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Low Blood Sugar Levels Linked to Worsening Diabetic Eye Disease

People with diabetes who experience periods of low blood sugar—a common occurrence in those new to blood sugar management—are more likely to have worsening diabetic eye disease, according to a new study from Johns Hopkins Medicine.

The research, published in the January issue of Cell Reports, involved human and mouse eye cells and intact retinas grown in a low sugar (low glucose) environment in the laboratory, as well as mice with low glucose levels.

The results showed that low glucose levels in human and mouse retinal cells caused a cascade of molecular changes that can lead to blood vessel overgrowth. Initially, the scientists observed that reduced glucose levels led to a diminishment of the retinal cells’ capacity to metabolize glucose for energy.

The consequence of this was an uptick in the manufacture of proteins like VEGF and ANGPTL4, which are responsible for the proliferation of abnormal, permeable blood vessels – the primary cause of vision impairment in those suffering from diabetic retinopathy.[0]

According to Akrit Sodhi, MD, PhD, the Branna and Irving Sisenwein Professor of Ophthalmology at the Wilmer Eye Institute at Johns Hopkins Medicine, “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.”

In the United States, blindness caused by eye diseases in individuals with diabetes is one of the most preventable conditions.

Worldwide, the most common cause of blindness is cataracts, which is the clouding of the lens of the eye. This is a frequent complication of type 2 diabetes. The “the sugar hypothesis” is the term used to describe the current hypothesis of diabetic cataract development, which postulates that elevated blood sugar levels, a symptom of diabetes, precedes cataract formation.[1]

Sodhi added in the news release that the HIF-1α pathway may serve as an effective target for developing new treatments for diabetic eye disease.[0]

The researchers will investigate if people with diabetes who have low levels of glucose might have an effect on similar molecular pathways in organs like the kidney and brain.[0]

Sodhi says the current study suggests that people with diabetic retinopathy may be particularly vulnerable to periods of low glucose, and keeping glucose levels stable should be an important part of glucose control.

0. “Study examines why episodes of low blood sugar worsen eye disease in people with diabetes” Modern Retina, 27 Jan. 2023,

1. “Research challenges “sugar hypothesis” of diabetic cataract development” EurekAlert, 25 Jan. 2023,

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