Diabetes is caused by circadian rhythm disruption

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Type 2 diabetes is an epidemic. It seems like everyone these days is diabetic or pre-diabetic (or I’ve even heard the term pre-pre-diabetic used). We all seem headed down that path…

So what is going on? Everyone knows that sugar is evil…  But sugar consumption is down considerably. It peaked in the late 90s and has gone down steadily since. Yet, diabetes has continued to increase.

If it isn’t sugar consumption that is causing everyone to have diabetes, could it be something else that is ubiquitous and new to our modern lifestyle?

My theory: Circadian disruption is causing the diabetes epidemic.

Let me explain how research is painting a big arrow towards circadian disruption causing diabetes.

Circadian disruption -> insulin resistance -> diabetes

Why do most of us have disrupted circadian rhythms?

We have had a fundamental change in the amount of blue light we are exposed to at night. This started with color TV in the ’70s and ’80s and multiplied many-fold in all of our LED lightbulbs and LED screens (laptop, cell phone, tablet, TVs).

Thomas Edison’s light bulb flickered some soft light into the night over a century ago. But those yellowish colored lights didn’t have the same effect on our core circadian rhythm as the very bright, blue-enriched LED lighting of today.

This bright light at night has shifted us into a 24-hour society where it is the norm to stay up past midnight, surfing on the phone and watching some Netflix. Mealtime and snacking have shifted later. The overall quantity of sleep has been reduced, and quality of sleep decreased. 

For millions of years, the rhythm of the sun has been unchanging. Almost all species on earth – from cyanobacteria to plants to animals to us humans – have at our core a circadian rhythm that is based on light. It turns out, this is a foundational part of our well being.

What does circadian rhythm have to do with diabetes?

(How can I have the audacity to think that anything other than an evil, giant food corporation is at the root of our diabetes crisis? )

How does your body know it is night? Melatonin acts as a signaling molecule, rising at night when the light grows dimmer.  (Of course, these days that doesn’t happen until you turn off the TV and lights at midnight and lay there wondering why you can’t sleep.)

Melatonin being present (or absent) signals to the core circadian clock, resetting it to be in sync with daylight and night time.

Melatonin also acts upon melatonin receptors in the beta cells of the pancreas, controlling insulin levels overnight. This system is then dependent upon melatonin rising at the right time.

Animal studies show that if you eliminate melatonin from rising at night (by removing the pineal gland) the animals develop glucose intolerance and insulin resistance. They gain some weight and basically become pre-diabetic or diabetic. BUT – add back in some melatonin and they return to normal, even when fed a crappy diet. [ref]

Let’s look at the other research that shows that disrupting circadian rhythm causes ‘insulin resistance’ and type-2 diabetes:

Epidemiological research that points toward it:

Researchers have known for a couple of decades that working the night shift increases the risk of diabetes. How much? Studies differ, of course, but the increased risk ranges from a 20% increase in risk to a 2-fold increase (double the risk).  [ref][ref][ref][ref]

You may argue that shift workers eat a crappy diet, and that no matter how well the researchers try to control for that, it still is what is causing diabetes.  (Perhaps you wouldn’t argue that — but that was the first thing that popped into my mind.)  I did a quick search to find out how much sugar intake increases diabetes risk.  A study of 39,000 + women found that neither sugar intake nor fructose intake increased diabetes risk.

Epidemiological studies are interesting, but they don’t explain why and they don’t actually show if one thing causes another.  So we need a lot more research.

Animal research explains how circadian rhythm increases diabetes: 

One key factor in diabetes is the skeletal muscles’ ability to take up and use glucose out of the bloodstream. This regulates your blood glucose levels.

When researchers deleted one of the core circadian clock genes (BMAL1) in muscles in animals, it caused significantly impaired glucose uptake in the muscles.  This was discovered in 2014 in an important study that points to the fundamental role of the core circadian clock in insulin resistance. [ref]

Researchers also have discovered that circadian disruption causes the failure of pancreatic islet cells, which control insulin release. Exposing the animals to light at night for 10 weeks changed the circadian rhythm in the pancreatic islet cells and decreased the glucose-stimulated secretion of insulin. [ref]

It may be more, though, than just exposure to light at night. It may be that a lack of daylight is also important here in the disruption of circadian rhythm and an increase in diabetes…

A recent study used a diurnal (active during the daytime) animal model. The animals were kept in the lab and exposed to artificial light for 12 hours and then with the lights turned off for 12 hours. They were all fed standard chow and kept under normal conditions – yet about 30% of them developed diabetes.  But when these same type of diurnal animals are kept in cages and fed the same chow — but kept outdoors in natural daylight and darkness — they don’t develop diabetes.  The only difference is the artificial day/ night in the lab – plus probably circadian temperature differences. [ref]

What about human studies?

A study from August 2019 found that all of the core circadian rhythm genes (CLOCK, BMAL1, CRY2, and PER1) are downregulated in people with diabetes. It also found that as HBA1C levels rose, the core circadian gene expression went down.  [ref]

You may be wondering why this is important– why it matters that the core circadian gene expression is depressed in people with diabetes. The core circadian genes rise and fall over the course of 24 hours, acting as a pacemaker for many of your body’s functions – such as metabolism and hormone release. A depressed amplitude of the core circadian genes alters the body’s insulin secretion and response to glucose.

Eating combined with light at night has been shown in humans to induce “profound derangements in GLP-1 and insulin responses such that postprandial GLP-1 and insulin levels were markedly elevated and the normal variation in GLP-1 responses was abrogated.” [ref]  Yep. Pretty clear that light at night + food is not good.

Another recent study found that as HbA1C levels (a marker for glucose levels) goes up the oscillation of the core circadian CLOCK gene is shorter.[ref]

What can we learn from genetics about circadian rhythm and diabetes?

When researchers find a connection between two things – such as diabetes and exposure to light at night – there is always a question of whether one thing (e.g. light at night) is causing the other (diabetes). Or perhaps there is a third player — such as light at night causing people to eat a full bag of candy corn, which then causes diabetes.

One way to figure out cause vs effect vs innocent bystander is to look at genetics.

Researchers have found that several of the core circadian rhythm genes are related to diabetes.

Let me explain: Say you have 100 people in a research study. 75 of those people carry one version of a core circadian gene (let’s say BMAL1, here), and 25 out of the group carry a version of BMAL1 with a slight change to it (genetic variant). If the researchers follow those 100 people for 10 years to see who ends up getting diabetes, they can then look at proportion of the people with the genetic variant that get the disease. The scientists then do some statistical magic (crunch some numbers) and figure out if a bigger percentage of people with the genetic variant end up getting diabetes.

This type of experiment has been done many times, on a larger scale.  The core circadian genes – BMAL1, CRY2, and CLOCK – all have variants that predispose people to diabetes. [ref][ref]

One well-studied genetic variant that is linked with an increased risk of type-2 diabetes is in the MTNR1B gene, which codes for a melatonin receptor.  This melatonin receptor is expressed in the pancreas and regulates insulin release overnight. The genetic variant in MTNR1B is tied to an increased risk of type-2 diabetes, but only in people who eat dinner later at night. Thus when there is a mismatch between melatonin and meal timing, the overnight insulin release is altered. [ref][ref][ref]

Conclusion and Reality Check:

There is a large pile of evidence pointing to the idea that disrupting circadian rhythm results in insulin resistance, leading to type-2 diabetes.

Is that the only cause of diabetes? Of course not. But I think that it is a vastly underappreciated cause. Just imagine the lives that could be impacted through simple changes to lighting at night.



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