Hyperglycemia causes leaky gut, new study shows

Hyperglycemia causes a number of problems in people who regularly experience it. In the US, 1 in 3 people have either pre-diabetes or Type 2 diabetes. But you don’t need to have either to experience hyperglycemia. Hyperglycemia occurs in most everybody when the conditions are right. Unfortunately, the 2 primary conditions that cause it are common: Inactivity and overeating.

Over the last few years, “leaky gut” has moved from pure quackery to one of the leading topics in research.  Part of this is because people refer to it as leaky gut, which doesn’t lend scientific credence to the topic.  Truth be told, I hate this term, preferring the much more scientifically accurate intestinal permeability.  But I can’t control what people search for on the internet.

As you’ve guessed by the name of my blog, I feel gut health is important for overall health.  But my perspective is quite different than most on the subject. Most people focus on probiotics, supplements, and food that we eat. But my approach is firmly planted in lifestyle that includes many factors.  Things like circadian rhythms and such.

The study last year showing the microbiome of healthy older people being similar to the microbiome of healthy younger people shows this. Lifestyle is very important to maintain a healthy microbiome AND make it in to your 80s and 90s.  You just don’t see obese 90 year olds walking around.  You can throw genetics in there too, obviously.

Further support for this idea comes from a new study I believe will become a game-changer.  Researchers wanted to determine if causing hyperglycemia caused leaky gut.  They found quite a bit…

Hyperglycemia and leaky gut

It’s part and parcel of gut health protocols to avoid sugar.  You want to avoid sugar because it will feed bad bacteria. Then they’ll overgrow, cause leaky gut, and make your life a living hell.  And let’s not forget the chronic inflammation this causes.

This theory falls through on one very important point. A normal amount of sugar won’t make it to the colon where most of our gut bacteria live. We’ll absorb it way before then.  You could eat enough sugar that you don’t absorb it all, but that would be a huge amount of sugar.  Then the question becomes is the problem the sugar or the gi-normous amount of calories you just consumed? Note: It’s the latter.

But there’s another way excess sugar increases leaky gut. By increasing blood glucose to the point of hyperglycemia and/or hyperinsulinemia.  And that’s just what these researchers found.

Changes caused by hyperglycemia

In the study, researchers took mice and induced hyperglycemia.  I won’t bore you with the details of how this worked, but what they found was very interesting.  First, inducing hyperglycemia reliably caused leaky gut. It also cause bacteria from the gut to enter the blood and organs of mice.  And it was the increase in blood glucose that caused it. Neither insulin nor the appetite hormone leptin had any effect on their own.

Hyperglycemia reprogrammed the way the cells lining the gut worked by changing the expression of more than 1000 genes.  Immune cells were also skewed in the gut and spleen towards myeloid cells. I discussed this as being a telltale sign of “inflammaging” and promoter of aging-related disease in my last blog.

To find out if changes in the microbiome caused this, they did a fecal microbiota transfer(FMT).  They found changes in the microbiome of mice with hyperglycemia. But transplanting their microbiome into healthy mice didn’t cause leaky gut.  Altered glucose metabolism in the cells of the gut due to hyperglycemia was the culprit.

While your first response to this may be that mice aren’t humans, the study doesn’t end here.  Next, the researchers recruited 27 healthy human volunteers to look for measures associated with leaky gut.

Of the measures, HbA1c most reliably predicted the amount of bacterial components in the blood.  HbA1c functions as a 3 month average of your blood glucose.

Circadian rhythms, hyperglycemia, & leaky gut

These findings give us some very clear insights in to the damaging effects of hyperglycemia on the gut.  Not only does it cause leaky gut, it reprograms both the gut and systemic circulation towards inflammation.

Thus, reducing sugar in the diet isn’t a good target, maintaining healthy blood glucose levels is.  Fortunately, HbA1c tests are very easy to find. CVS has them for $40. If you can get your hands on a continuous glucose monitor that’s even better.

That’s the good news, now for the bad news.  This appears to be a self-perpetuating problem.  One thing the researchers found was that insulin blocked the leaky gut-inducing effects of hyperglycemia.

Insulin protects against leaky gut

Insulin, and thus blood glucose, follows a circadian rhythm. Inducing mild chronic hyperglycemia in healthy men disrupts circadian rhythms via the autonomic nervous system.  Within 48 hours, heart rate and blood pressure circadian rhythms are lost via reduced activity of the vagus nerve.

While we know poor sleep begets poor blood glucose control, poor blood glucose control also begets poor sleep.  But it’s not a “Circadian disruption causes hyperglycemia” situation. They all feed in to one another causing blood glucose to be elevated during the day. You know, when you eat.  Probably not a great time to be experiencing hyperglycemia-induced leaky gut.

Even though insulin and blood glucose follow a natural circadian rhythm, many lifestyle factors affect it. Factors such as

  • Meal content, timing and spacing
  • Light exposure
  • Physical activity
  • Sleep
  • Stress

All of these factors adjust the circadian rhythm of both insulin and blood glucose.  Keeping both in an optimal range all comes down to layering the above factors appropriately throughout the day.


The focus on avoiding sugar consumption to prevent leaky gut is misguided.  Based on recent evidence, a better target is to maintain good blood glucose control. This isn’t necessarily accomplished by avoiding sugar.  The best way to accomplish proper blood glucose control is through a multilayered approach addressing lifestyle.

Addressing factors such as physical activity, light exposure, sleep quality and quantity, meal content and timing are important. How you layer these things throughout the day provides far better control over your blood glucose than avoiding sugar.  Using HbA1c as a way to measure your progress allows you to determine if you’re doing things properly.

The data clearly shows paying attention to your circadian rhythms is an important factor to living a long, healthy life.  It certainly makes sense. The entire point in having circadian rhythms is to adjust your physiology to the environment.  In the past, this helped us find food and survive long enough to pass on our genes to our offspring.  Now, it just may be the key to avoiding chronic disease, including those with origins in the gut.

13 thoughts on “Hyperglycemia causes leaky gut, new study shows

  1. Susie says:

    My first thought was this is really bad news for new moms that generally lack good sleep for around a year (sooner if your lucky)! And wouldn’t that in turn affect breast milk quality? I’ve often wondered why my breastfed babies have food sensitivities and other formula fed babes have no issues. I know there’s a lot more to it…

    • cincodm says:

      There’s definitely more to it and you’d think that would be factored in there from an evolutionary standpoint. Reasons for food sensitivities can range from birthing method, microbial exposure, antibiotics, how early they’re exposed to a food, etc.

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