(This is one of three Health Insight blogs based on the three parts of Dr Benjamin Bikman’s book: Why we get sick. The three blogs are: INSULIN RESISTANCE AT THE ROOT OF MOST CHRONIC DISEASES, INSULIN RESISTANCE CAUSES, and INSULIN RESISTANCE CURES.)
Insulin plays a vital role in the harmony in which some of the biochemical processes in the body work. For example, when you eat carbohydrates, it gets converted into dietary sugars (called glucose) which end up in the bloodstream to act as fuel for the cells in the body. Easier said than done, as blood glucose needs to be partnered by insulin to be able to enter the cells in the body. Insulin is a hormone released by the pancreas that tells cells to open up so glucose can enter and be converted into energy. The more glucose in the blood, the more insulin is released. In this way insulin regulates blood sugar levels in the bloodstream.
Insulin resistance happens when cells in the muscles, fat, and liver have built up a resistance and don’t respond well to insulin, leading to a build-up of excessive blood glucose levels, to the point of being in the diabetic range.
Why the body develop insulin resistance has no easy answer, as so many factors can play a role, from age to Zee’s.
How age influences insulin:
Growing old is truly not for the faint of heart! Generally, the older we get, the more insulin resistant we become, and hormonal changes are a major contributor to the development of insulin resistance. The hormone estrogen helps to maintain insulin sensitivity in both men and women. Due to aging, the reduction in producing estrogen can contribute to the development of insulin resistance. The same applies to the reduced production of testosterone in men, which can also lead to insulin resistance.
How genetics influence insulin:
Chances are that if both your parents were insulin resistant, you may also become insulin resistant. However, genetic mutations that cause insulin resistance are very rare, accounting for approximately 5% of all cases of type 2 diabetes.
How hormones cause insulin resistance:
Hormone insulin itself is the most relevant factor that causes insulin resistance, as too much insulin drives insulin resistance. A fundamental feature of how the body works is when a biochemical process is excessively activated, the body may dampen its response to the excess stimulus, in order to reduce the activation. When a cell in the muscle, fat, or liver is inundated with insulin, it cannot reduce the amount of insulin produced in the pancreas, but it can alter itself to reduce the effect of insulin by becoming insulin resistant. When this occurs in a magnitude of cells, the body as a whole becomes insulin resistant. The high levels of insulin in the body often stems from lifestyle factors, such as foods loaded with sugar, eating the wrong unhealthy fats, lack of exercise, and chronically high levels of stress.
The body’s stress response involves stress hormones epinephrine and cortisol, both released by the adrenal glands. During the early stages of stress (fight or flight response), epinephrine increases heart rate and blood pressure, priming the body for action. However, too much epinephrine over too long a period is capable of causing insulin resistance. Cortisol is involved in the longer-term stress response and boosts energy to help us through a stressful situation. Cortisol tells the liver to make glucose for energy out of anything it can get, including glucose stores, amino acids from muscle protein, and glycerol from fats. While cortisol is trying to increase blood glucose, insulin is trying to reduce blood glucose, with cortisol winning this battle, contributing to insulin resistance.
All cells respond to thyroid hormones as they do multiple things throughout the body. Having too little thyroid hormone production (hypothyroidism) means the average cell will have fewer insulin receptors, resulting in insulin having a smaller effect. This will result in the pancreas producing more insulin to control blood glucose levels, but having fewer insulin receptors can result in insulin resistance.
On the other hand, having too much thyroid hormone (hyperthyroidism) results in about 70% more insulin receptors on fat cells, which may potentially improve insulin sensitivity.
Obesity and insulin resistance:
Insulin resistance and obesity have a strong connection, with a bit of a chicken and egg situation, as obesity can both be a result of insulin resistance, and a cause of insulin resistance, with evidence pointing to both perspectives.
The location where body fat is stored is very relevant, as body fat can be stored in the wrong place. Fat stored beneath the skin is referred to as subcutaneous fat, typically on the hips and thighs, with less fat on the upper body and trunk. Fat inside the trunk of the body surrounds the visceral organs (liver, kidneys, intestines, and heart) and is referred to as visceral fat.
An easy test to determine your own type of fat is to grab some fat and shake it. If you can shake it, it is subcutaneous fat. If you can’t easily grab it or if your belly is big and hard, it is likely that you have more visceral fat, which is worse, as studies have shown that storing fat inside the core of the body is harmful.
The most important aspect of obesity and insulin resistance is where your fat is stored, as visceral fat is more strongly linked to insulin resistance.
Not only the location of your fat matters, but of equal importance is the size of your fat cells. As we gain fat, our fat tissue can grow in two ways – either via an increasing number of fat cells, or growth in cell size. Enlarged fat cells can become insulin resistant, while multiplying smaller fat cells can remain insulin sensitive. Enlarged fat cells that have grown beyond their borders not only leaks fat into the surrounding tissue but also becomes inflamed and dump inflammatory proteins into the blood. The toxic combination of too much fat and too much inflammation both drive insulin resistance.
A number of processes can make the liver fat, such as too much alcohol, fructose, or insulin, leading to insulin resistance.
Muscle is the largest tissue in most of our bodies and the main consumer of glucose, which means it relies heavily on insulin to enable glucose to enter muscle cells. High levels of insulin for a prolonged period of time can result in muscle cells becoming insulin resistant.
How inflammation and oxidative stress influence insulin resistance:
Inflammation occurs when the body release chemicals that trigger an immune response to fight off infection or heal damaged tissue.
Oxidative stress is a condition that may occur when there are too many unstable molecules called free radicals in the body and not enough antioxidants to get rid of them, which may lead to cell and tissue damage.
Inflammation and oxidative stress are closely related and are tightly linked pathophysiological processes. One of them may appear before or after the other, but when one appears the other one is likely to follow. They are critical components of the immune system to help defend against infections. These two doing good deeds in the fight against infections may change to harmful actions directed at the body in the event of chronic inflammation, such as in conditions like autoimmune disease, rheumatoid arthritis, and even obesity – which is described as a state of chronic inflammation.
Chronic inflammation and high levels of oxidative stress drive insulin resistance.
Lifestyle factors influence insulin resistance:
Lifestyle factors refer to the things we put in our bodies and the things we do to our bodies.
Research has linked air pollution to insulin resistance. When these toxic molecules enter the lungs, it triggers pro-inflammatory responses, ending up in the blood stream from where it may spread and interact with other organs and tissue, such as the liver and muscles, potentially causing them to become insulin resistant.
Cigarette smoke is viewed as the most common cause of preventable death. Apart from its effects on lungs and heart health, cigarette smoke also desensitizes the whole body to insulin. Fat cells in particular are one of the direct sites where nicotine acts to create insulin resistance.
The mouth is another common route of exposure to harmful substances, such as monosodium glutamate (MSG) in food, products made from petrochemicals, and pesticides, which have all been linked to insulin resistance.
Modern society’s increasing consumption of sweetened foods coincides with increasing rates of insulin resistance.
While the high consumption of salt has been linked to high blood pressure, too little salt also affects our health and has been linked to insulin resistance. The hormone aldosterone helps to regulate the balance of salt and water in the body. As salt consumption drops, the kidneys reabsorb salt from urine and back into the blood, and this happens through the actions of aldosterone. While aldosterone is working to recover salt from urine, it antagonizes insulin, resulting in insulin resistance. A few studies have linked low salt diets to insulin resistance.
Some of the things we do also contributes to insulin resistance, such as not getting enough sleep (Zee’s) and sedentary living – the less we use our bodies, the more insulin resistant we become. Interestingly, unused muscles experience an increase in inflammatory events, which drives insulin resistance in these areas.
Conclusions:
With insulin resistance becoming a common occurrence and seen as the root cause of many chronic diseases, it is of vital importance to understand what makes us insulin resistant in the first place. While some of these causes may be unavoidable, others are well within our control.
References:
Why we get sick. The hidden epidemic at the root of most chronic diseases – and how to fight it. Book by Dr. Benjamin Bikman. Published in 2021 by BenBella Books, Inc. Dallas, Texas. USA. P. 259.
HEALTH INSIGHT.
December 2024
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