Glucose Homeostasis and Hypoglycaemia ✅ Flashcards
How does the glucose requirements of neonates compare to adults?
3x greater in neonates
Why do neonates have a higher glucose requirement than adults?
Glucose is the primary fuel for the brain, and neonates have a larger brain to body size ration
How do neonates meet their increased need for glucose?
They have a higher hepatic glucose production rate
What is the hepatic glucose production rate of a neonate?
Up to 60mg/kg/minute
What processes are involved in energy metabolism in a neonate?
- Glycogen production and glycogenolysis
- Gluconeogenesis
- Lipolysis
Where does glycogen production and glycogenolysis occur in neonates?
Mainly in the liver and muscle
Why are liver glycogen stores important?
They are rapidly available for breakdown to glucose
What is gluconeogenesis?
The process of glucose synthesis
What substrates are used in gluconeogenesis?
- Amino acids
- Lactate
- Pyruvate
- Glycerol
What is lipolysis?
Breakdown of lipids into fatty acids and triglycerides
What can fatty acids and triglycerides be metabolised into?
Ketone bodies
What are ketone bodies important for?
Important substrate for the brain
Can glycerol metabolised from adipose tissue be directed utilised through gluconeogenesis?
Yes
What closely controls glucose homeostasis?
Endocrine hormones
What endocrine hormones are involved in the control of glucose homeostasis?
- Insulin
- Glucagon
- Cortisone
- Growth hormones
What effect does insulin have on blood glucose?
It reduces it
How does insulin lower blood glucose?
By stimulating the formation of glycogen and glucose uptake into tissue cells
What effect does glucagon have on blood glucose?
It raises it
How does glucagon raise blood glucose?
Stimulating glycogen breakdown
Can a fetus make glucose from glycogen?
No
How does a fetus obtain glucose?
It is completely dependent on the placenta to provide glucose
Does a fetus make glycogen?
Yes
How long are fetal liver stores of glycogen sufficient for at term?
Only a few hours of fasting
What happens at birth, regarding glucose supplies?
The fetus is disconnected from the continuous supply of glucose and has to adapt to intermittent feeding
What is the result in the changes in glucose supply at birth?
- Glucose levels fall
- Surge of glucagon and fall in insulin level
How long does it take for a newborn baby to switch on gluconeogenesis?
A few hours
What is relied on for energy in the first few days of life?
Alternative energy substrates, such as ketone bodies
Why are alternative energy substrates relied on for the first few days of life?
Because an infants food volume intake is very low, with only a small volume of colostrum
What are the risk factors for transient hypoglycaemia of the neonate?
- Maternal diabetes mellitus
- Decreased glycogen stores
- Increased requirements and impaired metabolism
Why are babies born to mothers with diabetes mellitus at increased risk of transient hypoglycaemia?
Secondary to exposure to high blood glucose in utero
Why might babies have decreased glycogen stores?
- IUGR
- Preterm
Give an example of a cause of increased glucose requirements and impaired metabolism
Sepsis
What is the problem with the definition of hypoglycaemia in the newborn?
Lack of consensus about what constitutes hypoglycaemia
What can severe and prolonged symptomatic hypoglycaemia lead to?
Poor prognosis in terms of abnormal neurodevelopment or death
What is generally used as the threshold for hypoglycaemia in neonates?
2.6mmol/L
Why is the use of 2.6mol/L as a threshold for hypoglycaemia controversial?
Many normal breastfed infants tolerate lower glucose levels in the first few days of life, and unnecessary intervention should be avoided
Why are normal breastfed infants able to tolerate lower glucose levels in the first few days of life?
They are able to utilise ketones and other energy substrates
What symptoms do most babies with hypoglycaemia have?
Most are asymptomatic
What are the symptoms of hypoglycaemia in a neonate when present?
- Jitteriness
- Irritability
- High-pitched cry
What are the symptoms of more severe hypoglycaemia in a neonate?
- Depressed consciousness
- Lethargy
- Hypotonia
What can severe hypoglycaemia result in?
- Apnoea
- Coma
- Seizures
How is hypoglycaemia prevented in infants with risk factors?
- Provision of energy
- Good temperature control
- Treatment of any underlying cause, e.g. infection
How can energy be provided in infants with risk factors for neonatal hypoglycaemia?
- Enterally (early and frequent feeds)
- Parenterally
What monitoring should infants with hypoglycaemia have?
BM monitoring until >2.6mmol/L
What may be needed to maintain BMs >2.6mmol/L in neonates with hypoglycaemia?
- Extra feeds
- IV glucose
What does symptomatic hypoglycaemia require in terms of management?
Urgent correction and investigation
What should be done if hypoglycaemia is identified using a bedside glucometer?
A laboratory measurement
Why should a laboratory measurement be obtained when hypoglycaemia is identified by a bedside glucometer?
They do not measure blood glucose levels accurately
When does hypoglycaemia require detailed investigation?
Prolonged, persistent, or refractory hypoglycaemia despite glucose intake of over 8-10mg/kg/min
What can the causes of transient neonatal hypoglycaemia be divided into?
- Antenatal
- Neonatal
What are the antenatal causes of transient hypoglycaemia?
Maternal diabetes mellitus
What kind of maternal diabetes mellitus can cause transient hypoglycaemia in the neonate?
- Insulin-dependent
- Gestational
What are the neonatal causes of transient hypoglycaemia?
- IUGR
- Large for gestational age
- Preterm
- Infection
- Iatrogenic
- Polycythaemia
- Perinatal asphyxia
- Rhesus disease
- Hypothermia
What are the iatrogenic causes of transient hypoglycaemia of the neonate?
Reduced feeds with inadequate IV glucose
What can the causes of persistent neonatal hypoglycaemia be divided into?
- Reduced glucose availability
- Increased glucose consumption
What are the causes of reduced glucose availability leading to persistent neonatal hypoglycaemia?
- IUGR
- Prematurity
- Panhypopituitarism
- Cortisol deficiency
- Growth hormone deficiency
- Glucagon deficiency
- Accelerated starvation (ketotic hypoglycaemia)
- Inborn errors of metabolism
What are the causes of increased glucose consumption leading to persistent neonatal hypoglycaemia?
- Congenital hyperinsulinism
- Transient neonatal hyperinsulinism
- Maternal diabetes
- Persistent hypoglycaemic hyperinsulinism of infancy
- Beckwith-Wiedemann syndrome
- Rhesus haemolytic disease
- Perinatal asphyxia
What investigations should be done in persistent hypoglycaemia?
- Glucose
- U&E
- pH
- Liver function tests
- Lactate
- Pyruvate
- Free fatty acids
- ß-hydroxybutyrate
- Acylcarnitine
- Ammonia
- Insulin
- C-peptide
- Cortisol
- ACTH
- Growth hormone
When should blood tests for investigation into persistent hypoglycaemia be taken?
At the time of hypoglycaemia
What treatment might be required in prolonged and refractory hypoglycaemia due to hyperinsulinism?
Insulin suppression
What treatments can achieve insulin suppression?
- Diazocide
- Somatostatin analogues (octreotide)
- Pancreatic resection
- Glucagon
What might be required for specific endocrine deficiencies causing hypoglycaemia?
Hormone replacement therapy
