In this document we will discuss hypoglycaemia in neonates and then we will discuss hypoglycaemia in children and adults.
The definition of hyoglycaemia can differ between term and preterm neonates, and term neonates may be asymptomatic or symptomatic:
- Asymptomatic term neonates - <2.5mmol/L or <45mg/dL in the first 24-48 hours of life.
- Symptomatic term neonates - <2.2mmol/L (<45mg/dL) in the first 24-48 hours of life.
- Preterm neonates - <1.7mmol/L (<30mg/dL) in the first 48 hours of life.
It can also be deemed as transient or persistent.
Pathophysiology
Transient neonatal hypoglycaemia may be due to a number of causes, such as:
- Inadequate glycogen - neonates with perinatal asphyxia, or who are small for gestational age (SGA) or are preterm may have inadequate glycogen stores. This is because they may undergo anaerobic glycolysis which involves the breakdown of glycogen. The glycogen stores are used up faster than they are replenished as there is insufficient intake or prolonged intervals between feeds.
- Immature enzymatic function - leading to deficiencies in glycogen stores once again.
- Hyperinsulinism - this is especially true in maternal diabetics or babies born from mothers who had gestational diabetes. The foetus is exposed to higher than normal amounts of glucose passing through the placenta. This causes the foetus to produce more insulin. Insulin is also responsible for foetal growth hence why gestational diabetes causes macrosomia. After birth, the exposure to excessive glucose disappears, yet the insulin levels remain elevated due to the half-life of insulin being longer. It therefore remains circulating in the neonate’s bloodstream → hypoglycaemia.
Babies who are SGA also have higher incidences of hypoglycaemia due to the physiological stress leading to hyperinsulinism.
Other causes of transient hypoglycaemia may be:
- Issues with IV dextrose infusion or malpositioninig of an umbilical catheter
- Neonatal sepsis
This is rarer and may be due to the following causes:
- Congenital hyperinsulinism - and other genetic causes for hyperinsulinism such as Bekwith-Wiedemann.
- Defects in counter-regulatory hormones - these. Include hormones such as growth hormone, thyroid hormones, corticosteroids, glucagon and catecholamines.
- Inherited disorders of metablolism
- Glycogen storage diseases
- Gluconeogenesis disorders
- Fatty acid oxidation disorders
😷 Presentation
Many children will be asymptomatic.
Symptoms, if shown, may include:
- Hypotonia
- Poor feeding
- Listlessness (lacking energy or enthusiasm)
- Tachypnoea
There may also be signs that show due to failure of the autonomic nervous system, such as:
- Diaphoresis
- Tachycardia
- Lethargy
- Weakness
- Trembling
Symptoms that may indicate neuroglycopenia include:
- Seizures
- Coma
- Cyanotic episodes
- Bradycardia
- Apnoea and respiratory distress
- Hypothermia
🔍 Investigations
- 🥇 Immediate bedside blood glucose check using a capillary sample.
- 🏆 We can confirm the diagnosis using a venous blood sample.
🧰 Management
Asymptomatic neonatal hypoglycaemia
🥇 First-line options include
- Increase breast feeding frequency
- Supplement with formula feeding
- IV glucose
- Buccal glucose
Re-check the baby in 1 hour to ensure there has been an appropriate response.
🥈 Glucose 10% IV infusion and re-check within 15 minutes.
Symptomatic neonatal hypoglycaemia
🥇 IV glucose infusion
🥈 Buccal glucose gel or IM glucagon if there is a delay in getting IV access. If the blood glucose is <1mmol/L then buccal glucose is only an interim measure while IV glucose is being arranged.
💡 If the neonate requires ≥12mg/kg/minute of glucose to maintain normoglycaemia → investigate for congenital hyperinsulinism.
🚨 High-risk neonates are often treated prophylactically with either oral glucose or 10% dextrose infusion.
At-risk neonates who are not sick can start with early and frequent formula feeding.
Hypoglycaemia is when the blood glucose levels are <3.5mmol/L.
Pathophysiology
In non-diabetics, a drop in blood glucose levels causes a paracrine response in the pancreas to inhibit the ß-cells in the Islets of Langerhans to inhibit insulin secretion. As the glucose levels continue to fall the regulatory mechanisms help maintain normoglycaemia:
- α-cells - these secrete glucagon which converts glycogen → glucose in the liver (glycogenolysis).
- Adrenaline release - this stimulates the liver to increase glycogenolysis as well as
- Growth hormone and cortisol - these are counter-regulatory hormones that decrease muscle glucose uptake and also promote glycogenolysis and gluconeogenesis.
In diabetics, the response is not the same. The glucagon release in response to hypoglycaemia is abnormal as there is less glycogenolysis and less gluconeogenesis → hypoglycaemic events.
What could precipitate the hypoglycaemia is?
- Exogenous insulin - this is not subject to the normal negative feedback loop and so even if the counter-regulatory mechanisms are intact, they do not work on exogenous insulin, therefore hypoglycaemia is still a concern.
- Exercise - exercise increases non-insulin dependent glucose uptake through GLUT4 translocation to the cell surface of muscle cells. Because of this, glucose uptake increases despite low insulin levels. This translocation effect remains high after exercise too. Now if the patient has diabetes and exercises, the pancreas does not regulate the insulin levels in response to the exercise and the counter-regulatory mechanism may be impaired → hypoglycaemia again.
Let’s take a look at the causes of non-diabetic hypoglycaemia and then the causes of diabetic hypoglycaemia:
- Alcohol use disorder - this is the most common non-iatrogenic cause. This is because the alcohol affects the micro circulation of the pancreas which causes redirection of blood into the endocrine parts which releases insulin.
- Insulin misuse
- Endocrine causes:
- Hyperthyroidism
- Addison’s disease (due to a lack of counter-regulatory hormones)
- Growth hormone deficiency
- Hypopituitarism
- Cancers:
- Tumours secreting insulin-like compounds.
- Neuroendocrine tumours (such as an insulinoma)
- Hypoglycaemia due to malnourishment (in terminal cancer)
- Iatrogenic - certain drugs like antibiotics, heparin, PPIs and tramadol may precipitate hypoglycaemia.
- Insulin-related:
- Altered eating patterns
- Insulin misuse
- Over-exercising
- Prescription/administration errors
- Renal or liver failure
- Sepsis
- Adrenal, thyroid or pituitary dysfunction
- Malnutrition
If the patient is unwell, hypoglycaemia may occur due to:
- Discontinuation of long-term corticosteroid therapy acutely
- Vomiting/reduced appetite
- Mobilisation after illness
- Recovery from acute illness
😷 Presentation
The severity of symptoms do not always correlate with the blood glucose levels, especially in diabetic patients.
If the concentrations are less than <3.3mmol/L it is more likely to present with the autonomic symptoms due to the release of glucagon and adrenaline:
- Sweating
- Anxiety
- Shaking
- Nausea
- Hunger
- Palpitations
If the concentrations are <2.8mmol/L it is more likely to present with the neuroglycopenic symptoms due to inadequate glucose supply to the brain:
- Weakness
- Visual changes
- Confusion
- Dizziness
- Blurred vision
- Dysarthria
- Somnolence
- Focal neurological deficits
If it gets more severe it can sometimes even lead to convulsions and coma.
🔍 Investigations
Symptomatic hypoglycaemia is confirmed through documentation of Whipple’s triad of hypoglycaemia:
- Symptoms or signs of hypoglycaemia
- Low plasma glucose concentration while having the symptoms
- Resolution of symptoms after plasma glucose returns to normal
🧰 Management
Symptomatic with blood glucose >4mmol/L:
🥇 Carbohydrate snack (such as bread or a normal meal if they haven’t eaten for a while).
Blood glucose <4 but conscious and able to swallow:
🥇 Oral fast-acting carbohydrate - such as glucose liquids, tablets, gels, pure fruit juice and sucrose solutions.
🥈 Repeat treatment after 15 minutes for a maximum of 3 times.
🥉 IM glucagon or 10% glucose infusion + thiamine supplementation (in alcoholics)
🚨 Unconscious/seizures due to hypoglycaemia
Hypoglycaemia that results in seizures or unconsciousness is an emergency and should be treated as such.
- Stop IV insulin immediately (if on IV insulin)
- If IV access is possible → 10% glucose infusion is the first-line choice. A bonus dose can be given prior to infusion to prevent the neuro glycogen is.
- If not possible (e.g. in the community setting) → IM glucagon is the first-line choice.