Andrea Lukács, Emőke Kiss-Tóth, Beatrix Varga, Andrea Soós, Peter Takác and
László Barkai (2013). BENEFITS OF CONTINUOUS SUBCUTANEOUS
INSULIN INFUSION ON QUALITY OF LIFE. International Journal of
Technology Assessment in Health Care, 29, pp 48-52.
Benefits of continuous subcutaneous insulin infusion on quality of life
Andrea Lukács1, Emőke Kiss-Tóth1, Beatrix Varga2, Andrea Soós3, Peter Takác1, László
1Faculty of Health Care, University of Miskolc, Miskolc, Hungary
2Faculty of Economics, University of Miskolc, Miskolc, Hungary
3Department of Pediatrics, Borsod County University Hospital, Miskolc, Hungary
4Miskolc, Hungary, Postgraduate Institute of Pediatrics, Medical and Health Science Center,
University of Debrecen, Debrecen, Hungary
Purpose: The aim of this study was to compare the general health-related quality of life
(HRQoL), the metabolic control (HbA1c), the anthropometric measurement, and the
cardiorespiratory fitness (expressed by VO2max) in youths with type 1 diabetes treated with
continuous subcutaneous insulin infusion (CSII) to those receiving multiple daily injections
(MDI). We looked for factors influencing the HRQoL and metabolic control.
Methods: A total of 239 patients treated with CSII (51 girls and 53 boys) or MDI (64 girls and
71 boys) between ages 8 and 18 years were assessed with the Pediatric Quality of Life
Inventory, Generic Core Scales, and Diabetes Module. VO2max was evaluated using the 20-
meter shuttle run test.
Results: CSII group had significantly better HRQoL according to both child self-report and
parent proxy-report. Youths with CSII reported better physical, emotional, and school-related
functioning, and had less diabetes-related fear and symptoms than the MDI group. There were
no significant differences in body mass index z-scores, insulin doses, HbA1c, and VO2max
between the groups. HRQoL was predicted by the CSII therapy (β =−0.220; p < .001) and the
VO2max (β = 0.386; p < .001), other clinical and anthropometric parameters had no effect; the
HbA1c was predicted only by VO2max (β =−0.353; p < .001).
Conclusions: Diabetic youths treated with CSII therapy have better HRQoL than those treated
with MDI. There are no differences between the investigated groups in anthropometric data,
glycated hemoglobin, and physical fitness. Moreover, good physical fitness has an important
role in achieving better metabolic control and HRQoL, which underlines the importance of
regular aerobic exercise in the treatment and care of type 1 diabetes in childhood.
Keywords: Type 1 diabetes mellitus, Children, Adolescents, Health-related quality of life,
Continuous subcutaneous insulin infusion
Type 1 diabetes mellitus (T1DM) is a life-long disease, the incidence of which is increasing
worldwide among children and adolescents (1). Multiple daily injection (MDI) treatment is
the most widely used method of insulin administration. This regimen involves intermediate or
long acting insulin once or twice a day as basal dose and rapid acting insulin at each meal
time, and patients need to administer at least three or more injections a day (2). A
technological alternative to this method of insulin delivery is the continuous subcutaneous
insulin infusion (CSII or insulin pump therapy), which was developed in the 1970s (3),
but gained popularity among diabetic patients in the 1990swhen theDiabetesControl and
ComplicationTrial showed the benefits of intensive insulin therapy for achieving tight
metabolic control and reducing the risk of micro- and macrovascular complications
(4). Insulin pump therapy is a commonly used alternative to MDI in the treatment of pediatric
T1DM. The portable insulin pump is a mechanical medical device that offers the most
physiological way of insulin delivery because it simulates the normal pattern of insulin
secretion. The insulin pump gives flexibility to the patients in many areas of life (5). The
insulin pump therapy can be used even for a very young age-group (6). Although the
number of patients treated with CSII is growing rapidly, there is an issue about the clear
advantages of insulin pump therapy over MDI in childhood (7–10). The strength of evidence
of the utilization data in the recent randomized controlled trials and meta-analyses was low or
insufficient comparing CSII with MDI for health-related quality of life (HRQoL), metabolic
control, and anthropometric measurement. There have been only a few studies included
assessing children and adolescents, and all trials suffered from limited sample sizes. Research
into the use of CSII in children and adolescents is needed.
Regular exercise plays an important role in the treatment protocol for diabetes mellitus.
Especially good cardiorespiratory fitness is essential for patients with T1DM as the diabetes is
associated with a substantially increased risk of developing cardiovascular disease (11). It has
several health-related benefits; advantages include psychological well-being, normalization in
blood lipid profile, lower blood pressure, and reduced exogenous insulin requirements
(12;13). Studies found that youths with T1DM have lower cardiorespiratory fitness compared
with healthy peers (14;15), but we did not find studies that compared the cardiorespiratory
fitness of youths with T1DM treated with CSII to MDI therapy.
The present study was designed to compare the HRQoL, the metabolic control, the
anthropometric measurement and the cardiorespiratory fitness in youths withT1DM treated
with CSII to MDI therapies. It also aimed to assess the factors influencing the HRQoL and
metabolic control in patients with T1DM.
PATIENTS AND METHODS
Patients and Settings
The study participants were recruited from diabetes-based summer camps and were eligible
for this study if they were diagnosed with T1DM for at least 2 years, were 8–18 years old,
treated with CSII or MDI. Exclusion criteria were physical problems that made it difficult for
the patient to carry out the shuttle run test. There were 239 patients with T1DM treated with
CSII (51 girls and 53 boys) or MDI (64 girls and 71 boys) who took part in this cross-
sectional survey. The camps were supported by foundations so the participation was made
possible for everyone regardless of the financial background of the families. All the patients
from 8 to 18 years old were invited to take part in the study, but there were fourteen children
who did not meet the requirements for the 20-meter shuttle run test due to musculo-skeletal,
cardiac or respiratory disorders; and there were fifteen parents who did not complete the
questionnaire. Participants were white/non-Hispanic. The investigated groups did not differ
significantly in gender, age and in insulin dose. Table 1 presents the sample characteristics.
The youths and their parents were informed about the purpose and methods of the research
verbally and in written form. Written consent was obtained from the parents and verbal assent
from youths under age 18 before the completion of study measurement. This research study
was approved by the Borsod-Abaúj-Zemplén County Regional Scientific and Research Ethics
Health-Related Quality of Life Measurement. HRQoL was assessed with the Pediatric Quality
of Life Inventory (PedsQL) 4.0 Generic Core Scale (GCS). The PedsQL is a measurement
model for HRQoL of healthy and chronically ill and youths with acute illnesses. The scale
contains developmentally appropriate child self-report (5–18 years) and parent proxy-report
(2–18 years) versions. The twenty-three-item GCS encompasses four subscales: physical
functioning (eight items), emotional functioning (five items), social functioning (five items),
and school functioning (five items) (16). The participants rated how much of a problem they
have had in the previous month on a five-point Likert-type response scale. The answer was 0
if there were no problems with the above-mentioned functions and 4 if it was almost always a
problem. Items were reverse-scored and linearly transformed to a 0–100 scale, where 0 = 100,
1 = 75, 2 = 50, 3 = 25, and 4 = 0. Scores were computed as the sum of the items divided by
the number of items answered.
The multidimensional PedsQL DiabetesModule (DM) was developed to measure disease-
specific HRQoL for T1DM (17). The DM has five subscales: diabetes symptoms (eleven
items), treatment barriers (four items), treatment adherence (seven items), worry (three items),
and communication (three items (17).
Normal range of total and subscale scores of GCS and DM are not available in the literature.
Higher scores indicate better quality of life. In this study, the total scores and subscale scores
of the GCS and subscale scores of DMwere used for comparing HRQoL of the CSII and MDI
Cardiorespiratory Fitness. Cardiorespiratory fitness was measured using the 20-meter shuttle
run test. This test was originally developed by Léger and Lambert. The participants had to run
between two lines, 20 meters apart, at the sound of a prerecorded CD signal. The initial speed
was 8.5 km/hour and it progressively increased by 0.5 km/hour every minute until the runner
could no longer keep up with the required speed. The maximal oxygen consumption was
predicted from the speed of the last stage the participants completed using the regression
equation of Léger et al. (18). The validity of the 20-m shuttle run test to predict VO2max has
been previously established (19). VO2max is the best measure of cardiorespiratory fitness. It
varies greatly between individuals. The normative data for VO2max (ml/kg/min) in 10- to 19-
year-old males, who are not athletes, are 47–56, and 36–46 in females (20). If blood glucose
measured before the test was out of the target range (5–10 mmol/L), a new appointment was
given to perform the test on another day.
Body Mass Index and Metabolic Control. Height and weight were measured for calculating
BMI (kg/m2) and BMI z-score (adjusted forchild age and sex). Z-scores (or standard
deviation scores) was calculated according to the formula (Xi-Mx)/SD, where Xi is the actual
measurement, Mx is the mean value for that age and sex, and SD is the standard deviation
corresponding to that age and sex. In accordance with the guidelines of the Hungarian
National Institute of Child Health, a z-score between the 3rd and 90th percentile was
considered normal (21). The hemoglobin A1c (HbA1c) values for the metabolic control were
extracted from the medical records of the study participants.
We used SPSS 19.0 statistical software for data analysis. Descriptive statistics were presented
as mean and ± standard deviation. All reported results were two-tailed; significance level
was set at p values ≤.05. To compare the results of patients treated with CSII and MDI we
used an independent t-test. Gender difference was evaluated with the Pearson Chi-square test.
Stepwise multiple regression analysis was carried out to establish the factors that influenced
the generic HRQoL and the metabolic control (HbA1c).
Health-Related Quality of Life
We observed significant differences in HRQoL between the CSII and MDI groups regarding
both the child self-report (CSR) (p < .001) and the parent-proxy report (PPR) (p < .001)
according to the GCS total scores. Youth with CSII therapy had higher scores. The difference
was caused by the divergent emotional functioning (CSR: p < .001; PPR: p < .001) and better
physical functioning (CSR: p = .008; PPR: p = .005) between the two groups. The youths
treated with CSII reported significantly better school functioning than those with MDI therapy
(CSR: p = .004). Regarding the diabetes-specific subscales, we found that CSII patients had
significantly a higher subscale score in Diabetes symptoms (CSR: p = .001; PPR: p = .001)
and in Worry subscale (CSR: p < .001; PPR: p < .001). The GCS total score and subscale
scores and DM subscale scores are presented in Table 2.
Cardiorespiratory Fitness, Metabolic Control, and Anthropometric Measurement
We computed themaximal oxygen consumption (VO2max) separately by gender using the 20-
meter shuttle run test.We found no significant differences between the CSII and MDI groups
either in boys or girls. The metabolic control between the CSII and MDI groups, as well as the
BMI z-scores, was similar without any notable differences (Table 1).
Predictors of General Health-Related Quality of Life and Metabolic Control
Using stepwise multiple regression analysis, we found that two factors, the VO2max value and
the method of intensive therapy proved to be significant independent predictors of the general
HRQoL. Age, gender, diabetes duration, HbA1c, insulin dosage, and BMI z-scoreswere not
significant in the model. The results of the regression indicated that VO2max and the method
of therapy explained 21.4 percent of the variance (Table 3). When HbA1c was used as a
dependent variable in the multiple regression model, only the maximal oxygen consumption
proved to be the single significant predictor of metabolic control (B = −0.093, SE(B) = 0.016,
β = −0.353, t = −5.813; p < .001; R = 0.353; R2 = 0.125).
The main strength of our study is that we evaluated two modalities of intensive insulin
therapy from clinical, anthropometric, HRQoL, and physical fitness points of view using the
same cohort and a great sample size. The investigated groups were comparable, and
represented patients from different parts of Hungary. There are a few limitations in this study.
The findings of this cross-sectional nonrandomized cohort study design may have been
caused by selection bias to the treatment groups, not the treatment modality, although the
whole childhood population, who participated in the summer camps and met the inclusion
criteria, was addressed to take part in the study. Costeffectiveness data to determine
superiority between the two interventions and the socioeconomic status of the families were
not available. The insulin pump is almost fully supported by the National Health Insurance in
Hungary, so the use of an insulin pump device does not depend on the family’s financial
situation in Hungary. Our groups represented one ethnicity. These imperfections may limit the
generalizability of the findings.
In this study, we compared the HRQoL, the metabolic control, theBMIz-score, and the
cardiorespiratory fitness expressed by VO2max in youths with T1DM treated with CSII to MDI
therapy with age range of 8–18 years. Patients treated with insulin pump therapy had better
HRQoL than those treated with MDI. This result was confirmed by the parents’ answers.
Recently, SEARCH for Diabetes in Youth Study from the United States had similar results
using the PedsQL GCS (22). Both the child self-report and the parent proxy-report indicated
significantly more stable emotional and physical functioning due to flexibility of the use of an
insulin pump.Youths with CSII therapy reported better school achievement, although this was
not confirmed by the parents’ answers. The CSII group had less annoying signs of diabetes-
related symptoms that might affect their everyday quality of life. An important finding of our
study is that youths with CSII therapy and their caregivers worry less about the efficiency
of the medical treatment, the long-term complications and hypoglycemic episodes. This
finding is supported by survey of Bode et al. (23).
Results from previous studies are controversial regarding the relationship between
metabolic control and HRQoL. In this study, there were no significant differences in HbA1c
between the two investigated groups, suggesting that the method of the intensive therapy had
no effect on metabolic control. Our finding with greater sample size agrees with Pánkovska’s
systematic review and meta-analysis, namely that there is no important difference in glycemic
control in patients treated with insulin pumps compared with MDI (24). We had no
comparison data from the literature regarding the maximal oxygen consumption between the
CSII and MDI groups. Studies examining the physical fitness in patients with T1DM did not
distinguish between the methods of intensive insulin therapy. Our result is unique in this field;
the method of the intensive insulin therapy has no significant effect on the young patients’
cardiorespiratory fitness (expressed by VO2max). Analyzing the total patients with T1DM in
the regression model, we found two predictors that explained the better HRQoL. From these
results, we would conclude that the CSII therapy and the better maximal oxygen consumption
are related to better HRQoL perception in pediatric diabetic patients. The favorable metabolic
control was explained only by the higher VO2max value. These results underline the
importance of the cardiorespiratory fitness both in achieving better HRQoL and more
favorable metabolic control. Although CSII therapy had no effect on the metabolic control
and cardiorespiratory fitness, this type of treatment influenced the HRQoL positively, which
is a remarkable finding. This could be due to greater emotional balance and less fear of
diabetes-related symptoms. Parental anxiety is known in the literature (25). We also found
that parents ofMDI group had more diabetes-related worry and stress associated with their
child’s medical care than parents of children using CSII. The long-term parental fear may be
correlated with overprotection and may limit the diabetic child’s self-esteem and build panic
issues in children as well (26). The main goal in diabetes management is to achieve good
metabolic control and improve quality of life of the young patients. CSII therapy seems to be
a more effective way to make the young patient feel better, mainly by giving psychological
stability and reducing the burden of diabetes-related anxiety.
In conclusion, children and adolescents with T1DM treated with CSII therapy have better
HRQoL than those treated with MDI of insulin. There are no differences between the
investigated groups in anthropometric data, glycated hemoglobin, and physical fitness.
Moreover, good physical fitness has an important role in achieving bettermetabolic control
andHRQoL which underlines the importance of the regular aerobic exercise in the treatment
and care of T1DM in childhood.
CONFLICTS OF INTEREST
Andrea Lukács has received a Hungarian Diabetes Association grant and László Barkai
reports a grant to his institution by the European Union, co-financed by the European Social
Fund. The other authors report no potential conflicts of interest.
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