A pharmacist's perspective on health and metabolic disease
If long-term insulin resistance leads to poor health, why do we become insulin resistant in the first place?
To understand this, we need to understand a bit more about how the body uses the two main energy sources, glucose and fat. When we are metabolically flexible we can burn both glucose and fat, depending on what is available. Glucose is good for fast aerobic exercise – such as running down the antelope, (or away from the tiger) but fat is what keeps you going when you have to walk for miles to find the antelope in the first place. A lean, but healthy, body holds about three months worth of energy in fat stores, but only about 4 hours worth of glucose – mostly stored as glycogen. So which would you rather be burning for your everyday fuel requirements?
Being metabolically flexible means we should be able to burn either fuel as needed. Insulin resistance is another tool for the body to maintain metabolic flexibility. Historically, what you ate, and how much exercise you got would vary depending on the season, your current health status, and your place in society. This mean that the body often had to partition energy in and out of storage in response to available food, or energy needs.
Certain body cells can only absorb certain amounts of food before they become ‘full’. If these cells absorb more nutrients, then the cell becomes very metabolically stressed and starts producing large amounts of reactive oxidative species (ROS) and advanced glycation end-products (AGEs). ROS and AGEs weaken many cells, but especially the cells in which they are formed. For example, excessive amounts of ROS and AGEs in heart muscle cells, can result in cardiomyopathy, resulting in a weak heart.
Historically, autumn was a time of plenty and a good time to make sure everyone had a healthy amount of fat on them to ensure survival though a long, lean winter, Physiologically, there also needed to be a mechanism to make sure fat was stored, without weakening other vital systems. This mechanism is insulin resistance.
When there is plenty of food, insulin resistance is designed to shunt nutrients away from delicate tissues such as the heart and muscles and to store the excess in adipose tissue (fat cells). In times of famine, the fat is burnt and we become lean again. But we are still insulin resistant. Why? During periods of starvation, insulin resistance is also necessary to keep the available glucose for the cells that can’t burn fat…and just in case we need to chase down some food, or escape being eaten ourselves.
What is important is that we cycle in and out of insulin resistance. Times of plenty (insulin resistance) transition into times of just enough food (insulin sensitive) into times of starvation (insulin resistance) and back into times of just enough food (insulin sensitive). These transitions could be measured in days, or seasons.
When we break the cycling and stay permanently in the state of excess food, is when we change from being metabolically flexible into being metabolically inflexible, which is the first stage to developing hyperinsulinaemia, the precursor to many metabolic diseases. This is when insulin resistance stops being our friend and starts becoming our foe.