Chronic complications of hypoglycemia and hyperglycemia
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Introduction
Chronic abnormalities in glucose regulation can lead to long-term complications affecting multiple organ systems. Hyperglycemia is the primary driver of chronic diabetic complications, while recurrent hypoglycemia is especially problematic in patients treated with insulin or sulfonylureas. Both conditions negatively impact quality of life and may cause permanent damage if not properly managed.
Chronic Complications of Hypoglycemia
Recurrent or unrecognized hypoglycemia occurs mostly in insulin-treated patients, especially those with type 1 diabetes. Chronic hypoglycemia does not directly damage organs, but it leads to dangerous functional impairments.
Hypoglycemia Unawareness
Frequent episodes of hypoglycemia reduce the autonomic warning response, so the patient does not perceive early symptoms. This increases the risk of severe hypoglycemia, seizures, and coma.
Impaired Counterregulation
Repeated hypoglycemia blunts glucagon and adrenaline release. As a result:
- The patient cannot correct hypoglycemia quickly
- Risk of prolonged or severe episodes increases
Cognitive and Psychological Effects
- Reduced attention, memory, or concentration
- Fear of hypoglycemia
- Avoidance of tight glycemic control
Impact on Daily Functioning
Patients may restrict driving, work activities, and physical exercise due to unpredictability of episodes.
Chronic Complications of Hyperglycemia
Long-term hyperglycemia leads to structural and functional damage of blood vessels and tissues. These complications are divided into microvascular and macrovascular.
Microvascular Complications
Diabetic Retinopathy
Chronic hyperglycemia causes retinal vessel damage, microaneurysms, hemorrhages, neovascularization, and potential visual loss.
Diabetic Nephropathy
Glomerular injury leads to:
- Microalbuminuria → proteinuria
- Declining renal function
- Hypertension
- Risk of chronic kidney disease or renal failure
Diabetic Neuropathy
Long-standing hyperglycemia damages peripheral nerves, leading to:
- Sensory loss
- Burning pain
- Autonomic dysfunction (gastroparesis, orthostatic hypotension)
- Foot ulcers due to loss of protective sensation
Macrovascular Complications
Coronary Artery Disease
Increased risk of myocardial infarction and heart failure.
Cerebrovascular Disease
Higher risk of ischemic stroke and transient ischemic attacks.
Peripheral Arterial Disease
Leads to claudication, poor wound healing, gangrene, and increased risk of limb amputation, especially when combined with neuropathy.
Other Long-Term Effects of Hyperglycemia
Diabetic Foot
Results from neuropathy, poor perfusion, and impaired immunity, leading to chronic wounds and infections.
Impaired Immune Function
Hyperglycemia weakens neutrophil function and increases susceptibility to infections.
Skin and Connective Tissue Changes
Includes limited joint mobility, dermopathy, and fungal infections.
Pathophysiology Summary
Chronic hyperglycemia causes tissue damage through several mechanisms:
- Formation of advanced glycation end-products (AGEs)
- Oxidative stress
- Activation of protein kinase C
- Increased polyol pathway activity
These contribute to vascular injury and organ dysfunction.
Conclusion
Chronic hypoglycemia leads mainly to impaired awareness, defective counterregulatory responses, and reduced quality of life. Chronic hyperglycemia, in contrast, causes progressive microvascular and macrovascular complications, including retinopathy, nephropathy, neuropathy, and cardiovascular disease. Good long-term glycemic control is essential to prevent or delay these outcomes.
References
- American Diabetes Association. Standards of Medical Care in Diabetes. Diabetes Care.
- Guyton & Hall. Textbook of Medical Physiology.
- Powers AC. Diabetes mellitus. In: Harrison’s Principles of Internal Medicine.
- Cryer PE. Hypoglycemia in diabetes. Diabetes.
- UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control and complications. Lancet.
