The Curious Link Between Blood Sugar Balance and Leaky Gut

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Blood sugar imbalance and related diseases such as diabetes, obesity, neuropathy, and cardiovascular disease have a well-established relationship to dysfunction within the gut. In fact, the intestinal barrier and microbiome have a bidirectional relationship with blood sugar meaning that while blood sugar can impact the health of the gut, the health of the gut also impact blood sugar.

However, the correlation between these conditions has not been clearly understood. While theories have blamed increased fat mass or decreased leptin sensitivity, it seems that hyperglycemia (high blood sugar) might actually be a primary culprit in the destruction of the gut and gut dysfunction can also directly impact blood sugar control. This relationship is a critical component for improving blood sugar management and gut health, as diseases impacted by these factors continue to skyrocket in the US.

Blood Sugar Imbalance on the Rise

Conditions related to high blood sugar and diabetes are responsible for over 3 million deaths per year and this number is expected to increase. In fact, the CDC is estimating between 20-33% of all Americans will develop diabetes by 2050. While that may sound shocking, those numbers don’t even include the countless Americans that are not diabetic but are experiencing giant swings between high and low blood sugar without realizing it.

Although this is often overlooked in conventional medicine, I see an ever-increasing number of patients with healthy “average” blood sugar levels but upon further investigation, their symptoms are linked to poor glucose balance causing spike and dips throughout the day. The newest research indicates that glucose consumption and blood sugar spikes (hyperglycemia) may be the missing link between tying diabetes and other blood sugar imbalance and gut dysfunction.

In fact, studies are revealing that high blood sugar can harm the function of the gut barrier, impair microbiota balance and increase risk of infection within the gut. This is imperative because leaky gut is not only associated with high blood sugar and obesity, but also with neurodegeneration, cancer and aging.

Is Fat to Blame?

Leaky gut can lead to dangerous microbes making their way into circulation (endotoxemia), and is often associated with obesity, overweight and metabolic syndrome. So, it makes sense that practitioners and researchers have been suspicious that being overweight may be a cause of leaky gut. With obesity affecting over 39% of the US adult population, identifying how excess body fat affect the gut is imperative! People experiencing obesity or metabolic syndrome often have low-grade inflammation and poor glucose tolerance, meaning that their bodies are not efficiently using glucose for fuel and the immune system is overburdened.

A group of researchers set out to answer whether how extra body fat is related to gut dysfunction. At first, researchers began with a hypothesis that leaky gut could be caused by a deficiency in leptin or problems with leptin receptors. Leptin is the circulating hormone responsible for telling us we are satiated or full. If a person does not have enough leptin or their body isn’t recognizing it, it can cause overeating and weight gain. In animal studies, mice with leptin dysfunction have higher risk of obesity, leaky gut, gut infection and increased microbes making their way from the gut into circulation.

However, this theory didn’t hold up when they put it to the test. While the researchers were able to create and track gut permeability by inducing leptin resistance and obesity, when they reversed these conditions in mice, leaky gut remained. That led them to conclude that the obesity and leptin resistance could not be behind the cause of gut permeability.

It’s the Sugar, not the Fat

Impacting fat mass and leptin did not prove their case, so they moved onto their next idea. A high carbohydrate and processed diet is often associated with obesity and gut dysfunction. Researchers wondered if the high-carb diet was behind the leaky gut connection. Carbohydrates whether from wheat, corn, sugar, high-fructose corn syrup, etc. are broken down during digestion. By the time they are fully digested, they have been broken into single sugar molecules or monosaccharides, most common being glucose.

Those sugar molecules must then be shuttled through the intestinal cells by GLUT2 proteins and spit out the other side into our circulation. Glucose travels to cells accompanied by insulin which is necessary to trigger our cells to take glucose in and use it for fuel. When glucose hits the bloodstream, it increases blood sugar levels and if it can’t get into the cells efficiently, it stays in the blood maintaining high blood sugar. It was using this mechanism that researchers were able to study carbohydrate metabolism and gut dysfunction.


Researchers used mice with normal body weight and induced hyperglycemia using a drug called streptozotocin (STZ). STZ shuts down pancreatic function in mice simulating a condition similar to type 1 diabetes. This caused high blood sugar and led to gut barrier dysfunction and endotoxemia.

But they could not make a conclusion by ending the study there. Remember that they found obesity and leptin resistance also caused leaky gut, but reversing those conditions did not positively impact the gut. Researcher gave the insulin to the mice to restore glucose metabolism and observed that the gut function was restored. They concluded that elevated blood glucose actually changed the integrity of the gut barrier leading to leaky gut and endotoxemia and reversing hyperglycemia led to healing.

The scientists had now shown the relationship between hyperglycemia and gut permeability in mice, but did this hold true for human? To confirm the relationship in humans, they looked at 27 healthy adult subjects and found direct correlation between average blood sugar levels and the level of endotoxemia. This was independent of body weight.

Sugar Sabotages the Intestinal Cells

At this point, researchers had a good case for the causative relationship between hyperglycemia and gut dysfunction. Now, they wanted to know if consumption of sugar, even in the absence of high blood sugar, was damaging to intestinal cells. They bathed intestinal cells in glucose and watched the results unfold on a molecular level. The results were staggering – not only was intestinal barrier dysfunction induced but over 1000 genes within the intestinal cells changed expression as a result of excess glucose. This suggested that not only were structural changes happening, but epigenetic changes as well.

Researchers blocked the glucose transporters in the intestinal cells and the conditions reversed. This led scientists to conclude that glucose uptake was required for the short and long-term damage to occur. The takeaway from this is that it is not just high blood sugar that can cause leaky gut and endotoxemia, but a high sugar diet, alone, can put a person at high risk.

Researchers also found that hyperglycemia caused significant changes in the microbiome within the gut, independent of translocation of bacteria into the circulation. When they corrected the hyperglycemia, the microbiome was restored.

Does Leaky Gut Cause Blood Sugar Problems?

Yeah, it goes the other way too. In an earlier 2007 study, a group of researchers found that a high-fat diet fed to mice caused an increase in bacteria that produce a toxin called lipopolysaccharide (LPS). Increased levels of LPS damage the intestinal cells and leak into the circulation. As a result, the mice experienced insulin resistance and high blood sugar. To confirm, the researchers injected LPS directly into the bloodstream and provoked the same response. Elevated circulating endotoxins not only caused insulin resistance in the liver (a major risk factor for non-alcoholic fatty liver disease) but also high blood sugar and weight gain.

What does all of this mean?

Based on these studies, we currently believe that either leaky gut can lead to high blood sugar and obesity but that high blood sugar can also lead to leaky gut, so what do we do? It’s critical to look at the whole body and approach these conditions keeping all of this in mind. Here are some primary takeaways from these important studies.

    1. A high-sugar diet, even in the absence of diabetes and obesity is dangerous.

      As researchers demonstrated, intestinal cells are damaged and leaky gut can be caused by excessive sugar intake even if blood sugar is regulated. This means that maintaining a low-carb diet is likely very beneficial for healing a leaky gut.

    2. Blood sugar spikes, even without an elevated average blood sugar, increases risk of leaky gut.

      Because researchers were able to show that insulin therapy lowered blood sugar and prevented damage to the gut, we can conclude that even occasional spikes in blood sugar are harming intestinal barrier tissue. That means that keeping blood sugar tightly controlled and not allowing for it to spike or dip is critical to safeguarding the intestinal barrier.

    3. Leaky gut increases the movement of toxic bacteria and their bi-products into circulation which can lead to hyperglycemia and obesity.

      We also know that leaky gut can lead to increased levels of LPS in the circulation. Microbial toxins can trigger the spiral into hyperglycemia, diabetes and obesity. For this reason, people that struggle with these conditions should be focusing on repairing the gut and preventing endotoxemia.

    4. A high fat diet is not likely to blame for leaky gut or obesity.

      Conventional providers often blame a high-fat diet for conditions linked to metabolic syndrome, diabetes and obesity. Although in animal studies in which the animals are fed a high-fat diet, the diet is also high in carbs. These studies suggest that the carbs and not the fat are causing the molecular changes that lead to disease.

Final thoughts

The relationship between diet, intestinal barrier integrity and disease manifestation is an ever-growing area of focus for researchers. In my clinical experience, I have seen great success in reversing these conditions by implementing a whole food and low-carbohydrate diet alongside therapies that support blood sugar balance and a strong gut barrier.

As I mentioned, many of my patients are not considered overweight or diabetic, but upon further testing, they experience wide swings between high and low blood sugar in response to foods that are often considered healthy. This is why we take a individualized approach to each patient and address their unique nutritional and biological needs to encourage maximum healing potential!

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