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Hypoglycaemia is a common condition in diabetic patients, but few know how it can affect the blood-retinal barrier, a very important structure for eye health. This barrier protects the retina from potentially harmful substances in the blood, but in the diabetic patient, its effectiveness can be compromised. Understanding how hypoglycaemia can affect the structure of this barrier is essential to prevent ocular complications that can result from this increasingly common disease.

Diabetes Mellitus (DM) has, in fact, now taken on the character of a health emergency, which has been called 'a silent pandemic'.

Among the main causes of the rise in diabetes cases are an ageing population and the increasing incidence of obesity and other metabolic disorders.

In 2015, there were 415 million adults worldwide with diabetes (1 in 11), with a prevalence rate of 8.8%, by 2040, 642 million adults are expected to have diabetes (1 in 10), with a prevalence rate of 10.4% (Italian Diabetes Monitor - IBDO Foundation 2017 data).

Hypoglycaemia

Hypoglycaemia is a condition in which blood glucose levels fall below the normal level.

In many cases, hypoglycaemia is associated with diabetes and can occur during treatment with insulin or other hypoglycaemic drugs, but can also occur in people without diabetes.

Symptoms that signal hypoglycaemia may vary, but the most common include tremors, sweating, confusion e tachycardia. These signals are the first warnings that the body is entering a state where the glucose level is too low.

Many people with diabetes develop the ability to recognise these symptoms early so that they can intervene quickly to correct hypoglycaemia.

Counteracting hypoglycaemia is crucial to prevent serious episodes, which can lead to more severe symptoms such as cognitive difficulties, convulsions or even unconsciousness.

Main Causes of Hypoglycaemia

The causes of hypoglycaemia can be many. In diabetics, an overdose of insulin is one of the main causes. Dosage errors can occur, especially when changing diet or exercise levels.

Other factors that promote hypoglycaemia include prolonged fasting, alcohol intake (especially away from meals) and certain diseases such as kidney or liver failure. These conditions may contribute to lower blood glucose levels, increasing the risk of hypoglycaemia.

Finally, the physical or emotional stress can affect glucose regulation and contribute to hypoglycaemia. Identifying and managing these underlying causes is key to preventing recurring episodes.

The Haematoretinal Barrier

The blood-retinal barrier is an anatomical structure that regulates the passage of substances between the bloodstream and the retina. It consists of endothelial cells and plays a crucial role in keeping the retinal environment stable and protected.

In fact, the barrier acts as a filter, allowing essential nutrients to pass through and blocking harmful substances. This balance is crucial for the health of the retina and the prevention of many eye diseases.

When the barrier is damaged, potentially toxic substances can reach the retina, causing cell damage and impairing vision.

The health of the blood-retinal barrier is directly linked to the prevention of eye diseases. Protecting the retina from harmful agents, the barrier supports visual function and prevents long-term damage.

When the barrier is compromised, there is an increased risk of developing degenerative retinal diseases, conditions that can lead to permanent vision loss if not treated promptly.

Risk Factors

Several factors can compromise the blood-retinal barrier. Among the elements that can alter the function of the barrier, increasing the likelihood of retinal damage, are: diabetes, l'hypertension, high blood lipid levels e chronic inflammation.

Even lifestyle, such as the smoke and the poor dietcan adversely affect the health of the barrier.

How Diabetes Affects the Barrier

The diabetes affects the blood-retinal barrier through the effect of thechronic hyperglycaemia. High blood sugar concentrations can damage the endothelial cells that form the barrier.

The long duration of diabetic disease leads to an increase in barrier permeability. As a result, harmful substances can accumulate in the retina, causing inflammation and cell damage.

These structural and functional changes in the blood-retinal barrier are often the first signs of ocular complications in diabetics. Identifying these signs early is essential to prevent further damage to vision.

Ocular Complications in Diabetes

Ocular complications are common in diabetic patients, partly due to impaired blood-retinal barrier.

The most important and frequent ocular complication of diabetes mellitus, both type 1 and type 2, is the Diabetic Retinopathy. The conditions associated with earlier onset and more rapid progression of Diabetic Retinopathy are the duration of diabetic disease, blood glucose levels and the possible presence of other cardiovascular risk factors, such as hypertension and hypercholesterolaemia.

Untreated diabetic retinopathy can lead to progressive vision loss.

This condition is, in fact, characterised by alterations in the retinal blood vessels, which can cause blood and fluid loss in the retina. Diabetic retinopathy can evolve into more severe forms, such asdiabetic macular oedema, which can impair central vision. The frequency of onset of EMD increases with the duration and degree of severity of diabetes: in fact, among patients who have had diabetes for more than 20 years, approximately 30% develop EMD.

VEGF (Vascular Endothelial Growth Factor) and inflammatory phenomena play a key role in the pathogenesis of EMD. As the disease progresses, the role of inflammation becomes predominant.

Other ocular complications that may develop more rapidly in diabetic patients include cataract and the glaucoma. Careful monitoring and preventive management of diabetes can reduce the risk of these eye complications.

Prevention through Diabetes Management

Prevention of eye complications in diabetics starts with effective management of the blood glucose level. Monitoring blood glucose regularly is essential to prevent damage to the blood-retinal barrier.

Other aspects of diabetes management include controlling blood pressure and lipid levels, factors that can affect barrier health and must be kept under control.

Finally, regular eye examinations are crucial to identify early signs of onset and progression of eye complications.

Relationship between Hypoglycaemia and Barrier

The relationship between hypoglycaemia he blood-retinal barrier is complex. During episodes of hypoglycaemia, rapid changes in glucose levels can cause stress to the barrier.

This stress can lead to a temporary impairment of barrier function, making the retina more vulnerable to damage. Frequent episodes can, therefore, have cumulative effects on ocular health.

Recent studies and discoveries

Recent studies have confirmed how repeated episodes of hypoglycaemia may increase the risk of damage to the blood-retinal barrier. This research confirms that stable glycaemic control is essential in diabetic patients to prevent the onset and progression of ocular damage.

A recent study on mice has also identified the mechanism by which damage to the blood-retinal barrier can favour an aggravation of diabetic retinopathy: low blood glucose levels lead to an increase in theHIF (hypoxia-inducible factor), a protein linked to abnormal blood vessel growth and exudation.

Blocking HIF with an experimental drug could, therefore, prevent the progression of retinal damage by offering new perspectives to patients who, despite close monitoring of glucose levels, still show progression of diabetic retinopathy

Prevention and Management

Tips for Protecting the Barrier

Here are some practical tips to protect the blood-retinal barrier from damage caused by hypoglycaemia:

• Maintaining a regular glucose control to avoid sudden sugar drops.
• Planning meals on a regular basis to prevent hypoglycaemia.
• Follow a moderate exercise plan to avoid excessive glucose drops.
• Regularly consult a ophthalmologist to monitor the health of the retina.

Glucose Level Monitoring

The regular monitoring of blood glucose levels is essential to prevent hypoglycaemia and its effects on the blood-retinal barrier.

Using a glucometer helps to keep sugar levels under control by following this protocol:

1. Measuring glucose at least twice a day.
2. Record the results to monitor trends.
3. Consult your doctor to adjust the doses of insulin or medication.

These monitoring practices can prevent hypoglycaemic episodes and protect long-term ocular health.

Support and Resources Available

If you have been diagnosed with diabetes and may have to manage the risk of hypoglycaemia and its consequences, it is important to take advantage of support and resources.

Organisations such as the Italian Society of Diabetology offer information and support.

• Support groupsThey offer practical advice and emotional support.
• Training CoursesThey provide up-to-date knowledge on diabetes management.
• Monitoring ApplicationsThey help track glucose levels and plan meals.

Using these resources can improve diabetes management and the prevention of eye complications.

• Guo C, Niu Y, Pan X, Sharma D, et al. Hypoglycemia promotes inner blood-retinal barrier breakdown and retinal vascular leakage in diabetic mice. Sci Transl Med. 2025 Apr 30;17(796):eadq5355. doi: 10.1126/scitranslmed.adq5355. Epub 2025 Apr 30. PMID: 40305573.
• O'Leary F, Campbell M. The blood-retina barrier in health and disease. FEBS J. 2023 Feb;290(4):878-891. doi: 10.1111/febs.16330. Epub 2021 Dec 28. PMID: 34923749.