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Indian Pediatr 2019;56:595-602 |
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Continuous vs.
Intermittent Insulin Delivery in Children and Adolescents with
Type 1 Diabetes Mellitus
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Source Citation :
Blair JC, McKay A, Ridyard C, Thornborough K, Bedson E,
Peak M, et al. Continuous subcutaneous insulin infusion versus
multiple daily injection regimens in children and young people at
diagnosis of type 1 diabetes: pragmatic randomised controlled trial and
economic evaluation. BMJ. 2019;365:l1226.
Section Editor:
Abhijeet Saha
|
Summary
This multicenter, open label, parallel group,
randomized controlled trial was conducted to compare the efficacy,
safety, and cost utility of continuous subcutaneous insulin infusion
(CSII) with multiple daily injection (MDI) regimens during the first
year following diagnosis of type 1 diabetes mellitus (T1DM) in children
and adolescents (7 mo – 15 y) in UK. A total of 294 participants with a
new diagnosis of T1DM were randomized, stratified by age and treating
center, to start treatment with CSII (n=145) or MDI (n=149)
within 14 days of diagnosis. Primary outcome was glycemic control, as
measured by glycated hemoglobin (HbA1c), at 12 months. At 12 months,
mean HbA1c was comparable with clinically unimportant differences
between CSII and MDI participants (60.9 mmol/mol vs 58.5 mmol/mol;
mean difference 2.4 mmol/mol; 95% CI -0.4 to 5.3; P=0.09).
Achievement of HbA1c lower than 58 mmol/mol was low among the two groups
(66/143 (46%) CSII participants vs. 78/142 (55%) MDI participants
(RR 0.84; 95% CI 0.67 to 1.06). Parents (but not children) reported
superior pediatric quality of life inventory scores for those patients
treated with CSII compared to those treated with MDI. The authors
concluded that during the first year following diagnosis of T1DM, no
clinical benefit of CSII over MDI was identified in children and young
people in the UK setting, and treatment with either regimen was
suboptimal in achieving HbA1c thresholds. CSII was not cost-effective.
Commentaries
Evidence-based Medicine Viewpoint
Relevance: Blair, et al. [1] recently
published the data from a pragmatic randomized controlled trial (RCT)
comparing the efficacy, safety and cost-effectiveness of insulin therapy
delivered over a period of one year, either as continuous infusion
(through a pump) or multiple daily injections, in children with newly
diagnosed type 1 diabetes mellitus (T1DM). The rationale for this study
was the significant rising burden of T1DM in European countries,
considerable economic as well as non-economic consequences of managing
T1DM in young people, and the availability of multiple methods of
insulin delivery to achieve glycemic control. Limited available data
suggested that superior glycemic control (and its consequent clinical,
social and economic benefits) could be possible by using insulin pumps
designed for continuous (rather than intermittent) insulin delivery [2].
However, the limited evidence pool is based on small clinical trials
with inherent biases, thereby making it difficult to draw a robust
conclusion. This trial [1] is a value addition against this backdrop of
scientific uncertainty. Table I summarizes the
broad outline of the trial [1].
TABLE I Outline of the Trial Comparing Continuous and Intermittent Insulin Delivery
Characteristic |
Comments |
Clinical question |
Although the authors did not state a clinical question in the
PICOT format, it could be expressed as: “What is the efficacy,
safety and cost (O=Outcomes) of insulin therapy delivered by
continuous infusion (I=Intervention) compared to multiple,
intermittent injection (C=Comparison) in children with newly
diagnosed T1DM (P=Population) over a period of one year (T=Time
frame)?” |
Study design |
Pragmatic, randomized controlled trial with individual
participants |
Study setting |
Clinical centers based in 15 cities in the United Kingdom with
expertise in managing pediatric diabetes |
Study duration
|
May 2011 to January 2017 |
Inclusion criteria |
Children and adolescents (7 mo to 15 y) with newly
diagnosed T1DM based on (undefined) standard clinical practice.
The trial protocol also mentioned an additional inclusion
criterion viz children aged >8 y able to adhere to the treatment
and study protocols; although, it was unclear how this was
ascertained. |
Exclusion criteria |
A number of exclusion criteria were laid down; notably, prior
treatment for T1DM, hemoglobinopathy, unspecified co-morbidities
that could impact glycemic control, psychological or psychiatric
disorders, known allergy to any component of insulin as part or
insulin glargine, intake of unspecified medication(s) that could
impact glycemic control, thyroid disorder, and poorly controlled
celiac disease .
|
Intervention and Comparison groups |
All participants underwent pre-trial analysis of blood glucose,
HbA1c level, pH, thyroid function, anti-islet cell and anti-glutamic
acid decarboxylase antibodies, and antibodies for coeliac
disease. They were provided formal education using the syllabus
prescribed by the International Society for Paediatric and
Adolescent Diabetes. Children/caregivers were trained to deliver
insulin, and record blood glucose by glucometers. The
intervention arm received training to use infusion pumps as
well. The total insulin dosage per day was calculated as 0.5
U/kg/d (in pre-pubertal children) or 0.7 U/kg/d in pubertal
children. Those in the Comparison arm received half of the total
insulin dosage as long-acting insulin glargine or detemir once a
day, and the other half as short-acting insulin as part
delivered thrice daily before meals. Additional insulin as part
was delivered when >10 g carbohydrate was consumed. The
Intervention arm received half the daily dose as insulin as part
infused at a continuous basal rate, and the other half as
boluses before meals. Additional insulin as part was delivered
when >5 g carbohydrate was consumed. Correction doses for
hyperglycemia were calculated for both groups. |
Outcomes |
Primary: HbA1c measured 12 months after the start of therapy |
|
Secondary:· |
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• Proportion of children achieving the national target range
HbA1c. |
|
• Frequency of severe hypoglycemia (ie associated with altered
sensorium). |
|
• Frequency of diabetic ketoacidosis (DKA). |
|
• Change in height z score |
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• Change in BMI z score |
|
• Insulin requirement per day. |
|
• Partial remission rate |
|
• QoL score at 6 and 12 months |
|
• Serious adverse events |
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• Adverse event rate |
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• Incremental cost per quality adjusted life year (QALY) gained
|
Follow-up protocol |
Children were followed-up with formal study visits every 3
months after enrolment. During these visits, HbA1c, adverse
events, anthropometry measurements, usage of insulin, records
from glucometers and insulin pumps, treatment diaries etc were
examined. In order to determine access of health care services
outside the study, local hospital databases were also examined.
|
Sample size |
A priori sample size calculation was performed for a superiority
trial, to detect 0.5% (5.46 mmol/mol) difference in HbA1c at the
end of 12 months as this difference is considered to be
clinically significant.
|
Data analysis |
Intention-to-treat (ITT) analysis was performed, analyzing
participants in the groups to which they were randomized.
Additional per protocol analyses were also performed.
|
Comparison of groups at baseline |
The groups were comparable at baseline with respect to age,
gender, ethnicity, socio-economic deprivation, body mas index,
height, HbA1c, blood glucose, and pH. |
Summary of results (Intervention vs
|
Primary outcome: |
Comparison groups) |
• HbA1c (ITT) at 12 months (mmol/mol): 60.9 (58.5, 63.3) vs 58.5
(56.1, 60.9).
|
|
• HbA1c (per protocol) at 12 months (mmol/mol): 60.2 (56.4,
63.9) vs 59.3 (55.3, 63.2). |
|
Secondary outcomes: |
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• Proportion of children achieving the national target range
HbA1c. |
|
- <58 mmol/mol: 46.2% vs 54.9% |
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- <48 mmol/mol: 15.4% vs 20.4% |
|
• Frequency of severe hypoglycaemia (%): 4.2 vs 1.3 |
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• Frequency of DKA (%): 1.4 vs 0.0 |
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• Change in height z score: -0.1 vs 0.0 |
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• Change in BMI z score: 0.6 vs 0.5 |
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• Insulin requirement (U/kg/day): 0.7 vs 0.6 |
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• Partial remission rate (%): 24.4 vs 32.8 |
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• QoL score at 6 and 12 months: |
|
- Statistically insignificant difference in child-reported QoL
scores. |
|
- Statistically significant but clinically insignificant
difference in parent-reported QoL score.
|
|
• Serious adverse events (incidence density rate): 1.4 vs 0.0 |
|
• Adverse event rate (incidence density rate): 1.4 vs 0.0 |
|
• Incremental cost per quality adjusted life year (QALY) gained:
GBP 1863 (1620, 2137) |
|
The investigators undertook additional analysis of the primary
outcome based on baseline HbA1c and socio-economic deprivation.
They did not observe any difference in efficacy between the
groups.
|
T1DM: Type 1 diabetes mellitus; QoL: Quality of Life; HbA1c:
Glycated hemoglobin; GBP: Great Britain Pounds. |
Critical appraisal: Table II
outlines the methodological aspects of the trial.
Table II Critical Appraisal of Trial Methodology
Criteria |
Conclusion |
Comments |
Generation of random sequence |
Adequate |
Internet-based randomization using variable block sizes was done
by a statistician. Participant were also stratified by age bands
(7 months to <5 years, 5 years to <12 years, ³12 years)
and by treating center.
|
Allocation concealment |
Unclear |
The process has not been mentioned either in the protocol or the
study report. |
Blinding |
Inadequate |
There was no blinding of participants or outcome assessors. |
Completeness of reporting |
Adequate |
All randomized participants were included in the primary
intention-to-treat analysis. The required sample size was nearly
fulfilled for this. Detailed description of participants who
dropped out have been provided. Adverse events were analyzed on
the basis of actual intervention received rather than group to
which randomized. |
Selectiveness of outcome reporting |
Adequate |
All clinically relevant outcomes were included.
|
Overall impression |
Moderate risk of bias |
Well designed trial; although, allocation concealment should
have been clearly specified. |
This RCT [1] has a published protocol [3], although
the trial was started nearly 4 years prior to the protocol being made
public. Nevertheless, it is heartening that there are no deviations from
the protocol.
The trial was conducted as a pragmatic RCT. Pragmatic
trials are generally designed to examine the ‘effectiveness’ of
interventions in real-world clinical settings, rather than ‘efficacy’ in
highly controlled research settings. The latter trials are designated
explanatory trials these days [4]. Pragmatic trials are especially
useful to estimate the external validity and hence generalizability of
findings for interventions determined to be efficacious through
explanatory trials with high internal validity. However, in real-life
many trials including this one has elements of both types of trials.
Analysis of this trial [1] using the PRECIS tool
[5,6] suggests that it is not a completely pragmatic trial. A strictly
pragmatic trial is designed to mimic the real-world setting as closely
as possible. Thus, it may not have rigid inclusion or exclusion
criteria, and clinicians are not often constrained by guidelines on how
to apply the experimental intervention. Further, the intervention can be
applied by clinicians with all levels of expertise. There may not be
formal scheduled follow-up visits but data are collected as participants
report for follow-up. Mechanisms to ensure compliance to the trial
protocol and strategies to enhance adherence to prescribed treatment are
also not generally included. Understandably, an extremely pragmatic
trial could compromise internal validity considerably.
The title of this study [1] suggests that continuous
infusion of insulin was compared against multiple daily injections.
However, both groups received 50% of the total daily insulin dose as
three bolus injections prior to meals. Only the remaining 50% was
delivered either as a continuous infusion or a single bolus injection.
Thus, in effect, there was only one injection less (per day) in the
intervention group. Although this distinction is obvious to clinicians
managing pediatric T1DM, it may not be immediately understood by parents
of children newly diagnosed with the condition, who are offered either
option.
The trial [1] had numerous methodological
refinements. The study centers were carefully selected based on the
presence of personnel with expertise in pediatric T1DM and insulin pump
therapy. Children enrolled in the trial underwent an educational program
structured as per international guidelines. A noteworthy feature of this
trial is that potential beneficiaries appear to have been included in
designing the trial protocol, participation and outcomes to be measured.
The trial management committee and the trial steering committee included
parents of children with T1DM and children themselves. However, the
details of these and the impact thereof (positive or negative) are not
mentioned. The investigators reported that the study results and
clinical significance were discussed with the families of enrolled
children. This suggests a high degree of stakeholder involvement. This
stakeholder involvement is further evident as children/parents were
offered a choice of either intervention, and those who had fixed
preferences were not included in the study. It appears that even during
the course of the study, there was room to switch interventions. These
actions mimic the real-world scenario to a large extent.
In terms of methodology, the investigators chose a
large set of clinically meaningful outcomes reflecting efficacy and
safety of the intervention. Additionally, costing data were included to
assess value for money. It is difficult to confirm whether the efficacy
data in this study represent effectiveness in the real world. The
proportion of children with adequate glycemic control appears to be
fairly low in both groups. On the other hand, episodes representing poor
control such as severe hypoglycemia, DKA, and unscheduled medical visits
were also infrequent. In this regard, it is laudable that the
investigators did not solely rely on parental report of additional
medical care, but examined local hospital and clinic databases as well.
A recent systematic review [7] suggested that
continuous subcutaneous insulin infusion had a marginal but
statistically significant benefit (in terms of reduction in HbA1c) over
multiple daily injections, in adults as well as children. However, there
were no meaningful differences in terms of severity and duration of
hypoglycemic episodes.
Extendibility: This trial showed that (50%
of the daily) insulin dosage in children with T1DM, was comparable in
terms of efficacy and safety, whether delivered as a continuous infusion
(using a pump) or a single bolus injection. However, the pump-based
therapy was significantly more expensive – mostly due to the cost of the
pump, associated consumables and unscheduled hospital admission.
Conclusion: The findings in this well-conducted
RCT suggest that there is no pressing need to consider insulin
pump-based therapy in T1DM.
Funding: None; Competing interests: None
stated.
Joseph L Mathew
Department of Pediatrics,
PGIMER,
Chandigarh, India.
Email:
[email protected]
References
1. Blair JC, McKay A, Ridyard C, Thornborough K,
Bedson E, Peak M, et al. Continuous subcutaneous insulin infusion
versus multiple daily injection regimens in children and young people at
diagnosis of type 1 diabetes: pragmatic randomized controlled trial and
economic evaluation. BMJ. 2019;365:l1226.
2. Misso ML, Egberts KJ, Page M, O’Connor D, Shaw J.
Continuous subcutaneous insulin infusion (CSII) versus multiple insulin
injections for type 1 diabetes mellitus. Cochrane Database Syst Rev.
2010;20:CD005103.
3. Blair J, Gregory JW, Hughes D, Ridyard CH, Gamble
C, McKay A, et al. Study protocol for a randomised controlled
trial of insulin delivery by continuous subcutaneous infusion compared
to multiple daily injections. Trials 2015;16:163.
4. Patsopoulos NA. A pragmatic view on pragmatic
trials. Dialogues Clin Neurosci. 2011;13:217-24.
5. Thorpe KE, Zwarenstein M, Oxman AD, Treweek S,
Furberg CD, Altman DG, et al. A pragmatic-explanatory continuum
indicator summary (PRECIS): A tool to help trial designers. J Clin
Epidemiol. 2009;62:464-75.
6. Loudon K, Treweek S, Sullivan F, Donnan P, Thorpe
KE, Zwarenstein M. The PRECIS 2 tool: Designing trials that are fit for
purpose. BMJ. 2015;350:h2147
7. Benkhadra K, Alahdab F, Tamhane SU, McCoy RG,
Prokop LJ, Murad MH. Continuous subcutaneous insulin infusion versus
multiple daily injections in individuals with type 1 diabetes: A
systematic review and meta-analysis. Endocrine. 2017;55:77-84.
Pediatric Endocrinologist’s Viewpoint
Even a century after the discovery of insulin, the
quest for a treatment regimen that could achieve an optimal glycemic
control (HbA1c <7.5%) for a majority of patients with type 1 diabetes
mellitus (T1DM), is a never-ending search. Continuous subcutaneous
insulin infusion (CSII) using pumps have shown some promise in small
short-term trials, but even this costly therapy has not been able to
achieve optimal glycemic control in a majority of patients with T1DM.
This trial comparing CSII with multiple daily
injections (MDI) of insulin has some notable differences from previous
trials [1]. First, the patients were enrolled, and CSII (intervention)
was started within 15 days of onset of T1DM. Second, the duration of
intervention was fairly longer (1 year) when compared to previous
trials. Third, the enrolment spanned over 7 years at 15 different
centers in the UK. Most of the RCTs assessing the efficacy of CSII have
shown conflicting results. The index trial has shown no superior
efficacy of insulin pumps (CSII) over MDI over 1-year study period in
children aged between 7 months and 15 years. The study reported improved
Quality of Life (QoL) scores (reported by parents) among insulin pump
users compared to those treated with MDI. Further, the authors reported
that CSII was not cost effective for UK or NHS standards.
The results of this trial are in slight contradiction
to previous meta-analysis comparing CSII with MDI, where a modest
efficacy of CSII was shown. Most of the previous RCTs and meta-analysis
(as discussed in this article as well) are more than a decade old. Most
of the RCTs included in this meta-analysis have been of 6 months
duration and conducted on children with T1DM on long-term follow-up who
were randomized to either CSII or MDI. Outside the stringent trial
settings, most of the retrospective or prospective observational data
analysis from various registries of children with T1DM from the
developed world has shown that more than 50% of children with T1DM are
on CSII, and have better glycemic control compared to children on MDI
[2-5].
Even the paper published on the detailed methodology
of this trial has not mentioned the type of insulin pumps used in the
study [6]. As technology is evolving very fast, newer versions of
insulin pumps with advanced functions have come up over the duration of
this study, and after the study enrolment was done. Insulin pumps with
low (and predictive low) glucose suspend have more likelihood of
achieving time in range for target glucose. Further, the study has not
compared the sensor-augmented insulin pump therapy, which has been
associated with better glycemic control in previous studies comparing
the MDI with CSII treatment regimens. Another limitation of the study is
a failure to have the consent of more than 50% eligible children for
enrolment in the study. This could compromise the validity of the
results as it may not be a real reflection of the target population.
Moreover, the first 6 months of diagnosis of T1DM may not be the ideal
time to start a patient on the insulin pump as patients and parents are
still adjusting to the diagnosis (mentally and physically), and
acquiring knowledge on various aspects of home care of T1DM. It may be
an extra burden to learn and manage insulin pump therapy on top of other
day-to-day stringent regimens, which they are still trying to cope with.
Effective Insulin pump therapy needs a highly motivated patient and
family willing to give their best of efforts.
Another important component of this study was
cost-effectiveness analysis, which is more relevant to policymakers
rather than individual patients. Cost-effectiveness may not have much
relevance as long as an individual patient seeking CSII pays from
his/her (or parent’s) pocket as is the status in India. However, for
physicians working in poor or developing economies, it is even more
important to understand the efficacy of such a costly therapy.
Simultaneously, we also need to understand that there are several
aspects of the management of T1DM in children, and cost is just one of
the aspects that need consideration. The physicians, especially
Pediatric Endocrinologists, who manage children and adolescents with
T1DM on daily basis can understand the plight of these children and
families who have to follow a very stringent treatment regimen of at
least 8 needle pricks (4 for self-monitoring of blood glucose and 4
needle pricks for insulin injections) per day along with meticulous
measure of amount of meals and activity. Any intervention that could
make the life of these families and kids easy even by a small fraction
will be most welcome. CSII with insulin pumps reduces the number of
insulin injection pricks, and has shown to improve quality of life
across all the studies among all ages. Improvement of HbA1c, even if
modest, is a bonus.
This study is relevant to the Indian context because
of the sheer number of children and adolescent with T1DM in India.
Prevalence of T1DM among children and adolescents (<15 years) in India
is estimated at 1,28,000 (nearly 6 times the prevalence in the UK) as
per IDF Atlas, 2017 [7]. However, experts believe that actual numbers
may be far more than these estimates as there is no registry or formal
reporting of T1DM in India.
In India, where providing optimal insulin therapy for
children with T1DM could be a challenge for most of the families, CSII
is a far-fetched and unrealistic option for the majority at present.
However, with the widening gap between rich and poor in India, we do get
parents who can easily afford CSII for their children. It may not be
ethically correct not to offer a form of therapy which a patient
(parent) can afford. CSII is definitely a more convenient (could be
subjective) and physiological way of replacing insulin in T1DM, but it
has only shown modest efficacy in improving glycemic control compared to
MDI with insulin analogues. Especially for the Indian setting, it is
important to understand that this modest short-term improvement in
glycemic control comes at an exorbitant cost of CSII. For obvious
reasons, there are no RCTs on this subject from Indian children with
T1DM. There are few anecdotal reports of small series of patients
followed after they were shifted from MDI to CSII, where glycemic
control improved significantly [8].
In my personal experience (unpublished data) of 20
children (8 months to 15 years) on CSII, there was a significant
improvement of glycemic control in a majority of the patients after
changing from MDI to CSII. Most of the parents who sought insulin pump
for their children belonged to literate working-class getting
reimbursement of expenses on treatment of their kids from the employer.
To summarize, CSII should be discussed, as one of the
modes of giving insulin, with all patients with T1DM. As per the
existing evidence on the efficacy of CSII, the main indication for
starting CSII in children has to be patient’s or parent’s
convenience/preference rather than glycemic improvement. The recent
ISPAD guidelines [9], recommend CSII as the preferred (over MDI) mode of
insulin treatment for children less than 7 years, as it is practically
impossible to cover multiple small meals and snacks with as many insulin
injections (6-9 meals/snacks requiring an equal number of insulin bolus
injections). Further, all affording patients with poor glycemic control
on MDI may be offered CSII.
Funding: None; Competing interests: None
stated.
Rakesh Kumar
Department of Pediatrics,
PGIMER, Chandigarh, India.
Email:
[email protected]
References
1. Blair JC, McKay A, Ridyard C, Thornborough K,
Bedson E, Peak M, et al. SCIPI investigators. Continuous
subcutaneous insulin infusion versus multiple daily injection
regimens in children and young people at diagnosis of type 1
diabetes: pragmatic randomized controlled trial and economic
evaluation. BMJ. 2019;365:l1226.
2. Karges B, Schwandt A, Heidtmann B, Kordonouri
O, Binder E, Schierloh U, et al. Association of insulin pump
therapy vs insulin injection therapy with severe hypoglycemia,
ketoacidosis, and glycemic control among children, adolescents, and
young adults with type 1 diabetes. JAMA. 2017;318:1358-1366.
3. Blackman SM, Raghinaru D, Adi S, Simmons JH,
Ebner-Lyon L, Chase HP, et al. Insulin pump use in young
children in the T1D exchange clinic registry is associated with
lower hemoglobin A1c levels than injection therapy. Pediatr
Diabetes. 2014; 15:564-72.
4. Szypowska A, Schwandt A, Svensson J, Shalitin
S, Cardona-Hernandez R, Forsander G, et al. Insulin pump
therapy in children with type 1 diabetes: analysis of data from the
SWEET registry. Pediatr Diabetes. 2016;17:38-45.
5. Sherr JL, Hermann JM, Campbell F, Foster NC,
Hofer SE, Allgrove J, et al. Use of insulin pump therapy in
children and adolescents with type 1 diabetes and its impact on
metabolic control: comparison of results from three large,
transatlantic paediatric registries. Diabetologia. 2016;59:87-91.
6. Blair J, Gregory JW, Hughes D, Ridyard CH,
Gamble C, McKay A, et al. Study protocol for a randomized
controlled trial of insulin delivery by continuous subcutaneous
infusion compared to multiple daily injections. Trials. 2015;16:163.
7. International Diabetes Federation. IDF
Diabetes Atlas, 8th edn. Brussels, Belgium: International Diabetes
Federation, 2017. Available from: http://www.diabetesatlas.org.
Accessed February 17, 2019.
8. Swaminathan K, Mukhekar V, Cohen O. Breaking
socioeconomic barriers in diabetes technologies: Outcomes of a pilot
insulin pump program for the underprivileged in rural India. Indian
J Endocrinol Metab. 2019;23:242-5.
9. Sherr JL, Tauschmann M, Battelino T, de Bock
M, Forlenza G, Roman R, et al. ISPAD Clinical Practice
Consensus Guidelines 2018: Diabetes technologies. Pediatr Diabetes.
2018; 19:302-325.
Pediatrician’s Viewpoint
Intensive management is the key for improved
long-term outcome in diabetes [1]. Maintaining an optimal glycemic
control (as measured by HbA1c targets) especially in preschoolers and
adolescents remains a challenge worldwide.
In this randomized controlled trial and economic
evaluation of infants, children and young people in the first year of
Type 1 diabetes mellitus (T1DM) diagnosis, glycemic control was
suboptimal in both MDI and CSII arms. Moreover, CSII was neither more
clinically effective nor more cost-effective than MDI. The only benefit
of using CSII over MDI was a superior Quality of Life score by the
parents [2].
Insulin pumps provide superior metabolic control when
compared to 1-2 injection/day regimens. The latest ISPAD 2018 guidelines
recommend that if available, insulin pumps should be used in
preschoolers and certain other conditions [3]. Studies done to document
any benefit of CSII vs MDI have shown variable results. Most of
these studies have shown CSII to be superior to MDI in achieving better
glycemic control, superior health related quality of life/patient
satisfaction and lower insulin requirements [4,5]. Even in those studies
where HbA1c was comparable, a higher treatment satisfaction was noted in
pump users and many of them continued pump usage despite having no
benefit in HbA1C levels [6,7]. CSII have become the preferred insulin
delivery system in countries with high pump penetration; e.g.,
USA, Australia and many European nations. These centers are starting
many of their T1DM pediatric patients, particularly preschoolers, on
CSII right from the onset of disease.
Though HbA1c is the standard tool for checking
glycemic control, it has its own limitations such as lack of information
regarding acute glycemic excursions, hypo/hyper-glycemia,
intra/inter-day variability, and false low values in anemia and
hemoglobinopathies. Advances in diabetes care and technology have now
shifted the clinical target focus from HbA1c to more meaningful metrics
of "Time in Range" (time in range defined as blood glucose levels
between 70-180 mg/dL) [8]. In this SCIPI study, HbA1c was comparable
between the two arms but it was not designed to compare the time in
range and glycemic variability between the two arms of the trial.
Despite having comparable HbA1c, there might have been difference in the
time in range between the two groups (which signifies a better glycemic
control). Similar multicenter, longer term studies with the objective to
determine time in range are needed to ascertain which of the two
modalities is better.
Due to lack of affordability of insulin pumps,
multiple daily injections still remain the standard of care of T1DM in
India. Affordable Insulin regimen, extensive diabetes education of the
patient/parents and coupled psychological support system remain the
cornerstone for achieving good glycemic control during crucial first
year of diagnosis of T1DM.
Funding: None; Competing interests: None
stated.
Deepika Harit
Department of Pediatrics
UCMS and GTB Hospital, Delhi-110095,
India.
Email:
[email protected]
References
1. Nathan DM for the DCCT/EDIC Research Group. The
diabetes control and complications trial/epidemiology of diabetes
interventions and complications study at 30 years: overview. Diabetes
Care. 2014;37:9-16.
2. Blair JC, McKay A, Ridyard C, Thornborough K, Bedson
E, Peak M, et al. Continuous subcutaneous insulin infusion versus
multiple daily injection regimens in children and young people at
diagnosis of type 1 diabetes: pragmatic randomized controlled trial and
economic evaluation. BMJ. 2019;365:1226.
3. Sundberg F, Barnard K, Cato A, de Beaufort C, Di
Meglio LA, Dooley G, et al. ISPAD Guidelines. Managing diabetes
in preschool children. Pediatr Diabetes. 2017;18:499-517.
4. Szypowska A, Schwandt A, Svensson J, Shalitin S,
Cardona-Hernandez R, Forsander G, et al. Insulin pump therapy in
children with type 1 diabetes: analysis of data from the SWEET registry.
Pediatr Diabet. 2016; 17:38-45.
5. Sherr JL, Hermann JM, Campbell F, Foster NC, Hofer
SE, Allgrove J, et al. Use of insulin pump therapy in children
and adolescents with type 1 diabetes and its impact on metabolic
control: comparison of results from three large, transatlantic
paediatric registries. Diabetologia. 2016;59:87-91.
6. Weintrob N, Benzaquen H, Galatzer A, Shalitin S,
Lazar L, Fayman G, et al. Comparison of continuous subcutaneous
insulin infusion and multiple daily injection regimens in children with
type 1 diabetes: a randomized open crossover trial. Pediatrics.
2003;112:559-64.
7. Opipari-Arrigan L, Fredericks EM, Burkhart N, Dale
L, Hodge M, Foster C. Continuous subcutaneous insulin infusion benefits
quality of life in preschool-age children with type 1 diabetes mellitus.
Pediatr Diabetes. 2007;8:377-83.
8. Battelino T, Danne T, Bergenstal RM, Amiel
SA, Beck R, Biester T. Clinical targets for continuous glucose
monitoring data interpretation: recommendations from the
international consensus on time in range. Diabetes Care.
2019;8.doi:10.2337/dci19-0028.
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