As someone who had pre-diabetic blood glucose readings in his late 20s, I came to understand the many problems that awaited me if I didn’t get my posterior in gear.  I remember the first time I had a bad reading during my annual physical.  An aberration I thought.  I wasn’t extremely overweight and I exercised intensely 8-10 hours a week.

Of course, repeated observations had a way of eroding this notion of outliers, and I quickly came to the realization that I was on a pretty bad path.  This idea was confirmed when I purchased a glucometer and did regular readings on my own at home.  So I did what the vast majority of people don’t do and took the management of my health in to my own hands.

Don’t get me wrong, I was getting a nice dose of gut symptoms while this was happening.  I just chalked these up to getting older; I didn’t realize until much later that this is just what happens in people with poor blood glucose regulation.  Nerves don’t like high blood glucose levels, whether they’re nerves that serve your fingers and toes or the nerves that make up the enteric nervous system in the gut.

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Hyperglycemia and gut health

A couple of weeks back I posted a blog showing that hyperglycemia causes leaky gut in mice, and when we look at humans there’s a tight correlation between bacterial products in the blood and hemoglobin A1c levels, which function as a proxy way of estimating your average blood glucose levels over 3 month.  So this combination of evidence indicates that hyperglycemia likely has the same effect in humans.

There is a well-established link between Type 2 diabetes and gut problems.  As many as 75% of people with Type 2 diabetes have some form of gut problem with diarrhea(22%), and candida overgrowth being common issues.   The image below details other common gut symptoms in people with Type 2 diabetes.

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So what could be the cause of these problems?  The microbiome is certainly involved, but I’m not sure I’d put much of the blame there, at least not initially.  When we look at what hyperglcyemia does to nerves, we can get a clear picture of how it can destroy your gut health.  One of the primary symptoms of prolonged Type 2 diabetes is neuropathy, or damage to nerves.

We tend to only think of this in relation to nerves serving the hands and feet as this is where Type 2 diabetics tend to experience these symptoms.  But nerves of the autonomic and enteric nervous systems suffer damage due to hyperglycemia as well.

Of particular relevance here are the nerves of the enteric nervous system, which control everything from enzyme secretion to GI motility.  These nerves, along with the vagus nerve, function as the master control center for the process of digestion.  In addition to regulating motility, fluid absorption, and enzyme secretion, they also help regulate inflammation and the permeability of the gut wall.

Obviously not much good can come from destroying these nerves from a gut health perspective.  Most animal models show a selective decrease in nitric oxide in the gut of those with Type 2 diabetes, which functions as an inhibitory neurotransmitter in the gut.  It also appears to be a more significant issue for females than males.  Other pertinent changes in the enteric nervous system can be found here.

It’s odd that, while the underlying physiology seems to be pretty consistent, the symptoms can range from constipation to diarrhea, which one would assume to be opposite sides of a coin.  I’d chalk this up to individual susceptibility, as most people will experience one or the other.  There’s probably a pretty good dose of poor lifestyle contributing to this as well.

One interesting theory posits that the difference is one of time.   First, constipation sets in early, causing stagnation in the gut.  Over time, this leads to bacterial overgrowth and changes to the microbiome that promote gas, bloating, and eventually diarrhea.  I’d be surprised if this were a linear process that’s consistent across individuals, but it’s certainly an interesting theory for those who waffle between constipation and diarrhea.

Lifestyle factors that set the stage…

A number of lifestyle factors can contribute to this pathology.  Melatonin is a hormone secreted by the pineal gland at night when you’re no longer exposed to the blue wavelength of light.  When melatonin binds to melatonin receptors in the pancreas, it inhibits insulin secretion.

This process actually accomplishes 2 things.  First, it prevents blood glucose levels from tanking at night when you’re not eating.  Secondly, it helps reset insulin sensitivity for the next day.  A couple of factors can throw a monkey wrench in this whole thing.

Exposing yourself to blue light at night can delay melatonin secretion.  Over the long term this could cause a loss in circadian insulin sensitivity and make you more insulin resistant throughout the day.  Also, eating close to bedtime could lead to elevated blood glucose levels at night as insulin secretion is blocked by melatonin.

An issue worth noting here is what you do in the morning.  If you roll right out of bed and eat breakfast without adequate light exposure, you may drive your blood glucose up only to have it come crashing down when you go outside.  Basically, you abruptly remove the melatonin brake on insulin secretion and this could lead to reactive hypoglycemia.

Another issue that could lead to hypoglycemia is a poor circadian cortisol rhythm.  Among its many functions, cortisol acts as a counter-regulatory hormone to insulin that increases blood glucose levels.  People with Type 2 diabetes have a flattened circadian cortisol rhythm.  This coupled with poor sensitivity to insulin can cause large sways between hyper- and hypoglycemia.

Even in healthy individuals without Type 2 diabetes, one study showed prolonged hyperglycemia seems to have a pretty significant effect on factors that cortisol helps regulate.  Within 48 hours of chronic mild hyperglycemia induced in healthy individuals, the circadian variation of both heart rate and blood pressure were lost when compared to their standard circadian rhythm.  To produce this effect, the blood glucose levels of the participants was only raised to 116mg/dL, below the level of 125mg/dL inbdicative of Type 2 diabetes.

The consequences of a disturbed cortisol rhythm can have a wide range of effects throughout the body.  Specifically in reference to digestion, cortisol is responsible for the recycling of bile acids.  This could lead to altered bile acid metabolism and could help explain why insulin resistance leads to an elevated total bile acid pool as well as increased bile acids in the blood.

Conclusion

Chronic hyperglycemia can cause a number of issues that can lead to gut dysfunction.  Many of these tie in to factors that are both outputs and inputs of the circadian clock.  This includes insulin, cortisol, and bile as all 3 function as systemic signaling factors that are regulated by the clock or lifestyle factors known to impact circadian physiology.

It’s no coincidence that gut problems are noted in 3/4s of people with Type 2 diabetes.  The gut is under heavy circadian regulation and gut function will be heavily regulated by factors that impact the circadian clock including physical activity and the feeding/fasting cycle. While it is very common to look simply at your bodyweight as a way to measure your lifestyle, blood glucose regulation is accessible and cheap and easy to measure.  It’s a mistake to not use HbA1c or measure fasting or postprandial blood glucose.

 

For most people, declining health is the norm and poor blood glucose regulation contributes to this greatly.  But the story doesn’t have to have a sad ending.  While many just assume this is their genetic destiny, my genetic destiny went from an average 3 month glucose level of 140mg/dL to 93mg/dL.  Suffice it to say there’s a lot you can do to fix this problem provided you’re motivated to do so.