Hypoglycemia refers to an abnormally low level of blood glucose (usually <70 mg/dL), a critical condition since glucose is the primary fuel for the brain and body. When blood sugar levels drop significantly, the body experiences both neurogenic (autonomic) and neuroglycopenic symptoms. Recognizing the causes and understanding their mechanisms is vital for diagnosis, treatment, and prevention.
The mnemonic “RE-EXPLAIN” provides a systematic way to recall the major causes and characteristics of hypoglycemia:
- Renal failure
- Exogenous
- Endogenous/exogenous overlap
- Pituitary failure
- Liver failure
- Alcohol
- Infection
- Neoplasm
R – Renal Failure
Kidneys play an important role in gluconeogenesis and insulin clearance. In renal failure:
- Impaired gluconeogenesis: The kidney contributes significantly to glucose production, especially during fasting.
- Decreased insulin clearance: Reduced kidney function prolongs insulin half-life, increasing hypoglycemia risk.
- Medication accumulation: Drugs like sulfonylureas or insulin may accumulate in renal impairment.
Clinical Example: Patients with chronic kidney disease (CKD) on insulin therapy are at higher risk of hypoglycemia, especially during dialysis.
E – Exogenous
Exogenous hypoglycemia is the most common type, typically caused by external administration of glucose-lowering agents:
- Insulin overdose (accidental or intentional)
- Oral hypoglycemic drugs such as sulfonylureas and meglitinides
- Drug interactions (e.g., quinolones, beta-blockers, ACE inhibitors) that may potentiate hypoglycemia
Clinical Note: Exogenous hypoglycemia often presents in patients with diabetes on treatment, but can also occur due to accidental ingestion (e.g., in children).
E – Endocrine/Pituitary Involvement
Hypoglycemia can also result from hormonal deficiencies, especially of counter-regulatory hormones.
- Pituitary failure: Causes deficiency in ACTH and growth hormone, both crucial for maintaining blood glucose.
- Adrenal insufficiency: Cortisol deficiency reduces gluconeogenesis and increases insulin sensitivity.
- Hypothyroidism: Although rare, may contribute by slowing glucose metabolism.
P – Pituitary
The pituitary gland is essential for hormonal balance. Pituitary dysfunction can cause:
- ACTH deficiency → cortisol deficiency → impaired stress response and gluconeogenesis
- Growth hormone deficiency → reduced lipolysis and gluconeogenesis
This leads to fasting hypoglycemia, particularly in children and adolescents.
L – Liver Failure
The liver is the central hub of glucose metabolism. In liver failure:
- Decreased glycogen stores: Limits the body’s ability to mobilize glucose during fasting.
- Impaired gluconeogenesis: Prevents new glucose synthesis.
- Increased insulin circulation: Due to reduced hepatic clearance.
Clinical Correlation: Patients with cirrhosis or acute liver failure often present with recurrent hypoglycemic episodes.
A – Alcohol
Alcohol can severely impair glucose balance, especially during fasting.
- Alcohol inhibits gluconeogenesis by increasing the NADH/NAD+ ratio in the liver.
- Fasting + alcohol consumption is a dangerous combination, often leading to hypoglycemia in non-diabetic individuals.
- Chronic alcoholism also causes malnutrition, which worsens the problem.
I – Infection
Severe infections can precipitate hypoglycemia due to:
- Increased glucose utilization by immune cells
- Sepsis-related adrenal insufficiency
- Impaired hepatic gluconeogenesis
- Cytokine effects on insulin sensitivity
This is particularly common in neonatal sepsis and critically ill patients.
N – Neoplasm
Certain tumors can cause paraneoplastic hypoglycemia:
- Insulinoma: A pancreatic tumor that secretes insulin, leading to recurrent hypoglycemia.
- Non-islet cell tumors: Some produce insulin-like growth factor (IGF-2), mimicking insulin action.
Key Symptom: Recurrent episodes of confusion, sweating, and tremors relieved by glucose intake.
Symptoms and Characteristics of Hypoglycemia
Hypoglycemia manifests in two major ways:
1. Neurogenic (Autonomic) Symptoms
- Tremors
- Palpitations
- Sweating
- Anxiety
- Hunger
- Tingling
2. Neuroglycopenic Symptoms
- Confusion
- Drowsiness
- Blurred vision
- Seizures
- Coma
Diagnosis
Hypoglycemia is typically confirmed using Whipple’s Triad:
- Symptoms consistent with hypoglycemia
- Low plasma glucose concentration (<55–70 mg/dL, depending on lab and patient factors)
- Relief of symptoms after glucose administration
Management
Immediate Treatment
- Oral glucose (if patient is conscious)
- IV dextrose in unconscious or severe cases
- Glucagon injection for emergency situations outside hospital
Long-Term Management
- Identifying and treating the underlying cause (renal, liver, pituitary disorders, or drug-induced)
- Adjusting diabetes medications
- Nutritional counseling to prevent fasting hypoglycemia
- Monitoring in high-risk patients (elderly, CKD, liver disease, insulinoma)
Comparative Table: Causes of Hypoglycemia
| Mnemonic Letter | Cause | Mechanism of Hypoglycemia | Example Condition |
|---|---|---|---|
| R | Renal failure | Impaired gluconeogenesis, ↓ insulin clearance | Chronic kidney disease |
| E | Exogenous | Overdose of insulin/oral drugs | Insulin overdose |
| E | Endocrine/Pituitary | Hormone deficiency (cortisol, GH) | Pituitary failure |
| P | Pituitary | ACTH/GH deficiency | Hypopituitarism |
| L | Liver failure | ↓ glycogen storage, ↓ gluconeogenesis | Cirrhosis |
| A | Alcohol | Inhibits gluconeogenesis | Alcohol binge fasting |
| I | Infection | ↑ glucose utilization, sepsis-induced adrenal insufficiency | Septicemia |
| N | Neoplasm | Insulinoma, IGF-2 secreting tumors | Pancreatic tumor |
Frequently Asked Questions (FAQ)
Q1. What is the normal range of blood glucose?
Normal fasting blood glucose is 70–100 mg/dL, while hypoglycemia is generally diagnosed below 70 mg/dL.
Q2. Can non-diabetic individuals develop hypoglycemia?
Yes. Conditions like liver failure, alcohol intake, sepsis, and insulinomas can cause hypoglycemia even in non-diabetics.
Q3. What is the most common cause of hypoglycemia in diabetics?
The most common cause is exogenous insulin or oral hypoglycemic agent overdose.
Q4. Why is alcohol-induced hypoglycemia dangerous?
Because alcohol suppresses gluconeogenesis, especially in fasting states, and patients often do not recognize symptoms until severe.
Q5. How is insulinoma diagnosed?
Through 72-hour fasting test with measurement of insulin, C-peptide, and glucose levels, followed by imaging studies.
Q6. Can hypoglycemia cause permanent brain damage?
Yes. Severe untreated hypoglycemia can lead to seizures, coma, or irreversible neuronal injury.
