Diabetes is characterized by high levels of glucose circulating in the blood, known as hyperglycemia. The circulatory system, consisting of the heart and all blood vessels, is highly vulnerable to this condition. Prolonged high glucose levels are directly toxic to the endothelium, the delicate inner lining of all blood vessels. This damage impairs the vessels’ function and structure, leading to systemic circulatory impairment.
The Core Mechanism of Vessel Damage
The biological process by which high glucose damages blood vessels begins with a chemical reaction called glycation. This process involves excess sugar molecules attaching non-enzymatically to proteins and lipids in the bloodstream and on the vessel walls. These sugar-modified molecules are known as Advanced Glycation End products, or AGEs.
The accumulation of AGEs causes the blood vessel walls to become stiff and thickened because these products cross-link with structural proteins like collagen and elastin. This stiffening reduces the natural elasticity of the arteries, forcing the heart to work harder to pump blood through the rigid vessels. Furthermore, when AGEs bind to specific receptors (RAGE) on the cell surfaces, they trigger a cascade of cellular problems.
This interaction with RAGE significantly increases oxidative stress within the vessel wall by promoting the production of free radicals. Oxidative stress is an imbalance where the body’s natural antioxidants cannot neutralize damaging reactive oxygen species. The resulting cellular stress and damage severely injure the endothelial lining, which maintains vessel health and tone.
This injury leads to endothelial dysfunction, compromising the vessels’ ability to expand and contract normally to regulate blood flow. The damaged endothelium also promotes chronic, low-grade inflammation, which is a major contributor to subsequent circulatory problems. This foundational damage is the starting point for both large and small vessel disease in diabetes.
Large Artery Complications
Damage to the vessel lining from AGEs and oxidative stress affects the body’s largest arteries, a condition referred to as macrovascular disease. Diabetes significantly accelerates atherosclerosis, the buildup of plaque—composed of fats, cholesterol, and calcium—within the artery walls. Chronic inflammation and endothelial dysfunction create an environment where plaque formation is faster and the plaques are often more unstable.
This accelerated plaque accumulation leads to a progressive narrowing and hardening of the large arteries throughout the body. When this process affects the arteries supplying the limbs, it manifests as Peripheral Artery Disease (PAD). PAD most commonly impairs circulation in the legs and feet, starving these tissues of necessary oxygen and nutrients.
A common symptom of PAD is claudication, which is pain or cramping in the legs that occurs during physical activity and is relieved by rest. Poor circulation resulting from PAD increases the risk of non-healing foot ulcers and infections. Because oxygen and immune cells cannot reach the injured tissue efficiently, these wounds often fail to heal, which is a leading cause of limb amputation among individuals with diabetes.
When the atherosclerotic process affects the arteries supplying the heart or the brain, it increases the risk of cardiovascular events. The accelerated hardening and narrowing of the coronary arteries can lead to a heart attack. Plaque buildup or the formation of blood clots in the carotid arteries, which supply the brain, can result in a stroke.
Capillary and Microvascular Damage
Distinct from large artery damage, chronic hyperglycemia also targets the smallest blood vessels, the capillaries, leading to microvascular disease. This damage is primarily responsible for complications in the eyes, kidneys, and nerves. The shared mechanism is a thickening of the capillary basement membrane and increased vessel permeability, which impairs the efficient exchange of oxygen and waste.
In the eyes, microvascular damage leads to diabetic retinopathy, affecting the delicate capillaries in the retina. The damaged vessels can leak fluid and blood, causing swelling and visual impairment. In advanced stages, the retina attempts to compensate by growing new, fragile blood vessels prone to bleeding, leading to severe vision loss and potential blindness.
The kidneys are vulnerable due to the intricate network of capillaries that form the filtering units, called glomeruli. Damage to these vessels causes diabetic nephropathy, impairing the filtering mechanism and allowing proteins, such as albumin, to leak into the urine. Over time, this progressive damage reduces the kidney’s ability to filter waste, leading to chronic kidney disease and kidney failure.
Diabetic neuropathy, or nerve damage, is another major complication linked to microvascular failure. Nerves require a steady supply of nutrients from their own network of small blood vessels, known as the vasa nervorum. When these tiny vessels are damaged by high glucose, the resulting poor circulation starves the nerves of oxygen, causing them to malfunction and die.
This nerve damage typically begins in the extremities and leads to symptoms like numbness and tingling. A dangerous loss of sensation prevents individuals from noticing minor injuries that can then progress to severe infections.