Prof. Dr.

Thomas Danne
DiabetesZentrum fr Kinder und Jugendliche Auf der Bult, Hannover

Exploring the role of benchmarking

in influencing patient outcomes in
diabetes
From clinical trials to clinical practice: when rubber hits the road
ISPAD 40th Anniversary 2014 Diversity in Diabetes

When rubber hits the road..

ISPAD 1974: 2 years

it is not only
about insulin..

ISPAD 1993: 20 years

but progress in Pediatric Diabetology ISPAD Registered Charity in the

a story of friendship and mentorship
U.K. 2009: 35 years

and comparing outcomes, because....

DIVERSITY in DIABETES is GOOD

Heterogeneity in outcomes is not

adjusted HbA1c (%) as measure
for long-term metabolic control

11

10
9
8
7

10

11

12

13

14

15

16

17

18

19

20

21

SWEET: Vision and Mission

Putting it into perspective

www.diamap.eu
Chapter 4. Clinical science and
care incorporating the development
of a European platform for clinical
research in diabetes (EPCRD)
John J. Nolan (Chair)
Thomas Danne
Michaela Diamant
Gillian Hood
Alexandra Kautzky-Willer
David Kerr
Asmina Mitrakou
Peter M. Nilsson
Giovanni Pacini

DPV-Initiative 1995 2013

(R. Holl et al.) see also ISPAD 2014 Plenary, Saturday 11:45
patient visits:
outpatient:
inpatient:
patients:
pre-DM:
type-1-DM:
type-2-DM:
type-3-DM:
gest.-DM:

2 558 639
2 178 893
379 746
313 907
2 021
85 439
203 852
11 607
10 988

age at diagnosis
< 20 years: 71 829
> 20 years: 242 078

Treatment centers:

393

Pediatric centers adult medicine

Type of Insulin Regimen (%)

German Annual Health Reporting: Multiple Injection

Therapy and Pumps have become the Gold
Standard for Children with Diabetes in Germany

Inj./day

p.138-147

Inj./day

Inj./day

Insulin pumps

year

German Benchmarking 1995 to 2009

HbA1c improves by 0.04% per year,
Severe hypoglycemia going down

Benchmarking challenges in the future

different hormones, algorithms and
technology

DREAM

Courtesy Roman Howorka, Cambridge

http://diatribe.us/issues/57/learning-curve

Trial and benchmarking challenges:

18 month development cycle of
diabetes technology

Closed loop multicenter

multinational studies are needed

Summary of published AP
results for Time in Range

Size in range:

DREAM publications
19 Feasability
41 Pilot
20 Hospital
6 Camp
21 - Home

The Issue of Center Differences

The Hvidre-Group

Hvidoere: Significant differences in avarage HbA1c

between leading international pediatric diabetes
centers
Belgium
11

adjusted HbA1c (%) as measure

for long-term metabolic control

mean HbA1c (year 2001,adjusted for age, duration and

gender) 8.62 0.03 %

10
HVIDOERE (2007)2 N=2,100 8.2%

SEARCH (2009)3 N=2,999

8.3%

1 2 3

6 7

8 9 10 11 12 13 14 15 16 17 18 19 20 21

1. Danne et al. (2001) Diabetes Care

2. de Beaufort et al. Diabetes Care 2007;30:224550;
3. Petitti et al. J Pediatr 2009;155:66872

center number

Canada
Denmark
Finland
France
Germany
Italy
Japan
Macedonia
Netherlands
Norway
Portugal
Spain
Sweden
Switzerland
U.K.
U.S.A.

Poster 47 (Tour 6, Today 14:00): Disease management

and treatment characteristics in 5960 children, adolescents
and young adults with Type 1 Diabetes (T1D):
the global TEENs study
Thomas Danne, Lori Laffel, Catherine Domenger, Valrie Pilorget, Christophe Candelas, Moshe Phillip, Carmen Mazza, Barbara
Anderson, Ragnar Hanas, Sheridan Waldron, Roy Beck, Chantal Mathieu, Franoise Calvi-Gries

Data were collected in 219 centers worldwide (N=5960 patients)

youth had a mean (SD) duration of diabetes of 6.9 (4.4) years:
812 y/o, 4.5 years [2.7]; n=1724
1318 y/o, 6.6 years [3.8]; n=2854
1925 y/o, 10.6 years [4.9] n=1382

Overall, the mean HbA1c was 8.5 1.8%

for the sample
Only 28% of participants attained HbA1c
target, with the proportion attaining
target decreasing with age

Overall

812

1318

1925

y/o

y/o

y/o

8.5

8.3

8.6

8.4

1.8

1.6

1.9

1.9

mmol/mol

69.4

67.2

70.5

68.3

19.7

17.5

20.8

20.8

Mean SD
HbA1c

In good centers a good HbA1c is present in patients with

short and long diabetes duration

mean HbA1c of patients with a

diabetes duration above 3 years

11

10

The first year of diabetes

is important

1995 R=0.83 p<0.001

1998 R=0.77 p<0.001

7
8
9
10
11
mean HbA1c of patients with a diabetes duration below 3 years
Danne et al. (2001) Diabetes Care

How benchmarking has changed our clinical

practice:
Prevention: The importance of a good start at onset
New onset cases per treatment year

2012 n=75 new cases

Largest center in Germany

Treatment year

New cases per center in Germany

In 2012

How benchmarking has changed our clinical

practice:
The importance of a good start at onset
DKA at onset / year

We put all new onset

cases on i.v. insulin

Inpatient days at onset

Treatment year

Comparison: Inpatient
days at onset

How benchmarking has changed our clinical

practice:
we see patients every 8 to 6 weeks and intervene early
Above German average (3.5) outpatient visits per patient per year (5.6)

outpatient visits per patient per year

Ten oclock a.m. visit on the ward

Pediatric Team Member Targets & Glycaemic

Control Swift et al. Ped Diabetes (2012) 13
<7.0

100.0
100.0
20.0
16.7
52.4

33.3
20.0

7-7.4

7.5-7.9

40.
100.0
83.3

40.0

42.9
100.
100.0
60.0
40.0
44.4
60.0
60.0
80.0
20.0
33.3

20.0

57.1
4.8

40.0
40.0
22.2
20.0
20.0
20.0
44.4
75.0
60.0
60.0

8-9.0

No specific
Target

42.9

10.0

10.0

20.0
20.0
60.0
22.2
100.0
25.0
20.0
20.0

20.0

Centre Mean
HbA1c
7.40
7.58
7.68
7.74
7.80
7.89
8.00
8.02
8.08
8.18
8.23
8.24
8.27
8.36
8.45
8.59
8.76
8.82
8.83
8.98
9.05

Wednesday 2:00 3:00 p.m.

Team meeting

Does a low average HbA1c in the outpatient

department relate to more hypos ?
Severe Hypo per 100 patient years

Severe Hypo vs HbA1c: German centres

ISPAD / IDF: Target indicators of

Glycemic Control
Ideal

Optimal

Clinical
assessment

Suboptimal

High Risk
(action required)

Polyuria
Polydipsia

Weight loss

Blurred vision
Cramps
Poor growth
Delayed puberty
Skin or genital
infections

Poor school
attendance

Signs of vascular
complications

Enuresis
Not raised

Raised BG

Low BG

Few mild hypos

No severe hypos

Few mild,
no severe
hypos

Preprandial or
fasting BG (mmol/l)

3.6 - 6.1

4.0 - 7.0 (2)

>8.0

>9.0

Post-prandial BG
(mmol/l)

4.4 - 7.0

5.0 - 11.0

11.1 - 14.0

>14.0

Nocturnal BG
(mmol/l)

3.6 - 6.0

Not < 3.6

<3.6 or >9.0

<3.0 or >11.0

<6.05

< 7.5

7.6 9.0

>9.0

Biochemical
assessment

(1)

(2)

These target indicators must

be adjusted according to
individual circumstances
If fasting morning BG is <4
consider the possibility of
antecedent nocturnal
hypoglycaemia

No
symptoms

Episodes of severe hypoglycaemia

(Unconscious convulsions)

(1)

HbA1c (%)
(DCCT standardized)

Plasma blood glucose and A1C goals for type 1 diabetes by age group
Values by age

Before meals

Bedtime/overnight

A1C

Rationale

Toddlers and
preschoolers
(<6 years)

100180

110200

<8.5 (but >7.5)

High risk and

vulnerability to
hypoglycemia

School age (6
12 years)

90180

100180

<8%

Risks of hypoglycemia
and relatively low risk
of complications prior
to puberty

Adolescents
and young
adults (1319
years)

90130

90150

<7.5%*

Risk of hypoglycemia
Developmental and
psychological issues

Key concepts in setting glycemic goals:

Goals should be individualized and lower goals may be reasonable based on benefitrisk assessment
Blood glucose goals should be higher than those listed above in children with frequent hypoglycemia or
hypoglycemia unawareness
Postprandial blood glucose values should be measured when there is a disparity between preprandial blood
glucose values and A1C levels

Silverstein J, Klingensmith G, Copeland K, Plotnick L, Kaufman F, Laffel L, Deeb L,

Grey M, Anderson B, Holzmeister LA, Clark N; American Diabetes Association.
Care of children and adolescents with type 1 diabetes: a statement of the American
Diabetes Association. Diabetes Care. 2005 Jan;28(1):186-212.

The new American type

1 diabetes guideline.
A consequence of
benchmarking ?

Harmonizing Targets
In light of the above
evidence, the ADA will
harmonize its glycemic goals
with those of ISPAD (as well
as the Pediatric Endocrine
Society and the International
Diabetes Federation) by
using a single A1C goal of
<7.5% across all pediatric
age groups.

New T1D ADA targets:the

evidence

More recent investigation and active ongoing research have dispelled

concerns regarding hypoglycemia and neurocognitive dysfunction. Studies
assessing neurocognitive function have failed to identify adverse effects
of a past history of hypoglycemia in the young child; however, as
always,further research needs to be conducted.
There are also questions regarding the premise that the years prior to
puberty do not impact the future risk of complications (51). Many
investigators and clinicians believe in the importance of controlling blood
glucose and A1C levels prior to puberty to reduce risk for both micro- and
macrovascular complications. Additionally, there is burgeoning evidence
that elevated blood glucose levels and glycemic variability in the very young
child with diabetes may produce adverse outcomes in the short term on
neurocognitive function and the central nervous system (52,53). These
recent articles suggest that hyperglycemia and glycemic variability are
associated with changes in the central nervous system white matter,
as observed in MRI scans.

The impact of bechmarking:

DPV vs. T1DX

40 years of ISPAD:
Assessment of Quality of Care

Data collection
Discussion
Comparison

SWEET: Establishing Centers of Reference (COR) &

Collaborative Centers, Benchmarking and Joint Scientific
Projects

EU Public Health project April

2008 March 2011
Now a registered legal entity
(SWEET e.V.)
www.sweet-project.eu

Electronic health records merge into

an anomyzed database
local IT-system
data from a national
database

DPV
software

Diamax

Reinhard Holl Michael Witsch

Benchmarking
SWEETreport

Scientific projects
Publications

Technical Basis:
Electronic health records kept
separately by treatment center

VFP
C#

Standalone PC
Client-ServerInstallation

RemoteAccess /
TerminalServer

SWEET Data Check

Peer review / Audit Cooperation of SWEETwith

the NHS Peer-Review Programme

Upload self-assesment
Peer-review reports
Check your status for benchmarking

HbA1c: raw data, median of

patients median, T1DM, all ages
10.00
9.15
9.00
8.00
7.05

8.00 8.00 8.10 8.10

7.80 7.90
7.73
7.70
7.70
7.65
7.60
7.40 7.55 7.55
7.20 7.30 7.30 7.30

8.30

8.50 8.50 8.60

HbA1c (%)

7.00
6.00
5.00
4.00
3.00

2.00
1.00
0.00

7
71
n=
2
0
00
16
10 n=
T
4
6
02 38
=
10
n
D
6
7
01
19
10
n= 5
U
07 12
=
00
I1 2n 1
02 21
10 n=
E
9
87
01
10 n=4
H
5
7
01
=1
10
n
P
7
3
17
02
1
10 n=
E
6
2
00 40
=
10
n
R
1
15
01
10
=2
n
O
7
9
01
35
10 n=
L
0
1
02 43
10 n=
G 13
36
0
=2
10
n
D
1
98
00
=1
10
n
M
2
1
01
54
10
n=
B
3
40
00
10 n=4
W
8
9
01 42
10 n=
A
8
3
00 24
=
10
n
Q
9
68
00
7
10 n=
K
1
3
02 22
=
10
n
N
4
01
5
10 n=7
C
0
1
01 17
10 n=
J
5
00 18
10 n=
F
4
00
10

HbA1c-RAW:
HbA1c-values WITHOUT ANY STANDARDIZATION: in particular this view is useful regarding your own values. You
can easily compare them with your own statistics

HbA1c_MedianofMEDIANpercentre_allAge_RAW.xls

HbA1c Histograms, T1DM

Centre 1

Centre 2

HbA1c Histograms, T1DM

Centre 3

Centre 4

10
01
2

10 n=0
00
4
J
n
10
0 1 =0
I1 0n
=7
00
5
07
H
n=
10
01 171
9
G
10 n=1
02
97
0
C
n=
10
01 364
4
D
10 n=2
01
14
3
M
n=
10
00 313
1
N
10 n=1
01
02
1
O
10 n=7
01
68
1
Q
n=
10
00 358
8
R
10 n=4
00
20
6
D
n=
10
02 759
4
A
n=
10
01 157
8
P
10 n=4
01
26
5
F
n
=
10
00 442
5
T
10 n=1
00
71
2
E
n=
10
65
02
8
2
L
n
10
=
01 119
7
K
n=
10
00 160
9
U
n=
10
01 211
6
W
10 n=3
00
83
3
n
E
=5
10
14
02
3
n=
16

SDS

Benchmarking: it is not only

about HbA1c

BMI-SDS: T1DM, patients 0-18y,

WHO 2007 reference

1.00

0.90

0.80
0.75 0.76

0.70
0.63 0.64

0.60

0.50
0.44 0.44 0.44 0.44

0.40

0.30
0.30

0.20

BMI_SDS_perCentre_pres.xls
0.46
0.48 0.49
0.51
0.54
0.56
0.59

0.40 0.41

0.32

0.26

0.19

0.12

0.10

0.00

SWEET Science:
Poster 25 Today 14:00: Seasonality
of Diabetes-onset Across Europe
lessons from the SWEET database

Onset:

Vazeo, Witsch, Kordonouri, Holl et al see Poster

Europe - North

Birth:

Europe - Central

Europe - South

Exchanging Best practices:

examples of young children
comprehensive initial education

Development of EU wide
Certified
Diabetes Educator Course
(EU-CDEC)

Become part of the

European Reference
networks

SWEET-Meetings
twice a year:

..or you
this could be you

23 certified SWEET Centers 2014

www.sweet-project.eu
Belgium
Croatia
Czech Republic
Denmark
France
Germany
Greece
Hungary
Italy
Luxembourg
Poland
Portugal
Romania
Slovenia
Sweden
The Netherlands
Turkey
United Kingdom

16 more SWEET Centers expected 2015

www.sweet-project.eu
Bulgaria
Canada
Denmark
Greece
India
Ireland
Israel
Latvia
Lithuania
Norway
Poland
Portugal
Spain
United Kingdom

Join us !

Thank you for your attention!

Thank you
to my team at the Kinder
und Jugendkrankenhaus AUF
DER BULT in Hannover
and
to all the children,
adolescents and parents that
gave us so many insights into
their daily lives through their
reports and the participation
in studies.