Most of us have heard of the metabolic disease called diabetes. It pops up as a headline on our social media feeds or in the night news bulletin. We hear about how it is a global epidemic, a massive burden on the healthcare system, the most serious health challenge for our generation.

But what we don’t hear a lot about is diabetic eye disease. This is a massive problem, because at least 1 in 3 people with diabetes will develop eye disease which can cause blindness. In fact, Diabetic Retinopathy is the most common cause of blindness in developed countries. More worrying, up to 50% of people with diabetes do not have regular eye tests. This means that this eye disease often remains undetected until it causes significant vision problems. By this point, treatment is invasive – injections in the eye and laser surgery to name a few.

So what can we do to improve diabetic eye disease?

In a recent paper published in the scientific journal Diabetes, Eleni Beli at the Indiana School of Medicine and colleagues including ophthalmology professor Dr. Maria Grant from the University of Alabama, Birmingham, found that intermittent fasting may prevent diabetic eye disease, at least in mice. This effect is potentially due to the release of hormones from the fasted gut that affected receptors in the eye. The study marks one of the first times that researchers have been able to make a direct connection between diet and diabetic eye disease. The findings hold promise for new ways to tackle the disease.

Diabetic retinopathy – the good, the bad and the ugly

Diabetic retinopathy is an eye disease that develops in the retina of individuals with diabetes. Small blood vessels in the retina become damaged from high sugar levels, causing them to become blocked or to leak. In early disease, these leaks and blockages appear as small hemorrhages and microaneursyms. In more advanced stages, new, abnormal blood vessels proliferate on the surface of the retina that lead to scarring and permanent damage to the retina.

Diabetic retinopathy. Centre for Eye Health, Sydney, Australia.

Images of the retina of a person with type 2 diabetes whose diabetic retinopathy has progressed over a year. Images courtesy from Centre for Eye Health, Sydney, Australia.

Can intermittent fasting help prevent diabetic retinopathy? 

A number of animal and human studies have shown that intermittent fasting is effective in managing and perhaps even treating diabetes. At the University of Southern California, researchers studied diabetic mice who underwent seven days of normal eating followed by four days of fasting. They found that during fasting days, the pancreas of the diabetic mice began to regenerate. After several fasting cycles, the pancreas was able to function properly again, producing insulin, lowering blood sugar and eliminating diabetes in these mice.

But can intermittent fasting be helpful in people who have already developed diabetic retinopathy?

In their recent paper, Beli and colleagues tested this idea in a mouse model. The researchers placed diabetic mice on an intermittent fasting diet consisting of one day of feeding followed by one day of fasting (alternate day fasting). After three months, intermittent fasting mice had less reactive immune cells in their retina, better quality retinal blood vessels and longer survival than diabetic mice that ate everyday.

But how is eye health connected to gut health?

Intestinal villi, small finger-like projections that extend into the lumen of the small intestine, and gut bacteria. Credit: ChrisChrisW.

The gut does more than digest food

There is a collection of bacteria in our gut (the microbiota) that work symbiotically with the body to break down indigestible food. Research now shows that these bacteria also regulate glucose and fat levels, produce hormones and metabolites and maintain the immune system.

In diabetes, gut microbiota diversity is reduced. In other words, there are fewer types of bacteria in the guts of people with diabetes compared to the guts of healthy people. Not surprisingly, this affects the body’s ability to break down foods into useful nutrients. It also affects the body’s ability to break down other molecules into nutrients in the absence of food.

Beli and colleagues theorized that these changes in the gut could actually be linked to downstream changes in the eye. When they assessed the gut microbiota of diabetic mice, they found that mice that were fasted intermittently had a significant increase in the “good” bacteria group Firmicutes and a decrease in the bacteria groups Bacteroidetes and Verrucomicrobia. They also found that TUDCA (tauroursodeoxycholate), a metabolite produced by bacteria in the gut, was increased in fasted diabetic mice.

Previous research shows that TUDCA, a beneficial bile acid, can protect cells from damaging events by interacting with a specific receptor protein called TRG5. Considering that the TRG5 protein is found in certain retinal cells (cell in the eye), perhaps TUDCA produced by bacteria in the gut is responsible for the protective effects of intermittent fasting in the eye. TUDCA has previously been found to protect light-sensitive eye cells from oxidative stress and cell death in animal models.

Testing the theory

The research group tested their theory using another mouse model with a more aggressive form of diabetes. They fed these diabetic mice with a drug that mimics TUDCA and assessed their eyes for diabetic retinopathy. They found mice treated with the drug had fewer signs of diabetic retinopathy than mice that were not treated with the drug. This experiment suggests that we could improve diabetic retinopathy through intermittent fasting, by way of metabolites like TUDCA produced by gut bacteria.

So what does this all mean?

Intermittent fasting is in theory significantly easier for people with diabetes to practice than it is for them to lose a significant amount of weight or to restrict their calorie intake on a daily basis. Other researchers have also speculated that since the gut microbiota is different in every individual, the changes seen in this study may explain why only some people with diabetes develop diabetic retinopathy, while others do note. Nevertheless, clinical trials in humans are still needed to confirm these findings and the safety of intermittent fasting for diabetic individuals long term.