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Three-year comparison of subcutaneous insulin pump treatment with multi-daily injections on HbA1c, its variability and hospital burden of children with type 1 diabetes

Department of Paediatrics, Oncology, Haematology and Diabetology, Medical University of Lodz, 36/50 Sporna St., 91-738, Lodz, Poland.
Acta Diabetologica (Impact Factor: 2.4). 10/2011; 49(5):363-70. DOI: 10.1007/s00592-011-0332-7
Source: PubMed
ABSTRACT
Treatment with continuous subcutaneous insulin infusion (CSII) allows a large degree of treatment individualization and intensification in children with diabetes. The study’s aim was to evaluate the impact of treatment with CSII on glycated haemoglobin level (HbA1c) in children with diabetes and investigate whether introduction of CSII is associated with an increased risk of acute complications of diabetes. Patients treated throughout the recruitment period exclusively with multiple daily injections (MDI) were matched for duration of diabetes and HbA1c level at baseline with patients treated exclusively with CSII in a 1:1 group ratio (n = 223 and 231 for MDI and CSII, respectively). The CSII group showed lower HbA1c after the observation period (7.98 ± 1.38 vs. 7.56 ± 0.97; P = 0.002). HbA1c variability measured as standard deviations of average values was also lower in the CSII group (0.73 ± 0.45 vs. 0.84 ± 0.54; P = 0.049). The rate of hospitalization due to acute events was similar in both groups (14.7/100 vs. 14.0/100 person/years in the MDI and CSII group, P = 0.72). Duration of hospital stay per year was on average 1.25 days shorter in the CSII group (P = 0.0004), but the risk of acute complications resulting in hospitalization did not differ between the groups (hazard ratio (HR) 1.16; 95% confidence interval (95% CI) 0.68–1.63). The most significant risk factor for hospitalization due to acute complications was baseline HbA1c concentration (HR 1.25; 95% CI 1.14–1.37). In conclusion, CSII treatment may improve glycemic control and reduce its variability. Change of MDI to CSII does not alter the risk of hospitalization and may reduce the annual duration of hospitalization in children with diabetes.

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Available from: Wojciech Młynarski, Nov 04, 2014
ORIGINAL ARTICLE
Three-year comparison of subcutaneous insulin pump treatment
with multi-daily injections on HbA1c, its variability and hospital
burden of children with type 1 diabetes
Wojciech Fendler
Anna Iza Baranowska
Beata Mianowska
Agnieszka Szadkowska
Wojciech Mlynarski
Received: 20 July 2011 / Accepted: 14 September 2011 / Published online: 1 October 2011
Ó The Author(s) 2011. This article is published with open access at Springerlink.com
Abstract Treatment with continuous subcutaneous insu-
lin infusion (CSII) allows a large degree of treatment
individualization and intensification in children with dia-
betes. The study’s aim was to evaluate the impact of
treatment with CSII on glycated haemoglobin level
(HbA1c) in children with diabetes and investigate whether
introduction of CSII is associated with an increased risk of
acute complications of diabetes. Patients treated throughout
the recruitment period exclusively with multiple daily
injections (MDI) were matched for duration of diabetes and
HbA1c level at baseline with patients treated exclusively
with CSII in a 1:1 group ratio (n = 223 and 231 for MDI
and CSII, respectively). The CSII group showed lower
HbA1c after the observation period (7.98 ± 1.38 vs.
7.56 ± 0.97; P = 0.002). HbA1c variability measured as
standard deviations of average values was also lower in the
CSII group (0.73 ± 0.45 vs. 0.84 ± 0.54; P = 0.049). The
rate of hospitalization due to acute events was similar in
both groups (14.7/100 vs. 14.0/100 person/years in the
MDI and CSII group, P = 0.72). Duration of hospital stay
per year was on average 1.25 days shorter in the CSII
group (P = 0.0004), but the risk of acute complications
resulting in hospitalization did not differ between the
groups (hazard ratio (HR) 1.16; 95% confidence interval
(95% CI) 0.68–1.63). The most significant risk factor for
hospitalization due to acute complications was baseline
HbA1c concentration (HR 1.25; 95% CI 1.14–1.37). In
conclusion, CSII treatment may improve glycemic control
and reduce its variability. Change of MDI to CSII does not
alter the risk of hospitalization and may reduce the annual
duration of hospitalization in children with diabetes.
Keywords Insulin delivery systems
Complications of diabetes Paediatric diabetes
Healthcare organization
Introduction
In Poland, the incidence of type 1 diabetes in the popula-
tion below 15 years of age tripled during the last three
decades [1, 2]. During that time, new methods of diabetes
management such as rapid and long-acting insulin ana-
logues, continuous subcutaneous insulin infusion (CSII)
and continuous glucose monitoring (CGM) systems have
been implemented. The primary goals of these technologies
were to improve metabolic control, decrease the frequency
of acute and chronic diabetes complications and minimize
the overall healthcare burden. Numerous studies have
unequivocally shown that better metabolic control
decreases chronic diabetes-related complications [3].
Although the quality of paediatric diabetes care has
markedly improved, hospital visits related to acute com-
plications still constitute a serious burden for the healthcare
system [4]. Several studies in children and adolescents
have shown improvements in terms of better metabolic
control, reduced rates of complications and better quality
of life [510]. Patients treated with CSII are not, however,
free from acute complications, e.g. rates of diabetic
ketoacidosis or hypoglycaemic events, and the hospital
Electronic supplementary material The online version of this
article (doi:10.1007/s00592-011-0332-7) contains supplementary
material, which is available to authorized users.
W. Fendler A. I. Baranowska B. Mianowska
A. Szadkowska W. Mlynarski (&)
Department of Paediatrics, Oncology, Haematology
and Diabetology, Medical University of Lodz,
36/50 Sporna St., 91-738 Lodz, Poland
e-mail: wojciech.mlynarski@joslin.harvard.edu
123
Acta Diabetol (2012) 49:363–370
DOI 10.1007/s00592-011-0332-7
Page 1
burden of diabetes in such patients is still considerable
[11]. Moreover, some reports are in favour of additional
precautions during the switching period, with regard to the
type of insulin used, its dose and patient’s age [12].
The aim of this study was to evaluate the impact of
treatment with CSII on the metabolic control (expressed as
glycated haemoglobin level—HbA1c) and its variability in
children with diabetes. The study also investigated whether
the introduction of CSII was associated with altered risk, or
rates, of acute complications of diabetes in prolonged
treatment.
Patients and methods
Patients
Throughout the observation period, the study centre treated
[90% of children with diabetes within the Lodz admin-
istrative region, inhabited by 2.6 million people. This was a
prospective observational study based on a standardized
computerized, manually curated database of discharge
summaries of all patients with type 1 diabetes hospitalized
at the study centre from January 2002 to December 2010.
The number of patients treated within the centre increased
from 520 to 632 throughout the study period. The centre’s
diabetes epidemiology database used in nationwide and
regional trials [2, 13] covers all patients registered at the
hospital discharge summaries database, which ruled out
the possibility of missing patients with diabetes treated in
the region. The CSII group was collected without any
specific restrictions concerning the patients; the decision to
introduce CSII was based on the patient’s or their parents’
willingness to change the treatment in view of more free-
dom in food intake and lifestyle, and on the clinical
judgment of the physician. Clinical indications for CSII
were high HbA1c levels (above 8–8.5%), dawn phenom-
enon, frequent hypoglycaemia (at least two episodes per
year of severe hypoglycaemia with need for intervention of
another person or loss of consciousness), concomitant
chronic illnesses or willingness to improve the patient’s
quality of life. The CSII group was collected between
January 2002 and December 2008. Subsequent follow-up
was continued until December 2010.
Methods
Patients treated throughout the recruitment period exclu-
sively with multiple dose injections (MDI) were matched
retrospectively for duration of diabetes and baseline
HbA1c level to the CSII group to ensure a 1:1 group ratio.
Propensity score matching was attempted; it is a technique
aimed at the elimination of group allocation bias through
calculation of individual probability of being assigned to
the treatment or control group on the basis of covariates
associated with group allocation [14, 15]. However, as it
would lead to imbalanced group numbers in terms of
individual patients (Electronic Supplementary Material,
Table 1), covariate matching was used instead. Criteria for
inclusion into the analysis were set as following: type 1
diabetes diagnosis according to WHO criteria, lack of
obesity (\90th centile of body mass index for age and sex),
treatment with insulin with a mean daily dose [0.3 units/
kg, age at onset greater than 12 months, duration of dia-
betes [1 year and presence of at least one anti-islet auto-
antibody at onset (islet cell antibody, anti-GAD, insulin
autoantibody or IA2). Patients with type 2 diabetes, cystic
fibrosis or confirmed monogenic diabetes were excluded
from both groups. Patients who changed treatment from
CSII to MDI, started CSII therapy prior to January 2002 or
switched their treatment regimen twice during the obser-
vation period were not considered eligible for the analysis.
Patients who were diagnosed with type 1 diabetes during
the observation period but were not subsequently treated as
inpatients or outpatients at the study Centre were excluded
from the analysis (n = 118). During the follow-up,
scheduled hospital admissions of patients with type 1 dia-
betes have been carried out every 2.5 year (to perform
screening tests for chronic diabetic complications, common
autoimmune diseases and for re-education). Only acute
hospitalizations were considered in this analysis. Consid-
ering the access to the treatment, the cost of insulin treat-
ment other than with long-acting insulin analogues was
fully reimbursed by the state throughout the study period.
Costs of insulin pumps and tubing for children were
covered either by a non-profit organization (the Great
Orchestra of Christmas Charity) or by the National Health
Fund.
Analysed outcomes
The primary outcome of the study was the risk of acute
hospitalization due to hypo- and/or hyperglycaemia and
acute hospitalization for any reason. Hospitalization due to
hypoglycaemia was defined as hospital admission due to:
(1) symptoms typical for hypoglycaemia that improved after
oral/parenteral glucose or parenteral glucagon administra-
tion or (2) documented low capillary/venous blood glucose
concentration, both acknowledged/recognized by the
admitting physician as requiring hospitalization because
of the severity (severe hypoglycaemia) or recurrence of
symptoms (i.e. due to gastrointestinal infection or insulin
overdose). Hospitalization due to hyperglycaemia was
defined as hospital admission due to: (1) ketoacidosis,
(2) high blood glucose levels (over 250 mg/dl) persisting for
at least 12 h and not improving in the ambulatory setting or
364 Acta Diabetol (2012) 49:363–370
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(3) incorrect glycaemic control as reflected by high
HbA1c level assessed by the guiding diabetologist as not
acceptable for the individual patient (typically over 8%—
depending on patient’s age, history of experienced severe
hypoglycaemia, concomitant illnesses and previous meta-
bolic control). The MDI group used various combinations
of long-acting analogues, NPH insulin, short-acting ana-
logues or human insulin. No subgroup analyses based on
insulin type used were possible, as changes were frequent,
occurred multiple times in numerous patients and may
have been dependent on the availability of particular
insulin preparations.
Measured outcomes included the following: HbA1c
level measured at the moment of CSII introduction or
matching (for MDI-treated patients) and at the end of the
observation period or censoring due to reaching the age of
18 years (mean HbA1c 8.05 ± 1.30); meeting the thera-
peutic goal of \7.0% of HbA1c [16]; number and duration
of hospital visits calculated for the whole observation
period; time to first hospitalization due to acute causes—
for this purpose, patients who reached 18 years of age or
had no acute visits since enrolment before the study closing
date were treated as censored observations.
Laboratory measurements
Glycated haemoglobin measurements
Throughout the whole study period, the laboratory method
for the assessments of HbA
1c
was consistent. HbA
1c
assays
were performed by ion-exchange high-performance liquid
chromatography (HPLC) using the Bio-Rad VARIANT
TM
Hemoglobin A1c Program (Bio-Rad Laboratories, Inc.
Hercules, California, USA). The VARIANT
TM
Hemoglobin
A1c Program has been certified by the National Glycohe-
moglobin Standardization Programme (NGSP) as meeting
the DCCT standard. The within-run coefficient of variation
(CV) determined by the manufacturer was 1.05% for people
without diabetes and 0.94% for people with diabetes; the
between-run CV was 1.61 and 1.16% for people without
diabetes and for people with diabetes, respectively. Blood
samples were collected with HbA1c Capillary Collection
System (Bio-Rad Laboratories, Inc. Hercules, California,
USA) and analysed according to the manufacturer’s
protocol.
C-peptide measurements
To determine whether residual beta cell function was similar
between the two groups, C-peptide levels were measured at
baseline whenever possible using radioimmunoadsorption
assays (IRMA-C-PEP, CIS Bio International). Both intra-
and interassay CV for this assay equalled 4.9 and 5.1%,
respectively, according to the manufacturer. Minimum
detectable C-peptide level equalled 0.036 mmol/ml, and its
concentrations in a group of 40 healthy individuals were
within the 0.35–1.17 mmol/ml range.
Statistical analysis
Analysis of covariance (ANCOVA) models were used for
the evaluation of mean HbA1c and its variability (expres-
sed as standard deviations—SD) with adjustment for
duration of diabetes. Correlations were evaluated using
Pearson’s correlation coefficient. Final HbA1c values were
additionally converted to percentile values of patients
treated within the centre to assess the profile of each group
with respect to metabolic profile of the clinic. For com-
parisons of percentiles of HbA1c and the number of hos-
pital days per patient-year, the Mann–Whitney U test was
applied with medians and interquartile ranges (IQRs) used
for result presentation. The log-rank test was used for
uncorrected comparison of survival without acute compli-
cations depending on treatment type. To adjust for covar-
iates, a multivariate proportional hazard regression analysis
including data on patient’s sex, initial HbA1c, age and
duration of diabetes at enrolment was developed. A P value
of \0.05 was considered to be the threshold of statistical
significance.
Results
Comparison of baseline characteristics
The study group consisted of 454 patients—231 on CSII
and 223 on MDI. Baseline study group characteristics are
given in Table 1. The CSII group used pumps manufac-
tured by Medtronic (Paradigm series and older devices;
67%), Roche (Accu-Chek; 24%) and Deltec (Cozmo; 9%).
Insulin pumps were loaded with insulin analogues (81%) or
human insulin (19%). No patient used sensor-augmented
pumps as they only became available in Poland in 2009.
Significant differences in between-group comparisons were
observed only in terms of age at initial visit. No differences
in gender distribution, metabolic control or duration of
diabetes were observed between the study groups as a
result of covariate matching. Glycated haemoglobin levels
showed moderate, significant correlations with patients’
age (r = 0.21; P \ 0.0001) and duration of diabetes
(r = 0.36; P \ 0.0001).
Comparisons of metabolic outcomes
Post-study HbA1c values deteriorated only in the MDI
group, but the increase in HbA1c was not statistically
Acta Diabetol (2012) 49:363–370 365
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significant [0.21% (95% CI -0.20 to 0.61); Fig. 1]. Mean
post-study HbA1c levels were statistically higher in MDI
than in CSII-treated patients (7.98 ± 1.38 vs. 7.56 ± 0.97,
respectively; P = 0.002); this difference persisted after
adjustment for patient’s age at enrolment and duration of
diabetes (P = 0.01; Fig. 1).
Variability of metabolic control differed significantly
between the groups—SD of HbA1c equalled 0.73 ± 0.45
in the CSII group in comparison with 0.84 ± 0.54 in MDI-
treated individuals (P = 0.049; Fig. 2).
Percentile comparisons performed to ascertain the rela-
tive improvement of HbA1c showed that the CSII group
ranked significantly better, with median percentile of final
HbA1c equal to 45% (IQR 24–68%) in comparison with
59% (IQR 29–81%) noted in MDI-treated individuals
(P = 0.001).
The percentage of patients reaching the therapeutic goal
of\7% of HbA1c equalled 32.9% in the CSII and 25.7% in
the MDI group (P = 0.12).
Comparisons of hospital burden in children treated
with CSII or MDI
Mean observation time was 3.05 years ± 1.74. The MDI
group was observed for a total of 674 and the CSII group for
714 patient-years. The number of acute visits in the
department equalled 99 and 100 for MDI- and CSII-treated
patients, respectively. Rates of emergency hospital visits
were similar in patients treated with MDI (14.7/100 patient-
years) versus CSII (14.0/100 patient-years; P = 0.72).
Total duration of hospital stays due to emergency admis-
sions did not differ significantly between the groups
(P = 0.94), although patients treated with CSII had a sig-
nificantly lower number of total hospital days per year than
the MDI group [3.5 (2.1–5.67) vs. 4.76 (2.46–9.63)
P = 0.0004)]. Throughout the observation period, 60
patients required at least one hospitalization due to acute
causes. In 69.2% of cases, the underlying problem was
hyperglycaemia and in 17.3%, severe hypoglycaemia.
Additional causes were identified in 13.5% of cases—most
were related to infectious diseases (n = 14), urolithiasis
Table 1 Baseline
characteristics of the study
group
MDI CSII P
Males/females 126/97 129/102 0.8877
Age at enrolment [years] 14.13 (10.82–16.18) 10.20 (7.17–13.15) \0.0001
Duration of diabetes at enrolment [years] 2.46 (0.70–5.53) 2.43 (1.47–5.21) 0.3607
Daily insulin dose [U/kg] 0.81 (0.63–1.09) 0.95 (0.53–1.57) 0.2770
C-peptide level [ng/ml]
(normal range [0.35 ng/ml)
0.19 (0.10–0.33) 0.17 (0.12–0.26) 0.4101
HbA1c at enrolment [%]
(normal range 4.3–5.7%)
7.4 (6.6–8.3) 7.2 (6.7–8.1) 0.6001
Fig. 1 Differences in age-adjusted glycated haemoglobin (HbA1c)
levels at baseline and at the end of the observation period in patients
treated with multiple daily injections (MDI) or continuous subcuta-
neous insulin infusion (CSII). The difference between MDI and CSII-
treated patients was significant at the end of the observation period
(P = 0.01). Data are depicted as means with 95% confidence
intervals
Fig. 2 Differences in standard deviation of glycated haemoglobin
levels in the studied groups. The difference between the multiple
daily injections (MDI) and subcutaneous insulin infusion (CSII)
groups was of borderline statistical significance (P = 0.049). Data are
depicted as means with 95% confidence intervals
366 Acta Diabetol (2012) 49:363–370
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(n = 4) or neurologic abnormalities [epilepsy, vertigo,
headache or alcohol abuse (n = 4)]. Univariate analysis
did not show any difference in the risk of acute hospital-
ization based on treatment (log-rank P = 0.77; Fig. 3). In
multivariate Cox regression analysis, the risk of acute
hospitalization depended only on initial HbA1c level.
Treatment regimen, sex, age and duration of diabetes at
enrolment were not statistically significant in this model
(Table 2). Results did not differ when only acute hospi-
talization due to hypoglycaemic or hyperglycaemic epi-
sodes was considered as joint or separate endpoints.
Adjusted hazard ratios for CSII treatment equalled 1.26
(95% CI 0.04–2.48) for hospitalization due to hypogly-
caemia, 1.30 (95% CI 0.69–1.92) for hospitalization due to
hyperglycaemia and 1.28 (95% CI 0.73–1.83) for hospi-
talization due to either of these causes. Duration of hospital
stay due to acute causes did not differ significantly between
the groups, although patients treated with CSII had a lower
number of total hospital days per year (Table 3). The fre-
quency of hospital visits did not differ between the groups;
median number of hospital visits per patient equalled 2
(25–75% 1–3) in the MDI group and 2 (25–75% 2–3) in the
CSII group (P = 0.11).
Discussion
Benefits gained through CSII application included a slower
deterioration of HbA1c values, evidenced by an increasing
difference in initial and final HbA1c levels depending on
CSII or MDI treatment. Curiously, baseline characteristics
of the presented study group suggest that the analysed
patients could have been in fact better controlled than those
in the STAR 3 trial [9], (mean HbA1c levels 7.6 ± 1.5 vs.
8.5 ± 0.6) making it more difficult to obtain a statistically
significant improvement of HbA1c. Stable HbA1c levels
despite ageing and duration of diabetes observed in CSII-
treated individuals in this trial do, however, mirror the
beneficial effect of the STAR 3 participants. Final mean
HbA1c levels in the paediatric group in STAR 3 equalled
7.7%, whereas in the presented cohort the final mean
HbA1c reached 7.6%. Despite the methodological differ-
ences and application of different insulin pumps (the STAR
3 pumps were sensor-augmented), results confirming the
overall benefit of CSII seem surprisingly convergent.
Moreover, the difference in final HbA1c levels was similar
to that reported in a recent meta-analysis by Monami et al.
[17] who showed a -0.3% reduction in favour of the CSII
group. This may be interpreted as showing that CSII offers
an advantage in terms of better metabolic control, but the
improvement will seldom exceed 0.5% in long-term
observation. Further improvements could theoretically be
gained through the use of more sophisticated therapeutic
approaches such as dual wave bolus (DWB) [18, 19].
However, due to the magnitude duration of observation,
changing patient preferences in using DWB, the authors
refrained from introducing this factor to stratify the CSII
group.
Although CSII was shown to offer better metabolic
control, this effect did not translate into the risk of acute
hospitalizations. A lack of difference in this endpoint
suggested that educational measures undertaken during the
switching phase were adequate and did not result in
Fig. 3 Cumulative probability of survival without acute hospitaliza-
tion of patients treated with multiple daily injections (MDI) or
continuous subcutaneous insulin infusion (CSII). The risk of hospi-
talization did not differ between the studied groups (P = 0.77)
Table 2 Multivariate Cox regression analysis of factors affecting the
risk of acute hospitalization
Variable Hazard
ratio
95% Confidence
Interval
P
Baseline HbA1c level [%] 1.25 1.14–1.37 0.0001
Male gender 1.29 0.84–1.75 0.2626
Treatment with CSII 1.16 0.68–1.63 0.5438
Age at enrolment 1.01 0.94–1.08 0.8270
Duration of diabetes 1.00 0.92–1.07 0.9496
Baseline C-peptide level 1.31 0.30–5.78 0.7236
CSII continuous subcutaneous insulin infusion
Table 3 Duration of hospital stay and number of visits for any reason
or emergency ones
MDI CSII P
Days in hospital per
year
4.76 (2.46–9.63) 3.50 (2.11–5.67) 0.0004
Days in hospital per
year due to
emergency visits
0 (0–0.47) 0 (0–0.43) 0.9328
Acta Diabetol (2012) 49:363–370 367
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shortened time to first hospital visit due to acute compli-
cations. Finally, rates of hospitalizations due to acute visits
did not differ between the groups which confirmed that no
additional risk of hypoglycaemia or ketoacidosis was cre-
ated by CSII treatment, in contrast to earlier studies on that
matter [20].
The obviously non-random allocation of patients is the
main limitation of the study and a potential for bias, but the
lack of differences in baseline HbA1c and duration of
diabetes justified this approach and made the groups
comparable. The authors performed covariate matching for
baseline HbA1c and duration of diabetes which lead to
balanced group numbers, apart from the age difference,
which was adjusted for in multivariate comparisons. The
perfect design—a randomized study—for a group of such
magnitude would be unfeasible from an organizational
point of view. Recently published results of an ambitious
project on the use of sensor-augmented CSII (the STAR 3
trial) [9] covered 156 children allocated to either CSII or
MDI. The observational approach with matching of MDI
and CSII patients used in this study, although potentially
biased by non-random selection, allowed the authors to
include a study group of 454 individuals, yielding greater
statistical power and robustness in terms of adjusted effects
estimation. The fact that the differences in HbA1c persisted
after correction for confounding factors further increased
the credibility of presented findings.
Presented patients were followed for 3 years, which
allowed the authors to evaluate the effect of CSII on hospi-
talization rates and variability of HbA1c. The latter effect of
CSII may be clinically important, as lower SD of HbA1c is a
result of reduced rates of prolonged periods glycaemia
maintained alternatively within the high or low concentra-
tion range. CSII treatment was already reported to reduce
blood glucose variability in a meta-analysis authored by
Pickup et al. [21]. Although variability of HbA1c is not yet
considered an endpoint in diabetes trials, it was proven to
increase the risk of long-term complications of diabetes in
DCCT data analysis [22]. Therefore, interventions aimed at
its reduction could be perceived as being potentially bene-
ficial and therefore worthy of further interest.
Results of this study in terms of HbA1c changes due to
CSII treatment were in line with those obtained by Jakisch
et al. [23] who in a group of 434 matched pairs of patients
with type 1 diabetes, showed an improvement of HbA1c
during the first year of the study. In their study however,
the difference disappeared after 3 years of observation,
showing that the benefit could be attributed to the ‘nov-
elty’ effect. In the presented study, the effect seemed to
persist throughout the observation period of similar dura-
tion (mean 3.05 years), possibly due to different educa-
tional approaches or changes in patients’ ability to cope
with diabetes and its management.
Persistent residual function of the beta cells could also
contribute to better metabolic control in CSII-treated
patients. However, as only 12% of analysed patients had
C-peptide levels within normal range and no difference
was detected between the groups, it seems very unlikely
that residual beta cell function contributed significantly to
the observed outcomes.
Over 30% of patients required at least one hospitaliza-
tion due to acute complications during the observation
period. This could result in a bias of study results, as the
older patients may have left the group after shorter obser-
vation periods before developing acute complications,
while younger ones could be observed for longer periods of
time increasing their chances of acute hospitalization.
However, the rate of acute hospitalizations per 100 patient/
years was nearly identical between CSII and MDI-treated
patients, as was the case for risk of the first acute hospi-
talization, which allowed the authors to assume that the
risk of being hospitalized due to acute conditions is the
same with MDI or CSII treatment. CSII did, however,
promote shorter overall hospital stays per year by nearly
25%, which could result in an economic benefit from this
type of treatment.
The rate of severe hypoglycaemia in an outpatient set-
ting among children with diabetes is hard to estimate, as
reported rates range widely from 6.63 events per 100
patient-years, reported by the PedPump study which
included patients from Poland [24], to 62 per 100 patient-
years reported earlier by Levine et al. [25]. In the Hvidore
study group, which formulated the criteria for assessment
of hypoglycaemic events used in the above-mentioned
studies, the rate of severe hypoglycaemia equalled 22 per
100 patient-years [26]. Introduction of CSII treatment was
shown to reduce the overall rate of hypoglycaemia [21] and
was expected to result in a reduction in hospitalizations due
to this complication in the studied group. The observed
lack of differences in this outcome could result from one of
the limitations of the presented study—the authors were
unable to objectively collect and analyse data from out-
patient clinics and match them with those from the hospital
database. All patients and their parents could contact their
attending diabetologists by phone and did so in critical
situations including severe hypoglycaemic episodes, but
precise recall of the overall and individual numbers of such
episodes was not possible. As a result, the authors were
unable to determine actual rates of hypoglycaemia not
resulting in hospital admission. Hospitalizations due to
hypoglycaemia, however, constituted 25% of all acute
diabetes-related hospital visits in our study group, which is
a similar value range as that noted in an earlier study by
Palta et al. [27] The authors reported a rate of 1.9 per 100
patient-years hospital admissions due to hypoglycaemic
events in patients with diabetes aged 0–29, which
368 Acta Diabetol (2012) 49:363–370
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amounted to 21% of all hospital admissions of their cohort.
Thus, it seemed that the group presented within this study
did not deviate significantly from those reported in previ-
ous reports in terms of hypoglycaemia incidence, with no
evident benefits gained through the introduction of CSII.
Confirmation of the fact that baseline HbA1c was the
main risk factor for hospitalization due to acute complica-
tions may be one with considerable clinical implications.
This association was previously reported in epidemiologic
studies on children with diabetes [25, 27, 28]. One could
therefore assume that patients with initially worse metabolic
control should be a group of particular interest for the phy-
sician, as any intervention leading to the improvement of
HbA1c could yield beneficial effects in terms of reducing the
risk of acute hospitalizations. The percentage of patients
reaching the therapeutic goal of ADA for HbA1c (\7.0%)
was considerably greater in the presented study in both CSII
and MDI groups than in the STAR 3 cohort. The difference
was particularly evident in MDI individuals (25.7% vs. 10%
reported by STAR 3), undermining the beneficial effect of
CSII and suggesting suboptimal diabetes management in the
MDI group in the cited study.
Conclusions
Treatment with CSII contributed towards better metabolic
control of diabetes in terms of HbA1c level and reduction in
its variability. Application of CSII did not affect the rate of
acute hospitalizations or the risk of acute hospitalization in
comparison with MDI in children with diabetes but was
associated with a shorter duration of annual in-hospital stay.
Acknowledgments The study was performed as part of the TEAM
project financed by the Innovative Economy Programme of the
European Union coordinated by the Foundation for Polish Science.
Open Access This article is distributed under the terms of the
Creative Commons Attribution Noncommercial License which per-
mits any noncommercial use, distribution, and reproduction in any
medium, provided the original author(s) and source are credited.
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  • Source
    • "Treatment with CSII contributed toward better metabolic control of diabetes in terms of HbA1c level and reduction in its variability [3]. Benefits gained through the use of CSII therapy included a slower deterioration of HbA1c values and allow greater flexibility in meal planning and food choice [4]. This, together with CHC, could lead to unbalanced eating habits, mainly in adolescents, with a lack of attention to total fat and protein content and too much emphasis on carbohydrates, which favored the choice of foods high in fat and cholesterol content [18]. "
    [Show abstract] [Hide abstract] ABSTRACT: Carbohydrate counting (CHC) in combination with nutritional education has been used to optimize the insulin dose in patients with type 1 diabetes (T1D). The aim of this study was to test the impact of CHC and nutritional education on changes in dietary habits, body composition and body fat distribution in children with T1D treated with insulin pumps (CSII). Twenty-five children with T1D and CSII were recruited and valuated at baseline and after 18 months of follow-up. They were trained in CHC and following standard nutrition education program (based on American Diabetes Association and International Society of Pediatric and Adolescent Diabetes guidelines); clinical, biochemical and nutritional variables were measured. In the total population, body composition, body fat distribution and biochemical variables did not change, at follow-up; HbA1c was significantly reduced (8.50 ± 0.77 vs 7.92 ± 0.74 %; p < 0.001) without changing insulin/kg/day requirement. In the sub-group of patients with a significant HbA1c reduction (ΔHbA1c ≥ 0.5 %, n = 12), the carbohydrate (CHO) intake was significantly higher at follow-up (53.0 ± 4.0 vs 57.6 ± 2.5 %; p < 0.01); on the contrary, fat (31.3 ± 3.6 vs 28.5 ± 1.6 %; p < 0.05) and protein intake (15.4 ± 1.8 vs 13.3 ± 1.6 %; p < 0.01) significantly decreased. Patients without a significant HbA1c reduction did not show any difference. CHC, in combination with nutritional education, does not affect dietary habits, body composition and body fat distribution in children with T1D treated with CSII. Moreover, the sub-group of subjects showing a significant improvement in glycometabolic control reported an increase in CHO intake and a reduction in fat and protein intake.
    Full-text · Article · Jun 2013 · Acta Diabetologica
  • Source
    • "For each patient, the mean HbA1c level from the preceding year was calculated. Prospectively collected HbA1c data from the diabetologic pediatric department were obtained from an existing long-term project addressing metabolic control in children with diabetes (23,24). Throughout the study period, laboratory methods for HbA1c assessment were consistent. "
    [Show abstract] [Hide abstract] ABSTRACT: OBJECTIVE To compare the diagnostic accuracy and time expenditure of screening models based on glycated hemoglobin (HbA1c) level and psychometric measures for mood disorder (MD) among children with type 1 diabetes. RESEARCH DESIGN AND METHODS With semistructured clinical interviews (Schedule for Affective Disorders and Schizophrenia for Children–Present and Lifetime version, 120 min/patient) as a reference for diagnosing MD, including major depressive disorder (MDD), we tested 163 subjects, aged 8 to 18 years, with type 1 diabetes. We evaluated four screening approaches: 1) Children’s Depression Inventory (CDI) at 30 min/patient, 2) HbA1c level, 3) HbA1c level plus CDI, and 4) HbA1c level plus Children's Depression Rating Scale (CDRS) at 40 min/patient. These tests were conducted with all participants, and the total time expenditure for all four approaches was calculated as the total time needed to implement successfully the screening for MD or MDD in the center. RESULTS HbA1c performed on par with individual psychometric tests in diagnosing MD or MDD. The HbA1c plus CDRS model was the best screening procedure for both MD and MDD, with diagnostic thresholds for HbA1c established at 8.7% and 9.0%, respectively. Cutoff points for CDRS assessed after filtering by HbA1c were 26 (MD) and 30 (MDD) points. Center-wide application of this procedure would result in an 83% reduction of the examination time necessary for the psychiatrist for MD screening and a 91% reduction for MDD screening, as compared with standard screening with CDI. CONCLUSIONS Use of HbA1c level followed by CDRS is a time-efficient procedure to screen for MD in children with type 1 diabetes.
    Full-text · Article · Sep 2012 · Diabetes care
  • Source
    • "The study group consisted of 1032 diabetic children treated in the Department of Paediatrics, Oncology, Haematology and Diabetology who were diagnosed with diabetes between 1991 and 2011. Partial data on treatment outcomes in this group and on genetic screening have been published in previous reports141516. Patients with confirmed monogenic background of their illness and type 2 diabetes (n=43) were excluded from the study group. "
    [Show abstract] [Hide abstract] ABSTRACT: Introduction: collection of family history of diabetes mellitus (DM) is commonly performed when this illness is diagnosed in children. However the significance of gleaned information may differ depending on the affected family members. Aim of the study: this study was performed in order to describe detailed familial history of DM in patients and to evaluate the impact of it on the natural course of childhood DM. Material and methods: After exclusion of patients with confirmed monogenic basis of the disease or type 2 diabetes, the study group numbered 989 diabetic children. The data on detailed family history of DM among the first- and second- degree relatives, age at the onset of DM, recent percentage of glycated hemoglobin (HbA1c), presence of diabetes-related antibodies and the highest observed fasting c-peptide level were collected. Results: Having siblings with DM was linked to early onset of diabetes in the study group (mean difference -2.83 95% confidence interval [cI] -4.24 to -1.42). Dominant mode of inheritance, particularly from the maternal side was significantly associated with diabetes onset at an older age. Children of diabetic mothers developed diabetes at a mean age of 10.83 in comparison to those without family history of DM - 8.75 years (p=0.0228). However, children whose mothers had any type of DM, had a significantly higher level of glycated hemoglobin than the others (8.34 vs 7.56%, p=0.0315). Additionally, a rising number of units of the family tree affected by any type of diabetes was associated with later onset of diabetes in children (p for trend = 0.0452). Conclusion: Familial factors influence the natural course of childhood diabetes, but their contribution is not equal, showing more pronounced effects of maternal factors.
    Full-text · Article · Jan 2012 · Pediatric endocrinology
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