How does hyperglycemia (high blood sugar) exacerbate diabetic retinopathy?

From the Guidelines

High glucose worsens diabetic retinopathy by damaging the blood vessels in the retina through several mechanisms, and maintaining target blood glucose levels is essential to prevent or slow the progression of diabetic retinopathy. According to the most recent and highest quality study, 1, high glucose levels cause the blood vessels to become weak and leaky, leading to fluid accumulation in the retina and the formation of microaneurysms. High glucose also promotes inflammation and oxidative stress, which further damages retinal cells. The body responds by growing new, abnormal blood vessels (neovascularization) that are fragile and prone to bleeding. Additionally, high glucose levels impair blood flow to the retina, causing ischemia and cell death. The accumulation of advanced glycation end products (AGEs) from chronic hyperglycemia damages retinal tissues and blood vessel walls. Elevated glucose also activates protein kinase C, which contributes to vascular permeability and impaired blood flow.

Some key points to consider in the management of diabetic retinopathy include:

• Implementing strategies to help people with diabetes reach glycemic goals to reduce the risk or slow the progression of diabetic retinopathy, as recommended by 1
• Optimizing blood pressure and lipid control to reduce the risk or slow the progression of diabetic retinopathy, as recommended by 1
• The importance of intensive diabetes management with the goal of achieving near-normoglycemia to prevent and/or delay the onset and progression of diabetic retinopathy, as shown in large prospective randomized studies 1
• The potential benefits of glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment in reducing the risk of retinopathy, although the long-term impact of improved glycemic control on retinopathy was not studied 1

Overall, the evidence suggests that maintaining target blood glucose levels through medication, diet, and lifestyle modifications is essential to prevent or slow the progression of diabetic retinopathy, and that a comprehensive approach to diabetes management, including glycemic control, blood pressure control, and lipid management, is necessary to reduce the risk of diabetic retinopathy.

From the Research

High Glucose and Diabetic Retinopathy

• High glucose levels can worsen diabetic retinopathy through various mechanisms, including the activation of protein kinase C, increased vascular endothelial growth factor expression, and enhanced angiogenesis 2, 3.
• The renin-angiotensin system plays a crucial role in the pathogenesis of diabetic retinopathy, with angiotensin II type 1 receptors contributing to microvascular abnormalities and retinal damage 4, 3.
• Rapid improvements in systemic glucose control can lead to early worsening of diabetic retinopathy, possibly due to large and rapid reductions in blood-glucose levels 5.
• Hyperglycaemia, oxidative stress, and other biochemical changes can cause cell stress and biochemical abnormalities, contributing to the development and progression of diabetic retinopathy 6.

Mechanisms of Diabetic Retinopathy

• Diabetic retinopathy is characterized by functional and morphological changes in the retinal microvessels, leading to macular edema, neovascularization, and vision loss 4.
• The neurovascular unit, composed of neuronal, glial, and vascular cells, responds to biochemical changes imposed by reactive metabolites and high glucose, contributing to the development of diabetic retinopathy 6.
• Activation of the renin-angiotensin system can induce a variety of tissue responses, including vasoconstriction, inflammation, oxidative stress, cell hypertrophy, and proliferation, angiogenesis, and fibrosis, all of which can contribute to diabetic retinopathy 3.

Treatment and Management

• Tight metabolic and blood pressure control can significantly decrease the risk of development and progression of diabetic retinopathy 2.
• Laser photocoagulation and vitrectomy are important tools for preventing severe visual loss from sight-threatening diabetic retinopathy and its complications 2.
• New pharmacological therapies, such as protein kinase C inhibitors, intravitreal injections of steroids, vascular endothelial growth factor inhibitors, and angiotensin converting enzyme inhibitors, are being evaluated to target the underlying biochemical mechanisms of diabetic retinopathy 2, 4, 3.