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Frida Sundberg1,2 | Katharine Barnard3 | Allison Cato4 | Carine de Beaufort5,6 |
Linda A DiMeglio7 | Greg Dooley8 | Tamara Hershey9,10 | Jeff Hitchcock11 |
Vandana Jain12 | Jill Weissberg-Benchell13,14 | Birgit Rami-Merhar15 |
Carmel E Smart16 | Ragnar Hanas2,17
 
1 |  EXECUTIVE SUMMARY AND
RECOMMENDATIONS
The target hemoglobin A1c (HbA1c) for all children with type
1 diabetes, including preschool children, is recommended to be
<7.5% (<58 mmol/mol) (B).
 
This target is chosen with the aim of minimizing hyperglycemia,
severe hypoglycemia, hypoglycemic unawareness, and
reducing the likelihood of development of long-term complications
(B).
 
Intensive insulin therapy, i.e. as close to physiological insulin
replacement as possible with preprandial insulin doses and basal
insulin, should be used, with frequent glucose monitoring and
meal-adjusted insulin regimens. (C).
 
○ Insulin pump therapy is the preferred method of insulin administration
for young children (aged <7 years) with type 1 diabetes
(E). If pump therapy is not available, multiple daily injections
(MDIs), with consideration of use of an injection port, should be
used from the onset of diabetes (E).
○ For preschool children using intensive insulin therapy, preprandial
administration of bolus insulin given for correction if blood
glucose is high and for at least part of the meal is preferable to
giving the whole dose during or after the meal (C).
Greg Dooley is parent of a child with type 1 diabetes diagnosed at age 2, cofounder
of the type 1 diabetes blog Inspired by Isabella (www.
inspiredbyisabella.com); Jeff Hitchcock is parent of a child with diabetes diagnosed
at age 2, founder and president of Children with Diabetes (www.
childrenwithdiabetes.com)
 
This article is a new chapter in the ISPAD Clinical Practice Consensus Guidelines
Compendium. The complete set of guidelines can be found for free download
at www.ispad.org. The evidence grading system used in the ISPAD Guidelines
is the same as that used by the American Diabetes Association. 
 
Carbohydrate counting is best introduced at onset of diabetes (E).
○ The small insulin doses of preschool children may necessitate
diluting insulin for precise dosing (E).
○ Syringes with ó unit marking and pens with at least ó unit dosing
increments should be used to facilitate more accurate insulin
dosing if a pump is not used (or as a back-up to pump use) (E).
○ Continuous glucose monitoring (CGM) can be helpful as an
approach to adjusting insulin doses (E). Some CGM devices are
approved for this use. If CGM is not available, 7 to 10 plasma
glucose checks per day are usually needed for satisfactory glucose
control (E).
○ Injection, infusion, and CGM sites should be properly prepared
and regularly rotated in order to reduce the likelihood of lipohypertrophy,
scarring, infection, rashes, skin reaction, and dry
skin (E).
○ Injection, infusion, and CGM sites should be inspected by diabetes
team members at every clinic visit to detect and treat any
skin problems, such as skin reactions, lipohypertrophy, or lipohypotrophy
(E).
○ The use of pumps and CGM are often limited by skin reactions
to the adhesive. A skin moistener that preserves water can be
used to prepare the site a few days prior to insertion. Topical
corticosteroid (group I or II) can be used to treat skin reactions
and to manage itching after removal (E).
 
Life style interventions designed to reduce the risk of subsequent
cardiovascular disease in children with type 1 diabetes are
needed, and should be directed toward the entire family and not
just the individual child with type 1 diabetes (C).
Family-centered meal routines with restrictions on continuous
eating habits (grazing) are important to ensure dietary quality and
optimize glycemic control in preschool children (C).
Diabetes education should be provided to staff at preschools and
schools where children with type 1 diabetes are enrolled, in order
to ensure that equal participation in all preschool/school activities
occurs and is safely managed (E).
 
Optimal glycemic control, involving the minimizing of both hypoglycemia
and hyperglycemia will give the child the best opportunity to
concentrate, participate, and learn while at preschool and school (C).
Weight, height (or length if <18 months), and Body Mass Index
Standard Deviation Score (or percentiles) should be monitored on
growth charts in all children with type 1 diabetes (E).
 
2  | INTRODUCTION
This chapter focuses on components of care unique to toddlers and
preschool-aged children with type 1 diabetes. These guidelines are written
in particular for children with type 1 diabetes aged 6 months to
6 years. Children <6 months of age at diagnosis should be suspected of
having diabetes other than type 1 including monogenic diabetes, and
their management is discussed in the International Society for Pediatric
and Adolescent Diabetes (ISPAD) guidelines on “The diagnosis and management
of monogenic diabetes in children and adolescents”.1
Preschool children are dependent on others for all aspects of their
care. For the families (primarily parents) of preschool children with type
1 diabetes, their diabetes teams, and other caregivers, including school
and day care staff members and babysitters, treatment is a constant
challenge. Yet, despite this hurdle, it is important to strive for normoglycemia,
as current knowledge about the implications of dysglycemia
makes reducing the likelihood of acute and chronic complications
imperative from the time of diabetes onset. Optimizing glycemic control
for children in this age group often requires treatment using strategies
that differ from those employed for older children and adolescents
with type 1 diabetes. These strategies need to take into consideration
the cognitive, motor, and social immaturity of preschool children as
well as their small body size and growth pattern.
In addition to their dependence on others for insulin administration
and glucose monitoring, preschool children are also dependent on
others for aspects of their lifestyle related to healthy eating and engagement
in physical activity. Lifestyle choices and preferences established
during early childhood provide a window of opportunity for ingraining
healthy habits that will be perpetuated throughout the child's life. The
early establishment of positive behaviors is necessary to ameliorate the
high risk of cardiovascular disease that is associated with diabetes. Providing
adequate education and support of lifestyle changes requires
that the multi-disciplinary diabetes team uses a family-based approach
to ensure that the whole family is appropriately supported.
Supporting the family is necessary for promoting health in the preschool
child with type 1 diabetes. Early childhood is important for
establishing the “salutogenic” (health promoting) capacity needed for a
long life with type 1 diabetes.2 The core aspect of a person's salutogenic
capacity is a good “sense of coherence”, consisting of an everyday
perception of comprehensibility, manageability, and meaningfulness of
health promoting actions taken in everyday life. The main sources of
the child's salutogenic capabilities are the parents. Supporting the parents
to endure the burden of intensified insulin treatment, including
their need for counseling and sleep, is essential to promote and maintain
the health and well-being of the child. It is also important to support
the parents to involve the child in diabetes-related tasks such as
helping to select a finger for monitoring, site for injection/infusion, and
to encourage age-appropriate positive problem solving strategies when
diabetes-related problems occur.
Screening and promotion of optimal health-related quality of life
should be regularly undertaken in preschool children with type 1 diabetes
as in any child with type 1 diabetes. It is important to use validated
parent and parent-proxy screening questionnaires to capture
factors important to the quality of life of children and their parents as
both are important and impactful on diabetes management.
Children younger than 7 years with type 1 diabetes constitute a
minority of the population of all pediatric patients with type 1 diabetes.
In small centers, this will make the number of very young patients small
and the time needed to gain experience in care of this patient group will
be longer. Close collaboration between centers is necessary in order to
optimize quality of care for preschool children with type 1 diabetes.
 
3  | GROWTH AND DEVELOPMENT IN THE
FIRST YEARS OF LIFE
Growth and development in the first years of life are characterized by
an intricate interplay between genetic, metabolic, hormonal, and
environmental factors. “Growth” is an increase in size of the body and
its constituent organs. “Development” is the differentiation of the
form and function of the organs, and refers to not only somatic development
but also neurocognitive, and psychosocial development. Rapid
changes in growth and development occur in the first years of life.
In the first year of life children grow 25 to 30 cm, in the second
year approximately 12 cm, (comparable to the growth spurt in
puberty) and in years 3 to 6 around 6 to 8 cm/y. Weight triples in
the first year of life, increases by approximately 2.5 kg in the second
year, followed by an increase of around 2 kg/y in the next 3 to
4 years. A peak in subcutaneous tissue mass is observed around
9 months of age, which subsequently decreases until 6 years of age.
In order for preschool children to experience normal growth and
development, it is essential that they maintain near normoglycemia,
aiming to increase glucose time in range, and are provided with sufficient
nutrients.3–6 Restrictive diets or lack of food make it difficult to
provide essential nutrients for growth and development, and should
be avoided. It is essential to monitor weight, height (or length if
<18 months), and BMI-SDS (or percentiles) on growth charts in all
children with type 1 diabetes at every clinic visit.
This requirement of sufficient nutrition is in part due to the
brain's high metabolic expenditure in infancy and childhood (3 times
higher than in adults). Body proportion at birth is characterized by a
large head and prominent abdomen. After birth, the brain and the
cranium continue to grow and reach 4/5 of the adult size by the end
of the second year, growing much faster than many other body parts
including the extremities.7
 
4  | THE BRAIN AND COGNITIVE
DEVELOPMENT IN CHILDREN WITH EARLY
ONSET TYPE 1 DIABETES
The brain is metabolically highly demanding, accounting for 20% of
the total energy requirement in adults.8 In the adult, the brain
depends on a continuous supply of glucose as fuel. In the neonate,
glucose is essential for different intracerebral pathways.9 Brain development
requires different nutrients to support the 5 key processes:
(1) neuron proliferation, (2) axon and dendritic growth, (3) synapse
formation, pruning, and function, (4) myelination, and (5) neuron
apoptosis. Regional and temporal variation in glucose utilization suggests
that glucose is essential not only for energy production in the
brain, but potentially for cellular proliferation and synaptogenesis as
well.10 In the neonatal and infant brain, alternative energy sources
may be identified such as ketone bodies, which are transported over
the blood-brain barrier in times of glucose shortage. The ketone
bodies are a substrate for lipid synthesis, although not essential.11
In addition to somatic growth, preschool children experience
rapid cognitive development. Children start by investigating objects
in their immediate environment, eventually expanding to exploring
anything within reach. Mobility and thus physical activity increases
with age.
Multiple risk factors have been associated with potential suboptimal
cognitive and fine motor development in children and adolescents
with type 1 diabetes. These factors include early onset of
disease (typically defined as <5 years of age),12 disease duration, history
of moderate to severe ketoacidosis (including those at
diagnosis),13,14 severe hypoglycemia (including seizures or
unconsciousness),15 cumulative exposure to hyperglycemia, and possibly,
the sex of the child.16 A meta-analysis showed that the risk of
cognitive disruption is largest for children with early-onset diabetes
and that the effect is detectable after a mean diabetes duration of
6 years.17 The mean effect size is moderate but might not be large
enough to affect school performance. Clinicians should be concerned
about diabetic ketoacidosis (DKA), severe hypoglycemia and hyperglycemia,
all being detrimental for the health of the preschool child.
When reviewing these findings, it is important to distinguish
between statistically significant group differences vs clinically significant
findings. Statistically significant group differences may or may
not translate into a functional impact on the daily life of a child,
which has not been fully explored in children with type 1 diabetes.
However, we know that early brain and cognitive development are
important for later success in school and beyond.
Glucose uptake by the brain is insulin-independent and mainly
driven by the concentration of glucose. This directly exposes the neuronal
cells of the brain to oxidative stress and glucotoxicity in hyperglycemia,
and to lack of fuel in hypoglycemia.
The maturation of gray matter in the brain is intense throughout
the toddler and preschool years. Gray matter development slowly
curtails over time beginning around puberty. In contrast, white matter
maturation (that is necessary for processing speed and coordinated,
fluid movements) continues until early adulthood.18,19
 
During toddler and preschool years, the brain is highly sensitive
to metabolic disturbances, and potential abnormalities have repeatedly
been identified in magnetic resonance imaging (MRI) studies of
young brains exposed to glycemic extremes, as in type
1 diabetes.20–23 The mechanisms by which early brain development
is affected by type 1 diabetes are not clearly understood. Long-term
exposure to hyperglycemia as well as hypoglycemia (especially with
seizures) and oxidative stress caused by glycemic variability have
been suggested as contributing factors. The main effects seem to
occur in the early phase of the disease. It has been suggested that
metabolic conditions such as hyperglycemia and ketoacidosis at diagnosis
can be predisposing events that makes the brain more vulnerable
to subsequent metabolic insults.13,16
Some, but not all, studies investigating cognition in childhood
onset type 1 diabetes, report decrements in the domains of intelligence
quotient (IQ) (verbal IQ in particular), executive functions
(attention, working memory, and response inhibition), delayed memory
(episodic recall), and processing speed (paper-pencil); however,
these differences are generally not reported until the children are
studied later in childhood.24,25 One possibility is that chronic exposure
to different aspects of dysglycemia is additive, and that brain
and cognitive changes only become apparent over time.
Studies that specifically target the youngest children with type
1 diabetes have found only modest differences in cognitive function
compared with peers. Among a large group (n = 144) of children
aged 4 to 7 years, small differences in the following areas were
reported: IQ, especially verbal, executive functions, and internalizing
mood disorders.26 The cognitive differences remained when
controlled for parental IQ and level of internalizing mood disorders.
Longitudinal follow-up of these children is ongoing and may reveal
how these differences change with time, further exposure to diabetes
(including hypoglycemia and hyperglycemia), and brain
development.27
 
A young child who has executive functioning difficulties, language/
literacy deficits, slowed processing speed, or fine motor coordination
difficulties will likely require professional attention at some
point in their youth. Typically, these children are referred to a neuropsychologist
or other learning specialist during the early elementary
years. These children can require specialized tutoring, small group
instruction, support in the classroom, or other assistance. For all children
with cognitive development issues, early identification and
remediation are crucial to avoid poor outcomes. Optimal glycemic
control will give young children with type 1 diabetes the best opportunity
to concentrate, participate, and learn while at preschool and
school. By achieving good glycemic control, including mitigating prolonged
exposure to hyperglycemia, and by providing early identification
and intervention of academic, cognitive, or motor issues, health
care professionals are best able to help children avoid any negative
impact of type 1 diabetes on everyday function.
For further reading, the ISPAD guidelines on psychological care
of children and adolescents with type 1 diabetes comprehensively
addresses this subject.28 See also the ISPAD Guidelines on
hypoglycemia.29
 
5  | GLYCEMIC TARGETS AND CONTROL IN
PRESCHOOL CHILDREN WITH TYPE
1 DIABETES
Optimizing glycemic control for preschool children with type 1 diabetes
is crucial for their future, both with respect to acute and longtime
diabetes complications as well as their neurocognition, brain
structure, and health-related quality of life (HRQoL).
ISPAD published glycemic targets for hemoglobin A1c (HbA1c;
<7.5%, (<58 mmol/mol) and for self measured blood glucoses
(SMBGs) (from optimal to high risk) in the latest guidelines 2014
(Table 1).30 The targets are applicable to all pediatric age groups,
including preschool children, and the aim should be to achieve optimal
glycemic control. The American Diabetes Association31 in 2014
redefined blood glucose targets for all pediatric age groups to be at
the same level as ISPAD.32 In United Kingdom, glycemic targets for
all pediatric age groups are recommended in the National Institute
for Clinical Excellence (NICE) guidelines, recently updated to an even
lower HbA1c level of ≤6.5% (≤48 mmol/mol; the numbers are based
on the published studies).33
It is important that the diabetes team and family share the same
target HbA1c and glucose ranges. Otherwise, there is a high risk of
discrepancy that can go both ways. Sometimes parents strive for
lower glucose levels than the diabetes team, who at times may articulate
that the family is too strict and take too many glucose checks,
especially at night. At other times, the parents have their own set of
higher glucose targets that they feel fit better with their daily life,
finding the targets set by the health care team unachievable.
When evaluating glycemic targets together with the family, it
might be useful to express them as time spent within target and time
below or above target. It is important that both the diabetes team
and the families consequently use a language that tells the child that
a glucose value can be high, low or normal, and that the glucose level
is never “bad”. The knowledge of a glucose value often calls for
action, but never for blaming or punishing the child.
Parents express that diabetes management style can make a difference.
A positive, non-judgmental, attitude will likely have a
positive influence on the way a young child views and manages
his/her type 1 diabetes as he/she gets older. Parents should be
encouraged to adopt a “matter-of-fact” approach to the routines
(injections/pump site changes, finger pricks, and meal times),
treating numbers as just numbers/data points, and not apologizing
for aspects of care such as finger pricks, site changes, and
injections that cannot be avoided.
Maximizing the amount of time glucose values are in range needs
to be the target for multi-disciplinary diabetes teams, as well as the
family/caregivers. Diabetes education34,35 and a clearly set glycemic
target36 are very important.37,38 Age-specific challenges need to be
considered and age-appropriate actions taken to achieve these.
As discussed above, there are detrimental effects of hyperglycemia;
yet it is an existing practice to allow glucose levels to reach the
hyperglycemic range in the youngest age group in order to avoid hypoglycemia
at all costs. This is unsafe, and treatment should instead aim
to minimize both hyperglycemia and hypoglycemia in the effort to
achieve (near) normoglycemia. If the diabetes team is inexperienced in
treating preschool children with type 1 diabetes, support and advice
should be sought from more experienced colleagues.
 
TABLE 1 Glycemic targets in preschool children with type 1 diabetes according to ISPAD, ADA and NICE guidelines
ISPAD30 American Diabetes Association31 NICE33
Preprandial glucose target 4.0-8.0 mmol/L (70-145 mg/dL) 5.0-7.2 mmol/L (90-130 mg/dL) 4.0-7.0 mmol/L (72-126 mg/dL)
Postprandial glucose target
(2 h post meal)
5.0-10.0 mmol/L (90-180 mg/dL) 5.0-9.0 mmol/L (90-162 mg/dL)
Bedtime 6.7-10 mmol/L (120-180 mg/dL) 5.0-8.3 mmol/L (90-150 mg/dL)
Overnight 4.5-9.0 mmol/L (80-162 mg/dL)
HbA1c target <58 mmol/mol (<7.5%) <58 mmol/mol (<7.5%), a lower target of
<53 mmol/mol (<7%) can be set if it can
be achieved without hypoglycemia
≤48 mmol/mol (≤6.5%)
Abbreviations: HbA1c, hemoglobin A1c; ISPAD, International Society for Pediatric and Adolescent Diabetes, NICE, National Institute for Clinical
Excellence.
 
It might not just be the HbA1c level that is important. Glycemic
variability may play a role in the development of diabetic
complications,39,40 but the long-term impact of glycemic variability
remains controversial.41,42 In adults using continuous glucose monitoring
(CGM), glycemic variability was significantly lower in those without
complications compared with those with complications (Standard Deviation
SD 3.4 vs 4.1 mmol/L), despite comparable HbA1c values.43
Age-specific, family-centered diabetes education plays a key role
in achieving metabolic targets, together with flexible insulin regimens,
glucose monitoring, and carbohydrate (CHO) counting.30,34,44
Hyperglycemia is a major risk factor for (recurrent) ketoacidosis45
and microvascular complications later in life.46,47
Long-term tracking of glycemic control from childhood until
adulthood has been reported.48–52 There is a correlation between the
HbA1c achieved within the first few months after diabetes diagnosis,
the glycemic control later in life, and the risk for cardiovascular complications.
A lower HbA1c achieved at an early phase of life with diabetes
is associated with a lower HbA1c later on.48–52
Long-term studies, for example, the Diabetes Control and Complications
Trial-Epidemiology of Diabetes Interventions and Complications
(DCCT-EDIC), describe a prolonged effect of prior glycemic
levels on diabetic complications, called glycemic memory. This effect
is independent of more recent glycemic control. The DCCT showed a
significant difference of around 2% in HbA1c between the intensive
and conventional groups, but 1 year after the closeout of the study,
HbA1c levels were approximately the same (around 8%).46,47 Nevertheless,
the intensive group showed fewer microvascular complications,
with a risk reduction in retinopathy even 18 years after the
end of the study.53 The DCCT-EDIC results have led to the recommendation
of early tight glycemic control to reduce the risk for diabetic
microvascular and macrovascular complications.47,54,55 The ISPAD
guidelines on microvascular and macrovascular complications provides
a more detailed discussion.56
Early onset of diabetes at a very young age will lead to a longer
duration, which in itself is associated with a higher lifelong risk of
complications, compared with persons with later onset type 1 diabetes.
57 So far, conflicting data exist to whether the prepubertal years
contribute to the same degree as the pubertal years for the development
of microvascular complications.58 Suboptimal metabolic control
in children with early prepubertal diabetes onset may further contribute
to the risk of complications.59–61 Persons with poor glycemic control
during childhood have a high risk of long-term complications,
even if substantial improvement is achieved as young adults,62 and
NICE emphasizes the need to reduce the risk of long-term complications
of type 1 diabetes in a population that will have a long duration
of diabetes because the condition starts before adulthood.
 
6  | INSULIN THERAPY IN PRESCHOOL
CHILDREN
Insulin treatment guidelines for preschool children are essentially similar
to older children and adolescents, but age-dependent aspects have
to be taken into consideration. See the ISPAD guidelines for further
reading on insulin and insulin analogs in pediatric use.63 Worldwide,
most preschool children with diabetes use insulin injections to manage
their diabetes. Although insulin pump use should be considered for
many of these children,” injection, injection therapy is used in many
centers in the following instances: early in the course of the disease in
their remission period; children who were using an insulin pump but
have experienced pump failures “or skin reactions”, “inexperience of
the diabetes team in using pumps in this young age group,” and if living
in limited resource settings where insulin pumps are unavailable.
Approval of insulin analogs in different age groups is regulated
by authorities. Two examples are the European Medicines Agency
(EMA) (www.ema.europe.eu) approvals and the US Food and Drug
Administration (FDA) (www.fda.gov) as of June 2017 (Table 2).
When using injections for insulin delivery, pain can be reduced
by usage of subcutaneous catheters changed every third day (Insuflon;
Unomedical, Lejre, Denmark or I-port: Medtronic MiniMed,
Northbridge CA, USA).64
6.1  | Insulin dosing
Preschool children with optimal glycemic control usually need somewhat
less insulin than older children. The total insulin dose has been
reported to be 0.4 to 0.8 U/kg/d (median 0.6 U/kg/d) in preschool
children with well controlled type 1 diabetes after the remission
phase.65 Insulin pumps offer both greater flexibility in insulin dosing
and a better means to deliver very small, precise doses of insulin than
when using injections,66 and are thus considered the preferred method
for insulin delivery in infants, toddlers, and preschoolers with diabetes,
although earlier randomized studies have failed to show an effect on
glycemic control.63 If pump therapy is not available due to lack of economic
resources, multiple daily injections (MDIs), with consideration of
use of an injection port, can be used. If the diabetes team is not experienced
enough in pump treatment of preschool children, advice should
be sought from a more experienced center to optimize quality of care.
6.2  | Basal insulin
When using injections for insulin treatment, the special diurnal pattern
of insulin requirements in preschool children should be taken
into consideration in designing an individualized basal dosing scheme.
The low requirement of insulin and tendency toward low glucose
 
TABLE 2 Approved insulin analogs in different age groups according
to EMA and FDA
Approved by EMA
from age
Approved by FDA for
(studied from age)
Insulin lispro “Adults and children”
(2 y)
“Adults and children”
(3 y)
Insulin aspart ≥2 y “Adults and children”
(2 y)
Insulin glulisine ≥6 y “Adults and children”
(4 y)
Insulin detemir ≥1 y “Adults and children”
(2 y)
Insulin glargine ≥2 y Adults and pediatric patients”
(6 y)
Insulin degludec ≥1 y ≥1 y
Abbreviations: EMA, European Medicines Agency; FDA, Food and Drug
Administration.
 
levels are often most obvious during the night and especially
between 3 and 6 AM. Preschool children often need much more insulin
late in the evening between 9 PM and 12 midnight.67–69 This creates
typical patterns when programming the basal rates of an insulin
pump used by a preschool child. With MDIs, a basal insulin analog
can reduce hypoglycemia, including nighttime hypoglycemia, compared
with NPH insulin.70–72
 
The combination of the low body weight, and thus low total insulin
dose, demands special consideration when using commercially available
insulin pumps. A pump with a very high precision in delivering very
small basal rates should be chosen for a preschool child. Sometimes further
reduction in the dose is needed, necessitating dilution of the current
U-100 insulin,65,73,74 or an intermittent basal rate of 0 U/h for
limited periods, i.e. every second hour during the night. Use of these
approaches may help to meet the needs of the young child and the
planning of the child's insulin treatment has to be carefully discussed
(with advantages and disadvantages) with the parents so that they are
well aware of the benefits and risks of the chosen strategy. The given
insulin should always be prescribed and documented in normal units to
avoid hazardous misunderstandings regarding insulin dosing, especially
if the child is admitted to hospital. A pump containing diluted insulin
should be labeled with information regarding the currently contained
concentration of insulin (Table 3).
A glucose and meal-adjusted basal-bolus insulin regimen (delivered
by injections or pump) requires that the basal rate can be fine-tuned
by the parents in accordance with the child's current insulin sensitivity.
Insulin sensitivity can be increased after very active days, such as a day
at the beach or out in the snow (decreased insulin resistance). The
overnight basal might then be reduced by 10% to 30% when using a
pump or a similar decrease in bedtime long-acting insulin. Insulin sensitivity
can be markedly reduced (increased insulin resistance) for example
during fever when the basal rate might need to be increased by
20% to 100% according to glucose levels when using a pump, or a similar
increase in dose of long-acting insulin. Under these circumstances,
glucose levels have to be extremely carefully monitored and parents
need constant access to support from the diabetes team.
 
6.3  | Bolus dosing
Although still often used, twice daily insulin dosing in this age group
does not give the flexibility needed in adapting doses to varying
situations in daily life. It is difficult to fine-tune, and difficult for the
family to understand and adjust on their own, which is a necessity for
a successful insulin treatment. A glucose and meal-adjusted basalbolus
insulin regimen (delivered by injections or pump) can be
adapted to the preschool child's daily activities, and is the preferred
type of insulin treatment.
 
Preschool children often need proportionally larger bolus doses
than older children, often constituting 60% to 80% of the total daily
insulin dose (TDD). The often used rule of 500 (500/TDD = how
many grams of CHO is covered by 1 U of insulin) for bolus calculations,
as detailed in the ISPAD guidelines on insulin therapy63 rarely
fits the youngest children as it often underestimates the insulin
dose.70,75,76 Different strategies can be used; either use a 330 or
250 rule (gives 50%-100% more insulin) instead of 500, or, which is
preferable, to observe and calculate the correct proportion between
insulin and CHO from real life meals. To calculate the insulin to CHO
ratio from a given meal, divide the CHO content in the meal
(in grams) by the insulin dose in units that gives an appropriate glucose
profile after the meal. The need for insulin at breakfast is often
very high, and one might consider using 150/TDD in the calculation,
or calculate from real life meals as above.
The timing of the prandial bolus is important. As outlined in the
review by Bell et al,77 several studies show that preprandial bolus
insulin is preferable to insulin administered during or after the meal
and should thus be routinely advised for all toddlers and preschoolers,
even the most unpredictable eaters. However, the dose can be
split into 1 preprandial and 1 during the meal when eating is erratic
or new foods are offered.
 
The dose given during the meal can be based on what the parent
estimates the child will eat of the remaining meal, taking into consideration
the food that has just been eaten and the child's remaining
appetite. Small inaccuracies in calculation of up to 5 to 7 g CHO will
usually not be problematic.78 Larger inaccuracies may result in possible
hypoglycemia or hyperglycemia 2 to 3 hours after eating, but not
immediately.79 These can be anticipated and treated with additional
CHO or a small correction dose of insulin. With a pump, a combination
bolus (also called combo or dual wave bolus) can be helpful, i.e.
part of the bolus is given before the meal and the remainder over
20 to 40 minutes. If the child stops eating before the meal is finished,
the remainder of the bolus can be suspended.
When giving these relatively large bolus doses, one must remember
that they interact with the need for basal insulin in the following
hours. Thus, the total basal rate can be relatively low, around 20% to
40% of TDD. In preschool children, it is often estimated that the
effect of a subcutaneous bolus of rapid-acting insulin analogs (eg, as
lispro, aspart, or glulisine) lasts for only 2 to 3 hours (active insulin
time in pumps).75
 
At breakfast there is often some degree of insulin resistance, and
it is common to experience a marked glucose peak after breakfast in
spite of an adequate insulin dose taken before the meal. The nutritional
content of the breakfast has to be discussed and planned by
the dietitian together with the parents. Increasing the insulin dose
(lower insulin-to-CHO ratio) too much can risk hypoglycemia before
lunch. In this situation, it may be helpful to give the prandial insulin
10 to 20 minutes before breakfast. The need for a large bolus dose
of insulin to cover breakfast might necessitate a very low or suspended
basal rate during the following 3 hours. For some children, a
small amount of fruit (5-10 g of CHO) may be given 2 hours after
breakfast (without insulin) to avoid hypoglycemia, but it is preferable
not to establish a practice that necessitates skipping a bolus as this
may continue as the child gets older.
 
When using MDIs with frequent glucose checking and mealadjusted
insulin dosing, one possible strategy is to give a rapid-acting
insulin analog for all meals, with the exception of the last meal of the
day when short-acting regular insulin can be used to meet the increase
in glucose before midnight. Part of the dose can be given as rapid-acting
analog insulin to avoid needing to give the dose 30 minutes before the
meal; the insulins can be mixed in a syringe or given as separate injections
(if an injection aid is used).
 
TABLE 3 Different strategies for delivering minute basal rates. No pumps that are available today can be adjusted to the insulin concentration.
Thus, if using diluted insulin, recommended doses from the bolus calculator must be recalculated to the diluted concentration
Advantages Disadvantages
Diluted insulin (i.e. 10 or 50 U/
mL)
Fine tuning of basal rates is possible. All technical features of the pump can be used,
such as temporary basal rate changes and bolus
calculations.
Possible to set extremely low basal rates and make
changes in small increments.
Risk of mistakes due to the delivered insulin dose not
being the same as that displayed on the screen.
Pain can occur when large volumes are given as bolus
doses.
Impractical to prescribe doses with diluted insulin More expensive insulin.
“Empty” hours without basal rate • The pump gives exactly the doses displayed on the
screen, decreased risk of mistakes in dosing for
instance when insulin is given temporarily with pen.
Use of more stable commercially available insulins is
possible.
Increased risk of occlusion in tubing due to low flow rate. Increased risk of ketosis due to planned hours without
insulin.
Some of the pumps’ technical features (as temporary basal
dose changes) cannot be used.
 
7 |  NUTRITIONAL NEEDS OF THE
PRESCHOOL CHILD WITH TYPE 1 DIABETES
Breastfeeding should be encouraged for all infants, including infants
with diabetes (World Health Organization [WHO] recommendation,
www.who.int). Complementary foods, preferably iron-rich, should be
commenced from 4 to around 6 months of age.80 If breastfeeding is
not possible, an iron-fortified infant formula should be given as the
main milk drink until 12 months of age.
A routine regarding breast- or formula-feeding is important for
infants with diabetes as this enables appropriate interpretation of glucose
levels and basal and bolus insulin adjustments. This may involve
3 to 4 hourly feeds (of approximately 150-240 mL) during the day
with complementary solids. Continuous or hourly breastfeeding is discouraged
as this makes insulin dosing difficult. Breast milk has
approximately 7.4 g CHO per 100 mL; so for infants 6 months and
older it is possible to bolus before the feed for at least 5 to 7 g CHO
and 15 g CHO in older babies (>9 months).
Optimal nutrition is required to provide sufficient energy and
nutrients to meet the rapidly changing needs of children at this stage
of life. Dietary recommendations are based on healthy eating principles
suitable for all preschool children, with the aim of establishing
family based meal-time routines that promote glycemic control and
reduce cardiovascular risk factors. CHO counting is important to permit
the matching of insulin dose to CHO intake on intensive insulin
regimens,44 and should be taught to the family at the onset of diabetes.
Nutritional advice must be individualized and adapted to cultural
and family traditions. A pediatric diabetes dietitian should provide
education, monitoring, and support at regular intervals throughout
the preschool years, as parents of preschool children with diabetes
report meal-times as one of the most difficult components of their
child's care.81 Preschoolers require more frequent review than older
children,44 with a suggestion for reassessment twice annually until
the age of 6.
There is international agreement that CHO should not be
restricted in children with type 1 diabetes as it may result in deleterious
effects on growth. Care should be taken when giving dietary education,
so that methods of quantifying CHO do not increase total fat
and/or saturated fat intake.44 Although caregivers may prefer highfat
snacks to avoid affecting glucose levels, this should be discouraged
as they will provide unnecessary calories, an unhealthy fat
intake, and negatively impact dietary quality.
Preschool children with type 1 diabetes should consume a diet
that emphasizes fruit, vegetables, whole grain bread and cereals, dairy
foods and appropriate types and amounts of fats. Low fat diets are
not suitable for children under 2 years of age. Lower glycemic index
(GI) choices, such as wholegrain bread and cereals can be introduced
as substitutes for higher GI food choices from 2 years of age. Iron
deficiency can be a concern in this age group; adequate consumption
of lean meat or alternatives is important and should not be overlooked
because of the increased focus on CHO.
A guide to the macronutrient distribution of the total daily
energy intake in preschool children is as below. However, this should
be based on an individualized assessment.
Carbohydrates: 45 to 55 Energy (E) %.44,82 Average intakes
150 g/d in children aged 1ó to 3 years; 200 g/d in children 4 to
10 years.83
Protein: 15 to 20 E % (decreasing with age from approximately
1.5 g/kg body weight/day in 6-month-old infants to 1 g/kg body
weight/day in preschoolers)84
Fat: 30 to 35 E % (less than 10 E% saturated fat, less than 10 E%
polyunsaturated fat, and more than 10 E% mono-unsaturated
fat). Infants less than 12 months may consume up to 40% energy
from fat.
It is important to encourage all children, including children with
type 1 diabetes, to eat plenty of fruit and vegetables. Examples of
recommendations from Australia,85 United States,86 and the Nordic
countries87 are expressed in different ways but consistent in content,
and state 180 g vegetables (2ó servings) and 150 g fruit (1 serving)
daily from 2 years of age85; or 1ó serving of fruit and vegetables
daily between 1 and 3 years.86 400 g of fruits/vegetables are recommended
each day from 4 years of age.87
Research has shown the dietary quality of preschool children with
diabetes is poorer than their healthy peers.88Studies have shown that
preschool children with type 1 diabetes consume less fruit and vegetables
and have higher saturated fat intakes than peers89 and than recommendations
would advise.90,91 Poor food intake may increase the risk
of cardiovascular disease. Eating habits in young children can influence
food choices later in life,92 so early intervention with increased attention
to an increase in fruit and vegetable intake and decrease in saturated
fat is needed. Just like healthy children, children with diabetes
may require up to 10 exposures to a new food before it is accepted.93
Several studies show that children with type 1 diabetes are more
overweight compared with children in the general population,91,94
with the youngest children (<6 years) being the most overweight.95,96
It is important to plot the growth chart including assessments of
weight for length or height regularly to identify excessive weight gain,
in order to commence interventions that involve the whole family.
Encouraging participation in family meals has been recommended to
promote dietary quality97 and social interaction.
Age-appropriate finger foods should be encouraged for self-feeding,
and the reintroduction of a bottle as an easy method of CHO
intake discouraged. Bottles can lead to overconsumption of fluids,
increasing CHO intake and placing other nutrients at risk.
 
8  | ESTABLISHING POSITIVE FOOD
BEHAVIORS AND MEAL-TIME ROUTINES
Establishing positive food behaviors and meal-time routines are
important for preschool children with type 1 diabetes, as these behaviors
impact glycemic control81,98 and encourage life-long nutrition
practices.92 Normal early childhood development, including seeking
independence, transient food preferences, variable appetite, food
refusal, and behavioral resistance often make meal times challenging
for parents and carers. Parents of children with type 1 diabetes
report more disruptive meal behaviors, including longer meal duration
and more frequent food refusal compared with controls99,100; even
for children using insulin pump therapy.101 Research has demonstrated
positive correlations between suboptimal dietary adherence
and higher glucose levels.81,89,101,102 Caregivers’ fear of hypoglycemia
associated with food refusal or unpredictable dietary patterns can
result in force feeding, grazing continually over the day, and postprandial
insulin administration, causing prolonged periods of
hyperglycemia.
Family-centered meals are important to model eating practices
and to encourage new foods. For small children, meal times should
be limited to approximately 20 minutes per meal.103 Conventional
insulin regimens require adherence to a structured plan of CHO
intake, and parents frequently report problems with this approach.81
Intensive insulin management offers greater flexibility in meal timing
and CHO quantities.
To assist the reliable intake of CHO at meal-times and to minimize
food refusal, the following strategies should be adviced:
structured meal-times avoidance of continuous eating habits small snacks including limits on low CHO foods as these fill the
child up
limits on the time spent at the table avoidance of force feeding reassurance by all team members regarding the usual nonseverity
of hypoglycemic episodes related to inadequate CHO
consumption.
Parents should be adviced that postprandial bolus insulin is
problematic as it can become an established habit and also
reinforces anxiety about the child under-eating. Fear of hypoglycemia
can lead to under-bolusing for meals, resulting in inadequate
bolus doses given over the day and subsequent hyperglycemia.
Continuous eating (grazing) makes interpretation of glucose levels
and insulin dose adjustments difficult. A regular meal pattern with
1 small snacking episode between meals (7-15g CHO preceded by
an appropriate insulin dose) will assist with preventing food refusal
as the child will be hungrier at main meals. A dietitian should advise
regarding age appropriate CHO amounts as it is necessary to ensure
the anticipated CHO intake is reasonable based on age, growth, and
the child's previous intake. Unreasonable expectations of a child's
intake may result in food refusal and subsequent hypoglycemia.
Food refusal should generally be dealt with effectively and similarly
to toddlers without diabetes. Preschool children becoming increasingly
independent can recognize parental stress and quickly learn to
use their diabetes as a way of getting their favorite foods. It is
important to emphasize parental patience and to encourage parents
not to use food bribes.
 
All diabetes team members should provide the family with clear
and consistent messages regarding food and meal-time behaviors.
Distractions such as the television and toys should be removed at
mealtimes. Research has demonstrated that disruptive child behaviors
can be reduced by establishing specific rules and consequences for
mealtimes and teaching parents behavioral strategies for meals.104
There is consensus that continuation of support by a pediatric
dietitian throughout childhood and adolescence is essential for optimal
care.
In parental experience, it can be difficult at times to give preprandial
bolus doses of insulin due to the fear of food refusal and
resultant hypoglycemia. Strategies to handle this need to be discussed
with the parents (as above) and all aspects of the risk of
dysglycemia following postprandial bolus doses need to be
explored.
Should a child have a high plasma glucose because of eating
something unplanned, a calm explanation of the need to cover
food with insulin is necessary.
 
9  | LIFESTYLE FACTORS IN PRESCHOOL
CHILDREN
The American Heart Association (AHA) has identified certain childhood
conditions (including type 1 diabetes) associated with extremely
high risk of cardiovascular disease, calling for treatments to minimize
this risk.105
Lifestyle habits, such as nutritional preferences,92 physical
activity,106 and time spent sedentary,107 that are established in childhood
have a great propensity to follow into adulthood. Thus, lifestyle
factors in early childhood have a dual impact on later cardiovascular
risk, observable both as early markers of atherosclerosis during adolescence108
and also as a set of behaviors that influences the child's
risk of cardiovascular disease as an adult and even into senescence.
Children tend to follow the lifestyle habits of their parents and
entire family regarding physical activity,109 TV watching110 and food
choices,97,111,112 and this has been found to influence children´s food
habits throughout their lives.92 Lifestyle supporting interventions
should thus be directed toward the parents and entire family and not
the individual child with type 1 diabetes mellitus (T1DM).
There is no contradiction between population-based interventions
to promote increased physical activity or healthier food choices
in all children and interventions that are routinely part of the diabetes
care delivered by the diabetes team. Preschool children with type
1 diabetes can benefit from both efforts, but targeted interventions
are necessary to meet the specific needs of children with type
1 diabetes.
 
10  | PHYSICAL ACTIVITY
Physical activity confers many health benefits for all children. A
strong graded inverse cross-sectional association has been observed
between physical activity, insulin resistance,113,114 and body fat.115
Spending more time in moderate and vigorous physical activity is
associated with decreased cardiometabolic risk factors in children.
116 When designing physical activity interventions to reduce
the risk of cardiovascular disease in children, including children with
type 1 diabetes, it is important to focus on high-intensity physical
activity to be most effective.116 Engaging in regular physical activity
is also necessary in order to acquire and improve gross motor
skills.117
Many countries recommend at least 60 min/d of moderate and
vigorous physical activity for all children,118 and WHO recommends
this at least from 5 years of age.119 Some countries have changed
their recommendations for physical activity in preschool children
from 60 minutes of moderate and vigorous physical activity to
180 minutes of any intensity of physical activity per day.120,121 This
change of recommendation has been questioned because the reduction
in the risk of cardiovascular and metabolic problems might be
too low with lower intensity of physical activity.115,116
It has been shown that outdoor playing and especially spacious
outdoor playing environments are associated with increased physical
activity in preschool children.122 Asking families about the amount of
time spent playing outdoors can be a useful way to quantify the
physical activity of a preschool child with type 1 diabetes.
Physical activity should be promoted in all children with type 1 diabetes.
Both having diabetes and being a girl has been reported to be
associated with lower levels of physical activity in preschool children
with type 1 diabetes, indicating that particularly young girls with type
1 diabetes are at high risk of being too physically inactive.123
 
11  | PRACTICAL MONITORING OF
GLYCEMIC CONTROL
In this section, “blood glucose” values refer to glucose values measured
by capillary blood check (“finger prick” and “blood glucose monitoring”)
although meters generally display plasma glucose. Since plasma glucose
is 11% higher than whole blood glucose, this term is used when exact
numbers are mentioned.
11.1  | Blood glucose checking
Glycemic control is often evaluated with blood glucose monitoring
(SMBG). All families with a child with diabetes should be taught how
to measure and interpret plasma glucose values. A high precision
glucometer (error less than 10%) should be used in preschool children,
both when relying on SMBG for glycemic monitoring and when
using the glucometer for calibration of CGM. Accuracy in everyday
monitoring situations should be ensured by follow-up with the diabetes
team. This shall include education on the importance of ensuring
that the fingertips are clean and dry before monitoring blood glucose,
as sugar on the fingertips is a common reason for erroneously high
blood glucose levels. The child should be introduced to checks glucose
monitoring and interpretation according to age appropriate and
individual capabilities, as the development of the mathematical
understanding of numbers and time is gradual.
Most children with type 1 diabetes can by the age of 7 be capable
of taking blood glucose checks and performing some basic interpretation
of glucose levels under supervision. However, this should always
be overseen by a parent or other caregiver, as independent self-care is
not expected from any preschool child with type 1 diabetes.
General advice on SMBG monitoring is available in the ISPAD
guidelines on Assessment and monitoring of glycemic control.29 In
children younger than 7 years of age, the recommended checking frequency
of 4 to 6 times per day is rarely sufficient when striving for
target glucose and HbA1c levels. Even with a higher monitoring frequency
of 7 or 10 checks per day, the number of undetected hypoglycemia
and hyperglycemic events in insulin treated preschool
children are high.124,125
Observational studies from different countries show that a common
frequency of SMBG in preschool children with type 1 diabetes
is 7 to 10 checks per day.125,126 Nighttime SMBG is recommended
by many diabetes teams, and performed by most families with preschool
children.127 Preschool children with diabetes can spend a long
time in the hypoglycemic range without detection, despite nighttime
monitoring of SMBG.125
Many parents are sleep-deprived due to nighttime checking of
plasma glucose.127,128 The normal activities of the child have to be
interrupted in order to measure a blood glucose value during daytime.
Thus, SMBG has several limitations as a method of monitoring glycemic
control.
11.2  | Continuous glucose monitoring
CGM can provide an effective mode of monitoring for low and high
glucose levels, allowing for efficacious insulin adjustment. When
available, CGM with alarms is generally the preferred method for
monitoring of glucose levels in children younger than 7 years of age
with type 1 diabetes. CGM should be available and utilized as a tool
for adjusting insulin doses.
Parent experience from Children with diabetes (CWD) conferences:
“I have seen many young children in the age group of 5 to
6 who understand both the numbers and trend arrows on their
CGM”. We also know from personal experience that children
who are diagnosed young sometimes grasp ‘the numbers’ of diabetes
very quickly.
Data on CGM use in preschool children are limited, but suggest
low overall rates of use,126,129 often due to financial constraints.
Parental satisfaction with CGM use is high, in large part because
the technology can decrease the likelihood of severe
hypolycemia.130
When parents/caregivers share their thoughts and interpretations,
real-time CGM information, including a color-coded screen
with arrows, and alarms can often be understood by preschool
children from around age 5 to 6 years. Talking with the child in
an age-appropriate way about actual CGM information gradually
increases the child´s understanding and participation in their
insulin treatment.
Even if children can have some understanding of this, interpretation
and necessary steps of action are always the responsibility
of the parent/caregiver.
Use of CGM devices in preschool children can be hampered by
issues of adhesion and skin irritation.131,132
The ability of some CGM devices to remotely transmit glucose
values to a phone can be of benefit for parents/caregivers who
rely on others for part-time care of their child with diabetes, for
example, while at day care or preschool.
CGM enables deepened analysis and understanding of glycemic
patterns (such as postprandial glycemic excursions), and downloading
data from the device is a pedagogic tool for the team
when discussing solutions to various problems with the parents
of a child with diabetes.
Downloading at home by parents should be encouraged, and can
form a basis for self-adjustment of insulin doses for experienced
families.
 
12  | USE OF INSULIN PUMPS WITH AND
WITHOUT CGM IN PRESCHOOL CHILDREN
Preschool children are unique consumers of novel insulin delivery
and device technologies, as they are dependent on caregivers for all
aspects of device use. Recent technologies, such as pumps and CGM,
can be particularly helpful to parents and caregivers of preschool children
who are extremely dependent on fine-tuning of small insulin
doses, both with regard to size and timing of insulin doses.
An insulin pump system is available that can suspend insulin
delivery when glucose levels, as measured by CGM, are predicted to
become low, and thus reduce the risk and duration of hypoglycemia.
133 On the other hand, insulin pumps and CGM are associated
with increased cost and may increase the provider burden; insulin
pumps may also carry additional risks associated with pump and infusion
set malfunctions.
Insulin doses in preschool children need to be modified frequently
as children of this age are growing rapidly and have changing
patterns of eating and sleeping.
The decrease in size of insulin pumps and CGM devices (including
the infusion sets/sensors) over the past few years make these
therapies more acceptable for preschool children.
The safety of insulin pump and CGM use in this population
appears to be similar to that seen in other age groups.130,134
It is essential for the family to have access to blood ketone
checking to detect problems with the supply of insulin from the
pump. See the section on ketone monitoring below and the
ISPAD guidelines on sick days.135
Regular downloading of data from the pump (and CGM if used),
both at home and in clinic, allows patterns of dosing136 and glucose
levels to be recognizable.
Always give extra insulin with a pen or syringe in case of suspicion
of problems with insulin delivery from the pump.
If the child is prone to ketosis, replacing part of the overnight
basal (30%-40%) with a small dose of long-acting insulin (detemir,
glargine or degludec) may help, but might also reduce the flexibility
in basal insulin administration by temporary basal rates.
Parents of preschool children who switch from MDI to insulin
pumps report more flexibility and freedom, as well as less stress
and anxiety related to their child's care.137
Data suggest a decrease in HbA1c129,134 and reductions in rates
of severe hypoglycemia95,134 after implementation of insulin
pumps in preschool children.
Insulin pump features that enable automatic bolus calculations
based on insulin sensitivity factors and insulin to CHO ratios can
aid caregivers in insulin administration.
Insulin pump therapy may be effective in helping to manage toddlers'
eating behaviors by facilitating split bolus dosing.
The pump calculates “insulin on board”, i.e. how many units from a
previous dose of insulin that still exerts a glucose-lowering effect. A
phone app that can calculate “insulin on board” can be used for calculation
of bolus doses of insulin when on injection therapy.
Although CGM provides an overwhelming amount of data, it is
important to look for daily patterns (eg, the “modal day” when
downloading data), and adjust insulin-to-CHO ratios and correction
factors only after a repeated pattern has been identified.
The frequency of insulin pump and CGM use varies between
centers. Barriers to the use of these treatment options in preschool
children need to be explored.
 
13  | SKIN CARE
There are very few data on special considerations regarding skin care in
preschool children with type 1 diabetes but CGM-related skin problems
seem to be most common in very young users.132 CGM-related skin problems
are not associated with atopy.138 In general, recommendations for
site use (including site selection, site preparation, and site rotation) are similar
as for older children. Many preschool children receive insulin injections
and insert infusion sets and CGM sensors in their buttocks, an area often
covered by a diaper. The abdomen, upper arm, and upper thigh regions
are also commonly used. For children under the age of 6 using insulin
pumps, data suggest that rates of scarring and lipohypertrophy are high
(50% and 45%, respectively) but not different than in older children.139
Injection, infusion, and CGM sites should be properly prepared
and regularly rotated in order to reduce the likelihood of
lipohypertrophy, superficial scarring, infection, rashes, skin reactions,
and dry skin.
Injection, infusion, and CGM sites should be inspected by diabetes
team members at every visit to the clinic to detect any skin problem
or lipo-hyper/hypotrophy early, in order to treat promptly.
The use of pumps and CGM are often limited by skin reactions
to the adhesive. Prepare the site a few days prior to insertion by
the use of a skin moistener that preserves water. Topical corticosteroid
(group I or II) can be used to treat skin reactions and
break the vicious circle of itching after removal.
 
14  | KETONE MONITORING
Measuring ketone bodies in blood (betahydroxybutyrate, BOHB)
should be recommended as the primary method of detecting and
monitoring ketosis in preschool children with type 1 diabetes; see the
ISPAD Guidelines on Sick days.135 Measurement of acetoacetate in
urine can be used as an alternative, but gives less precise information.
As preschool children do not urinate on command, especially when
sick, results from blood ketone monitoring will be more easily available
both for the child and parent. Blood ketone checking also gives
the health care professional much better information to provide
advice over the phone or in the emergency room.
Ketones should be monitored when there is a suspicion of lack
of insulin raised either by high blood glucose (2 values above
14 mmol/L within 2 hours that do not decline on a correction insulin
dose) or when the child shows symptoms suggestive of ketosis (vomiting,
nausea, stomach pain, fever, or unclear illness).
Elevated glucose levels and ketone levels suggest lack of insulin
and should promptly be treated with injection of insulin 0.1 U/kg
(or 10% of TDD) every second hour until BOHB is below 0.5 mmol/L. If
levels are above 3.0 mmol/L, the family should seek guidance by phone
or in person immediately, possibly in an emergency room, due to the
high risk of ketoacidosis. Slightly elevated BOHB (usually <1.0 mmol/
mol) in combination with normal or low glucose levels indicates combined
lack of CHO and insulin, commonly associated with gastroenteritis
in preschool children. This can most often be treated at home with
ingestion of sugary fluids and administration of extra insulin subcutaneously.
See the ISPAD Guidelines on Sick days for further advice.135
Ketoacidosis is a life-threatening acute complication of diabetes that
demands care at a skilled hospital unit. Six percent of children younger
than 6 years in the United States and 4% of children in Germany/Austria
(from data from the Type 1 Diabetes Exchange clinic registry and the
Prospective Diabetes Follow-up Registry: DPV) have suffered from
ketoacidosis during the past year.45 Education of families on prevention
of ketoacidosis is an essential part of diabetes care.140 See the ISPAD
Guidelines on Diabetic Ketoacidosis for further advice.140
 
15  | HYPOGLYCEMIA
Hypoglycemia, including fear of hypoglycemia, is a limitation to striving
for normoglycemia. The risk of hypoglycemia presents a major
physiological and psychological barrier to achieving optimal glycemic
control, and may result in significant emotional morbidity for patients
and caregivers.29,141,142 Young age is traditionally regarded as a
marker of high risk of severe hypoglycemia during insulin treatment.
29The frequency of severe hypoglycemia has decreased over
time in all children.29,35,143,144 In Germany and Austria, fewer than 2%
of children younger than 6 years with type 1 diabetes have experienced
a severe hypoglycemic event with seizures/unconsciousness during the
previous year; in the United States this figure is less than 3%.126
The erratic daily life of a preschool child (food intake, activity,
sleep, and sick days) has been regarded as the explanation for the historically
high risk of severe hypoglycemia in preschool children with
type 1 diabetes. Preschool children are not yet able to identify and
articulate their symptoms and it can be very difficult for caregivers to
detect these symptoms. Prolonged nocturnal hypoglycemia is not
uncommon in children younger than 7 years with type 1 diabetes as
detected in CGM studies,125,145–147which is associated with a higher
risk of severe hypoglycemia.146
The fear of an hypoglycemic event, rather than the frequency of
hypoglycemic events, is associated with higher HbA1c and poorer
HRQoL.141 The role of fear of hypoglycemia cannot be underestimated
for parents of children with type 1 diabetes.142 Asking about
frequency and severity of hypoglycemia is typical in a clinic visit, and
it may also be helpful to ask about thoughts and feelings during and
after the hypoglycemic event. Fear of nocturnal hypoglycemia is a
particular challenge.142 Fear is not correlated with the numbers of
hypoglycemic episodes, but is related to their severity, especially in
mothers of children who have experienced a hypoglycemic seizure.
The use of insulin pumps and CGM has been reported to
decrease the risk of hypoglycemia.148,149 Insulin pumps with low glucose
suspend features appear to further reduce the time spent in
hypoglycemia.150,151
The comparison of data between the United States T1D Exchange
and German/Austrian DPV registries showed that an HbA1c of <7.5%
(<58 mmol/mol) can frequently be achieved in children younger than
6 years with type 1 diabetes without an increased risk of severe hypoglycemia.
126 In many countries, children younger than 7 years most
frequently have the lowest HbA1c. In Sweden, 74% of insulin-treated
children younger than 7 years have HbA1c < 7.4% (<57 mmol/mol),
and the overall frequency of severe hypoglycemia (seizures/unconsciousness)
in the pediatric age (0-18 years) is 2.5%.152
For definitions and further information see the ISPAD Guidelines
on Hypoglycemia.29
 
15.1  | Treatment of mild hypoglycemia in infants
and preschool children
Oral glucose as tablets, gel, or a drink (0.3 g glucose/kg bodyweight)
is the preferred method of hypoglycemia treatment.29,153 This dose
will raise plasma glucose approximately 2.5 to 3.6 mmol/L (45-
64 mg/dL).29 It is important not to give too much CHO when treating
hypoglycemia, in order to avoid subsequent hyperglycemia. Giving
something that contains fat (ie, milk and chocolate) will slow down
the gastric emptying, and cause a slower rise in plasma glucose.154
Sucrose sweetened confectionary should not be routinely used to
treat hypoglycemia, as it can lead to increased risk of dental caries
and food refusal if the child learns that sweets are substituted for
unconsumed food. It is important that hypoglycemia is not over-treated,
as 5 to 7 g CHO is usually adequate in raising the plasma glucose
to normal levels for small children using intensive therapy.
To treat hypoglycemia in breast- or formula-fed infants, CHO gel,
diluted juice, or a glucose polymer from a spoon or bottle can be
offered. Honey should not be given to infants younger than 1 year
due to risk of botulism.
 
16  | SCREENING FOR ASSOCIATED
DISEASES
Early onset of type 1 diabetes is associated with a higher frequency
of celiac disease compared with older children, which affects the
treatment situation of the child,155–157 and may influence the risk of
complications and quality of life. Repeated screening for celiac disease,
thyroid disease, and other autoimmune disorders is essential.158
 
17  | LIVING WITH DIABETES IN THE
FAMILY
For people living with type 1 diabetes and their families, the management
of the condition is complex and individual. Daily challenges
imposed by type 1 diabetes include cognitive and emotional burdens
that can take the form of increased vigilance to dietary intake, symptom
monitoring, and frustrations with glucose excursions. For caregivers
of preschool children with type 1 diabetes, additional
complexities are encountered, including the necessity to adapt to
developmental changes to ensure adequate psychological adjustments
for the child and themselves, and to facilitate care in the context
of other care providers such as preschool staff.159 Clinicians
need to be aware of the overwhelming sense of responsibility and
worry which parents of preschool children with type 1 diabetes can
feel. Parents who have access to a supportive network (relatives
and/or friends) have lower risk of diabetes-related stress and burnout.
128 It is important to educate secondary caregivers about type
1 diabetes and insulin treatment. Attention should be given to the
needs of the siblings of a child with type 1 diabetes.
As children grow, they understand more about health and illness.
When appropriate, it needs to be explained that diabetes is not
caused by eating too much sugar, and that you cannot catch diabetes
from another person. This needs to be actively taught to friends and
relatives as well to avoid common misconceptions about diabetes.
Parents are an integral part of the diabetes team and have the
most important supportive role to play over the years as their children
eventually learn to self-manage their diabetes. Providing this
support can be difficult when parents have their own stressors to
deal with, and struggle with the constant vigilance needed to ensure
the safety of their child. Dashiff et al160 report that parents of older
children with type 1 diabetes experience an ongoing struggle, worry,
and frustration about their parenting role. During young childhood,
parents take responsibility for all diabetes-related tasks such as insulin
administration, dosing calculations, blood glucose checking, and so
It is important that they do this in a way that is neither
threatening nor frightening for their child. Involving the child in
aspects of diabetes management as soon as possible (eg, finger pricks
and CHO counting) is recommended, so the child can begin to
develop a sense of ownership/management of their own health. A
supportive and emotionally warm parenting style is important for promoting
improved quality of life for children with type 1 diabetes.161
Establishing good habits in the early years will form the basis for
optimal diabetes self-management during adolescence and into adulthood.
2,92,106,107 In order to create an environment in which parents
feel confident and comfortable, it is crucial that they are appropriately
supported by all members of their multi-disciplinary team and
that they have adequate access to appropriate support when they
need it. The way that parents model diabetes-related tasks will have
a direct impact on the way their children learn. Supporting parents
toward a positive adjustment to living with diabetes will help them to
effectively model those tasks and assignments involved in daily life
with diabetes. It is important to engage both fathers and mothers in
diabetes care from the onset, and to keep them both involved in everyday
diabetes care throughout the childhood years.
Parents express that it is important to explain to their child in
very simple and clear terms what type 1 diabetes involves. There
are certain aspects of diabetes management that are not negotiable
(glucose checking, insulin injections/pump site changes, CGM
use, etc), and the child needs to begin to understand that as early
as possible. It is important to involve the child in diabetes management
as soon as possible so they can begin to develop a
sense of ownership/management of their own disease. Reinforcing
such an attitude early on will help to shape the child's attitude
and approach to diabetes in the future.
Parents report that diabetes will often initially disrupt the normal
parent-child relationship, as diabetes frequently comes first in the
mind of the parent in response to a child's requests. It is important
for parents to ask themselves, “If my child didn't have type
1 diabetes, would I say no to this request?”, and thus strive to reestablish
the normal parent-child relationship.
 
18  | SCREENING CHILDREN FOR
PSYCHOSOCIAL DISTRESS
Regular screening of children for psychosocial distress is important to
ensure that difficulties are identified early, and appropriate support
and treatment plans established as soon as possible. Most children
are not able to complete questionnaires or report on their own level
of emotional distress in a reliable manner until they are approximately
7 to 8 years of age. Therefore, either talking with them directly about
how they feel, or asking their parents to report on their children's
psychosocial well-being is recommended. For children who are older,
there are several pediatric measures of depressive symptoms that are
validated and reliable for use with children as young as 7 years of
age, varying in length and depth of detail. These include the
Children's Depression Inventory (CDI)162 and the Center for Epidemiologic
Studies – Depression (CES-D) scale.163 Both measures are
self-reported questionnaires containing items on types of symptoms
(eg, sadness and low self-esteem) and functional areas (eg, not having
friends, schoolwork is not as good as it was before, and arguing with
others). Pediatric quality of life can be addressed by specific questionnaires
such as the Pediatric Quality of Life Inventory (PedsQL)
generic and Type 1 Diabetes modules.164 These measures offer a
child self-report for youth ages 5 to 7 and also for youth ages 8 to
There are also PedsQL parent proxy reports for children ages 2 to
18.164 Diabetes-specific emotional distress can be assessed in children
ages 8 to 11 Problem Areas in Diabetes Survey-Children (PAIDC)
and teens Problem Areas in Diabetes Survey-Teens (PAID-T) and
parent's diabetes-specific emotional distress can also be assessed (PPAID-
C and P-PAID-T) in measures developed by Weissberg-
Benchell and colleagues. Similarly, diabetes-specific emotional distress
from age 8 can be assessed by the PAID-Parent (PAID-PR) scale
and from age 8 in youth with the PAID-Peds scale, both developed
by Markowitz et al.165,166
Parental anxiety can have a direct and negative effect on diabetes
management and health outcomes. There can often be a comorbidity
of depression; however, they are 2 separate conditions and
should be treated separately. They may act in opposite directions
with regard to diabetes management and control, so we recommend
assessing anxiety separately from depression. The Center for Epidemiological
Studies-Depression Scale (CESD) is often used as a measure
of depressive symptoms in adults, and the Beck Depression as
well as the Beck Anxiety scales are also often used. Worries about
diabetes impact on glycemic control in children, should be acknowledged
and addressed.
 
19  | PRESCHOOL CARE
Many preschools provide excellent care for children with type 1 diabetes.
Parents and health care professionals should work together to
overcome any difficulties and ensure the safety and well-being of the
child with type 1 diabetes when cared for outside the home setting.
It is crucial that every child is supported effectively to achieve their
full potential. Legislation protects children with type 1 diabetes in
many countries. One example is the Equality Act 2010 (England,
Scotland, and Wales) which dictates that schools must make reasonable
adjustments to ensure that children with disabilities are not put at
a substantial disadvantage compared with their peers. For diabetes,
this means schools ensuring they have enough staff trained so that
the child with diabetes can take part in all aspects of preschool and
school life. Contingency plans must be in place to train replacement
staff quickly. The Kids and Diabetes in Schools (KiDS) program of the
International Diabetes Federation (IDF) offers education and guidance
for families and school staff on ways to help children with type
1 diabetes manage in school. KiDS information is available in 10 languages
(as of June 2017) and can be accessed online at http://www.
idf.org/education/kids.
In addition to ensuring the rights of the child with diabetes, it is
important to create trust and cooperation between the preschool,
the family, and the diabetes team. An individually written diabetes
management plan is helpful in this cooperation to help the child with
type 1 diabetes,167 and should include information about and
practical training for the use of diabetes-related technologies.168 Both
the parents and the diabetes team need to share the responsibility
for educating the preschool institution, especially when the child is
newly diagnosed with diabetes or when additional diagnosis such as
celiac disease occurs. Preschool staff often find CHO counting helpful
as it gives them a tool to assess the dose of insulin to be given in
relation to the food intake and current glucose level. In countries
where there are no regulations to support the child with diabetes, the
diabetes team together with the parent organizations should advocate
for improved regulations.
Parents express that while regulations certainly help to ensure
documentation and agreements on daily care, maintaining a close
relationship with the school (staff, teachers, etc) is equally if not
more important to ensure effective daily management of their
child's diabetes. Parents can be in very close contact with the
school, including offering training sessions, educational materials
for other parents etc, which will lead to better and more effective
diabetes management. This helps them to feel more comfortable/
less stressed when sending their child to preschool.
20  | ALTERNATIVE AND COMPLEMENTARY
THERAPIES
At times families try alternative indigenous remedies and even discontinue
insulin. This can be avoided if parents are counseled regarding
the absolute necessity of insulin for the child's survival.
Alternative therapies may be tolerated if important for the family as
long as they do not interfere with the regular diabetes care, including
insulin doses, glucose monitoring and healthy food choices, or impact
the child's growth or development or deplete economic resources
needed for insulin treatment.
 
21  | CARE FOR THE PRESCHOOL CHILD
WITH TYPE 1 DIABETES IN LIMITED
RESOURCES SETTINGS
Whenever possible, the guidelines described above in the preceding
sections should be followed.
It is important to remember that building a good rapport with the
family and providing comprehensive diabetes education are inexpensive,
and remain the most effective strategies to improve diabetes
management by the family.37 Knowledge about the effects of insulin,
food, and physical activity on glucose levels are essential to protect
the child from acute and chronic complications of diabetes under all
circumstances. The first few visits of the family are the most crucial
in this regard. Initial approach to diagnosis and treatment is based
upon staffing and facilities at specialized centers for the care of
young children with diabetes, with many centers recommending hospitalization.
Parents should be counseled and educated in detail.
The challenges in managing type 1 diabetes in the preschool child
are several-fold higher in resource limited settings. Awareness, health
infrastructure, and number of medical professionals trained in the
management of childhood diabetes are inadequate for a significant
proportion of the population in many countries in South East Asia
and sub-Saharan Africa. The diagnosis is often delayed, and may even
be missed in some cases, resulting in death before diagnosis. Common
misdiagnoses are gastroenteritis, pneumonia, asthma, urinary
tract infection, genital tract infection (candidiasis), enuresis, and
malaria. Parents may take longer to come to terms with the diagnosis
and the need for life-long insulin therapy. The financial implications
of the condition add to the psychological distress brought about by
the diagnosis. Risk of acute and chronic complications, as well as
mortality, is higher in these children due to suboptimal management.
169 In the United States, young people of African descent have
increased risk of short-term complications (ketoacidosis and severe
hypoglycemia) when adjusted for socioeconomic status,170 and higher
HbA1c even when adjusted for mean glucose levels.171 HbA1c was
higher even when fasting glucose is <7 mmol/L in black individuals
both with and without diabetes compared with white, but the prognostic
value of HbA1c for predicting cardiovascular disease, nephropathy
and retinopathy were similar.172
The financial issues need to be addressed upfront by the treating
team. The challenge of finding ways to support the families lies
chiefly with the care providers. The team should be familiar with the
governmental and non-governmental agencies in the area that may
provide financial assistance for procuring insulin and glucose strips,
and ensure that parents have access to these before the child is
discharged home.
Most preschool children in resource-limited settings remain on
regular and NPH insulin administered by insulin syringes. With only
regular and NPH available (as in the DCCT study), a multiple injection
therapy with regular insulin for meals and NPH insulin at bedtime can
be effective in teaching the family the relationship between insulin
dose and CHO content of the meal. CHO counting can be used in
this situation. The challenge to overcome will be the lunchtime injection
at school. It is very important to motivate and explain this to the
school staff as the alternative of giving a twice daily mixture of regular
and NPH does not result in a physiological insulin profile. In a situation
where food availability is unpredictable, a child on twice daily
injections will experience hypoglycemia, while the child on multiple
injections can adjust mealtime doses accordingly.
Few patients are able to afford analog insulin and pen devices.
The use of insulin pumps is only affordable by a low percentage of
the population. Administration of small doses is therefore a practical
challenge. In young infants, parents may be taught to dilute insulin
with normal saline (available in 10 mL vials). The use of 0.3 mL insulin
syringes (100U/ml, 30 U in total) allows an accurate administration of
half units, appropriate for most preschool children. Similarly, use of
CGM remains unavailable for most children with type 1 diabetes in
the resource-limited scenario, and frequent self-monitoring of blood
glucose is the only method for monitoring glycemia. However, even
this may not be feasible for some families due to the high cost of
blood glucose strips. If possible, the child can be recommended a
meal plan with a relatively consistent CHO intake at meal and snack
times during the day to match the insulin regimen. The family can be
taught to have a high index of suspicion for hypoglycemia and treating
it on suspicion, relying mostly on urinary glucose monitoring for
insulin dosing, and to use SMBG at least on sick days if available.173
With limited number of strips, the family can, for example, measure
before and 2 hours after lunch 1 week, and before and after dinner
the next to get a more stringent picture of the day compared with
random checks. Urine strips should be available for ketone monitoring
during sick days.
Another issue that may compound the challenge in resourcelimited
settings is that some parents may have low levels of literacy
and health literacy, meaning thereby that they cannot read the numbers
on the insulin syringe and on the glucometer. For example, in
India, literacy rate is 74.04% according to the 15th official census in
2011 (http://www.census2011.co.in/literacy.php). In such cases, it is
helpful to identify a suitably literate relative, friend or neighbour who
can undergo diabetes education along with the parents and assist
them in the domiciliary management. The parents should also be
encouraged to learn the basics of reading and writing. In the case of
low literacy, a simpler insulin regime such as twice daily dosing with
premixed insulin can be given. Hearing the number of clicks from an
insulin pen can obviate the need to read the number of units. Teaching
the parents to recognize “Hi” and “Lo” on glucometer, to treat
hypoglycemia based on symptoms alone, and to recognize hyperglycemia
and ketonuria by urinary strips is also useful to prevent lifethreatening
episodes.
Vomiting in a child with diabetes should always be regarded as
imminent ketoacidosis, and appropriate treatment should be sought
immediately in the absence of knowledge and diagnostic measurements.
If the child is not feeling well with other symptoms, the first
line of treatment should be something containing sugar to treat
impending hypoglycemia. This should be well known by all the older
children and adults who are close to the child with diabetes, and they
should know where to readily find a source of sugar.
To conclude, the goals of management of type 1 diabetes in
resource-limited settings must be situated in the context of the
resource-limited environment and based on the family's educational
and financial status. Avoidance of acute life-threatening complications
and continuation of regular treatment and follow-up are the
immediate goals.
 
22  | FUTURE NEEDS OF PRESCHOOL
CHILDREN WITH TYPE 1 DIABETES
“Diabetes during early childhood creates a psychosocial
challenge to the families of these children. Successful
management of infants and toddlers with
diabetes depends on a well functioning and educated
family, the availability of a diabetes health care team
experienced in the treatment of these youngsters,
and the involvement of the extended family, child
care personnel and others who play a role in their
daily care” (Daneman).174
The addition of new tools should enable families living with type
1 diabetes to provide increasingly effective therapy and support for
preschool children with diabetes. The cognitive, motor and social
immaturity, as well as the small body size of preschool children must
be considered when designing new equipment, including sensors,
insulin pumps, and (hybrid) closed-loop solutions for insulin delivery.
It is important to include children younger than 7 years in both
epidemiological and clinical studies regarding treatment strategies
and tools (both technical equipment and pharmacological) and outcomes;
moreover, when the youngest children with type 1 diabetes
are included in these studies, data regarding children with early-onset
diabetes must be presented separately to enable subgroup analysis.
Children younger than 7 years with type 1 diabetes constitute only
approximately 10% of the population of all children and adolescents
with type 1 diabetes,126,152 but in many countries the incidence in
this subgroup is increasing most quickly. Collaboration between centers
is thus necessary in order to conduct studies that are sufficiently
powered.
 
REFERENCES 1-174 and better tables
from www.ispad.org
 
How to cite this article: Sundberg F, Barnard K, Cato A, de
Beaufort C, DiMeglio LA, Dooley G, Hershey T, Hitchcock J,
Jain V, Weissberg-Benchell J, Rami-Merhar B, Smart CE,
Hanas R. Managing diabetes in preschool children. Pediatr
Diabetes. 2017;0:1–19. https://doi.org/10.1111/pedi.12554
 
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