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Paediatric Diabetes . Nicola Trevelyan Consultant Paediatrician Nov 2007. Aims. Case history Diagnosis Diabetic ketoacidosis Treatment regimens Insulin analogues. Case history.
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Paediatric Diabetes Nicola Trevelyan Consultant Paediatrician Nov 2007
Aims • Case history • Diagnosis • Diabetic ketoacidosis • Treatment regimens • Insulin analogues
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
What is the diagnosis? • Newly diagnosed type 1 diabetes mellitus with diabetic ketoacidosis
Types of diabetes sugar lack of useful insulin insulin produced tissues resistant to insulin by pancreas & pancreas unable to produce enough insulin type 1 type 2
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
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
What are the 2 problems which need treating? Insulin 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
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
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
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 26000 = 1300ml Given over 48hrs 100 • Maintenance = (100 x 10)+(50 x 10)+(20 x 6) = 1620ml per 24 hours • Hourly rate = (1300/2) + 1620 = 2270 = 94.6ml/hr 24 24
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.
Complications of DKA • Cerebral oedema • Other complication • Gastric stasis • Pancreatitis • Complications of treatment • Hypoglycaemia • Hypokalaemia
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
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
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
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
Cerebral oedema • Symptoms • Headache • Drowsiness • Incontinence • Vomiting recurrence • Signs • Decreased LOC • Bradycardia • Rising BP • Decreasing O2 sats • Neurological signs • Abnormal pupil responses • Abnormal posturing
Treatment of cerebral oedema • Mannitol 0.5g to 1.5g / kg (= 2.5 to 7.5ml / kg 20% Mannitol) over 30mins • 3% saline
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?
Treatment options – Type 1 • Insulin sub cut injection • Fast acting • Insulin mixes • Long acting • Pump (CSII) • ? Inhaled insulin • ? Stem cell transplant
Fast acting insulin • Soluble insulin • 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 30-70 mins • Last around 2 to 5 hours
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.
Long acting insulin • Isophane insulin (intermediate) • 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
Glargine Once daily Lasts 24hrs Acidic injection which stings 5-10% Poor pen device Detemir Once / twice daily Lasts 20-24 hrs Evidence of reductn in nocturnal hypos Good pen Glargine vs Detemir
Insulin regimes – BD insulin mixes 12MN 8am 12MD 5pm 10pm 12MN inject inject
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
Insulin regimes – Basal Bolus with Glargine (Lantus) 12MN Breakfast lunch tea bed
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
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
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
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
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 £2400 + ~£1500/yr consumables)
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
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
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
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
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
Hypoglycaemia symptoms & signs hunger comapins & needles anxiety abdominal pain headache palpitations weakness nausea & vomiting tremor blurred visionfainting dizzinessabnormal confusionconvulsionscry irritability apnoea hypotonia
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