Diabetes in Young Children
The 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
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 ?
Question
What are the glycemic targets for young
children?
Glycemic Targets
Glucose 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
<8%
Adolescent
(12-19 yrs)
90-130
90-150
<7.5%
Diabetes Care 28:186-212, 2005
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
Question
Can Intensive Management Be Done Safely in
Young Children?
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
Mean 8.4 8.6 8.5 8.2 8.3 8.5 8.5 8.2 8.3 8.2 8.07
A1c
% <7
18 20
% 7- 46
7.99
% 37
8-10
% 17
>10
37
44
51
47
42
42
50
48
29
34
45
42
38
40
44
44
39
40
42
35
18
14
11
13
14
14
11
12
11
11
HbA1c Statistics for CHLA 2003 Type 1:
Diabetes > 1 year, followed > 1 year
Enrolled 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
<5
61
7.8 ± 1.3
5-10
450
7.9 ± 1.3
11-16
579
8.4 ± 1.8
17-19
>20
157
127
8.3 ± 1.5
7.4 + 1.3
Evaluation of Young Children
at CHLA
Kaufman, et al, Pediatr Diabetes, 3:179-183, 2002.




Retrospective analysis of data
147 children < 8 years of age
2 year data from July 99 – July 2001
Study Question : Is HbA1c < 8.0 associated
with more severe or assymptomatic
hypoglycemia?
<8.0
>8.0
P
Age
5.77
5.67
0.7
Duration
2.56
2.88
0.2
HbA1c
7.0+.76
8.7+.74
<0.001
Regimen
2.9
3.0
0.29
U/kg
0.57
0.62
0.15
n
89
58
Hypoglycemia
5.6
3.4
NS
DKA
1.1
3.4
NS
Competency
4.0
3.6
0.019
% within
40.3
29.2
<0.0001
% above
37.1
51.7
<0.0001
% below
22.7
19.1
0.23
Question
What are the principles of management?
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

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
Basal/Bolus Treatment Program with
Rapid-acting and Long-acting Analogs
Plasma insulin
Breakfast
Lunch
Dinner
Aspart
Aspart
Lispro
Lispro
Glulysene Glulysine
Aspart
Lispro
Glulysine
Glargine
or
Detemir
4:00
8:00
12:00
16:00
Time
20:00
24:00
4:00
8:00
Type 1 Diabetes: Serum Insulin Concentrations
Following Subcutaneous Injection of Insulin Lispro or
Human Regular
3.0
2.5
Injection
Insulin Lispro (n=10)
Human Regular (n=10)
Serum 2.0
Insulin
Conc. 1.5
(ng/mL)
1.0
Mean + SE
0.5
0.2 mU/min/kg insulin infusion
0.0
-60
0
60
Meal
120 180 240 300 360 420 480
Heinemann et al. Diabetic Medicine,13:625-629, 1996
Time (minutes)
Effectiveness of Postprandial
Humalog in Toddlers
Rutledge, Chase, Klingensmith et al Pediatrics 100:968,97




Determine if postprandial rapid-acting insulin
effective
Subjects < 5 years old
Results: 2-hour glucose excursions lower with
postprandial Humalog compared to preprandial
regular
Similar to preprandial Humalog
Glucose Infusion Rates
(mg/kg/min)
Insulin Glargine - Pharmacokinetics by
Glucose Clamp
6
NPH
5
4
Glargine
0.4 U/kg
3
2
Placebo
1
0
0
2
4
6
8 10 12 14 16 18 20 22 24 26 28 30
Hours
Linkeschowa R, et al. Diabetes.1999;48(Suppl
1):A97.
Insulin Detemir – Pharmacokinetics by
Glucose Clamp
Glucose Infusion Rate
(mg/kg/min)
2.0
1.5
1.0
DetemirHigh
DetemirLow
0.5
Placebo
0.0
100
100
300
500
700
900
1100
1300
1500
Elapsed Time (min)
Brunner et al. Exp Clin Endocrinol Diabetes.
2000;108.
21
GHb, FBG, and Nocturnal Hypoglycemia
in Children With T1DM
(Plus Regular Insulin) (N=349)
NPH
8
6
18
4
2
p<0.05
6
% of Patients
Change in GHB (%) and
FBG (mmol/L)
Glargine
0
-2
-6
Nocturnal
Hypoglycemia*
*Nocturnal hypoglycemia with FBG <36 mg/dL, month 2 to study end
GHb
FBG
Schoenle et al. EASD 1999; Abst 883. Study 3003
Variable Basal Rate:
CSII Program
Plasma insulin
Breakfast
Lunch
Dinner
Bolus Bolus
Bolus
Basal infusion
4:00
8:00
12:00
16:00
Time
20:00
24:00
4:00
8:00
Year
A1c by Treatment type at
CHLA:
2000
2001
2002
2003
3
Injections
BasalBolus
CSII
8.1
± 1.2
2004
2005
8.5
± 1.5
8.4
± 1.5
9.2
± 1.7
8.8
± 1.5
8.4
± 1.5
8.4
± 1.4
8.2
± 1.4
8.1
± 1.2
7.9
± 1.2
7.9
± 1.1
7.8
± 1.0
7.6
± 1.2
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
Hypoglycemia
0.06
0.03
0.05
0.15
0.09
0.05
events/pt/y
DKA
events/pt/y
Results of Insulin Pump Therapy
In Young Children
Kaufman, et al, Diabetes Spectrum, 2001
Pre
Post
P Value
HbA1c
8.5+1.8
7.4+1.1
0.01
Mean
BG
157+ 64
92 + 31 0.03
Hypoglycemia
0.18
0.09
ND
Quality of
Life
Family
Cohesion
82 + 6
90 + 5
0.009
A Randomized Controlled Trial of Insulin Pump Therapy
in Young Children With Type 1 Diabetes
Larry A. Fox, et al Diabetes Care 28:1277-1281, 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

CSII in Young Children
CONCLUSIONS
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

CGMS Tracing
Use of CGMS to Improve
Clinical Care
13
47 Patients
29 girls
Age
years
11.8 ± 4.6
Duration
years
5.5 ± 3.5
A1c start
8.61 + 1.51
A1c end
8.36 + 1.28
HbA1C (%)
18 boys,
12
11
10
9
8
7
6
Baseline
3 months post
Sensor
p=0.01
Kaufman, et al: Diabetes Care 24:2030, 2001.
Mean Data for All Pts by Sensor
350
# of readings
mean glucose level
SD mean glucose
300
250
200
150
100
50
0
Ist Sensor
3rd Sensor
5th Sensor
7th Sensor
Result Summary:
Treatment Changes
Basal (57%)
Bolus (43%)
50%
45%
40%
42%
35%
30%
30%
25%
20%
15%
15%
10%
9%
5%
4%
0%
Increase Basal
Rate
Decrease
Basal Rate
Increase in
CHO Dose
Increase in
Correction
Dose
Percent of Total Changes
Other
Result Summary: Glucose
Changes
Subject
#1
#2
#3
#4
#5
#6
#7
#8
#9
#10
A1c Start
7
6.9
9.4
7.5
7
8.3
9.3
8.8
8.2
8.3
A1c End
7.3
6.7
8.7
7.3
6.7
7.7
9.4
7.7
8.2
8.2
Daily Glucose
Sensor 1-2
(First Week)
194 143 187 154 153 175 183 138 171 174
± 55 ± 34 ± 23 ± 14 ± 23 ± 24 ± 21 ± 21 ± 31 ± 46
Daily Glucose
Sensor 6-7
(Last Week)
182 120 172 163 145 138 167 123 177 169
± 26 ± 21 ± 22 ± 38 ± 38 ± 28 ± 24 ± 25 ± 20 ± 31


HbA1c reduced from 8.1 to 7.8% after only 30 days
Average glucose decreased from 167 to 156 mg/dl
Question
Why About the Risk of Hypoglycemia
From Intensive Regimens?
Intensive Management and
Hypoglycemia
HbA1c Association
Is There Greater Risk of Hypoglycemia at
Lower HbA1c Levels?
Or with
Intensive Regimens?
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
Levinehighest HbA1c tertile,
36/pt/yr
Kaufman et al Endocrinologist 9:342,99
Analysis of data to determine
bedtime BG level

167 nights

Analyze the number of glucose values
<40 and < 50 mg/dl through the night
Kaufman FR, et al, J Pediatr. 141:625-630, 2002.
Results

45 nights (27%) – at least one reading
< 40 mg/dl
59 nights (35%) – at least one reading
< 50 mg/dl
For nights < 100 at HS – 86.4 minutes

No relation to A1c or regimen


Kaufman FR, et al, J Pediatr. 141:625-630, 2002.
Adverse Events in Intensively Treated
Children and Adolescents with Type 1
Nordfeldt, Ludvigsson Acta Pediatr 88:1184,99



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,p<0.0001

DKA rate 0.015 events/pt/yr

MDI effective and safe
How Well Are We Doing? Metabolic
Control in Patients with Diabetes
Thomsett, Shield, Batch, Cotterill J Pediatr & Child Health 35:479,99 Brisbane

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268 < 19 yrs
mean 11.2 yrs
Duration 4.4
0-16 yrs
Mean HbA1c
8.6+1.4%, range 5.2-14%
Puberty 8.7+1.5%, Prepubertal 8.5+1.2%
33% < 8.0%
HbA1c correlated


insulin dose, duration
Not correlated

severe hypoglycemia, DKA, age, # of injections, # clinic
visits
Prediction of Hypoglycemia
Good Predictors







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Weighted assessment of
low BG for 2-3 wks
Nighttime BG < 100-108
mg/dl
Age < 5-7 yrs
> 2 previous episodes
Daily dose > 0.85 U/kg
Duration > 2 yrs
> 2 consecutive low BG in
2 wks
> 4 BG < 50 mg/dl in 2
wks
Poor Predictors



Glycated hemoglobin level
Number of insulin
injections
Intensive vs conventional
treatment
Kaufman et al Endocrinologist 9:342,99
Question
What are the Developmental Issues of
Young Children?
Babies and Toddlers
0-3
Physical
 Rapid growth
 Erratic eating and sleeping
Cognitive
 Differentiates self
 Learns language to represent
objects/people
Moral Development
 Judgments based on personal
preference
Preschool
4-6
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
Babies and Toddlers
0-3
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
Preschool
4-6
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
Babies and Toddlers
0-3
Preschool
4-6
School
 At home/daycare Beginning
to learn routines
 Adjusting to different
caretakers
School
 Entering school /Separation
from parents
 Learning routines, rules outside
of home
 School readiness skills
Extra-Curricular Activities
 Babysitters
Extra-Curricular Activities
 School aftercare
Playdates
Incentives
 Immediate and can be
symbolic (stickers, stars, etc)
Incentives
 Immediate and concrete
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”
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
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
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?
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
Solution







Ana’s 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
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?
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
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
Solution

Every day before snack and recess



After the snack



Pick a small prize from a treasure chest
Terrel liked being involved
He was more inclined to eat and check


BG test
Choose a gluten-free snack provided by mother
Getting a prize an extra incentive
In a short time, this routine became the norm and
hypoglycemia resolved
Conclusion
Ultimate 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