Diabetic retinopathy, which can lead to blindness in severe cases, has been previously attributed to high blood sugar levels, but new research results suggest that low blood sugar can also worsen the disease. Experts analyzed that this means blood sugar must be kept stable to prevent complications.
Professor Akrit Sodhi and his research team at Johns Hopkins University in the United States noted on the 1st that they have newly revealed that low blood sugar exacerbates diabetic retinopathy. The research findings were published that day in the international journal "Science Translational Medicine."
The research team explained that low blood sugar activates "hypoxia-inducible factors (HIFs)" to cause retinal damage. HIFs are generally gene regulatory proteins that operate when oxygen is scarce, leading to the production of substances that are involved in angiogenesis and inflammatory responses, such as vascular endothelial growth factor (VEGF).
For a long time, the medical community viewed diabetic retinopathy as a condition where high-sugar blood flows through microvessels, causing circulation disturbances that damage the retina and lead to vision deterioration. This time, the experiment showed that even in sufficient oxygen conditions, quickly lowering blood sugar activates HIF, resulting in retinal damage.
The research team confirmed that inducing a sudden low blood sugar state by injecting insulin into laboratory mice with diabetes increased HIF levels in the retina and intensified vascular leakage. Vascular leakage is the phenomenon where fluids that should remain inside the blood vessels, such as plasma, escape outside.
The research team explained that this indicates that rapid changes in blood sugar itself stress the retina. When HIF functions strongly, blood vessel walls loosen, and plasma leaks out, causing retinal edema and inflammation.
Previous large-scale clinical trials have also reported that among patient groups receiving intensive treatment to rapidly lower blood sugar, there were more cases of worsening retinopathy in the initial year. While it is important for diabetes patients to lower their blood sugar levels, this implies that too sudden or excessive reductions can actually be harmful.
The research team also presented the potential of a new drug candidate called "32-134D." This substance effectively inhibits abnormal blood vessel formation and vascular leakage by simultaneously suppressing HIF-1α and HIF-2α. It showed better therapeutic effects compared to the existing anti-VEGF treatment, aflibercept (brand name Eylea).
The research team explained that this study reconfirms the fact that for diabetes patients, it's far more important to maintain stable blood sugar levels rather than simply reducing them. Professor Sodhi stated, "Both high blood sugar and low blood sugar can lead to retinal damage, and it has been revealed that HIF plays a central role in this process," and he predicted that controlling the magnitude and speed of blood sugar changes will become an important consideration in future treatment strategies.
Experts evaluated the results as presenting a new method to prevent complications from diabetes. However, they pointed out that since HIF plays an important role in maintaining homeostasis, methods to regulate it require long-term safety verification.
References
Science Translational Medicine (2025), DOI: https://doi.org/10.1126/scitranslmed.adq5355