Causes of hypoglycemia depend on age; neonatal causes are transient neonatal hypoglycemia, Prematurity, intrauterine growth retardation, perinatal asphyxia, sepsis, congenital hypopituitarism, beta sympathomimetic drugs, congenital hyperinsulinism, infant of a diabetic mother, Beckwith-Wiedemann syndrome and inborn errors of carbohydrate metabolism. Causes of adult hypoglycemia are: insulin or insulin secretagogue drugs, alcohol, hepatic failure, renal failure, cardiac failure, sepsis, non-islet cell pancreatic tumors, insulinoma, reactive hypoglycemia, post gastric bypass hypoglycemia, and autoimmunee hypoglycemia.

• Transient neonatal hypoglycemia:
  • Blood glucose level in healthy newborns falls due to loss of the mothers’ glucose supply that passes the placenta.^[1] Plasma glucose level is corrected by glycogenolysis and gluconeogenesis.^[2]

• Prematurity
• Intrauterine growth retardation
• perinatal asphyxia
• Maternal hyperglycemia due to diabetes or iatrogenic glucose administration
• Sepsis
• Congenital hypopituitarism:
  • Cortisol and growth hormone regulate glucose level
• Maternal use of beta-sympathomimetics
  • Interrupts glycogenolysis by blocking epinephrine’s effect.^[3]
• Hypothermic infants who have increased rates of glucose utilization and decreased glucose availability.
• Severe hepatic dysfunction
  • Leads to impairment of both glycogenolysis and gluconeogenesis.
• Congenital hyperinsulinism:^[4]
  • Infant of a diabetic mother is most commonly affected by hypoglycemia due to hyperinsulinism. Prolonged intrapartum hyperglycemia in fetus leads to hypertrophied and hyperfunctioning beta cells causing hyperinsulinism. It is transient and resolves two days after birth.
  • Beckwith-Wiedemann syndrome
  • Persistent hyperinsulinemic hypoglycemia of infancy: it is a mutation in genes encoding enzymes that control intracellular metabolic pathways of the pancreatic beta cell.
  • Excess exogenous insulin given to newborns with hyperglycemia may result in hypoglycemia.^[5]
  • Neonatal conditions associated with excessive insulin secretion include alloimmune hemolytic disease of the newborn, heart failure and sepsis.^[6]
  • Polycythemia may lead to greater glucose utilization by the increased mass of red blood cells.
  • Nesidioblastosis
• Inborn errors of metabolism:^[7]
  • Disorders of gluconeogenesis: fructose-1,6-bisphosphatase deficiency, pyruvate carboxylase deficiency.
  • Disorders of carbohydrate metabolism: hereditary fructose intolerance, galactosemia.
  • Disorders of fatty acid metabolism: medium or long-chain acyl-CoA dehydrogenase deficiency).^[8]

• Drugs are the most common cause of hypoglycemia in adults.^[9] The most important causes of hypoglycemia in adults include:
  • Insulin or insulin secretagogues such as sulfonylurea and glyburide are the most common drugs that may cause hypoglycemia due to longer duration of action^[10]. They suppress hepatic glucose production and stimulate glucose utilization which may result in hypoglycemia.
  • Quinolones
  • Pentamidine
  • Quinine
  • Beta blockers
  • Angiotensin-converting enzyme inhibitors
  • IGF-1
    • Especially in older patients with underlying renal or hepatic dysfunction^[11]
  • Alcohol
    • Due to hepatic glycogen depletion in fasting patients
    • Alcohol can induce hypoglycemia alone or associated with other hypoglycemic drugs
• Critical illnesses:
  • Hepatic failure
  • Renal failure
  • Cardiac failure
  • Sepsis
    • It occurs due to impaired liver gluconeogenesis
    • Sepsis induced cytokines secretion cause suppression of gluconeogenesis^[12]
• Hormone deficiency: cortisol in acquired adrenal insufficiency or acquired hypopituitarism^[13]
• Non islet cell tumor: hypoglycemia usually occurs as a result of tumor production of IGF-2
• Insulinoma
• Reactive hypoglycemia or postprandial
  • A hypoglycemia that occurs as a reaction to food ingestion within 4 hours after meals due to functional hyperinsulinism^[14]
• Post gastric bypass hypoglycemia
  • Rapid jejunal emptying with exaggerated insulin response
• Insulin autoimmune hypoglycemia
  • Occurs in patients who have antibodies directed to endogenous insulin or to the insulin receptor^[15]
• Accidental, surreptitious, or malicious hypoglycemia