is converted to fat through a process called de novo lipogenesis. The buildup of fat in the liver impairs its ability to respond to Insulin, contributing to systemic Insulin Resistance. High fructose syrup is commonly added to soda, fruit juices, cereals and baked goods, fast food, and packaged sweets. Always check your food labels!

• Consider going gluten free. Gluten, a type of protein found in wheat, rye, and barley, has been shown to increase intestinal permeability, or “leaky gut”. Leaky gut is a condition  where the lining of the intestines becomes more porous than normal, allowing substances such as toxins, undigested food particles, and bacteria to leak into the bloodstream [8]. This often results in chronic immune system activation and systemic inflammation, which can cause Insulin Resistance.

Supplement Recommendations

Numerous natural supplements have been studied for their ability to aid blood sugar regulation and enhance Insulin sensitivity. These supplements work in various ways, such as facilitating glucose transport, stimulating Insulin secretion, and reducing inflammation. In multiple instances, natural supplements have demonstrated efficacy comparable to the leading mainstream medications used for treating Insulin Resistance [9]. Some of our favorite blood-sugar supportive supplements include:

• Berberine

• Cinnamon

• Magnesium Glycinate

• American Ginseng

• Chromium

• Apple Cider Vinegar

Final Thoughts

Despite the rise in popularity among medications used to combat Insulin Resistance, the fact of the matter remains that poor metabolic health continues to be the leading contributing factor in deaths in the US today. Diabetes and diabetes-related conditions result in approximately 8 million hospitalizations annually. In order to solve this problem once and for all, a whole-systems approach must be implemented that involves taking into account diet, lifestyle, stress, sleep, inflammation, digestive, and hormonal health. If you suspect you may have Insulin Resistance, or if you would like to learn more about how to improve your metabolic functioning, click here to work directly with a member of the DLW team.

References

Freeman, A. M., Acevedo, L. A., & Pennings, N. (2023). Insulin Resistance. In StatPearls. StatPearls Publishing.

1. Rosenbaum, M., Knight, R., & Leibel, R. L. (2015). The gut microbiota in human energy homeostasis and obesity. Trends in endocrinology and metabolism: TEM, 26(9), 493–501. https://doi.org/10.1016/j.tem.2015.07.002

2. Kamba, A., Daimon, M., Murakami, H., Otaka, H., Matsuki, K., Sato, E., Tanabe, J., Takayasu, S., Matsuhashi, Y., Yanagimachi, M., Terui, K., Kageyama, K., Tokuda, I., Takahashi, I., & Nakaji, S. (2016). Association between Higher Serum Cortisol Levels and Decreased Insulin Secretion in a General Population. PloS one, 11(11), e0166077. https://doi.org/10.1371/journal.pone.0166077

3. De Paoli, M., Zakharia, A., & Werstuck, G. H. (2021). The Role of Estrogen in Insulin Resistance: A Review of Clinical and Preclinical Data. The American journal of pathology, 191(9), 1490–1498. https://doi.org/10.1016/j.ajpath.2021.05.011

4. Tay, J., Thompson, C. H., Luscombe-Marsh, N. D., Wycherley, T. P., Noakes, M., Buckley, J. D., Wittert, G. A., Yancy, W. S., Jr, & Brinkworth, G. D. (2018). Effects of an energy-restricted low-carbohydrate, high unsaturated fat/low saturated fat diet versus a high-carbohydrate, low-fat diet in type 2 diabetes: A 2-year randomized clinical trial. Diabetes, obesity & metabolism, 20(4), 858–871. https://doi.org/10.1111/dom.13164

5. Hall, K. D., Ayuketah, A., Brychta, R., Cai, H., Cassimatis, T., Chen, K. Y., Chung, S. T., Costa, E., Courville, A., Darcey, V., Fletcher, L. A., Forde, C. G., Gharib, A. M., Guo, J., Howard, R., Joseph, P. V., McGehee, S., Ouwerkerk, R., Raisinger, K., Rozga, I., … Zhou, M. (2019). Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake. Cell metabolism, 30(1), 67–77.e3. https://doi.org/10.1016/j.cmet.2019.05.008

6. Monguchi, T., Hara, T., Hasokawa, M., Nakajima, H., Mori, K., Toh, R., Irino, Y., Ishida, T., Hirata, K. I., & Shinohara, M. (2017). Excessive intake of trans fatty acid accelerates atherosclerosis through promoting inflammation and oxidative stress in a mouse model of hyperlipidemia. Journal of cardiology, 70(2), 121–127. https://doi.org/10.1016/j.jjcc.2016.12.012

7. Cenni, S., Sesenna, V., Boiardi, G., Casertano, M., Russo, G., Reginelli, A., Esposito, S., & Strisciuglio, C. (2023). The Role of Gluten in Gastrointestinal Disorders: A Review. Nutrients, 15(7), 1615. https://doi.org/10.3390/nu15071615

8. Guo, H. H., Shen, H. R., Wang, L. L., Luo, Z. G., Zhang, J. L., Zhang, H. J., Gao, T. L., Han, Y. X., & Jiang, J. D. (2023). Berberine is a potential alternative for metformin with good regulatory effect on lipids in treating metabolic diseases. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 163, 114754. https://doi.org/10.1016/j.biopha.2023.114754