Calorie intake should be limited to one that is suitable for the body and limits foods that are sugar-laden. — CAIO/Pexels
Everyone is aware that a consequence of insulin resistance in the body is Type 2 Diabetes, a depressingly common outcome of metabolic syndrome. Diabetes currently affects around 10.5% of the global adult human population (14.39% in Malaysia), and an estimated 31% of the entire human population has metabolic syndrome to some extent. Look around you. If you see two healthy persons next to you, then statistically, you are the one with metabolic syndrome.
Curiously, for many years insulin resistance was deemed to only affect the body and not the brain. This may be because glucose uptake by the brain is not affected by insulin levels (as the brain uses different glucose uptake transport mechanisms than that used by the body).
Despite finding insulin receptors in the human Central Nervous System (CNS) in 1978, it is only within the last few years that researchers have pieced together evidence of the consequences of insulin resistance in the brain. It is a complex story partly because the type of insulin receptors (IR) in the brain are different from the IRs in the body. Neurons in the brain express only type IR-A receptors while the rest of the body uses type IR-B insulin receptors.
One difference is that IR-A insulin receptors are particularly sensitive to low levels of “insulin-like growth factor-2” (IGF-2), which is used to manage the plasticity and health of the brain. Recent research has shown that deficiencies in IR-A activation can lead to various brain disorders, which in turn can lead to neurodegenerative conditions such as Alzheimer’s, which many scientists now call “Type 3 Diabetes”.
Excess weight, especially weight centred around the abdomen, is strongly associated with insulin resistance in the brain. — ANDRES AYRTON/Pexels
Other disorders include various neurological problems, impaired cognitive functions, depression, etc, often resulting in changes to dietary patterns, which in turn may aggravate the original issues caused by brain insulin resistance.
Key factors
Insulin is a peptide hormone produced principally by the pancreas and is used by both IR-A and IR-B receptors. Some research suggests that parts of the brain (cerebral cortex and the hippocampus) can produce insulin but it is currently unconfirmed. Insulin crosses from the body into the brain via the Blood–Brain Barrier and the levels of insulin uptake by the brain and rate of physical transport into the brain can be significantly affected by several factors, as follows:
• Obesity: Excess body weight, particularly abdominal obesity, is strongly associated with insulin resistance in the brain. Obesity can promote the secretion of cell-signalling proteins called adipokines which can cause a chronic state of low-grade inflammation in the brain. This can disrupt insulin signaling pathways, a sign of insulin resistance.
• Poor diet: Consuming a poor-quality diet high in processed foods, refined carbohydrates, and sugary beverages contributes to insulin resistance in the body and brain. These dietary patterns can affect metabolism, the human gut microbiome (and in some cases also the CNS) in various ways, leading to elevated blood glucose levels, repeated insulin spikes, and chronic inflammation, all of which can eventually impair insulin signaling pathways.
• Inflammation: Some diseases may provoke chronic low-grade inflammation in the brain. This can disrupt insulin signaling by inhibiting the proper functioning of IR-A receptors. A persistent disruption can eventually lead to cognitive impairment and neurodegenerative diseases.
• Age: Aging is a factor that influences insulin resistance in the brain. With age, there is a natural decline in insulin sensitivity, usually resulting in higher insulin levels in the bloodstream. This chronic elevation in insulin levels can promote insulin resistance both in the body and brain and can increase the risk of cognitive decline and neurodegenerative diseases, such as Alzheimer’s.
• Physical inactivity: Lack of physical activity and a sedentary lifestyle contribute to insulin resistance in the brain. Regular exercise appears to promote insulin sensitivity and preserve brain health by enhancing insulin signaling in brain cells, for reasons yet unknown.
• Genetic predisposition: Genetic factors play a role in the development of insulin resistance in the brain. Certain genetic variations can disrupt insulin signaling pathways, making individuals more susceptible to insulin resistance and related brain dysfunctions.
• Socioeconomic factors: Socioeconomic factors, such as low income and limited access to nutritious food, contribute to insulin resistance in the brain. Individuals with lower socioeconomic status often have poor-quality diets and higher rates of obesity, increasing their risk of insulin resistance both in the body and the brain.
• Chronic stress: Prolonged exposure to stress hormones, such as cortisol, can lead to insulin resistance in the brain. Chronic stress disrupts insulin signaling, contributing to cognitive dysfunction and neurodegenerative diseases.
Sleep disorders and sleep deprivation have also been linked to insulin resistance. — KHA RUXURY/Pexels
• Sleep disorders: Sleep deprivation and sleep disorders, such as sleep apnea, have been linked to insulin resistance in the brain. Altered sleep patterns disrupt insulin signaling, increasing the risk of insulin resistance and cognitive impairment.
• Environmental factors: Environmental factors, such as exposure to pollutants and certain chemicals, may contribute to insulin resistance in the brain. These factors can induce inflammatory responses and disrupt insulin signaling pathways, leading to insulin resistance.
• Food additives: There is emerging evidence which indicates certain food additives may contribute to elevated insulin resistance. Some studies have shown that the widely used food preservative, propionate, can provoke the release of hormones such as glucagon and fatty acid-binding protein 4 (FABP4).
Glucagon acts oppositely to insulin, by signalling for higher glucose levels in the blood, while FABP4 instigates the liver to convert its energy storage and release it as glucose into the blood. Consequently, propionate can lead to glucose overproduction by the liver and other organs, resulting in elevated insulin levels in the blood and potentially inducing insulin resistance in both the body and brain. Propionate is used in many commercial food products to inhibit the formation of mold in foods. Almost all supermarket bread in the UK contains calcium propionate, for example.
The above elements often influence and interact with each other, creating a complex web of factors that can eventually promote insulin resistance in the human brain.
Correlation?
Insulin resistance can be simply defined as “a failure of target tissues to mount a normal response to insulin”. Within the body, insulin resistance is one of the more common consequences of metabolic syndrome (usually expressed as Type 2 Diabetes), but less understood are the consequences of insulin resistance in the brain, which can also play a part in inducing symptoms and behaviours which are similar to metabolic syndrome.
This is because the brain plays a crucial role in integrating and coordinating various signals related to hunger, satiety, and metabolic status, and these all ultimately influence food intake and energy balance. Insulin receptors are present throughout the brain, including regions involved in the regulation of eating behavior.
Limiting unhealthy foods like fried foods can limit the risks of metabolic syndrome and brain insulin resistance. — CHAN WALRUS/Pexels
The persistence of insulin receptors throughout the brain underscores the hormone’s major role in moderating neural circuits related to appetite and food preferences.
Neuroimaging studies using functional magnetic resonance imaging (fMRI) have provided interesting insights into the link between insulin and human brain activity related to appetite regulation. fMRI scans investigating the impact of hunger, satiety, and oral glucose on the effect of insulin and resting-state human brain activity curiously found that brain insulin activations respond differently to oral glucose intake depending on whether a person feels hungry or full.
And these responses are related to different neural processing pathways in the brain. This indicates the brain’s sensitivity/responses to insulin can vary under different metabolic conditions, and further suggests, for example, that a flawed brain insulin response may not reduce appetite even after eating food.
As with metabolic syndrome, there are no good outcomes from having insulin resistance in the brain. So an interesting question is: Which comes first?
Does metabolic syndrome lead to brain insulin resistance, or is it the other way around?
On the surface, it may seem obvious that a plausible consequence of chronic metabolic syndrome is the eventual development of brain insulin resistance. And in most cases, this is very probably true, especially in people with uncontrolled/unmanaged obesity. However, factors such as age, sleep deprivation, chronic stress, environmental and genetic factors, etc, are capable of disrupting insulin signalling in the brain, and evidence suggests this can also result in addictive, flawed dietary habits, which can in turn lead to metabolic syndrome.
Common ground
Metabolic syndrome and brain insulin resistance have one thing in common. The kinds of food that lead to metabolic syndrome are also the same ones that can significantly aggravate any tendencies toward brain insulin resistance. Hence, if one has any concerns about metabolic syndrome or brain insulin resistance, then it would make sense to limit calorie intake to a suitable level for the body, and avoid certain groups of foods, for example:
• Refined carbohydrates, including any foods made from refined flours or grains
• Sugar and any sugar-laden foods and beverages
• Fats, especially Omega-6 oils, which can provoke inflammation
• Processed, packaged, or frozen prepared meals, tend to contain a lot of refined carbohydrates, sugar, fats, and high amounts of salt
• Ultra-processed foods, which are processed foods but also additionally contain various chemical additives, such as colourings, emulsifiers, preservatives, texture modifiers, artificial sweeteners, etc
• Deep-fried foods, which are typically high in fats, calories, and unhealthy free fatty acids arising from the heat decomposition of cooking oils
• Commercial fast foods, because they almost always contain elements from most or all of the above groups of foods.
Some lifestyle changes can also help, such as an adequate level of physical activity, sleeping better, avoiding smoking, and drinking in moderation. I am still working on the last item.
The views expressed here are entirely the writer’s own.
