Hypoglycemia

Definition

Hypoglycemia is a clinical syndrome caused by low plasma glucose, resulting in autonomic and/or neuroglycopenic symptoms.

Biochemical Cut-offs (Adults)

(ADA / Endocrine Society aligned)

Whipple’s Triad (Diagnostic Cornerstone)

1. Symptoms of hypoglycemia
2. Documented low plasma glucose
3. Relief of symptoms after glucose correction

Pathophysiology 

• Brain depends almost exclusively on glucose
• Counter-regulatory hormones:
• Glucagon (first line)
• Epinephrine
• Cortisol
• Growth hormone
• Failure occurs due to:
• Excess insulin (endogenous/exogenous)
• Reduced gluconeogenesis (liver failure, alcohol)
• Increased glucose utilization (sepsis)
• Impaired hormonal response (long-standing diabetes, autonomic neuropathy)

Clinical Features

Autonomic (Adrenergic / Cholinergic)

• Palpitations, tremor
• Anxiety
• Sweating
• Hunger

Neuroglycopenic

• Confusion, behavioral change
• Slurred speech
• Seizures
• Coma

Exam Pearl: Elderly & long-standing diabetics may have hypoglycemia unawareness (blunted adrenergic response).

Etiology – Systematic Approach

1. Drug-Induced (Most Common)

• Insulin (overdose, missed meals)
• Sulfonylureas / meglitinides
• Quinolones, pentamidine, beta-blockers (mask symptoms)

2. Critical Illness–Related

• Sepsis
• Acute liver failure
• Renal failure
• Malnutrition

3. Endogenous Hyperinsulinism

• Insulinoma
• Post-bariatric hypoglycemia
• Autoimmune insulin syndrome

4. Hormonal Deficiency

• Adrenal insufficiency
• Hypopituitarism

5. Alcohol-Related

• Inhibits gluconeogenesis
• Typically fasting hypoglycemia

Diagnostic Evaluation (During Hypoglycemia)

Blood samples must be drawn at the time of hypoglycemia because

When plasma glucose falls:

• Insulin should be fully suppressed
• Counter-regulatory hormones rise

If blood is drawn after glucose correction:

• Insulin levels fall (even if pathologic earlier)
• C-peptide normalizes
• Ketogenesis restarts
• Diagnostic patterns disappear

➡️ You lose the pathological biochemical fingerprint

1️⃣ Normal Physiologic Response to Hypoglycemia

(NO excess insulin)

When glucose falls:

• Insulin ↓↓↓ (appropriately suppressed)
• Lipolysis ↑
• Ketogenesis ↑

➡️ β-hydroxybutyrate = HIGH

Seen in:

• Fasting hypoglycemia
• Malnutrition
• Adrenal insufficiency
• Liver disease

 This is the expected / normal response

2️⃣ Hyperinsulinemic Hypoglycemia

(Insulin present when it shouldn’t be)

Insulin blocks lipolysis & ketogenesis, even during hypoglycemia.

➡️ β-hydroxybutyrate = SUPPRESSED (LOW)

Seen in:

• Insulinoma
• Sulfonylurea-induced hypoglycemia
• Exogenous insulin overdose

 This is pathologic

What the “Critical Sample” Demonstrates

Blood drawn during hypoglycemia allows you to determine whether insulin is appropriately suppressed or inappropriately elevated.

Expected Physiology During Hypoglycemia

What Goes Wrong in Pathological States

Only a sample drawn at the time of hypoglycemia can reveal this:

➡️ After glucose correction, all these patterns may normalize

Management

Immediate Treatment

Conscious Patient

• 15–20 g oral glucose
• Recheck in 15 min (“15-15 rule”)

Unconscious / NPO

• IV dextrose
• Adults: 25 g (50 mL of 50% dextrose)
• If no IV access:
• Glucagon IM/SC

Special Situations

Sulfonylurea-Induced Hypoglycemia

• Octreotide (prevents recurrent hypoglycemia)
• Continuous glucose monitoring

Alcohol-Related

• Thiamine before glucose (prevent Wernicke’s)

ICU & Inpatient Considerations

• Avoid over-tight glycemic control
• Target glucose: 140–180 mg/dL (critically ill)
• Frequent monitoring in:
• Sepsis
• Renal failure
• Insulin infusions

Complications

• Seizures
• Arrhythmias
• Permanent neurological injury
• Death (especially nocturnal hypoglycemia)

Key Exam Pearls

• Neuroglycopenic symptoms = dangerous
• Sulfonylurea hypoglycemia → recurrent
• Insulinoma: fasting hypoglycemia + high insulin + high C-peptide
• Alcohol causes hypoglycemia by blocking gluconeogenesis
• Beta-blockers mask adrenergic symptoms