Causes of Insulin Resistance

August 19, 2020

Discovery of insulin, in 1921, was a Big Bang from which a vast and expanding universe of research into insulin action and resistance has issued. Growing evidence suggests that insulin resistance (IR) is an important metabolic driver behind numerous diseases and health risks.

Insulin resistance is when targeted cells primarily in your muscles, fat, and liver do not respond well to insulin and cannot use glucose from your blood for energy. Insulin, a hormone that the pancreas makes, allows cells to absorb and use glucose. In people with insulin resistance, the cells are unable to use insulin effectively.

Insulin resistance is when cells in your muscles, body fat and liver start resisting or ignoring the signal that the hormone insulin is trying to send out—which is to grab glucose out of the bloodstream and put it into our cells.

Causes of IR

The great majority of people with insulin resistance fall into the acquired categories, viz.,

  1. Obesity/Excessive fat (adipose tissue)- 

One of the most important risk factors for IR is Obesity or excessive fat accumulation. Possible mechanisms in different research studies suggest that excessive fat secret substances called Adipokines which are known to impair the targeted Insulin receptor tissues and cause IR. 

It has been suggested that obese individuals are associated with a greater rate of fatty acid breakdown and uptake compared with lean individuals, and this higher flux is postulated to be an important mediator of insulin resistance. 

  1. Lack of movement, exercise

It is well established that exercise is associated with substantial improvement in insulin sensitivity. A single bout of moderate intensity exercise can increase the glucose uptake by at least 40%.The beneficial impact of daily exercise on insulin resistance would be magnified if associated with diminished body fat because exercise can influence the fat deposition in your tissues.

Individuals with diabetes due to insulin resistance can be reversed by habitual physical exercise. As excess adiposity in the waistline contributes to insulin resistance, regular exercise assists in reduction of body fat, thus increasing cellular insulin sensitivity.

Indeed, combined with the fact that modest exercise reduces the morbidity and mortality associated with cardiovascular disease and diabetes, it is an effective therapeutic strategy for reducing insulin resistance and, more importantly, improving overall quality of life and wellbeing. 

  1. Nutritional imbalance 

Several nutritional insufficiencies can also ultimately lead to IR. Glucose toxicity or glucotoxicity is a condition resulting from untreated high blood sugar. It is accepted that glucose toxicity is involved in the worsening of IR by affecting the secretion of β-cells.

Glucotoxicity not only affects the secretion of pancreatic hormones but also participates in insulin resistance of insulin-sensitive tissues (liver, skeletal muscle, and adipose tissue). Oxidative stress is strongly suspected to be involved in glucotoxicity induced insulin resistance. 

High fat intake from n-6 PUFAs are known to worsen and cause Insulin resistance. Largely present in vegetable oils, these n-6 fats cause the adipocytes (fat stores) to signal to peripheral cells to become insulin resistant, as Paul Saladino, a Carnivore MD says. He also states that it is the n-6 PUFAs which initiates the process of IR rather than the carbohydrates.

Moreover, it is worth noting that vitamin D deficiency is very common and may be associated with the pathogenesis of insulin-resistance-related diseases, including obesity and diabetes. Evidence suggests that vitamin D seems to be a regulator of numerous sequential events that are responsible for enabling the pancreatic β-cells to secrete insulin, and thereby to control blood glucose level.

  1. Thyroid dysfunction (Hyperthyroidism and Hypothyroidism)

Insulin resistance is defined as a glucose homeostasis disorder involving a decreased sensitivity of muscles, adipose tissue, liver and other body tissues to insulin, despite its normal or increased concentration in blood. Thyroid hormones have a significant effect on glucose metabolism and the development of insulin resistance.

In hyperthyroidism, impaired glucose tolerance may be the result of mainly insulin resistance in the liver, whereas in hypothyroidism the available data suggests that the insulin resistance of peripheral tissues prevails.

  1. High inflammation/ elevated inflammatory markers

Development of IR is mainly associated with tissue-specific inflammatory responses induced by various pro-inflammatory and/or oxidative stress markers notably pro-inflammatory cytokines such as interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), numerous chemokines and adipocytokines, glucolipotoxicity.

Chronic exposure of pro-inflammatory mediators stimulates the activation of cytokine signaling proteins which ultimately block the activation of insulin signaling receptors in β-cells of pancreatic islets.

  1. Medications (glucocorticoids, anti-adrenergic, protease inhibitors, antipsychotics)

Treatment with cancer therapeutics such as glucocorticoids, chemotherapy, hormonal therapies and targeted drugs can actually induce insulin resistance. Current literature regarding the incidence of cancer-therapy induced insulin resistance describes the intracellular changes that occur in insulin signalling pathways and glucose metabolism.

Protease inhibitor use is associated with a potentially serious syndrome of metabolic abnormalities characterized by central adiposity, hypertriglyceridemia, hypercholesterolemia, and insulin resistance.

Other categories of drugs like anti-adrenergic and antipsychotics are also linked to cause Insulin resistance. 

  1. Aging

With increasing age, body’s insulin sensitivity and glucose regulation ability decreases gradually along with muscle wasting. Studies have shown that, compared with younger males (30 years old), older males (65–70 years) have reduced glucose metabolism and decreased expression of skeletal muscle.

The underlying mechanism behind aging and insulin resistance is related to a series of changes in skeletal muscle during the aging process. During skeletal muscle aging, a series of other changes also tend to occur, including mitochondrial dysfunction, fat accumulation, increased inflammation and oxidative stress. These changes can impair skeletal muscle insulin sensitivity and increase the risk of insulin resistance.

  1. Smoking 

Smoking reduces the effectiveness of insulin, inflames your whole body and also increases the oxidative stress. Nicotine from cigarettes makes the working of Insulin less effective, keeping you in a continued insulin-resistant state. Inflammation occurs when chemicals in cigarette smoke injure cells, causing swelling and interfering with proper cell function, explains the CDC.

Inflammation is one of the key factors responsible for insulin resistance. Oxidative stress is a condition that develops when the smoke inhaled from your cigarette combines with the otherwise healthy oxygen in your body. Your entire body relies on the healthy delivery of oxygen to keep it healthy — and now it’s receiving oxygen that is severely contaminated and can ultimately be the reason behind insulin resistance.

In addition to the above factors, there are a number of unrelated genetic syndromes with associated insulin resistance Myotonic Dystrophy, Ataxia-telangiectasia, Alstom syndrome, Rabson-Mendenhall syndrome, Werner syndrome, Lipodystrophy).

In our work at ThriveFNC we’ve seen that insulin resistance is a silent disease and dangerous and begins without any evident symptoms.  The only way to detect Insulin Resistance is by testing your blood for related parameters. You can approach ThriveFNC if you or your loved ones are suffering from insulin resistance.





















Ria Jain
Functional Nutritionist

Ria has a Master’s in Nutrition and Dietetics and is in a permanent research mode and keeps the rest of us at iThrive (Previously ThriveFNC) updated with her latest findings in the field of Nutrition. Her articles on iThrive's blog are an expression of her research findings. We really don’t know what we’d do without her support and her focus.

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