experiences from the hvidøre study group on childhood diabetes. henrik b. mortensen, department of...
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Experiences from the Hvidøre Study Group on Childhood
Diabetes.
Henrik B. Mortensen, Department of Henrik B. Mortensen, Department of Paediatrics, Glostrup University Paediatrics, Glostrup University
HospitalHospital
The Hvidøre Study Group on Childhood Diabetes The purpose of the group to improve the The purpose of the group to improve the
management of children and adolescents management of children and adolescents with type 1 diabetes on a worldwide scale by:with type 1 diabetes on a worldwide scale by:
Stimulating research Stimulating research Improve the quality of careImprove the quality of care Disseminate knowledge of childhood Disseminate knowledge of childhood
diabetes diabetes
The Hvidøre Study Group on Childhood Diabetes The task for the group is to establish a The task for the group is to establish a
research network to carry out multicenter research network to carry out multicenter investigations to share and compare data on investigations to share and compare data on childhood diabetes. childhood diabetes.
The Study Group consist of medical doctors The Study Group consist of medical doctors all specialized in paediatrics from 22 centres all specialized in paediatrics from 22 centres from 18 countries in Europe, North America from 18 countries in Europe, North America and Japanand Japan
Members of the Hvidøre Study Group on Childhood Diabetes
H.B. Mortensen, DenmarkH.B. Mortensen, Denmark S. Greene, U.K. S. Greene, U.K.
H.-J. Aanstoot, Netherlands H.-J. Aanstoot, Netherlands H.M.C.V. Hoey, Ireland H.M.C.V. Hoey, Ireland
J. Aman, Sweden J. Aman, Sweden E.A. Kaprio, Finland E.A. Kaprio, Finland
J.A. Atchison, USA J.A. Atchison, USA M. Kocova, Macedonia M. Kocova, Macedonia
F. Chiarelli, ItalyF. Chiarelli, Italy P. Martul, Spain P. Martul, Spain
D. Daneman, Canada D. Daneman, Canada N. Matsuura, Japan N. Matsuura, Japan
T. Danne, GermanyT. Danne, Germany O. Søvik, Norway O. Søvik, Norway
H. Dorchy, Belgium H. Dorchy, Belgium K.J. Robertson, U.K K.J. Robertson, U.K
B. Dinesen, Denmark B. Dinesen, Denmark E.J. Schoenle, Switzerland E.J. Schoenle, Switzerland
P. Garandeau, FranceP. Garandeau, France P.G.F. Swift, U.K P.G.F. Swift, U.K
R.W. Holl, GermanyR.W. Holl, Germany R.M. Tsou, Portugal R.M. Tsou, Portugal
P. Hougaard, DenmarkP. Hougaard, Denmark M. Vanelli, Italy M. Vanelli, Italy
Publications
Comparison of metabolic control in a cross-sectional study Comparison of metabolic control in a cross-sectional study of 2.873 children and adolescents with IDDM from 18 of 2.873 children and adolescents with IDDM from 18 countries. Diabetes Care 1997;20:714-720.countries. Diabetes Care 1997;20:714-720.
Insulin management and metabolic control of Type 1 Insulin management and metabolic control of Type 1 diabetes in childhood and adolescence in 18 countries. diabetes in childhood and adolescence in 18 countries. Diabetic Medicine 1998; 15:752-759.Diabetic Medicine 1998; 15:752-759.
Persistent center differences over 3 years in glycemic Persistent center differences over 3 years in glycemic control and hypoglycemia in a study of 3,805 children and control and hypoglycemia in a study of 3,805 children and adolescents with type 1 diabetes.adolescents with type 1 diabetes. Accepted for publication: Accepted for publication: Diabetes CareDiabetes Care
Good Metabolic Control is Associated with Better Quality of Good Metabolic Control is Associated with Better Quality of Life in 2,101 Adolescents with Type 1 Diabetes. SubmittedLife in 2,101 Adolescents with Type 1 Diabetes. Submitted
The Hvidøre Study Group on Childhood Diabetes Metabolic control and insulin management in the Metabolic control and insulin management in the
real worldreal world
The relation between HbAThe relation between HbA1c1c and insulin regimens and insulin regimens over a three year periodover a three year period
Metabolic control and quality of lifeMetabolic control and quality of life
Study designMulticenter cross-sectional investigation with 22 Multicenter cross-sectional investigation with 22 participating paediatric departments from 18 countriesparticipating paediatric departments from 18 countriesin Europe, Japan and North America.in Europe, Japan and North America.
The HbAThe HbA1c1c concentration was determined once and concentration was determined once andanalyzed both locally and centrally at The Stenoanalyzed both locally and centrally at The StenoDiabetes Center, Denmark.Diabetes Center, Denmark.
Age, sex, duration of diabetes, height, body weight,Age, sex, duration of diabetes, height, body weight,insulin regimen and number of severe hypoglycaemicinsulin regimen and number of severe hypoglycaemicevents were recorded.events were recorded.
HbA1c analysisSamples were collected locally using the Biorad- HbASamples were collected locally using the Biorad- HbA1c1c
Sample Preparation Kit and mailed to the centralSample Preparation Kit and mailed to the centralLaboratoryLaboratory
Automatic high pressure liquid chromatographyAutomatic high pressure liquid chromatography(Bio- Rad- Variant(Bio- Rad- VariantTMTM))
Normal range is 4.4 – 6.3 (mean 5.4)%Normal range is 4.4 – 6.3 (mean 5.4)%The interassay SD is 0.15%The interassay SD is 0.15%
HbAHbA1c1c results were found to be 0.3% higher than the results were found to be 0.3% higher than the DCCT level by direct sample exchangeDCCT level by direct sample exchange
2 inj.
11
10
9
8
7
62015
HbA
(%
)1C
1050
1.31.21.11.00.90.80.70.60.50.40.3
201510
Insu
lin d
ose
(U/k
g/24
h)
***
**
50
2524232221201918171615
2015
BM
I (k
g/m
)2 *
**
**
10Age (years)Age (years)
50
3 inj.4+ inj.
Female
50
40
30
20
10
02015
MalesFemales
Percentage of childrenusing any pre-mixed insulin
10Age (years)
50
11
10
9
8
7
62015
Short + intermPremixed
Two injections per day
** *
HbA (percent)1C
10Age (Years)
50
Summary
In 3000 children and adolescents only one third had HbAIn 3000 children and adolescents only one third had HbA1c1c values < 8%values < 8%
HbAHbA1c1c increased during maturation of both genders increased during maturation of both genders irrespective of insulin regimenirrespective of insulin regimen
HbAHbA1c1c differed significantly across 22 centres irrespective of differed significantly across 22 centres irrespective of insulin regimen insulin regimen
Adolescent females on 4 or more insulin injections had Adolescent females on 4 or more insulin injections had significantly higher insulin dose and BMI.significantly higher insulin dose and BMI.
The rate of severe hypoglycaemia was related to younger The rate of severe hypoglycaemia was related to younger
age and lower HbAage and lower HbA1c1c level. level.
The Hvidøre Study Group on Childhood Diabetes Metabolic control and insulin management in Metabolic control and insulin management in
the real worldthe real world
The relation between HbAThe relation between HbA1c1c and insulin and insulin regimens over a three year periodregimens over a three year period
Metabolic control and quality of lifeMetabolic control and quality of life
Objectives
To investigate if blood glucose control changes from 1995 to 1998 in an international cohort of children with type 1 diabetes aged 11-18 years in 1998
To analyse differences in blood glucose control among centres in the 3 year period and relate possible changes to insulin regimen and daily insulin dosage
To assess centre differences in incidence of severe hypoglycaemic events
Flow diagram for patients participating in the international cohort investigation
229 DM duration < 1 year in 1995
55 Transferred to other Paed.Clinic178 Transferred to Adult Clinic223 Other (narrow window)105 Unknown 30 Declined
1,767 patients age 8-15 years in ‘95
This study group consisted of891 patients
55 Insufficient data
1 Dead
HbA1c in 1998 (grand mean): 8.9% (1.6%)
Distribution of HbA1c
% o
f pa
tient
s
30
25
20
15
10
5
0
35
40
< 5 5-6 6-7 7-8 8-9 9-10 10-11 11-12 12-13 > 13
HbA1c (%)
Year 1995 1998
HbA1c in 1995 (grand mean): 8.7% (1.6%)
Injection frequency70
60
50
40
30
20
10
0 1995 1998
Number of injections
2
3+
Year
HbA1c in 1995 (grand mean): 8.7% (1.6%)
HbA1c in 1998 (grand mean): 8.9% (1.6%)
% o
f pati
ents
HbA1c by centre for ‘95 and ‘98
The 1995 baseline level, and the three year change for HbA
1c for the 21 centres.
6
7
8
9
10
11
12
Centers sorted by HbA 1c in 1995
HbA1c
percent
*
*****
Centre changes in HbA1c adjusted for sex, age, duration of type 1 diabetes
Number ofinjections HbA1c %
- o ++ 2 6 3o 0 9 1- 0 0 0
Insulin dose HbA1c %
1 7 11 8 30 0 0
+o-
- o +
+) significant increase, o) no significant change, -) significant decrease
Rate of severe hypoglycaemic events according to the Poisson model
Age (13 yr), duration (5 years)
Inci
denc
e p
er 1
00 p
atie
nts
year
s 20
15
10
5
0 5 6 7 8 9 10 11 12 13 14 15
Individual HbA1c (per cent)
above
HbA1c (grand mean): 8.9% (1.6%)
Centres significantly:
different
below
Centres not significantly:
Summary
No significant change in HbANo significant change in HbA1c 1c for the 3 year for the 3 year period despite the use of three or more daily period despite the use of three or more daily insulin injection increased from 42 to 70%.insulin injection increased from 42 to 70%.
HbAHbA1c1c varied significantly among centres. varied significantly among centres.
Only 2 centres improved their metabolic control Only 2 centres improved their metabolic control significantly in the 3 year period.significantly in the 3 year period.
Fewer severe hypoglycaemic events in Fewer severe hypoglycaemic events in centres with a HbA centres with a HbA1c1c significantly below significantly below the grand mean. the grand mean.
Metabolic Control and Quality of Life
The DCCT study and the recent ISPAD guidelines recommend a treatment target for HbA1c of 7.5% in children and adolescents.
Will strict metabolic control influence the quality of life in adolescents with diabetes?
COMPARISON WITH OTHER QOL STUDIES
AuthorAuthor n n age (yrs) Correlation with QOL age (yrs) Correlation with QOL
Fonagy P,Fonagy P,
Arch Dis Child, 1987Arch Dis Child, 1987 Poor control = better QOL Poor control = better QOL
Ingersoll and Marrero, Ingersoll and Marrero,
Diabetes Educ, 1991Diabetes Educ, 1991 74 74 10.8-20.8 None except health perception 10.8-20.8 None except health perception
Guttman-Bauman,Guttman-Bauman,
Diabetes Care, 1998Diabetes Care, 1998 69 69 10-20 10-20 Good control=better QOL Good control=better QOL
Grey, Grey,
Diabetes Care, 1998Diabetes Care, 1998 52 52 12-20 12-20 None None
Metabolic Control and Quality of Life
The study involved 20 centres in 17 countries in The study involved 20 centres in 17 countries in Europe, Japan and North America.Europe, Japan and North America.
Adolescents aged 10-18 yrs at each study centre Adolescents aged 10-18 yrs at each study centre were invited to participate.were invited to participate.
2,101 adolescents were enrolled.2,101 adolescents were enrolled. Samples and information from 79% of all patients Samples and information from 79% of all patients
registered at the centres were obtained.registered at the centres were obtained.
Demographic data and metabolic control on 2,101 adolescents with type 1 diabetes
Age (yr)
Diabetes duration (yr)
BMI (kg/m2)
HbA1C (%)
Incidence of severe hypoglycemia (events per 100 patient-years)
Boys(n=1085)
13.8 ± 2.1
5.1 ± 3.8
20.8 ± 3.2
8.6 ± 1.6
15.5
Girls(n=1016)
13.8 ± 2.1
5.4 ± 3.8
21.8 ± 3.6
8.9 ± 1.7
15.7
Results as means ± SD Results as means ± SD *Adjusted for Center, + Adjusted for center and age, *Adjusted for Center, + Adjusted for center and age, # Adjusted for center, age and duration of diabetes.# Adjusted for center, age and duration of diabetes.
P-value
0.86*
0.06+
<0.0001#
<0.01#
0.90#
Daily insulin regimen
1 injection
2 injections
3 injections
4 or more injections
Premixed insulin, n (%)
Insulin dose (U/kg/day)
Boys(n=1085)
8
472
295
307
445 (41)
0.94 ± 0.32
Girls(n=1016)
10
380
287
339
407 (40)
1.01 ± 0.32
Results as means ± SD# Adjusted for center, age and duration of diabetes.
P-value
<0.05
0.66
<0.0001#
Patient characteristics on insulin management.
Quality of Life Questionnaires
AdolescentAdolescent - DQOL questionnaire- DQOL questionnaire
- (Ingersoll and Marrero, 1991)- (Ingersoll and Marrero, 1991)
ParentParent - Family Burden questionnaire - Family Burden questionnaire constructedconstructed
Health - Health - - Family Burden questionnaire - Family Burden questionnaire
ProfessionalProfessional
constructedconstructed
Questionnaire for Adolescent DQOL
23 questions on impact of diabetes23 questions on impact of diabetes
11 questions on worries11 questions on worries
17 questions on satisfaction17 questions on satisfaction
1 question on health perception1 question on health perception
Questionnaire for Parents and for Health Professionals
Burden relating to diabetesBurden relating to diabetes a) Medical treatment/nursing tasksa) Medical treatment/nursing tasks
b) Disruption in family routinesb) Disruption in family routinesc) Physical or psychological problems in the childc) Physical or psychological problems in the childd) Restriction in child's social and school activitiesd) Restriction in child's social and school activitiese) Long term health concerns.e) Long term health concerns.
We assessed family burden as one aspect of QOLWe assessed family burden as one aspect of QOL in the family setting, which is of particular in the family setting, which is of particular concern to health professionals. concern to health professionals.
Translation and cross-cultural adaptation of the questionnaire to each of the 14
languages:
Forward translation from English to the Forward translation from English to the national language of the countrynational language of the country
Backward translation from the national Backward translation from the national language to English language to English
Local lay panel testing Local lay panel testing The consultant and the Originator discussed The consultant and the Originator discussed
the report and prepared the final validationthe report and prepared the final validation
Completion of the questionnaires
Patients and parents completed questionnaires Patients and parents completed questionnaires confidentiallyconfidentially
Staff completed questionnaires independently. Staff completed questionnaires independently. All forms were forwarded to the coordinating center. All forms were forwarded to the coordinating center. All questionnaires were received within 2-3 weeks of All questionnaires were received within 2-3 weeks of
blood collection for glycated haemoglobin. blood collection for glycated haemoglobin. A middle score of 3 was used for missing questions A middle score of 3 was used for missing questions
when at least 70% questions on the relevant when at least 70% questions on the relevant subscale was answered.If <70% answered forms subscale was answered.If <70% answered forms discarded.discarded.
Internal validity and consistency of the multiple item instrument Questionnaire completion rates for adolescents, Questionnaire completion rates for adolescents,
parents and health professionals (93 percent, 89 parents and health professionals (93 percent, 89 percent and 94 percent, respectively)percent and 94 percent, respectively)
Item completion rates for all three groups (98.6–Item completion rates for all three groups (98.6–99.8 percent). 99.8 percent).
Cronbach’s a coefficient values for the Cronbach’s a coefficient values for the questionnaires were: questionnaires were:
Adolescent DQOL- impact 0.79, worries 0.84, Adolescent DQOL- impact 0.79, worries 0.84, satisfaction 0.92;satisfaction 0.92;
Parents 0.80 and health professionals 0.86, Parents 0.80 and health professionals 0.86,
Quality of life scores with age perceived by adolescents, parent and health
professionals
Age, gender, high and low HbAAge, gender, high and low HbA1c 1c selected as selected as 10th (6.8%) and 90th percentiles (10.8%) 10th (6.8%) and 90th percentiles (10.8%)
Illustrate the variation in QOL score due to Illustrate the variation in QOL score due to metabolic control.metabolic control.
All QOL scores were linearly transformed: All QOL scores were linearly transformed:
Best possible score 0Best possible score 0
Worst possible score 100Worst possible score 100
Impact of diabetes in adolescents by age, gender and HbA1C
Years
Age
Imp
act
of
dia
be
tes
1211
22
24
26
28
30
1413 1615 18
F 10.9%
HbA1 C
F 6.8%
M 10.9%
M 6.8%
17
Score
Worries about diabetes in adolescents by age, gender and HbA1C
Score
Wo
rrie
s a
bo
ut
dia
be
tes
1211
15
20
25
30
1413 1615 18
F 10.9%
F 6.8%
M 10.9%
M 6.8%
17
HbA1 C
Years
Age
Satisfaction with life in adolescents by age, gender and HbA1C
Score
Sa
tisf
act
ion
wit
h li
fe
1211
20
25
30
35
1413 1615 18
F 10.9%
F 6.8%
M 10.9%
M 6.8%
17
HbA1 C
Years
Age
Health perception in adolescents by age, gender and HbA1C
Hea
lth
pe
rce
pti
on
1211
15
20
25
30
35
40
1413 1615 18
F 10.9%
F 6.8%
M 10.9%
M 6.8%
17
HbA1 C
Score
Years
Age
Metabolic Control and Quality of Life Key messagesKey messages
First large international multi-language study First large international multi-language study evaluating the relationship between metabolic control and evaluating the relationship between metabolic control and
QOL in 2,101 adolescents with diabetes. QOL in 2,101 adolescents with diabetes.
Lower HbALower HbA1c1c is associated with better QOL of is associated with better QOL of adolescents and lesser perceived family burden by adolescents and lesser perceived family burden by
parents and health professionals.parents and health professionals.
No relation between QOL and the actual insulinNo relation between QOL and the actual insulin
regimenregimen..
Speculation Speculation
Young people with excellent QOL: Young people with excellent QOL:
Good physical and psychological balanceGood physical and psychological balance
Facilitate better metabolic control through Facilitate better metabolic control through
improved self-careimproved self-care
Bad metabolic control = poor QOLBad metabolic control = poor QOL
Conclusion
Our studies showed Our studies showed
No relationship between blood glucose control, No relationship between blood glucose control, insulin dose and number of dailly injections insulin dose and number of dailly injections
Good metabolic control Good metabolic control cancan be achieved without be achieved without increasing the risk of severe hypoglycaemic events increasing the risk of severe hypoglycaemic events
A clear relationship between metabolic control and A clear relationship between metabolic control and quality of lifequality of life