The Deep-Dive Series: Understanding Insulin Resistance

Insulin Resistance - Nutrova

We often come across the term “insulin resistance” and how it is the underlying cause of type-II diabetes, as well as a causative factor in other diseases such as PCOS. What is insulin, though? And how do we develop a “resistance” to it?

To understand insulin resistance, we need to understand Insulin – a versatile hormone that plays key roles in how the body organizes the use of fuels (carbohydrates, protein and fats) for either storage, or conversion to energy. Insulin has profound effects on both carbohydrate and fat metabolism, and significantly influences protein and mineral metabolism as well.

Insulin’s primary role is to signal various cells in our bodies to take up glucose from the blood stream. When we eat a meal that contains carbohydrates, these carbohydrates are broken down through the process of digestion into glucose (and other sugars, depending on the food source). Glucose is absorbed in our gut and subsequently enters our bloodstream.

Our body strives to regulate the amount of sugar in our blood, trying to maintain it within a narrow band. Too little and our cells won’t have access to the fuel they need to function, and too much insulin can cause damage in a variety of ways. This regulation is achieved by a signal to our cells to take up glucose following a meal – a signal given by Insulin. The β-cells (beta cells) of our pancreas produce and store insulin and release it into our blood stream when they sense an increase in blood sugar, generally following a carbohydrate containing meal.

Insulin functions by binding to insulin receptors, which are found on the surfaces of most cells in the human body. Our cells have specialized proteins (the GLUT family of proteins, short for GLUcose Transport) that form a gateway for glucose to enter cells to be utilized as fuel. However, unlike insulin receptors, these gateway proteins are present inside the cell, and need to be instructed to move to the surface to let circulating glucose in.1

When insulin binds to the insulin receptor, it activates a protein known as IRS-1, which triggers a signal for the GLUT proteins to move to the cell surface thereby creating a channel for glucose to move into the cell.  Once inside the cell, glucose is used as a fuel source for energy or is stored as glycogen – a chain of glucose molecules – for later use.


Aside from this critical function, insulin also plays a role in other processes:

  • It stimulates the liver to store glucose as glycogen for later use. When our body is deprived of food or carrying out an energy-intensive activity (such as running a marathon), it starts breaking down this stored glycogen for fuel.
  • Once glycogen levels in the liver increase substantially, Insulin stimulates pathways that cause the liver to start synthesizing fats, which make their way into our bloodstream.
  • Insulin triggers adipocytes, or fat storing cells, to start storing fat.2
  • Insulin increases the rate of protein synthesis, by activating the machinery involved in the making, the reason why consuming carbohydrates along with protein after a resistance training workout is recommended. It also aids the transport of some amino acids (building blocks) into tissues.3,4
  • In addition to these roles, Insulin also helps the entry of essential minerals such as potassium, magnesium, and phosphate into various cell types. These minerals are crucial to the functioning of cells that make up muscles and nerves.


Insulin resistance

 Insulin resistance, in brief, is a condition in which cells do not respond to insulin. Specifically, insulin is present along with glucose in our blood, but the insulin cannot trigger the uptake of glucose by cells, leading to elevated blood sugar.


Acute Insulin resistance, the kind that sets in within minutes or hours, is observed in infections, traumatic injury, and pregnancy, and is believed to be an evolutionary response to stress, as it leaves glucose in the bloodstream for ready use by the immune system and our brain 5. This is a complex process that is not very well understood and only applies to extreme illness or trauma, which is beyond the scope of this article.


However, chronic insulin resistance, the kind that takes months, if not years, to set in is an established cause of type 2 diabetes and is associated with a host of other lifestyle diseases, including PCOS.


Every time we consume carbohydrates, there is an increase in blood sugar and insulin is released in proportion to this increase. Simple carbohydrates cause our blood sugar to spike dramatically, leading to a higher amount of insulin entering our bloodstream. When an individual’s diet contains consistently high levels of simple carbohydrates, it leads to a series of events that lead to systemic stress, which in turn leads to insulin resistance.


Chronically elevated levels of blood sugar and insulin lead to the production of certain enzymes within cells which modify the structure of proteins involved in Insulin’s signaling processes, such as IRS-1. These changes to the signaling proteins effectively reduce the movement of glucose transport proteins to the cell surface, preventing the excess glucose in our blood from entering the cell.1

Other factors that can contribute to the onset of insulin resistance along with a bad diet include:


  • Sedentary living: Evidence has emerged showing that early insulin resistance also occurs after very short-term exposure to physical inactivity (1-7 days), even without a bad diet! That’s because immobilization reduces the signals that make cells take up glucose. This has been shown in the case of bed rest and space flight where insulin resistance occurred muscle cells due to the lack of gravity. This is likely an adaptive response of the body to deal with the stress it perceives the inactivity to be caused by. Prolonged physical inactivity worsens this by leading to fat gain. 6
  • Obesity: High energy intake and low physical activity favour the storage of surplus fat that far exceeds our body’s storage capacity. The expanded fat tissue releases higher than normal amounts of inflammatory compounds into the blood, which also leads to the development of insulin resistance by the cells. 7 Proinflammatory compounds and fat metabolites, accumulated in liver and muscle cells, activate the mechanism of insulin resistance as would occur in the case of infection or stress. 8
  • Psychological stress: The stress hormone, cortisol, works in multiple ways to help us deal with stress. Our body goes into a state of hypermetabolism, where high amounts of glucose are maintained in the blood. Cortisol also directly affects the beta-cells in the pancreas to stop making more insulin. 9,10

These additional factors form a vicious circle which further promotes insulin resistance. Over time, the capacity of beta cells to produce insulin is affected, and this eventually leads to the onset of type 2 diabetes.

As insulin resistance progresses, it can cause a range of complications to our health:


  • Chronically elevated blood sugar: This causes damage to nerves, blood vessels, and organs.
  • Impaired muscle integrity: This happens due to muscle loss over time, and the accumulation of fat in muscle tissue.
  • Imbalance of cholesterol: When insulin resistance takes place, low density lipoproteins (LDL) and triglycerides are higher than normal in blood, and HDL  levels are lowered. LDL pass through blood vessel walls and slide into your arteries, where they can cause the build-up of plaque (blockages), which is why these metabolic issues increase the risk of heart disease.
  • Chronic Inflammation: Inflammation is both the cause and the effect of insulin resistance. This keeps the body is a constant state of stress, further perpetuating the circle of insulin resistance.
  • High blood pressure: Through the potential effects on blood pressure control, levels of potassium in our blood represent a link between insulin and blood pressure. High blood pressure is a risk factor for heart disease. 11
  • Effects on the brain: Glucose is our brain’s preferred fuel source, and it obtains glucose from our blood. Insulin resistance in the brain is believed to play a critical role in the onset of dementia and Alzheimer’s disease. 12
  • Other metabolic complications: Since the endocrine system is a tightly regulated one, any changes to the functioning of one hormone can have cascading effects on other hormones as well. PCOS (or Poly Cystic Ovary Syndrome) in women is one such issue which is associated with insulin resistance. 13

This vicious cycle that fools our body into thinking that we are in a constant state of stress is simply just an adaptation mechanism gone wrong, largely due to our current diet and lifestyle. In addition to changing lifestyles, Indians also have a genetic predisposition to type-II diabetes, which is no surprise given we have the highest number of diabetics in the world (62 million as of 2014).


What we can do

The good news is that small changes to our diet and lifestyle can help us prevent and even reverse insulin resistance to a large degree.


1.Diet: What we eat is responsible for the release of inulin and ensuring that we limit foods that dramatically increase blood sugar (and Insulin) is a great first step. An easy way to do this is to limit the intake of foods with a high Glycemic Index and Glycemic Load. The glycemic index (or GI) is a measure of how much a particular food will raise your blood sugar in comparison to pure glucose. The Glycemic Load takes into account the serving size of the particular food. 14

Glycemic Index Glycemic Load
Low 0 – 55 1 – 10
Medium 56 – 69 11 – 19
High 70 or more 20 or more


For example, the GI of fibrous whole wheat bread (about 51), is much lower than that of refined white bread (73). That means refined white bread gives us a lot of glucose quickly – possibly with some added sugar as well – which also means that we get hungry sooner (remember the blood sugar rollercoaster).

There are several books, websites and smartphone applications that are dedicated to helping you get this information about your food. However, generally speaking, a balanced, healthy diet that’s full of fruits and vegetables can keep you in the clear if you don’t overeat.


2. Exercise: Our muscles are responsible for a large part of glucose utilization, and research has shown that a single bout of exercise can improve insulin sensitivity for up to 16 hours after it. When muscles are active, they burn their stored glucose for energy. They then use glucose from the bloodstream to refill their reserves – keeping blood sugar levels in check.15, 16


3. Sleep and Hormonal Balance: Sleep disturbances, including insufficient sleep, poor sleep quality, and obstructive sleep apnoea have been associated with insulin resistance. Ensuring that we get sufficient sleep is another important step in decreasing our risk of developing insulin resistance.


4. Awareness: It’s a good idea to notice your body’s individual trends over time. Feeling fatigued or thirsty all the time could be a symptom of an oncoming insulin resistance. 17

We now know there’s a condition known as prediabetes, where blood glucose levels are above normal but below the threshold of diabetes. An estimated 77.2 million people in India (as of 2012) suffer from it. Studies have shown that lifestyle interventions in prediabetic adults can reduce diabetes risk by 40-70%. 18

What we eat, how active we are and the amount we sleep, are almost entirely in our control, and taking charge of just these three aspects of our life can go a long way in reducing our risk of insulin resistance and staying healthy overall.



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