Insulin Overdose

Mechanism

Clinical Manifestations

A. Autonomic Symptoms (~BG ≤54 mg/dL)

• Sympathetic: tachycardia, palpitations, diaphoresis, anxiety, tremors
• Parasympathetic: nausea, increased hunger

B. Neuroglycopenic Symptoms (~BG <50 mg/dL)

• Confusion, irritability, blurred vision, fatigue, headache, dysarthria

C. Severe Hypoglycemia (BG continues to fall)

• Dizziness, abnormal behavior, generalized weakness, muscular incoordination, hyperreflexia, cerebral edema, seizures, loss of consciousness, coma, hypoglycemic encephalopathy

Note: Patients on beta-blockers may have hypoglycemic unawareness - beta-blockers mask adrenergic symptoms (tachycardia, tremors), making hypoglycemia clinically silent until neuroglycopenia supervenes. - Tintinalli's Emergency Medicine, p. 1462

Insulin-Type Matters for Duration of Toxicity

Management

Mild Symptoms (Patient conscious and able to swallow)

• Administer 15-20 g oral glucose - dextrose tablets, dextrose gel (40% preferred), glucose-containing beverage, or plain sugar
• Repeat after 15 minutes if symptoms persist
• Sublingual glucose (40% dextrose gel) is effective in resource-limited settings
• Note: Pure fructose does not cross the blood-brain barrier and will not correct hypoglycemia. Protein (peanut butter, cheese) also has negligible effect on blood glucose.

Severe Symptoms (Unconscious, unable to swallow)

• IV Dextrose: 50 mL of 50% dextrose (25 g) IV over 10 minutes - treatment of choice
  • In pediatrics / if 50% is unavailable, 10% dextrose is preferred to avoid hyperosmolar injury
• Glucagon 1 mg IM or SC - if no IV access; raises BG by ~100 mg/dL; takes 7-10 minutes to work
  • Also available as intranasal glucagon (FDA-approved)
  • Caution: Glucagon is ineffective in glycogen-depleted patients (chronic alcoholics, marathon runners after a race, malnourished patients)
  • Glucagon can cause rebound hypoglycemia - requires monitoring after administration
  • Do NOT use glucagon for sulfonylurea-induced hypoglycemia

After Initial Correction

• Establish IV access and start a dextrose infusion (e.g., D10W) to maintain euglycemia
• Once alert enough to swallow: give oral glucose/carbohydrate snack immediately
• Correct electrolyte imbalances (insulin drives K⁺ intracellularly - watch for hypokalemia)
• Treat seizures with appropriate anticonvulsants if needed

Adjunct: Octreotide

• 50-100 mcg SC every 6-8 hours, or continuous IV infusion (125 mcg/h)
• Use only after initial glucose therapy; helps reduce recurrent hypoglycemic episodes

Disposition and Monitoring

• Blood glucose should be rechecked 15 minutes after each treatment
• The goal is BG >100 mg/dL (Barash Clinical Anesthesia), with sustained euglycemia before discharge

Diagnosis of Exogenous Insulin (Medicolegal/Forensic)

• Measure C-peptide and proinsulin: endogenous insulin secretion always comes with C-peptide; injected (exogenous) insulin does NOT raise C-peptide - this is the key distinguishing test
• Radioimmunoassay (RIA) can differentiate human vs. bovine vs. porcine insulin in blood
• Vitreous humor glucose levels are reliable postmortem indicators of hypoglycemia
• Examine for needle marks at potential injection sites

Medicolegal Considerations

• It mimics natural death, with no distinctive postmortem findings - historically considered a "potential ideal homicidal poison"
• Intentional or accidental overdose is disproportionately seen in healthcare professionals (have access and knowledge)
• Severe hypoglycemia can cause noninsane automatism (impaired motor function, e.g., while driving) - relevant in vehicular accident cases

Insulin Overdose

Mechanism

Clinical Manifestations

A. Autonomic Symptoms (BG ~54 mg/dL)

• Sympathetic: tachycardia, palpitations, diaphoresis, anxiety, tremors
• Parasympathetic: nausea, intense hunger

B. Neuroglycopenic Symptoms (BG <50 mg/dL)

• Headache, irritability, confusion, drowsiness, dizziness, difficulty speaking (dysarthria), blurred vision, inability to concentrate
• May mimic acute ischemic stroke

C. Severe Hypoglycemia (BG continues to fall)

• Abnormal behavior, generalized weakness, muscular incoordination, hyperreflexia, cerebral edema, seizures, loss of consciousness, coma, hypoglycemic encephalopathy

Hypoglycemic unawareness: Patients with longstanding diabetes may have deficient counter-regulatory hormone responses, lacking the usual adrenergic warning signs. Beta-blockers compound this by masking tachycardia and tremor, allowing hypoglycemia to progress silently to neuroglycopenia. - Tintinalli's Emergency Medicine, p. 1462

Duration of Risk by Insulin Type

Management

Step 1 - Mild Symptoms (Conscious, able to swallow)

• 15-20 g oral glucose - dextrose tablets, 40% dextrose gel (preferred), glucose-containing beverage, or plain sugar
• Repeat after 15 minutes if hypoglycemia persists
• Sublingual 40% dextrose gel works in resource-limited settings
• Avoid pure fructose - does not cross the blood-brain barrier, will not correct hypoglycemia
• Avoid protein (peanut butter, cheese) - negligible effect on blood glucose
• Once resolved, give a full meal or carbohydrate snack to prevent rebound

Step 2 - Severe Symptoms (Unconscious, cannot swallow)

• IV Dextrose - first-line: 50 mL of 50% dextrose (25 g) IV - give as a bolus
• Onset: immediate

Step 3 - No IV Access Available

• Glucagon 1 mg IM or SC - stimulates hepatic glycogenolysis, raises BG by ~100 mg/dL
  • Onset: 7-15 minutes (slower than IV dextrose)
  • Intranasal glucagon is now FDA-approved as an alternative
  • As soon as the patient can swallow, give oral glucose immediately after
  • Glucagon will not work in glycogen-depleted patients (chronic alcoholics, malnourished, marathon runners post-race)
  • Do NOT use glucagon for sulfonylurea-induced hypoglycemia (causes paradoxical insulin release)
  • Monitor closely - glucagon can cause rebound hypoglycemia

Step 4 - Ongoing Management

• Start a continuous dextrose infusion (e.g., D10W) to maintain euglycemia
• Monitor blood glucose every 15-30 minutes
• Treat seizures with appropriate anticonvulsants
• Correct electrolyte imbalances - insulin drives K⁺ intracellularly, watch for hypokalemia

Adjunct: Octreotide (for sulfonylurea overdose only)

• 50-100 mcg SC every 6-8 hours (or continuous IV 125 mcg/h)
• Use only after glucose therapy has been started; reduces frequency of recurrent hypoglycemic episodes
• Not standard for pure insulin overdose

Disposition

Diagnosis of Exogenous Insulin (C-peptide Test)

• Endogenous insulin secretion always co-releases C-peptide (it is cleaved from proinsulin) - so insulin AND C-peptide will both be elevated
• Exogenous injected insulin suppresses endogenous secretion - insulin is HIGH but C-peptide is LOW or undetectable
• Normal insulin:C-peptide ratio = 0.1-0.5; if exogenous insulin was injected, the ratio becomes >1

Important caveat: Both insulin and C-peptide are unstable postmortem (especially in hemolyzed samples), so results must be interpreted carefully in forensic cases. - DiMaio's Forensic Pathology, 3rd ed.

• Radioimmunoassay (RIA) can differentiate human vs. bovine vs. porcine insulin source
• Vitreous humor glucose is more reliable than blood glucose postmortem (less subject to decomposition artifacts)
• Examine needle marks - excise suspected injection sites and submit for histological examination

Medicolegal Aspects

• Insulin overdose mimics natural death - no characteristic postmortem findings - historically described as a near-ideal homicidal poison
• Intentional/accidental overdose is disproportionately seen in healthcare professionals (access + knowledge)
• Non-diabetic with high insulin + low C-peptide = strong evidence of exogenous administration
• Diabetic on insulin therapy + overdose = much harder to prove (baseline exogenous insulin use)
• Severe hypoglycemia can cause noninsane automatism (impaired motor function without conscious awareness) - relevant in vehicular accidents and legal proceedings