Study Shows How Low Blood Glucose May Worsen Eye Disease

BY QUINN PHILLIPS | MARCH 10, 2023

Researchers have discovered how hypoglycemia (low blood glucose) may contribute to eye damage in people with diabetes, according to a new study published in the journal Cell Reports.

The connection between high blood glucose levels in people with diabetes and a variety of potential complications — including retinopathy and other eye diseases linked to diabetes — is well established for both type 1 and type 2 diabetes. Good blood glucose control has been linked to a lower risk for eye complications, and for people with both type 2 diabetes and obesity, bariatric (weight-loss) surgery is a proven way to reduce the risk for retinopathy (and a range of other potential diabetes complications).

According to research, certain other measures may reduce the risk for diabetic retinopathy, such as drinking coffee or taking aspirin or other anticoagulant drugs. Unfortunately, cases of diabetic retinopathy are expected to increase around the world in the coming years. If you have diabetes, it’s important to get regular eye exams to detect retinopathy and other potential problems. A variety of treatments are available to address retinopathy and other eye diseases linked to diabetes.

For the latest study, researchers at Johns Hopkins University in Baltimore were interested in looking — at the molecular level — at how low blood glucose might contribute to eye disease in people with diabetes. Low blood glucose isn’t seen in all people with diabetes, but is an established risk for some diabetes treatments, including insulin and sulfonylureas, a group of type 2 diabetes drugs. To look at what’s going on in the eyes when glucose levels are low, the researchers grew both mouse and human eye cells, as well as whole retinas — the back layer of the eye that transmits light signals to the brain — in a low-glucose environment in a laboratory. They then looked at levels of various proteins that play a role in eye damage in these cells and retinas, as well as in the eyes of living mice with low blood glucose, as noted in a press release on the study.

Low glucose linked to increase in certain retinal cell proteins

The researchers found that exposure to low glucose levels was linked to an increase in proteins in retinal cells that are linked to an overgrowth of blood vessels, which can interfere with vision. Overgrowth of blood vessels is a feature that’s commonly seen in retinopathy and further potential eye complications like diabetic macular edema. When the researchers looked at one particular cell type — known as Müller glial cells, which support neurons in the retina and use glucose for energy — they found that low blood glucose increased expression of a gene called GLUT1, which makes a protein that transports glucose into cells. The result was a flood of this protein (called HIF-1a) into the cell’s nucleus and an increase in other proteins (called VEGF and ANGPTL4) that are known to promote the growth of abnormal blood vessels that are prone to leakage — a key driver of vision loss in people with diabetes.

“Temporary episodes of low glucose happen once or twice a day in people with insulin-dependent diabetes and often among people newly diagnosed with the condition,” said study author Akrit Sodhi, MD, PhD, an ophthalmologist and professor at the Wilmer Eye Institute at Johns Hopkins Medicine, in the press release. “Our results show that these periodic low glucose levels cause an increase in certain retinal cell proteins, resulting in an overgrowth of blood vessels and worsening diabetic eye disease.”

Next, the researchers noted, they plan to study whether low blood glucose has similarly harmful effects in people with diabetes in other organs, such as the kidneys or brain.