1. Nicola Trevelyan Consultant Paediatrician Nov 2007
Paediatric Diabetes
Nicola Trevelyan
Consultant Paediatrician
Nov 2007

2. Aims Case history Diagnosis Diabetic ketoacidosis Treatment regimens
Insulin analogues

3. Case history
9 year old Hannah is brought to A&E by her mum with a 2 week history of increased thirst, increased weeing & being very tired. Over the last 2 days she has been very thirsty, breathing fast & vomiting.
O/E – Weight 26kg Alert co-operative afebrile
5% dehydrated
Blood gas – pH 7.16, pCO2 2.4, Bicarb 5, BE –24
Glucose 28mmol/L
Urine 4+ ketones, 4+ glucose

4. What is the diagnosis?
Newly diagnosed type 1 diabetes mellitus with diabetic ketoacidosis

5. Types of diabetes sugar lack of useful insulin
insulin produced tissues resistant to insulin
by pancreas & pancreas unable to produce enough insulin
type type 2

6. What are the abnormal results & what do they signify?
High glucose = diabetes
Ketones in urine = ketosis (in absence of glycosuria may be starvation ketones)
Low pH = acidosis
Low Bicarbonate & negative base excess = metabolic acidosis
Low pCO2 = compensatory respiratory alkalosis

7. The role of insulin
Uptake of glucose from blood into muscle & fat cells
Stops hepatic gluconeogenesis
Increases glycogen production in liver & muscle
Stimulates fat & protein synthesis

8. What are the 2 problems which need treating?
Insulin
What are the problems which need treating?
Decrease in glucose uptake from blood
MUSCLE LIVER
Gluconeogenesis
Decrease intracell glucose Rise in blood for metabolism glucose
Counter regulatory
hormones Osmotic diuresis
Lipolysis Ketones Vomiting Dehydration

9. Treatment of DKA Aims To slowly restore metabolic homeostasis
To correct lack of insulin
Correct dehydration over 48 hours
Switch off lipolysis and hence acidosis
Reduce hyperglycaemia

10. Treatment of DKA – IV fluids
Start IV fluids before insulin
0.9% saline with 40mmol/L KCl (if the child is PUing)
Once sugar drops to ~12mmol/L change to 0.45/5 dextrose saline with KCl added

11. What rate should Hannah’s fluids be given?
Deficit = weight (kg) x % dehydn x 10 = 1300ml
or 5% of 26kg = 0.05 x 26 = 1.3L
or 5 x = 1300ml Given over 48hrs
100
Maintenance = (100 x 10)+(50 x 10)+(20 x 6) = 1620ml per 24 hours
Hourly rate = (1300/2) = 2270 = 94.6ml/hr

12. What insulin?
Actrapid or any fast acting analogue available (Humulin S, Humalog, Novorapid)
50 units in 50ml Normal saline
Run at 0.1ml/kg/hour – only dose proven in literature to be effective at switching off ketosis.

13. Complications of DKA Cerebral oedema Other complication
Gastric stasis
Pancreatitis
Complications of treatment
Hypoglycaemia
Hypokalaemia

14. Cerebral Oedema Typically occurs 4 -12 hrs after starting treatment
Risk 7 / 1000 episodes of DKA
12 / 1000 episodes of DKA in new IDDM
24% morbidity
35% left with significant morbidity

15. What we do know about cerebral oedema…
We don’t seem to be getting any better at preventing it - overall risk stable over last 20 years
The sicker you are at presentation the more likely you seem to be to get it
Not related to type of fluid
HAS vs 0.9% saline
Not always related to treatment
Some develop it prior to reaching hospital

16. Why does it happen? No one really knows! Numerous mechanisms proposed
Cerebral hypoxia
Drop in plasma osmolality
Generation of inflammatory mediators
Disruption of cell membrane ion transport
Aquaporin channels
Generation of intracellular organic osmolytes causing influx water into brain cells

17. Risk factors for cerebral oedema
Younger child at highest risk
Newly diagnosed Diabetes
Lower pH at presentation
High urea
Administration of insulin within 1st hour (OR 4.7)
Administration of bicarbonate
Administration of large volumes of fluid in the 1st 4 hours of treatment
Edge 2005

18. Cerebral oedema Symptoms Signs Headache Drowsiness Incontinence
Vomiting recurrence
Signs
Decreased LOC
Bradycardia
Rising BP
Decreasing O2 sats
Neurological signs
Abnormal pupil responses
Abnormal posturing

19. Treatment of cerebral oedema
Mannitol 0.5g to 1.5g / kg (= 2.5 to 7.5ml / kg 20% Mannitol) over 30mins
3% saline

20. Case history… 24 hours later Hannah is feeling much better.
What are the different SC treatments regimens available to Hannah and what are their pros & cons?
How are you going to change her from IV to SC insulin?

21. Treatment options – Type 1
Insulin sub cut injection
Fast acting
Insulin mixes
Long acting
Pump (CSII)
? Inhaled insulin
? Stem cell transplant

22. Fast acting insulin Soluble insulin Insulin analogues Actrapid
Onset of action 30 mins Peak 1-2 hours
Lasts around 6 to 8 hours
Insulin analogues
Humalog, novorapid
Onset of action within 15 minutes peak mins
Last around 2 to 5 hours

23. Insulin mixtures Until recently most commonly used insulin in children
Convenient
Mixtard 30 or M3– 30% fast, 70% intermed
Mixtard 20 or M2 – 20% fast, 80% intermed
Humalog 25 – 25% fast 75% intermed
Etc.

24. Long acting insulin Isophane insulin (intermediate) Insulin analogue
Insulatard, Humulin I
onset of action 2 hours
Peak 4 to 6 hours
lasts 12 hours
Insulin analogue
Glargine (Lantus) – lasts 24 hours
Detemir (Levemir) – lasts around 20 hrs

25. Glargine vs Detemir Glargine Detemir Once daily Lasts 24hrs
Acidic injection which stings 5-10%
Poor pen device
Detemir
Once / twice daily
Lasts hrs
Evidence of reductn in nocturnal hypos
Good pen

26. Insulin regimes – BD insulin mixes
12MN 8am 12MD 5pm 10pm 12MN
inject inject

27. Insulin regimes – BD insulin mixes
Advantages
Convenient
Well understood
Lots of pens / mixes available
Only 2 injections a day
Disadvantages
Lack of flexibility
Have to be up & injected by 9am at latest
Have to have 3 snacks a day & 3 meals a day

28. Insulin regimes – Basal Bolus with Glargine (Lantus)
12MN Breakfast lunch tea bed

29. Insulin regimes – Basal Bolus
Advantages
Much more flexibility
Can alter doses according to size of meal
Less need to have between meal snacks
If child unwell & not eating can omit doses of fast insulin
Disadvantages
4 injections a day
Need injection at school
Easier to manipulate insulin
Need to have clear understanding of diabetes

30. Insulin pumps

31. Theory of Insulin Pump Therapy
Low rate insulin pumped in 24 hr/day
Background rate can be pre-programmed to change at different times during the 24 hours
Extra insulin bolus given when anything is eaten

32. Is a insulin pump better than multiple injections of insulin?
Control of sugars - Generally better on an insulin pump
Incidence of severe hypoglycaemia (low sugars) - Much lower on an insulin pump
Up to 50% reduction in severe hypos compared to having multiple injections of insulin (Bolland et al Diabetes Care 1999)
Weight - No increase in weight on an insulin pump
Quality of life - Increased flexibility in lifestyle

33. Advantages of CSII More flexible lifestyle & eating pattern
Delivers insulin in more physiological way
Can improve diabetes control
Lessens the risk of hypoglycaemia
Multiple injections a day replaced by insertion of cannula every 2 to 4 days
Positive effects on quality of life

34. Disadvantages of CSII
It is an intensive therapy and this can = hard work
Pump is intelligent but still needs to be told what to do
Not everyone wants to visible sign of their diabetes
Concerns about wearing a pump during sport & sex
Risk of skin infection at the cannula site
Expensive (pump cost £ ~£1500/yr consumables)

35. Are pumps safe? Modern pumps much more reliable
Lots of alarms, safety checks & warning systems
Can be programmed to have a maximum amount of insulin they’ll deliver in one go
Pump can be locked
Line blockages can cause problems

36. Are pumps safe?
Risk of diabetic ketoacidosis (insufficient insulin leading to high sugars, ketones and acid in the blood)
Higher in some clinical trials
No deposits of long acting insulin under the skin
Switching off insulin supply from the pump can lead to trouble within 1 or 2 hours
Risk decreases with increased experience using the pump
Need to measure sugars at least 3 or 4 times / day

37. Who is eligible for an insulin pump?
N.I.C.E. 2004
Type 1 diabetes on multiple daily injections of insulin including Glargine or similar
AND
HbA1c above 7.5%
Recurrent unpredictable hypoglycaemia (low blood sugars) or hypoglycaemia unawareness or night time hypoglycaemia
Patient willing and able to use therapy safely & effectively

38. The future CSII…

39. Changing from IV to SC insulin
Ensure the child is tolerating oral intake
Give SC insulin prior to stopping IV insulin
If starting a basal bolus regimen try to ensure the basal insulin (glargine / detemir) is given the night before stopping the IV

40. What other education will Hannah’s family need prior to discharge?
Able to do injections & blood glucose monitoring
Basic dietary advice
Hypoglycaemia management
Ketone monitoring if sugar levels high

41. Hypoglycaemia symptoms & signs
hunger coma pins & needles
anxiety
abdominal pain headache
palpitations weakness
nausea & vomiting tremor
blurred vision fainting
dizziness abnormal
confusion convulsions cry
irritability
apnoea hypotonia

42. Hypoglycaemia management
Conscious
10g fast carbohydrate followed by starchy snack
Conscious but unco-operative
Glucogel followed by starchy snack
Unconscious
Glucagon then starchy snack if possible & hospital

43. Any questions