Insulin Resistance - a silent killer - what you need to know

Humans need to eat.  Cells throughout the body are predominantly fueled by glucose delivered through the blood.

In evolutionary times food was not predictable, most often scarce, sometimes abundant. To maintain a consistent energy supply of blood glucose, evolution created a complex signaling system to control the process, delivering glucose when it is needed and efficiently storing it, when calories are abundant, ready to be mobilized in times of scarcity.  Two hormones are central to this signaling process: insulin and glucagon.  When blood sugar drops, pancreatic alpha cells release glucagon which then triggers the release of glucose from the liver.  Correspondingly, when blood sugars rise, pancreatic beta cells release insulin which promotes glucose uptake in the  liver and muscle, storing it as glycogen initially and then when glycogen stores are maximized, insulin prompts the conversion of carbohydrates and proteins to fat, our most efficient way to store calories for the future.  Both insulin and glucagon are small proteins recognized by specific receptors on individual cells.

This process, developed over 600M years of evolution, now is under challenge in humans.  The conditions for which we are optimized: calorie scarcity with intermittent abundance, no longer exist.  Instead we live in a world of continuous excess calories, with processed foods that rapidly spike blood sugars and trigger massive insulin release, and correspondingly massive insulin directed storage of excess calories as fat in adipose tissue.

For many this process has become a one-way street, the flexibility to shift metabolically from glucose to fat as fuel that was once the key to our survival has, for many people, been lost.  They are dependent on maintaining blood sugars through the constant consumption of carbohydrates. - if you find yourself craving sweats, getting tired after eating and feeling generally fatigued - this could be happening to you.

As a result of excess calories, sedentary lifestyles and this loss of metabolic flexibility, global levels of obesity are soaring:  2 Billion people are overweight - 650M are obese.  In Canada close to 50% of the population is overweight!.  With obesity has come a corresponding epidemic of obesity related diseases:

• Metabolic syndrome - 1 in 5 Canadians have metabolic syndrome - many are unaware
• Type II diabetes - by 2020 it is estimated that 10% of Canadians will be diabetic - with almost 1/3 unaware
• Atherosclerotic heart disease - 29% of Canadians die from heart disease
• Non-alcoholic fatty liver disease (NAFLD) - 75% of people who are obese are at risk for NAFLD

The process underlying this epidemic of epidemics is insulin resistance.

The cellular mechanisms by which insulin resistance manifests are complex and beyond the scope of this blog, but at a high level, dysfunctions in three areas appear to alone, or in combination affect the ability of insulin to efficiently activate the insulin receptor and trigger the cascade of reactions that allows insulin to do it's job:

1. ectopic lipid accumulation - lipids build up within the cells and in turn adversely affecting the insulin signaling pathways
2. unfolded protein response and endoplasmic reticulum stress - the endoplasmic reticulum is the organelle where complex proteins - including cell membrane receptors - are folded to gain their functional state.  A build up of mis-shaped proteins triggers the unfolded protein response that in turn leads to intracellular lipid accumulation, inflammation and in pancreatic beta cells affects insulin biosynthesis and can eventually lead to the cellular death of the beta cells - a key step in the progression of Type II Diabetes.
3. inflammatory response - activation of the inflammatory systems - starting with activated macrophages in adipose cells over-run with fat, results in a cascaded release of multiple inflammation signals - molecules called cytokines.  These inflammatory signals themselves disrupt the normal action of insulin and lead to disruption of normal metabolic processes.

The process by which insulin resistance progresses to pre-diabetes and diabetes is understandable and predictable - it is also very preventable.

As insulin resistance sets in, muscle, fat, and liver cells do not respond properly to insulin and thus cannot easily absorb glucose from the bloodstream. As a result, the body needs higher levels of insulin to help glucose enter cells.

The beta cells in the pancreas try to keep up with this increased demand for insulin by producing more. As long as the beta cells are able to produce enough insulin to overcome the insulin resistance, blood glucose levels stay in the normal range.

Over time, the processes that led to insulin resistance in the first place cause pancreatic beta cells to become less efficient and eventually triggers beta cell death.  As this begins to happen, blood sugars fall out of the normal range and people begin to be diagnosed with pre-diabetes or diabetes on the basis of abnormal blood sugars.

The time that it takes to progress from insulin resistance to pre-diabetes is generally in the order of 10-15 years - during this whole time a person will have normal blood sugars and may feel reassured that they do not have diabetes - YET - they are manifesting the underlying process of insulin resistance that will lead to diabetes and it's complications.  

So the big question that you should be asking is - how do I know whether I have insulin resistance?
Direct testing of insulin response is not broadly available, so we are most often left looking for other signs of insulin resistance.
For the most part, we can work with this:

• the TG/HDL ratio from a standard lipid panel correlates with insulin resistance - levels above 3.0 indicate a clear metabolic disruption.
• advanced metabolomic testing from Molecular You will also provide clues that insulin resistance is present (elevations in branched-chain amino acids for example)
• the accumulation of visceral fat (measured by DXA or by tape-measure) is also highly correlated with insulin resistance.
• hsCRP will give us a good measure of underlying inflammation which generally accompanies insulin resistance to some extent.
• and of course we can check blood sugars and HbA1c (the 120 average of blood sugars) but these will be normal until insulin resistance becomes pre-diabetes.

My blood sugars are normal, but I think I have insulin resistance, what do I do
The good news is the process that leads to diabetes is reversible through lifestyle changes:

• Food first - the absolute first step is to correct the patterns of eating that have led to insulin resistance.   Eliminating refined carbohydrates, eating a variety of whole foods, shifting to a mostly plant-based diet are all solid strategies.  More aggressive therapeutic nutrition strategies like a ketogenic diet have been shown to be very successful but definitely warrant medical direction and monitoring (especially if you are diabetic on medications).
• Activity - nothing crazy here - but building up your aerobic base will help restore a degree of metabolic flexibility as your body learns to burn fat while you exercise.  Weight lifting dramatically improves metabolic health by improving mitochondrial function.
• Sleep - undiagnosed sleep issues like sleep apnea can lead to obesity and insulin resistance.  If you snore or your spouse notices that you stop breathing in your sleep, you should get yourself screened for sleep apnea.  It is relatively straightforward and it is free.  Wellness Garage works with Clinical Sleep Solutions.

One of the major reasons we started Wellness Garage was to help people intervene early in preventable disease processes like insulin resistance  rather than wait until blood sugars become abnormal (after 10-15 years!) and prescribe medications.

If you think that you could be affected by insulin resistance - please reach out to us and book a free consultation, we can help you come up with a plan to address your health needs.