Diabetes mellitus is a chronic condition defined by sustained high levels of glucose in the bloodstream (hyperglycemia). While the disorder originates with a malfunction in blood sugar regulation, its effects are systemic. Diabetes damages tissues and organs throughout the body, driven by the toxic effects of excess glucose on the vascular system. This widespread damage affects virtually every major organ system, leading to severe, progressive complications.
The Pancreas The Regulatory Organ
The pancreas holds the primary responsibility for maintaining balanced blood glucose levels by producing specific hormones. Within the pancreatic islets of Langerhans, beta cells synthesize and release insulin, which acts like a key to allow glucose to enter cells for energy. The pancreas also produces glucagon from alpha cells, which signals the liver to release stored glucose when blood sugar is too low.
In Type 1 diabetes, the immune system attacks and destroys the insulin-producing beta cells. This autoimmune process leads to an absolute deficiency of insulin, meaning the body requires external replacement. Conversely, Type 2 diabetes begins with insulin resistance, where body cells fail to respond effectively to the insulin produced. The pancreas initially attempts to compensate by overproducing insulin, but over many years, the beta cells become exhausted, leading to insufficient insulin production.
The Cardiovascular System
The cardiovascular system is significantly compromised by chronic hyperglycemia, making heart disease and stroke the leading causes of death for people with diabetes. High glucose levels accelerate atherosclerosis, the hardening and narrowing of large arteries (macrovascular disease). This damage is partly mediated by the formation of Advanced Glycation End products (AGEs), harmful compounds created when sugars attach to proteins and lipids in the blood vessel walls. The accumulation of AGEs reduces the elasticity of the vessels, promoting inflammation and plaque buildup in the coronary arteries and the vessels supplying the brain.
This chronic damage significantly increases the risk for coronary artery disease, resulting in a higher likelihood of heart attack and stroke. Hyperglycemia also promotes a pro-thrombotic state, where blood platelets become stickier and more prone to clotting, further contributing to dangerous blockages.
Diabetic Cardiomyopathy
Beyond the large vessels, diabetes can directly damage the heart muscle itself, a condition known as diabetic cardiomyopathy. This develops independently of macrovascular blockages and is characterized by structural and functional changes in the myocardium. The heart muscle cells undergo a metabolic shift, relying more on fatty acids instead of glucose for energy. This shift leads to lipotoxicity and increased oxidative stress within the heart cells. The resulting damage triggers myocardial fibrosis, where scar tissue replaces healthy muscle, leading to a stiffening of the heart. This stiffness impairs the heart’s ability to relax and fill with blood (diastolic dysfunction) and can eventually progress to a reduced pumping capacity (systolic dysfunction) and heart failure.
The Kidneys
The kidneys serve as the body’s filtration system, and high blood sugar gradually destroys the delicate structures responsible for this function, a condition termed diabetic nephropathy. The filtering units, called nephrons, each contain a glomerulus—a dense tuft of capillaries that filters waste and fluid while retaining essential proteins.
Chronic hyperglycemia causes the blood vessels leading to and from the glomerulus to constrict abnormally, increasing the pressure inside the filtering unit. This elevated pressure damages the specialized cells and the glomerular basement membrane, causing it to become leaky. The earliest sign of this damage is microalbuminuria, the presence of small amounts of the protein albumin in the urine.
As the damage progresses, specialized mesangial cells within the glomerulus expand and secrete excessive extracellular matrix material. This mesangial expansion leads to the formation of characteristic Kimmelstiel-Wilson nodules, which reduce the surface area available for filtration. The loss of functional filtering units causes the kidney’s efficiency to fall, measured by the estimated glomerular filtration rate (eGFR). This progressive reduction can eventually lead to end-stage renal disease, requiring dialysis or a kidney transplant.
The Nervous System and Eyes
Diabetes causes damage to the body’s microvasculature, the network of small blood vessels supplying oxygen and nutrients to the nerves and eyes. This damage manifests as two major microvascular complications: diabetic neuropathy and diabetic retinopathy.
Diabetic neuropathy, or nerve damage, results from impaired blood flow to the nerves and chronic exposure to high glucose, which directly injure the nerve fibers. The most common form is peripheral neuropathy, which typically affects the longest nerves first, causing numbness, tingling, and pain, especially in the feet and hands. The loss of sensation in the feet is concerning because minor injuries can go unnoticed, leading to non-healing ulcers. These foot ulcers are a primary reason for diabetes-related amputations.
The eyes are highly susceptible to microvascular damage, resulting in diabetic retinopathy, the leading cause of new cases of blindness in working-age adults. High glucose weakens the tiny capillaries in the retina, causing them to leak fluid and small amounts of blood, forming microaneurysms.
To compensate for poor circulation, the retina may signal the growth of new, fragile blood vessels (neovascularization). These new vessels are prone to bleeding, which can obscure vision, and their scar tissue can cause the retina to detach. Furthermore, fluid leakage into the central part of the retina can cause diabetic macular edema, severely blurring central vision.