Transcript Slide 1

What’s New in Paediatric
T1DM
TCH Paediatric Multidisciplinary Diabetes Team
10 July 2013
Learning objectives
• Recognise clinical signs and symptoms to
allow for the earliest possible diagnosis and
referral of children with new-onset T1DM.
• Describe current insulins and regimen
options available in 2013.
• Develop an understanding of the various
technologies available for the management of
T1DM at home.
• Understand strategies for and review sickday management plans for children with
T1DM in your practice.
Case study1
• 4 yr old boy
• GP presentation: 3 week history of
weight loss, polyuria and polydipsia.
• 2 day history of sore throat
• Woke up in the morning with ‘heavy
breathing’
• Past medical and family history were
unremarkable.
Case study2
Physical examination
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Alert
GCS score 15/15
Kussmaul breathing present
PR 136 bpm, RR 44, BP 92/58
>5% dehydration
Dry cracked lips
Weight 16kg (~3kg weight loss in 4
weeks)
• Pharyngitis
Case study3
• At GP surgery: BGL 25mmol/L – referred
to ED
In ED:
• Capillary blood gas: pH 7.18, bicarbonate
(HCO3) 12 mmol/L, BGL 25 mmol/L, Na
136 mmol/L (corrected = 142) , K 4.9
mmol/L
Corrected Na = measured Na + 0.3 (glucose – 5.5)
Case study4
Management:
• 10ml/kg bolus Normal saline
• Re-assessed: PR 118, RR 36, BP 96/58
• IV insulin infusion: 0.1U/kg/hr
• Fluids: N/S + 40mmol/L KCL at maintenance
+ 5% replacement over 48 hrs
• Transferred to HDU – further management as
per DKA protocol
Case study5
At resolution of ketoacidosis:
• Initiated on MDI: Levemir at
bedtime; Novorapid with meals
using an insulin dosing card.
• DNE / Dietician / Social work
involvement
• Discharged home on day 5 with
nightly contact with on-call
Paediatric Endocrinologist for dose
adjustments
Classification of Diabetes
Diabetes Care 2013;36(suppl 1):S11.
Criteria for diagnosis of Diabetes
A1C ≥6.5%
OR
Fasting plasma glucose
≥7.0 mmol/L
OR
2-h plasma glucose ≥11.1 mmol/L
during an OGTT
OR
A random plasma glucose ≥11.1 mmol/L
Diabetes Care 2013;36(suppl 1):S13; Table 2.
Criteria for Prediabetes
Categories of increased risk for diabetes
(prediabetes)
IFG: 5.6–6.9 mmol/L
OR
IGT: 2-h plasma glucose in the 75-g OGTT
7.8–11.0 mmol/L
OR
A1C 5.7–6.4%
*For all three tests, risk is continuous, extending below the lower limit of a range and
becoming disproportionately greater at higher ends of the range.
Diabetes Care 2013;36(suppl 1):S13; Table 3.
Pathogenesis of T1DM
• Autoimmune destruction of
the pancreatic islet cell
• Hallmark = lymphocytic
infiltration of islets
• Progresses over years
• Leads to insulin deficiency
• Glucagon production is
preserved but impaired
action
Incidence of T1DM in Australia
Australian incidence (NDR) in children 0-14 years between 2000-2006
Diabetic Medicine 2009; 26(6): 596-601
Genetics of T1DM 1
• Susceptibility to T1DM is an inheritable
trait BUT >85% cases occur in the
absence of first-degree relative
• Lifetime risk: first-degree relative (5%) vs
general population (0.3%)
Genetics of T1DM 2
• Twin concordance: monozygotic (3050%) vs dizygotic (6-10%)
• Risk increases with early age at
diagnosis: 3-5 fold increase risk if first
degree relative diagnosed <5 years age
Genetics of T1DM 3
Susceptibility loci: HLA-DR3 and HLA-DR4
• At least one locus: 95% T1DM vs 3%
general population
Protective loci: HLA-DR2, HLA-DR5, and
HLA-DQB1*0602
• 1 in 15,000 people with HLA-DQB1*0602
develop T1DM
Environmental factors in T1DM
• Cow’s milk protein exposure (bovine serum albumin and
β-lactoglobulin)
• Vitamin D deficiency
• Viruses: coxsackie A or B, enterovirus, rubella,
cytomegalovirus, ECHO virus, EBV, mumps, retrovirus
• Drugs & toxins: eg alloxan-like or streptozotocin- like
agents that induce oxidant beta-cell damage
• Stress
The Environmental Determinants of Diabetes in the
Young (TEDDY) study
Islet-specific autoantibodies1
• Islet cell autoantibodies (ICA)
• Glutamic acid decarboxylase autoantibodies
(GADA)
• Insulinoma-associated 2 autoantibodies (IA-2A)
• Insulin autoantibodies (IAA)
• Zinc transporter autoantibodies (ZnT8A).
Multiple and specific combinations of
autoantibodies more predictive
Diabetes Care 2009;32:2269-74
Islet-specific autoantibodies2
• Not causative
• Present months to years before onset of
symptoms
• Persist for varying duration after onset
• 90-95% T1DM have at least one at
diagnosis
Cell Mol Life Sci 2007;64:865-72
Ann Intern Med 2004;140:882-6
J Clin Endocrinol Metab 2004;89:3896-902.
Diabetes 1999;48:460-8
The Pathogenesis of T1DM
Atkinson MA & Eisenbarth GS. Lancet 2001; 358; 221-229
Normal glucose homeostasis
Meal
Insulin secretion
Fasting blood glucose is not an
appropriate screen test for T1DM
Clinical Presentation
• Polyuria – 95%
• Weight loss – 61%
• Fatigue – 52%
Polyuria is often missed on history
The EURODIAB study
Diabetologia 2001;44(Suppl 3):B75-80.
Goals of T1DM Management
• Utilize intensive therapy aimed at near-normal
BG and A1C levels
• Prevent diabetic ketoacidosis and severe
hypoglycemia
• Achieve the highest quality of life compatible
with the daily demands of diabetes management
• In children, achieve normal growth and physical
development and psychological maturation
• Establish realistic goals adapted to each
individual’s circumstances
DCCT and EDIC Findings
• Intensive treatment reduced the risks of retinopathy,
nephropathy, and neuropathy by 35% to 90% compared with
conventional treatment
• Absolute risks of retinopathy and nephropathy were
proportional to the A1C
• Intensive treatment was most effective when begun early,
before complications were detectable
• Risk reductions achieved at a median A1C 7.3% for intensive
treatment (vs 9.1% for conventional)
• Benefits of 6.5 years of intensive treatment extended well
beyond the period of most intensive implementation
(“metabolic memory”)
Intensive treatment should be started as soon as is safely possible after the onset of
T1DM and maintained thereafter
DCCT/EDIC Research Group. JAMA. 2002;15;287:2563-2569.
Principles for Good Glycaemic
Control
The Multidisciplinary Team
Approach
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Paedaitric Endocrinologist
Diabetes Nurse Educator / Nurse Practitioner
Dietician
Social Worker
Psychologist
• Age-appropriate clinics
ISPAD Clinical Practice Consensus Guidelines 2006–2007
Contributors to good glycaemic
control
• Education for parents / child (age
appropriate)
• Correct insulin regimen
• Contact in between clinics for adjustments
• Good relationship with GP
ISPAD Clinical Practice Consensus Guidelines 2006–2007
Pharmacokinetics of insulin Products
Rapid (Humalog, Novorapid, Apidra)
Insulin
Level
Short (Humalin R, Actrapid)
Intermediate (NPH, Protaphane)
Long (glargine)
Long (detemir)
0
2
4
6
8
10
12
14
16
Hours
N Engl J Med. 2005;352:174-183.
18
20
22
24
Pre-mix
Increased
Complexity
Better control
Twicedaily
MDI
CSII
Less
Hypoglycaemia
Insulin dosing advice
INSULIN DOSING CARD
Ezy-BICC
SMART-METER
Accu-Chek Aviva Expert
INSULIN DOSING APP
Insulin Pro
DKA
Risk factors for DKA at
diagnosis of T1DM
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Younger age
Ethnic minority
No first degree relative
Low SES/poor medical access/uninsured
Lack of community health screening
Lower weight SDS at diagnosis
Rates of DKA inversely related to prevalence of T1DM
Diabet Med 2013. doi: 10.1111/dme.12252
Pediatr Clin N Am 2011; 58 : 1301–1315
DKA criteria
• Hyperglycemia BG > 11 mmol/l
(young or partially treated children, pregnant adolescents may
present with “euglycemic ketoacidosis”)
• Venous pH <7.3 and/or bicarbonate <15 mmol/L
– mild DKA
– moderate
– severe
pH <7.3
pH <7.2
pH <7.1
bicarbonate <15
bicarbonate <10
bicarbonate < 5
• Glucosuria and ketonuria/ketonemia (β-HOB)
ISPAD Clinical Practice Consensus Guidelines 2006–2007
Pathophysiology of DKA
ISPAD Clinical Practice Consensus Guidelines 2006–2007
DKA Clinical Manifestations 1
• Feeling unwell for a short period, often less than
24 hours
• Polyuria, polydipsia and increased thirst, nocturia
• Polyphagia
• Weight loss
• Nausea and vomiting, vomitus can have coffeeground colour due to haemorrhagic gastritis
• Abdominal pain, due to dehydration and acidosis
• Weakness
ISPAD Clinical Practice Consensus Guidelines 2006–2007
DKA Clinical Manifestations 2
• Neurologic signs: restlessness,
agitation,lethargy and drowsiness, coma.
Increased
• Osmolality is the main factor that contributes to
altered mental status
• Visual disturbances due to hyperglycaemia
• Deep and rapid breathing, known as Kussmaul
breathing, may have acetone odour on breath.
ISPAD Clinical Practice Consensus Guidelines 2006–2007
DKA Clinical Manifestations 3
• Signs of dehydration due to fluid loss
through polyuria, vomiting and breathing:
reduced skin turgor, dry mucous
membranes
• Signs of hypovolaemia: tachycardia,
hypotension, postural hypotension
ISPAD Clinical Practice Consensus Guidelines 2006–2007
DKA Clinical Manifestations 4
• Mild hypothermia due to acidosis-induced
peripheral vasodilation, warm dry skin.
• Fevers are rare despite infection. Severe
hypothermia is a poor prognostic sign
ISPAD Clinical Practice Consensus Guidelines 2006–2007
Measurement of Ketone bodies
Hypoglycaemia
Hypoglycaemia 1
Neuroglycopenic
Adrenergic
• Diaphoresis
• Tachycardia/Pa
lpitations
• Shakiness
• Tingling
• Pallor
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Confusion
Irritability
Behavoural changes
Difficulties concentrating
Headache
Visual disturbance
Slurred speech
Altered consciousness
Seizures
Hypoglycaemia 2
• Check BGL if symptoms: <4.0mmol/L
• To increase BGL by 3-4mmol/L:
<30kg child use 10g
≥30kg child use 15g
• Re-check BGL every 10-15 mins and
repeat treatment if necessary
ISPAD Guidelines
Pediatric Diabetes 2009: 10(Suppl. 12): 134–145
Hypoglycaemia 3
• Check 20-30 mins after resolution to
ensure BGL maintained
• Solid food should be avoided until BGL ≥
4mmol/L (impairs absorption of fast-acting
CHO)
• Severe hypoglycaemia: IM Glucagon –
0.5mg in <12 years; 1.0mg in ≥ 12 years
ISPAD Guidelines
Pediatric Diabetes 2009: 10(Suppl. 12): 134–145
Cognitive Effects of
Hypoglycemia in Children
• Repeated and early exposure to severe
hypoglycemia has been reported to reduce
long-term spatial memory in children
with type 1 diabetes
• Early exposure to hypoglycemia may be
more damaging to cognitive function than
later exposure
Diabetes Care. 2005;28:2372-2377.
Incidence of Severe Hypoglycemia:
T1DM Exchange
Garg S, et al. Presented at 5th International Conference on Advanced Technologies &
Treatment for Diabetes, Barcelona, 2012.
Causes of Hypoglycemia in
Toddlers and Preschoolers
• Unpredictable food intake and physical
activity
• Imprecise administration of low doses of
insulin
• Frequent viral infections
• Inability to convey the symptoms of low
blood sugar
J Pediatr. 2002;141:490-495.
Glucose Variability and Health
Outcomes: Direct and Indirect
Pathways
Glucose
variability
Fear of
hypoglycemia
Reluctance to intensify
therapy
Quality of life
High A1C
Severe hypoglycemia
Controversial
Complications
Morbidity Mortality
Health Psychol. 1992;11:135-138
Diabetes Care. 1996;19:876-879;
Diabetes Technol Ther. 2008;10:69-80.
MEDTRONIC
DEXCOM
HYPOMON
Sick Day Management
Sick Day Management 1
STRESS
COUNTERREGULATORY
HORMONE
HYPERGLYCAEMIA
INSULIN
RESISTANCE
KETOSIS
Also hypoglycaemia with ketosis eg gastroenteritis
Sick day management 2
• Regular BGL and ketone monitoring
• Additional insulin: 10-20% of total daily
insulin as regular corrections
• Encourage oral fluids
IV fluids necessary if unable to maintain
BGL to sustain additional required insulin
Paediatric Diabetes 2009; 10 (Suppl. 12): 134-145
Sick day management 3
Insulin pump:
• Check pump / line / site
• Subcutaneous injection may be
appropriate
• Increase basal rate: 150-200%
• Regular correction boluses
Paediatric Diabetes 2009; 10 (Suppl. 12): 134-145
Who and when to call
• Concerns regarding early presentation of
T1DM
• New diagnosis
• Existing patients – issues while reviewing
at GP surgery
0466 655 068