Tales from the Sugarbowl Glucose Homeostasis in the Neonate

1
Tales from the SugarbowlGlucose Homeostasis in
the Neonate

• K Pillay
• Westville Hospital and
• Paediatric Endocrine Clinic, IALCH, Durban

2
Coming up

• Physiology
• Hyperglycaemia
• Hypoglycaemia

3
Glucose Homeostasis

• Tightly regulated (4.0-7.8 mmol/l)
• Regulation is the same at all ages
• Abnormality of regulation results in morbidity
• Energy for cellular function
• Ketones, other metabolites and pathways can be
  used

4
The Sugarbowl
5
The Sugarbowl
6
The Sugarbowl
7
Sources of glucose (1)

• Diet (milk)
• Ingestion
• Absorption
• Digestion
• Metabolism
• Distribution
• 67 g/100mls (6.7 solution)

8
Sources of glucose (2)

• Diet (milk)
• Endogenous (stores)
• Liver, muscle, fat
• Require stimulation for release (adrenaline,
  cortisol, GH, glucagon, etc.)
• Enzymes systems
• 3-5 mg/kg/min

9
Disposal of glucose

• Required for energy
• Brain
• 10-25 of available glucose
• Can utilize ketones but no other substrate
• Insulin

10
Glucose utilization
Haymond M, et al. Endocrinol Metab Clin North Am
199928663
11
Insulin secretion
12
The falling glucose
4-7 mmol/l
3.5-4.0 mmol/l Insulin switched off
lt2.5 mmol/l Neuroglycopenia
3.0-3.3 mmol/l Activate glucose release.
Adrenalin, cortisol, GH, etc.
13
Glucose homeostasis
Glucose stores
Dietary glucose
Insulin
14
Neonatal diabetes

• Plasma glucose gt8 mmol/l
• Asymptomatic
• Symptomatic
• Dehydration
• FTT
• Fever
• Glycosuria, ketonuria, met acidosis
• 1-2 weeks

15
Risk factors

• LBW
• Prematurity
• Relationship with birth weight
• BW lt 2.0 kg 2
• BW lt 1.0 kg 45
• BW lt 0.75kg 80
• Associated with IV infusion rates

16
Aetiology

• IV glucose infusions
• 3-4 mg/kg/min
• Lipid infusion
• Stress
• Congenital insulin resistance
• Drugs
• Theophylline, Dexamethazone
• Insulin dependent diabetes

17
Complications

• Dehydration
• Electrolyte disturbances
• Intra-cranial haemorrhage
• Death

18
Treatment

• Depends on cause
• Decreased IV glucose infusion rates
• Review drug use
• Insulin infusion
• 0.02-0.05 u/kg/hour

19
Transient Neonatal Diabetes

• Onset at 1-2 weeks
• Resolve by 12 weeks
• 50 recur in childhood
• 23 have macroglossia
• Genetic abnormalities
• Chromosome 6
• KCNJ11, ABCC8

20
TNDM - Treatment

• Insulin
• Rapid decrease in dose
• With relapse
• Diet
• Insulin

21
Permanent NDM

• Onset 0-3 months
• Typical presentation
• Require insulin at diagnosis
• Neurological dysfunction 20
• New mutations in 90
• Genetics
• KCNJ11, GCK

22
PNDM - Treatment

• Insulin
• Depending on mutation
• Oral agents (Sulphonylurea)

23
Neonatal diabetes
PNDM
PNDM/TNDM KCNJ11, ABCC8
24
Genetic abnormalities
25
Hypoglycaemia

• Common problem
• Commonest metabolic problem in neonatal period
• Long term complications
• Identifiable cause
• Specific therapy

26
Frequency of Hypoglycaemia
DH Adamkin. J of Perinatology (2009) 29, S12-17.
27
Definition

• Controversial
• Depends on
• Physiological definition
• Neurological complications
• Avoid unnecessary intervention
• A man with a watch knows what time it is. A man
  with 2 watches is never sure Anon, Pantheon,
  1999.

28
Neurological complications

• No single value
• Depends on
• Availability of other sources of energy
• Symptomatic vs asymptomatic (?)
• Preterm babies (?)
• Day 1 vs later

29
Suggested Operational Thresholds

• Term babies 2.0 mmol/l
• Therapeutic target 2.5 mmol/l
• Symptomatic 3.5 mmol/l
• Preterm babies Term babies
• TPN 2.5 mmol/l

Cornblath M, et al. Pediatrics 20001051141
30
Neurological complications

• 35 term babies
• Symptomatic, no HIE
• White matter abn94
• Severe43
• Neurological abn at 18 months65
• No relation to severity, duration of hypo or
  severity of symptoms

CM Burns, et al. Peds 2008 122 65-74
31
Measurement and monitoring

• Rapid, reliable
• Glucometers
• Technology, HCT, reporting
• Technique variability
• Plasma glucose
• Gold standard

32
Pitfalls of GM monitoring

• Timing
• Frequency
• Duration
• Technique

33
Clinical features

• Jitteriness, tremors
• Poor feeding
• Change in LOC
• Hypotonia
• Apnoea, bradycardia, cyanosis
• Tachyopnoea
• Hypothermia
• Seizures

34
High risk babies

• Preterm babies
• Large or small for GA
• Infants of diabetic mothers
• Sepsis, asphyxia

35
Screening for Hypoglycaemia
2.5 mmol/l
3.0 mmol/l
DH Adamkin. J of Perinatology (2009) 29, S12-17.
36
Management

• Prevent neurological injury
• Prevent hypoglycaemia
• Early feeding
• Maintaining glucose values
• Determine cause
• Specific therapy

37
Maintaining glucose values

• Oral feeding
• Ability to feed
• Tolerance of oral feeds
• Glucose delivery
• IV fluids
• Concentration of fluids
• Milk vs IVF

38
Cause of hypoglycaemia

• Decreased glucose production
• lt6 mg/kg/hour
• Hyperinsulinaemia
• Transient / permanent
• Endocrine causes
• Decreased cortisol, GH, hypopituitarism
• Metabolic disorders
• GSD, AA, FA
• Increased requirement

39
The falling glucose
4-7 mmol/l
3.5-4.0 mmol/l Insulin switched off
lt2.5 mmol/l Neuroglycopenia
3.0-3.3 mmol/l Activate glucose release.
Adrenalin, cortisol, GH, etc.
40
Hyperinsulinaemia

• Commonest cause
• IDM
• Beckwith-Weideman Syndrome
• Rh iso-immunization
• Asphyxia
• SGA babies
• Genetic disorders

41
Hyperinsulinaemia
Diazoxide HCT
Calcium channel blockers
42
Hyperinsulinaemia

• IVF fluids (usually gt8 mg/kg/hour)
• Diazoxide / Hydrochlorthiazide
• Glucagon
• Somatostatin
• Calcium channel blockers
• Pancreatectomy

43
Glucose Homeostasis

• Tightly regulated (? -8 mmol/l)
• Regulation is less well understood
• Abnormality of regulation results in morbidity
• Appropriate and specific intervention required