Hypoglycemia

Hypoglycaemia occurs when glucose concentration falls below 3.3 mmol/L. The threshold for the onset of hypoglycemic symptoms varies with patients. Severe symptomatic hypoglycemia occurs in most adults at blood glucose levels ≤ 2.2-2.8 mmol/L.

Hypoglycemia in patients with diabetes is defined as a blood glucose level ≤ 3.9 mmol/L.

Whipple triad – Helps to confirm the diagnosis of hypoglycemia

1. Low blood glucose levels (patients with diabetes have symptoms of hypoglycemia at higher thresholds than healthy individuals)
2. Signs or symptoms consistent with hypoglycemia
3. Relief of symptoms when blood glucose increases after treatment

• Precipitating factors
  • Insulin related
    • Insulin excess – overdose or wrongly timed medication
    • Liver or renal disease – decreased clearance of insulin
    • Weight loss – increased sensitivity to insulin
    • Increased exercise – increased sensitivity to insulin
    • Drug interactions
  • Glucose related
    • Irregular ingestion of food
    • Alcohol ingestion
    • Extreme activity – increased utilization of glucose
    • Prior episodes of hypoglycemia leading to impaired awareness of hypoglycemia
    • Hypopituitarism and adrenal insufficiency
  • Acute illness
    • Sepsis
    • Trauma
    • Burns
    • Organ failure
• Pathophysiology
  • Hypoglycaemia → activation of the sympathetic nervous system → autonomic symptoms
  • Hypoglycaemia → brain dysfunction → neuroglycopaenic symptoms
  • Recurrent episodes of hypoglycaemia → reduced epinephrine release, which lowers the threshold needed to trigger symptoms → Hypoglycemia-associated autonomic failure (HAAF) → asymptomatic hypoglycaemia
  • Beta-blockers can mask signs of hypoglycemia by antagonizing the effects of epinephrine
• Signs and symptoms
  • Autonomic symptoms
    • Tremor
    • Pallor
    • Anxiety
    • Tachycardia
    • Sweating
    • Palpitations
    • Hunger
    • Paresthesia
    • Nausea
    • Vomiting
  • Neuroglycopenic symptoms
    • Agitation
    • Confusion
    • Behavioral changes
    • Fatigue
    • Seizure
    • Focal Neurologic signs
    • Somnolence → Obtundation → Stupor → Coma → Death
• Differentials
  • Stroke or transient ischaemic attack
  • Myocardial infarction
  • Sepsis
  • Epilepsy
  • Idiopathic postprandial syndrome (pseudohypoglycaemia)
• Investigations
  • Random blood glucose
    • < 3.3 mmol/L
  • Serum insulin
    • Elevated in insulinoma
  • Serum C-peptide
    • Elevated in insulinoma and sulfonylurea use
  • Serum cortisol
    • Reduced in adrenal insufficiency or hypopituitarism
  • Toxicology screen for illicit drug use
  • TSH for hypothyroidism
  • LFTs for chronic liver disease or liver failure
  • Blood alcohol for alcohol-induced hypoglycemia
  • U&E for chronic kidney disease
• Treatment
  • Reverse hypoglycemia and expect prompt recovery
    • 15-20g of quick-acting carbohydrate snack (200ml orange juice or sweets) for patients who can swallow
    • GlucoGel or Dextrogel between the teeth and gums in uncooperative patients
    • IV Dextrose 10% at 200mL/h or IV Dextrose 10% 200mL/15min if unconscious or not responding to treatment
    • Fast-acting carbohydrates cannot be used to treat hypoglycemia caused by alpha-glucosidase inhibitors
    • Glucagon will not work in malnourished patients since glycogen reserves have been depleted
  • Repeat snacks up to 3 times
  • Recheck Blood glucose q10-15min
  • Once blood glucose is >4.0 mmol/L, give long-acting carbohydrates such as bread
  • Diazoxide can be used in some patients with chronic hypoglycaemia from excess endogenous insulin secretion
  • Treat the underlying cause
• Complications
  • Coma
  • Seizures
  • Permanent neurologic deficits
    • Hemiparesis
    • Memory impairment
    • Diminished language skills
    • Decreased abstract thinking capabilities
    • Ataxia
  • Arrhythmia
  • Death
  • Hypoglycaemia unawareness is more common in type 2 diabetes. This increases the risk of neuroglycopenic complications of hypoglycemia.

Hyperinsulinism due to Exogenous insulin vs Sulfonylureas