Diabetes in Young Children The Lollipop Brigade

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Diabetes in Young ChildrenThe Lollipop Brigade
Francine R. Kaufman, M.D. Professor of
Pediatrics The Keck School of Medicine of
USC Head, Center for Diabetes and
Endocrinology Childrens Hospital Los Angeles
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What Will Be Discussed

• What are the Targets for Young Children?
• What are the Diabetes Regimens?
• Is There a Greater Risk of Hypoglycemia?
• What are the Developmental Issues ?

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Question
What are the glycemic targets for young children?
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Glycemic TargetsGlucose values are plasma
(mg/mL)
Age Pre-Meal BG HS/Night BG HbA1c
Toddler (0-5 yrs) 100-180 110-200 7.5 8.5
School-age (6-11 yrs) 90-180 100-180 lt8
Adolescent (12-19 yrs) 90-130 90-150 lt7.5
Diabetes Care 28186-212, 2005
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But What are the Goals?

• To give your child a loving, supportive
  environment where each day is taken at a time
  (not each blood sugar)
• Where your child can grow and thrive, learn and
  explore
• Where blood sugars are corrected, not
  interrogated
• Where the family is in balance like a mobile
• And where the long haul is what is important

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Question
Can Intensive Management Be Done Safely in Young
Children?
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CHLA Type 1 DM
Year 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
N 357 414 468 747 887 991 1072 1285 1375 1664 1635
MeanA1c 8.4 8.6 8.5 8.2 8.3 8.5 8.5 8.2 8.3 8.2 8.07
lt7 18 20
7-7.99 46 37 44 51 47 42 42 50 48 29 34
8-10 37 45 42 38 40 44 44 39 40 42 35
gt10 17 18 14 11 13 14 14 11 12 11 11
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HbA1c Statistics for CHLA 2003 Type 1 Diabetes gt
1 year, followed gt 1 yearEnrolled in Long-term
study total n 1375
n Average SD
All patients 1375 8.2 1.6
Males 673 8.2 1.6
Females 702 8.2 1.6
lt 5 61 7.8 1.3
5-10 450 7.9 1.3
11-16 579 8.4 1.8
17-19 gt20 157 127 8.3 1.5 7.4 1.3
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Evaluation of Young Children at CHLAKaufman, et
al, Pediatr Diabetes, 3179-183, 2002.

• Retrospective analysis of data
• 147 children lt 8 years of age
• 2 year data from July 99 July 2001
• Study Question Is HbA1c lt 8.0 associated with
  more severe or assymptomatic hypoglycemia?

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lt8.0 gt8.0 P
Age 5.77 5.67 0.7
Duration 2.56 2.88 0.2
HbA1c 7.0.76 8.7.74 lt0.001
Regimen 2.9 3.0 0.29
U/kg 0.57 0.62 0.15
n 89 58
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Hypoglycemia 5.6 3.4 NS
DKA 1.1 3.4 NS
Competency 4.0 3.6 0.019
within 40.3 29.2 lt0.0001
above 37.1 51.7 lt0.0001
below 22.7 19.1 0.23
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Question
What are the principles of management?
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Diabetes Management Principles

• An effective insulin regimen
• Monitoring of glucose
• As flexible with food and activity as possible
• Must remember
• Young children need routine and rules
• Young children need to develop autonomy
• Young children need to explore and experience
• Young children need to begin to make decisions

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Insulin management

• Fixed dose regimens
• requires scheduled meals and snacks and is not
  flexible enough for most young children
• Basal bolus regimens
• MDI
• useful only if child is willing to take frequent
  injections
• Insulin pumps
• child must be willing to wear the pump

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Basal/Bolus Treatment Program with Rapid-acting
and Long-acting Analogs
Breakfast
Lunch
Dinner
Aspart Aspart Aspart
Lispro Lispro Lispro Glulysene Glulysine
Glulysine
Plasma insulin
Glargine or Detemir
400
1600
2000
2400
400
800
1200
800
Time
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Type 1 Diabetes Serum Insulin Concentrations
Following Subcutaneous Injection of Insulin
Lispro or Human Regular
Injection
Insulin Lispro (n10)
Human Regular (n10)
Serum Insulin Conc. (ng/mL)
Mean SE
0.2 mU/min/kg insulin infusion
Time (minutes)
Heinemann et al. Diabetic Medicine,13625-629,
1996
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Effectiveness of Postprandial Humalog in Toddlers
Rutledge, Chase, Klingensmith et al Pediatrics
100968,97

• Determine if postprandial rapid-acting insulin
  effective
• Subjects lt 5 years old
• Results 2-hour glucose excursions lower with
  postprandial Humalog compared to preprandial
  regular
• Similar to preprandial Humalog

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Insulin Glargine - Pharmacokinetics by Glucose
Clamp
Linkeschowa R, et al. Diabetes.199948(Suppl
1)A97.
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Insulin Detemir Pharmacokinetics by Glucose
Clamp
Glucose Infusion Rate(mg/kg/min)
Elapsed Time (min)
Brunner et al. Exp Clin Endocrinol Diabetes.
2000108.
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GHb, FBG, and Nocturnal Hypoglycemia in Children
With T1DM(Plus Regular Insulin) (N349)
Glargine
NPH
8
6
18
4
of Patients
Change in GHB () and
FBG (mmol/L)
2
6
plt0.05
0
-2
-6
Nocturnal
GHb
FBG
Hypoglycemia
Nocturnal hypoglycemia with FBG lt36 mg/dL, month
2 to study end
Schoenle et al. EASD 1999 Abst 883. Study 3003
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Variable Basal Rate CSII Program
Breakfast
Lunch
Dinner
Bolus
Bolus
Bolus
Plasma insulin
Basal infusion
400
1600
2000
2400
400
800
1200
800
Time
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A1c by Treatment type at CHLA
Year 2000 2001 2002 2003 2004 2005
3 Injections 8.5 1.5 8.4 1.5
Basal- Bolus 9.2 1.7 8.8 1.5 8.4 1.5 8.4 1.4 8.2 1.4
CSII 8.1 1.2 8.1 1.2 7.9 1.2 7.9 1.1 7.8 1.0 7.6 1.2
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Outcomes of Pump Therapy Kaufman, et al,
Diabetes Metabolism and Reviews,2000 6 month
data 130 subjects
PRE POST P value
HbA1c 8.4 1.8 7.8 1.2 0.01
BMI 22.8 4 23.2 5 NS
Hypo-glycemia events/pt/y 0.06 0.03 0.05
DKA events/pt/y 0.15 0.09 0.05
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Results of Insulin Pump Therapy In Young
ChildrenKaufman, et al, Diabetes Spectrum, 2001
Pre Post P Value
HbA1c 8.51.8 7.41.1 0.01
Mean BG 157 64 92 31 0.03
Hypo-glycemia 0.18 0.09 ND
Quality of Life Family Cohesion 82 6 90 5 0.009
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A Randomized Controlled Trial of Insulin Pump
Therapy in Young Children With Type 1 Diabetes
Larry A. Fox, et al Diabetes Care 281277-1281,
2005

• 26 children randomly assigned to current therapy
  or CSII for 6 months, age 46.3 3.2 months
• RESULTS
• Mean HbA1c and BG did not change
• Frequency of severe hypoglycemia, ketoacidosis,
  or hospitalization was similar between groups
• Subjects on CSII had more fasting and predinner
  mild/moderate hypoglycemia
• All subjects continued CSII after study completion

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CSII in Young ChildrenCONCLUSIONS

• CSII is safe and well tolerated in young children
  with diabetes and may have positive effects on
  QOL
• CSII did not improve diabetes control when
  compared with injections
• The benefits and realistic expectations of CSII
  should be thoroughly examined before starting
  this therapy in very young children

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CGMS Tracing
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Use of CGMS to Improve Clinical Care
47 Patients 18 boys, 29 girls Age 11.8 4.6
years Duration 5.5 3.5 years A1c start 8.61
1.51 A1c end 8.36 1.28 p0.01
Kaufman, et al Diabetes Care 242030, 2001.
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Mean Data for All Pts by Sensor
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Result Summary Treatment Changes
Basal (57)
Bolus (43)
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Result Summary Glucose Changes

• HbA1c reduced from 8.1 to 7.8 after only 30 days
• Average glucose decreased from 167 to 156 mg/dl

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Question
Why About the Risk of Hypoglycemia From Intensive
Regimens?
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Intensive Management and HypoglycemiaHbA1c
Association

• Is There Greater Risk of Hypoglycemia at Lower
  HbA1c Levels?
• Or with
• Intensive Regimens?

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Lack of Association Between HbA1c and
Hypoglycemia

• Cox no association in 78 pts with mean
  level of 10.25
• Bhatia, Wolfsdorf incidence of 0.12/pt/yr in
  196 pts with HbA1 11.4 (nl 5.4-7.4)
• Daneman - 16 of 311 pts with HbA1 of 8.7
• Nordfelt, Ludvigsson 146 pts intensive therapy,
  no increase in severe hypoglycemia
• Levine- highest HbA1c tertile, 36/pt/yr
• Kaufman et al Endocrinologist 9342,99

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Analysis of data to determine bedtime BG level

• 167 nights
• Analyze the number of glucose values lt40 and lt 50
  mg/dl through the night

Kaufman FR, et al, J Pediatr. 141625-630, 2002.
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Results

• 45 nights (27) at least one reading lt 40
  mg/dl
• 59 nights (35) at least one reading lt 50
  mg/dl
• For nights lt 100 at HS 86.4 minutes
• No relation to A1c or regimen

Kaufman FR, et al, J Pediatr. 141625-630, 2002.
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Adverse Events in Intensively Treated Children
and Adolescents with Type 1Nordfeldt, Ludvigsson
Acta Pediatr 881184,99

• 139 Subjects, ages 1-18 yrs on MDI
• Mean HbA1c 6.9
• Severe Hypoglycemia - 0.17 events/pt/yr
• Decreased from 1-2 injections
• Correlated with previous severe hypoglycemia
  r.38,plt0.0001
• DKA rate 0.015 events/pt/yr
• MDI effective and safe

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How Well Are We Doing? Metabolic Control in
Patients with DiabetesThomsett, Shield, Batch,
Cotterill J Pediatr Child Health 35479,99
Brisbane

• 268 lt 19 yrs mean 11.2 yrs
• Duration 4.4 0-16 yrs
• Mean HbA1c 8.61.4, range 5.2-14
• Puberty 8.71.5, Prepubertal 8.51.2
• 33 lt 8.0
• HbA1c correlated
• insulin dose, duration
• Not correlated
• severe hypoglycemia, DKA, age, of injections,
  clinic visits

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Prediction of Hypoglycemia

• Good Predictors
• Weighted assessment of low BG for 2-3 wks
• Nighttime BG lt 100-108 mg/dl
• Age lt 5-7 yrs
• gt 2 previous episodes
• Daily dose gt 0.85 U/kg
• Duration gt 2 yrs
• gt 2 consecutive low BG in 2 wks
• gt 4 BG lt 50 mg/dl in 2 wks

• Poor Predictors
• Glycated hemoglobin level
• Number of insulin injections
• Intensive vs conventional treatment

Kaufman et al Endocrinologist 9342,99
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Question
What are the Developmental Issues of Young
Children?
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Babies and Toddlers0-3
Preschool4-6

•  Physical
• Rapid growth
• Erratic eating and sleeping
• Cognitive
• Differentiates self
• Learns language to represent objects/people
• Moral Development
• Judgments based on personal preference

• Physical
• Greater mastery of gross and fine motor skills
• Cognitive
• Egocentric/Classifies objects by a single feature
• Magical thinking/Simple
• Moral Development
• Judgment of good/bad based on punishment/ reward

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Preschool 4-6
Babies and Toddlers0-3

• Emotional and Sense of Self
• Begins to recognize that others' feelings are
  different from own
• Begins to have sense of self
• Social
• Parallel play
• Responsibility
• Total care by parents/ caretakers

• Emotional and Sense of Self
• Sex role differentiation
• Likes to help
• Wants to do things by self
• Deference to authority
• Social
• Cooperative play
• Responsibility
• Child begins to have some responsibility with
  adult assistance

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Preschool 4-6
Babies and Toddlers0-3

• School
• At home/daycare Beginning to learn routines
• Adjusting to different caretakers
• Extra-Curricular Activities
• Babysitters
• Incentives
• Immediate and concrete

• School
• Entering school /Separation from parents
• Learning routines, rules outside of home
• School readiness skills
• Extra-Curricular Activities
• School aftercare
  Playdates
• Incentives
• Immediate and can be symbolic (stickers, stars,
  etc)

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Management Issues     Babies and Toddlers 0-3 Preschool 4-6
Medication Regimen   Choosing a regime to fit eating patterns and lifestyle Getting child to accept injections Requiring supervision in all settings Needing insulin coverage at preschool
Pumps Picking the right catheter Finding the right catheter placement based on fat Using very small basal Choosing a person to be responsible for pump Child wanting to push buttons
Testing Choosing sites for testing Checking overnight Selecting the right meter Having a small sample size Needing to include child in care Progressing to do own checks Avoiding labeling blood glucose "good" or "bad
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CGMS Reducing anxiety about overnight hypoglycemia Evaluating basal bolus balance Checking overnight basal rates or long-acting insulin
Hypo/Hyperglycemia Unable to tell caregiver when high or low May not cooperate with treatment Learning meaning of high/low BG Needing help in identifying symptoms Fearing hypoglycemia
Insulin Administration and Adjustment   Using very small doses Needing quarter units Requiring diluted insulin Minimizing pain and fear Having needle phobia
Health Sick Day Having more frequent vomiting and diarrhea Becoming dehydrated rapidly Needing immunizations Having more outside exposures Increasing number of sick days Contracting childhood illnesses
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Nutrition Breastfeeding makes measuring intake difficult Introducing solid foods Eating habits often erratic Using food as power struggle Grazing eating patterns Using artificial sweeteners may be controversial Needing to involve child in meal plan
Exercise/Activity Growing very rapidly Becoming mobile Continuously in motion Energy level is high
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Case Study 1

• Ana is a two-year old recently diagnosed
• Very spirited toddler
• Fights blood glucose testing by screaming, hiding
  and clenching her fists.
• What should this family do with this challenge?

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Issues by Developmental Status

• Challenges of Diabetes Management Testing
• Factors Contributing to the Challenge
• Normal Growth and Development
• Family Dynamics
• Developmental Tasks
• Moral Development
• Emotional Development
• Incentives

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Solution

• Anas judgment about glucose testing based on
  personal preference she did NOT like
  fingersticks
• Not possible to convince Ana she needs to test
  her blood
• Parents worked together and developed
  matter-of-fact attitude
• Committed to routine, no bargaining, stalling,
  chasing
• Parents provided immediate and concrete
  incentives - a hug, a good job, let her pick
  finger, read book as reward
• Picked meter capable of alternate site testing,
  very small sample and results in five seconds
• Within a very short time, Ana willingly
  participated

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Case 2

• Terrel, 4-year old, type 1 for ten months and
  celiac disease
• BG testing 8-10 times per day, MDI, on
  gluten-free diet with few management problems at
  home
• Problems occurred in pre-school
• In school, regular episodes of hypoglycemia
• Continuous activity
• Not as much blood testing
• Skipped snacks related to less supervision
• What does family do?
•  

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DEVELOPMENTAL ISSUES

• Challenges of Diabetes Management Testing,
  Hypoglycemia, Nutrition
• Factors Contributing to the Challenge Normal
  Growth and Development, School
• Developmental Tasks
• Physical Moral Development Emotional
  Development Responsibility Incentives

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Solution

• At age four, Terrel likes to help, wants to do
  things by himself and adapts well to routines
• He is able to understand the meaning of low blood
  glucose and the importance of eating his
  carbohydrates
• In the school setting, he needs supervision while
  at the same time he needs to learn to take some
  responsibility for participating in testing and
  eating
• Incentives he likes - praise, stickers and
  providing choices

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Solution

• Every day before snack and recess
• BG test
• Choose a gluten-free snack provided by mother
• After the snack
• Pick a small prize from a treasure chest
• Terrel liked being involved
• He was more inclined to eat and check
• Getting a prize an extra incentive
• In a short time, this routine became the norm and
  hypoglycemia resolved

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ConclusionUltimate Goals Of Diabetes Treatment
Sustained Normal Blood Glucose Control Lowest
Possible Incidence of Hypoglycemia
No Long-Term Diabetes Complications No Acute
Diabetes Complications


Best Quality of Life with Diabetes For the child
and your family