ISPAD Debate

Is New Technology Improving Diabetes

Care for Children and Adolescents?
The Pro Argument
Margaret Lawson, MD, MSc, FRCP
Childrens Hospital of Eastern Ontario
University of Ottawa

Disclosure of Conflicts of Interest

I have spoken at Medtronic and Animas sponsored

educational events and participated in a Medtronic
Advisory Board.

I accept coverage of travel expenses only if I have no other

reason to attend the meeting.
I do not accept speaker/consulting honorariums.

I lead an investigator-initiated multicentre study which

uses Medtronic pump and CGM devices (The CGM
TIME Trial).

Supplies for the pilot study were provided by Medtronic Canada

Supplies for the CGM TIME Trial were purchased, at a discounted rate,
from Medtronic Canada.

Assumptions / Definitions

New diabetes technology includes:

BG meters, lancets, pens, clinic-based A1C

(e.g. DCA), smart phones, apps, digital
games, pumps, CGM, closed loop systems

Diabetes care includes:

Metabolic control

A1C, frequency of hypo and hyperglycemia

Patient experience

Patient-reported outcomes (child/parent)

What is the impact of new

technology on diabetes care
for children and adolescents?

Professional and
personal
confidence in
technology

Adapted from Hirose, Beverly & Weinger, Curr Diab Rep, 2012

Impact of new technology

CSII
Improves QOL
+/- improves glycemic control

CGM

Improves glycemic control & QOL, when

used consistently

Closed Loop System

Improves glycemic control & QOL

Insulin Pump Therapy

Effect of CSII on metabolic control

RCTs and systematic reviews show

no benefit of CSII compared to MDI on mean A1C

in children/youth

Prospective and retrospective case-control

studies, clinic-based series & registries show
that pediatric CSII users

have lower A1C than those on injections

are more likely to achieve A1C targets

Insulin Pump Treatment in Danish Children

and Adolescents (Olsen et al)
Danish Childhood
Diabetes Registry
Compared 1493
children/youth who
started CSII to 1846
who stayed on
injections
Mean A1C was
lower amongst CSII
users over 5 year
period in all age
groups (p< 0.0001)

Olsen et al, Pediatric Diabetes, 2014

Registry data: Multinational comparison of

insulin pump use in pediatric T1D (Maahs
ISPAD 2014)

54,768 pediatric T1D patients

2011 & 2012 data from the T1D Exchange (US),
national pediatric diabetes audit (England & Wales),
DPV Initiative (Germany & Austria)

13,966
13,666

A1C
CSII
8.2%
8.5%

A1C
Injections
8.6%
9.0%

873
24,483
1,779

8.2%
7.9%
7.9%

9.0%
8.1%
8.1%

Country

USA
England
Wales
Germany
Austria

A1Cs amongst CHEO pump patients (n=252)

after mean of 45 months
Proportion with A1C < 8%:

% of patients

Proportion with A1C > 8.4%:

Pre pump 32%

On pump 62%

50
45
40
35
30
25
20
15
10
5
0

Pre pump 43%

On pump 17%

Pre pump
On pump

<7%

7-7.9%

8-8.4%

8.5-9%

>9%

Effect of CSII on patient-reported

outcomes for children/youth

Improved QOL (Muller-Godeffroy 2009, Alsaleh

2012)
Increased flexibility in dosage & timing of meals,
sleep schedule (Mednick 2004, Low 2005)
Improved diabetes self-efficacy (McMahon 2005) &
adolescent independence (Low 2005)
Improved treatment satisfaction (Weintrob 2003,
Mednick 2004, Low 2005, Skogsberg 2008)
Positive impact on friendships (Wagner 2005)

Effect of CSII on patient-reported

outcomes for parents

Improved QOL:
Increased flexibility in meal and sleep schedules, dose
adjustments (Mednick 2004, Low 2005)
Fewer mealtime behavior problems (Patton 2009)
Reduced frequency and intensity of parenting stress (MullerGodeffroy 2009)
Decreased fear of hypoglycemia (Muller-Godeffroy 2009,
Haugstvedt 2010)
Higher treatment satisfaction (Weintrob 2003, Mednick 2004, Low
2005, Skogsberg 2008)
More time to focus on their children without diabetes (SullivanBolyai 2004)

Effect of CSII on Diabetes Care for

Children and Adolescents
Pros
Flexibility with meals and sleep
Diabetes self-efficacy
Treatment satisfaction
Safety in school
Quality of life
Parenting stress
Effect on friendships
Fear of hypoglycemia
Decreased injections/pain

Cons
Effort involved

90-95% continue with CSII (Hofer 2010, de Vries 2011, Lombardo

2013)

Effect of CSII on diabetes care

for children and adolescents

Adapted from Hirose, Beverly & Weinger, Curr Diab Rep, 2012

Continuous Glucose Monitoring

Challenges with interpreting CGM

studies

Published studies used early versions of

CGM
3-5 day sensors (Medtronic, Freestyle)
Earlier versions of Medtronic, Dexcom and
Freestyle sensors - less accurate, painful
Earlier versions of pumps did not include
low glucose/threshold suspend (Medtronic),
not integrated with CGM (Dexcom)

Evaluation of current technology

shouldnt be based on studies of
outdated technology

SMBG Technology then vs now

1970

2014

Pump Technology then vs now

1976

2014

CGM Technology then vs now

2006

2014

Effect of CGM on metabolic control

Even when earlier versions used, CGM

had a positive impact on A1C as long as
it was used frequently and consistently

More frequent use of CGM improves

A1C across all ages
The individuals within all three age
groups, including teens and young adults,
who used the device at least 6 days a
week had substantially lower A1C levels
after six months compared with those
who used CGM < 6 days a week

JDRF CGM Study Group, 2008

Effect of Sensor-Augmented Pump Therapy in Children

and Adolescents in the STAR 3 Study (Slover et al)

7-12 year olds

Lower mean A1C

in those
randomized to
start SAP vs.
continuing with
MDI

MDI
SAP

13-18 year olds

Pediatric Diabetes
Volume 13, Issue 1, pages 6-11, 3 JUL 2011 DOI: 10.1111/j.1399-5448.2011.00793.x
http://onlinelibrary.wiley.com/doi/10.1111/j.1399-5448.2011.00793.x/full#f1

MDI
SAP

Effect of Sensor-Augmented Pump Therapy in Children

and Adolescents in the STAR 3 Study (Slover et al)

SAP

Higher
proportion of
SAP subjects
met A1C targets

MDI
7-12 year olds

13-18 year olds

SAP
MDI
Pediatric Diabetes
Volume 13, Issue 1, pages 6-11, 3 JUL 2011 DOI: 10.1111/j.1399-5448.2011.00793.x
http://onlinelibrary.wiley.com/doi/10.1111/j.1399-5448.2011.00793.x/full#f2

Real-Time CGM Use Among Participants in

the T1D Exchange Clinic Registry

17,317 participants
9% had used CGM in
previous 30 days
Those using CGM:

Lower mean A1C in

children & adults
Higher proportion
achieving A1C targets
(lower median A1C)

Wong JC et al, Diabetes Care 2014

Mean (circles) & median (bars) A1C in

CGM users (black) vs non CGM users
(white)

median

Italian Experience with Use of Sensor

Augmented Pump (SAP) in Children and
Adolescents
Retrospective study
of all Italian
pediatric diabetes
centres
Compared 129
children/youth on
SAP (0.6-3 yrs) to
493 on CSII

Scaramuzza et al, DTT, 2011

Effect of CGM on patient-reported

outcomes

Higher QOL and treatment satisfaction for youth and

parents (Beck 2010, Bergenstal 2010, Tansey 2011,
Tsalikian 2012)
Insulin adjustments are easier, and parents feel safer
(Tansey 2013)
Increased comfort in the classroom for parents and
teachers (Benassi 2013)
Fewer missed school days (SWITCH 2014)
Decreased hypoglycemia-related anxiety (Cemeroglu
2010)

Impact of fear of hypoglycemia

Higher A1C amongst those with greater fear of

hypoglycemia (Barnard 2010, Johnson 2013, Hawkes
2014)
Hypoglycemia avoidance behaviours increase A1C
(Barnard 2010)
Parents of T1D children/youth report that poor sleep
has major impact on QOL (Faulkner 1998), school
performance and daily functioning (Adolfsson 2014
ISPAD)
41% of parents report doing regular overnight SMBG
(Cogen 2009)

Low Glucose Suspend

Effect of Sensor-Augmented Insulin Pump Therapy and Automated Insulin

Suspension vs Standard Insulin Pump Therapy on Hypoglycemia in Patients
With Type 1 Diabetes: A Randomized Clinical Trial (Ly et al)

6 month RCT of standard pump therapy vs sensor augmented pump

(SAP) with Low Glucose Suspend (LGS)
65/95 were 4-18 years of age

Moderate & Severe

hypoglycemia (6 month
rate per 100 patient
months)
% of hours with BG <
3.9 mmol/L
Daytime
Overnight
Change in A1C

Insulin Pump (n=49)

SAP with LGS (n=46)

34.2 (22. to 53.3)

9.5 (5.2 to 7.4) *

6.9 (3.9 to10.6)

11.8 (6.4 to 16.2)

4.1 (2.6 to 7.6) **

4.4 (2.1 to 8.8) *

-0.06 (-0.2 to 0.09)

-0.1 (-0.3 to 0.03)

* p < 0.001;

JAMA. 2013;310(12):1240-1247. doi:10.1001/jama.2013.277818

** p = 0.02
Copyright 2014 American Medical
Association. All rights reserved.

Routine Sensor-Augmented Pump Therapy in

Type 1 Diabetes: The INTERPRET Study
SAP = Veo with Low Glucose Suspend

Norgaard, DTT, 2013

Effect of CGM on diabetes care for

children and adolescents

Adapted from Hirose, Beverly & Weinger, Curr Diab Rep, 2012

Closed Loop Systems

Overnight Closed-Loop Insulin Delivery in

Young People With Type 1 Diabetes: A FreeLiving, Randomized Clinical Trial

Randomized crossover trial of 16 adolescents

Sensor-augmented pump +/- overnight closed-loop (3
weeks each) from approx. 930 pm to 730 am
Overnight
Closed-Loop

Pump + CGM

P-value

Mean overnight SG

7.6 mmol/L

8.4 mmol/L

P<0.001

Mean morning SG

6.7 mmol/L

7.9 mmol/L

P< 0.001

% time in target overnight

(3.9-10 mmol/L)

64%

47%

P<0.001

# of nights when SG < 3.5

mmol/L for at least 20
minutes

27/270 (10%)

48/282 (17%)

P=0.01

Hovorka R, Diabetes Care, 37(5):1204-1211, 2014

Night glucose control with MD-Logic

Randomized crossover trial - 15 participants 10-64 years

of age)

4 nights of Closed-Loop & 4 nights on Pump + CGM

Closed Loop

Pump + CGM

P-value

3.8 minutes

48.7 minutes

p<0.022

% time with SG 3.9-10 mmol/L

87%

65%

p=0.005

# hypoglycemia sensor alarms

34

p=0.78

# physician interventions

2/45 nights

12/54 nights

p=0.21

Pre-breakfast Sensor Glucose

7.1 mmol/L

7.8 mmol/L

P=0.52

Time spent SG < 3.9 mmol/L

Moshe Phillip, Pediatric Diabetes, 2014

Outpatient Glycemic Control with a Bionic

Pancreas in Type 1 Diabetes

Randomized crossover study of Bi-hormonal Closed

Loop
32 adolescents at diabetes camp

Each spent 5 days on Closed-Loop & 5 nights on Pump +/- CGM

Closed
Loop

Pump +/CGM

P-value

Mean SG day 2-5 (mmol/L)

7.9+/-0.7

8.8+/-1.5

P=0.004

Mean SG overnight (mmol/L)

6.9+/-0.6

8.7+/-2.0

P<0.001

% time with SG 3.9-10 mmol/L

75.0+/-7.9

64.5+/-14.1

P<0.001

Russell et al, NEJM, 2014

Effect of closed loop systems on

patient-reported outcomes

CLOSED LOOP SYSTEMS AND

TEENAGERS (J. Weissberg-Benchell)

N=16 (night time only; mixed methods)

N=4 (dual hormone; 24-hour use; interview)
Improved BG control
Decreased glycemic variability
Nice to wake up in good control
Less time missing out on things to treat lows
No longer thinking about what/how much to eat
Decreased time thinking about diabetes

Struggles with calibration

Frustration with alarms
Frustration with size of devices/discomfort when
sleeping
Too many devices to manage

Barnard et al., 2014; Weissberg-Benchell, et al., 2014 (not published)

Effect of closed loop systems on

patient-reported outcomes
In 5 days, I never went below 3.9 (70) or above 11.1 (200)
mmol/L
I was free to eat whatever I wanted, wherever I wanted
I ate 2 slices of giant pizza and gelato and my BG never went
above 9.4 mmolL
I went to the gym, worked out, walked 20 minutes to work
and never went low or had to eat
The most amazing thing was that I never felt low or high no
matter what I did I didnt have to worry I just felt normal
GlucoAnna (Beacon Hill Study participant) - www.youtube.com

Effect of closed loop systems on

patient-reported outcomes
Mother of 10 year Gracie, Bionic Pancreas Camp
Study participant:
I had tears in my eyes when I looked at the CGM
graphs. When not on the closed loop, my daughter
had the typical roller coaster ride [with her BGs], but
when on the closed loop, the CGM line was in target
range all the time, except for one occasion when the
closed loop wasnt working

Effect of closed loop systems

on patient-reported outcomes
Christopher 13 years old - Bionic Pancreas Camp
Study participant:
It is like a dream for a diabetic. It takes away the
responsibility. It takes away the high blood sugar and
the low blood sugar. It prevents damage to the body
and it makes you feel better all the time.
It was like I was back to normalIt took away
everythingId love a product like this.

Effect of Closed Loop on diabetes care

for children and adolescents

Adapted from Hirose, Beverly & Weinger, Curr Diab Rep, 2012

Summary

CSII has vastly improved quality of life and treatment

satisfaction for children, adolescents and their parents
CSII has enabled more children and youth to achieve
A1C targets
CGM, when used frequently and consistently,
improves A1C, quality of life and treatment satisfaction
Low glucose suspend reduces risk of significant
hypoglycemia > reduce fear of hypoglycemia
Closed loop systems significantly improve glycemic
control compared to SAP -> reduce burden of
technology and improve quality of life

Impact of new diabetes technology

CSII
Improves

QOL
+/- improves glycemic control

CGM
Improves

glycemic control & QOL, when

used consistently

Closed Loop System

Improves

glycemic control & QOL

Impact of new diabetes technology

CSII
Improves

QOL
Improves glycemic control

CGM
Improves

glycemic control & QOL, when

used consistently

Closed Loop System

Improves

glycemic control & QOL

New technology is improving

diabetes care for children and
adolescents