13995448, 2022, 8, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/pedi.13427 by Egyptian National Sti. Network (Enstinet), Wiley Online Library on [25/12/2022].

See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Received: 29 September 2022 Accepted: 30 September 2022
DOI: 10.1111/pedi.13427

ISPAD GUIDELINES

ISPAD Clinical Practice Consensus Guidelines 2022: Managing

diabetes in preschoolers

Frida Sundberg 1,2 | Carine deBeaufort 3,4 | Lars Krogvold 5 |

6 7 8
Susana Patton | Thereza Piloya | Carmel Smart | Michelle Van Name 9 |
Jill Weissberg-Benchell 10 | Jose Silva 11 | Linda A. diMeglio 12
1
The Queen Silvia Childrens Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden
2
Department of Pediatrics, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
3
Clinique Pédiatrique, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg
4
Department of Pediatric Endocrinology, Universitair Ziekenhuis Brussel–Vrije Universiteit Brussel, Brussels, Belgium
5
Paediatric Department, Oslo University Hospital, Oslo, Norway
6
Center for Healthcare Delivery Science, Nemours Children's Health, Jacksonville, Florida, USA
7
Department of Paediatrics & Child Health, School of Medicine, College of Health Sciences Makerere University, Kampala, Uganda
8
Department of Paediatric Endocrinology and Diabetes, John Hunter Children's Hospital and School of Health Sciences, University of Newcastle, Newcastle, New
South Wales, Australia
9
Yale School of Medicine, New Haven, Connecticut, USA
10
Department of Psychiatry and Behavioral Sciences, Ann & Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern University,
Chicago, Illinois, USA
11
SummitStone Health Partners, Fort Collins, Colorado, USA
12
Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana, USA

Correspondence
Frida Sundberg, The Queen Silvia Childrens Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden and Department of Pediatrics, Sahlgrenska Academy,
Gothenburg University, Sweden.
Email: [email protected]

1 | S U M M A R Y O F W H A T I S N E W OR • Hybrid closed loop insulin pump therapy is valuable and needs to

DIFFERENT be made available to children with T1D in this age group as they
generally have a high day-to-day variation in insulin needs.
• Preschool children with type 1 diabetes (T1D) who have access to • Early onset diabetes is associated with a high lifetime risk of diabetes
modern diabetes care can safely achieve a HbA1c below 48 mmol/ complications, necessitating optimal glycemic control from onset.
mol (6.5%).
• Continuous glucose monitoring (CGM) is the recommended tool
for glycemic monitoring in preschoolers with T1D. 2 | EX EC UT IVE S UMMARY AND
• When using CGM, a reasonable treatment target is 50% time in RECOMMENDATIONS
target (TIT) 3.9–7.8 mmol/L (70–140 mg/dL) or 70% time in range
(TIR) 3.9–10 mmol/L (70–180 mg/dL). • The ISPAD target hemoglobin A1c (HbA1c) for children is <7%
• Insulin pump is the preferred method of insulin delivery in this age (<53 mmol/mol). As children diagnosed with T1D at preschool age
group whenever available and affordable. are expected to have a long diabetes duration and thus have a high risk

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any
medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
© 2022 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.

1496 wileyonlinelibrary.com/journal/pedi Pediatr Diabetes. 2022;23:1496–1511.

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SUNDBERG ET AL. 1497

of diabetes complications B. They benefit from a tight glycemic target • Weight, height (or length if <24 months), and Body Mass Index Stan-
and maximizing time spent in glycemic target range from the onset. C dard Deviation Score (or percentiles) should be monitored at least
• A reasonable treatment goal after the initial remission period in every third month on growth charts in preschool children with T1D. E
insulin treated children younger than 7 years can be >50% of time
in target (TIT) 3.9–7.8 mmol/L (70–140 mg/dL) or >70% TIR 3.9–
10 mmol/L (70–180 mg/dL). B Soon after diagnosis, during the 3 | INTRODUCTION
remission period, a higher TIT and TIR is preferable. E
• Intensive insulin therapy, that is, as close to physiological insulin This chapter focuses on components of care unique to toddlers and
replacement as possible, with a combination of basal insulin and preschool-aged children with T1D. These guidelines are written for
pre-prandial insulin boluses should be used, with frequent glucose children with T1D aged 6 months to 6 years, but practical aspects
monitoring and meal-adjusted insulin regimens. C might also be useful in younger children with insulin-treated diabetes.
• Insulin pump therapy is the preferred method of insulin administra- Children younger than 6 months of age at diagnosis should be investi-
tion for young children (aged <7 years) with T1D whenever avail- gated for other types of diabetes including monogenic diabetes, and
able and affordable. E their management is discussed further in ISPAD 2022 guidelines
• As pump treatment develops further with hybrid closed loop Chapter 4 on ‘The diagnosis and management of monogenic diabetes
(HCL)/automated insulin delivery (AID) this treatment modality in children and adolescents’.
needs to be made available and adapted for children younger than Early onset T1D is associated with a high risk of early cardiovas-
7 years. A The special needs of toddlers and preschoolers should cular disease and premature death.1 The strongest modifiable risk fac-
be addressed when developing these devices. E tor associated with diabetes-related mortality due to microvascular
• If pump therapy is not available, multiple daily injections (MDIs) and macrovascular complications is HbA1c.2,3 Glycemic target setting
should be used from the time of diagnosis. E has been shown to positively affect outcomes.4–6
• Pre-prandial administration of bolus insulin and insulin given for Preschool children are dependent on others for all aspects of their
correction if blood glucose is high is preferable to giving the insulin care. For the families (primarily parents) of preschool children with
dose during or after the meal. B T1D, their diabetes teams and other caregivers (including school and
• Studies in this age group support introducing carbohydrate count- daycare staff members and babysitters), treatment is a constant chal-
ing at onset of diabetes. C lenge. Despite the challenges, it is important to strive for normoglyce-
• Syringes with ½ unit markings and pens with at least ½ unit dos- mia, as current knowledge about the implications of dysglycemia
ing increments should be used to facilitate more accurate insulin makes reducing the likelihood of acute and chronic complications
dosing when injecting small doses of insulin in multiple daily injec- imperative from the time of diabetes onset.7,8 Optimizing glycemic
tion therapy. E control for children in this age group often requires treatment strate-
• Continuous glucose monitoring (CGM) is the recommended gies that differ from those employed for older children and adoles-
method of glucose monitoring. C cents with T1D. These strategies need to take into consideration the
• If CGM is not available, 7 to 10 blood glucose checks per day with cognitive, motor, and social developmental levels of preschool chil-
appropriate interpretation and action are usually needed to achieve dren as well as their small body size and growth pattern.
target glycemia in this age group. C In addition to their dependence on others (in this chapter referred
• Lifestyle interventions, such as food choices and physical activity, to as “caregivers,” i.e., parents) for insulin administration and glucose
designed to reduce the risk of subsequent cardiovascular disease monitoring, preschool children are also dependent on others for aspects
in children with T1D, should already start in preschool age children of their lifestyle related to healthy eating and physical activity. Lifestyle
and should be directed toward the entire family and not just the choices and preferences established during early childhood provide a
individual child with T1D. C window of opportunity for ingraining healthy habits that may be per-
• Family-centered meal routines with restrictions on continuous eat- petuated throughout the child's life. The early establishment of positive
ing habits (grazing) are important to ensure dietary quality and behaviors may help to ameliorate the high risk of cardiovascular disease
optimize glycemic control in preschool children. C that is associated with diabetes. Providing adequate education and sup-
• Breastfeeding is recommended for all infants in accordance with port for lifestyle changes requires that the multidisciplinary diabetes
WHO recommendations. This includes infants with diabetes. E team uses a family-based approach to ensure that the whole family is
• Insulin dosing in breastfed infants can preferably follow a basal- appropriately supported to promote health.
bolus pattern with bolus dosing based on carbohydrate counting. E Early childhood is an important time for establishing salutogenic9
• Diabetes education should be provided to staff at preschools and and adaptive health behaviors and parents and primary caregivers of
schools where children with T1D are enrolled, to promote equal and young children play an important role in this process. Supporting care-
safely managed participation in all preschool/school activities. E givers while they become increasingly comfortable with intensive
• Optimal glycemic control, minimizing exposure to both hypoglyce- insulin treatment is vital, including support for the caregiver's own
mia and hyperglycemia will give the child the best opportunity to physical and emotional health.10,11 It is also important to teach care-
concentrate, participate, and learn while at preschool and school. C givers, strategies for helping their young child to become an active
 13995448, 2022, 8, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/pedi.13427 by Egyptian National Sti. Network (Enstinet), Wiley Online Library on [25/12/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
1498 SUNDBERG ET AL.

participant in their own care. Young children can help caregivers com- mechanisms by which early brain development is affected by T1D are
plete diabetes-related tasks such as helping to select a finger for glu- not clearly understood. Long-term exposure to hyperglycemia as well as
cose monitoring, a site for injection/infusion, and selecting healthy hypoglycemia (especially with seizures) and oxidative stress caused by
foods. It is also recommended that caregivers employ think aloud glycemic variability are possible contributors. Both the duration and age
strategies to begin to teach young children problem-solving skills. of onset of diabetes appear to play a key role. For instance, metabolic
Screening and promotion of optimal health-related quality of life conditions such as hyperglycemia and ketoacidosis at diagnosis may make
should be regularly undertaken in preschool children with T1D as in the brain more vulnerable to subsequent metabolic insults.7,8,19
any child with T1D. Existing meta-analyses report decrements in domains of intelligence
Children younger than 7 years with T1D constitute a minority of the quotient (IQ and verbal IQ in particular), executive function (attention,
population of all pediatric patients with T1D. Small centers will have few working memory, and response inhibition), delayed memory (episodic
very young patients and it will take longer to gain experience in the care recall), and processing speed (paper-pencil) among children with T1D
of this patient group. Close collaboration between centers is necessary to compared to age-matched children without diabetes, although these dif-
optimize quality of care for preschool children with T1D. ferences are generally not reported until the children are studied later in
childhood.12 It is possible that chronic exposure to different aspects of
dysglycemia is additive, and that brain and cognitive changes only
4 | G RO WTH A N D D EV E L O P M E N T I N T H E become apparent over time or that children need to achieve a threshold
FIRST YEARS OF LIFE of cognitive maturity for differences to become measurable.7
Optimal glycemic control will give young children with T1D the
For preschool children to experience normal growth and develop- best opportunity to concentrate, participate, and learn while at pre-
ment, it is essential that they maintain near normoglycemia, aiming to school and school. Health care professionals are best able to help chil-
maximize glucose time in target range, and are provided with suffi- dren avoid any negative impact of T1D on everyday functioning by
cient nutrients. Restrictive diets or lack of food make it difficult to mitigating prolonged exposure to hyperglycemia, and by ensuring
provide essential nutrients for growth and development and must be early identification and providing interventions for academic, cogni-
avoided. This requirement of sufficient nutrition is in part due to the tive, or motor issues. For further reading, the ISPAD 2022 guidelines
brain's high metabolic requirement in infancy and childhood. Chapter 15 on Psychological care of children and adolescents with
It is essential to monitor weight, height (or length if <24 months T1D comprehensively addresses this subject.
in accordance with national health care recommendations), and BMI-
SDS (or percentiles) on growth charts in preschool children with T1D
at least every third month. When telemedicine is used it is important 6 | G L Y C E M I C T A R G E T S I N P RE S C H O O L
to have access to valid data measured by health care professionals on CH I L D RE N WI T H T Y P E 1 D I A B ET E S
height/length and weight at least every third month.
Optimizing glycemic control for preschool children with T1D is crucial
for their future, both with respect to acute and long-term complica-
5 | T H E B R A I N A N D CO G N I T I V E tions2 as well as their neurocognition, brain structure,7 and health-
D E V EL OP M E NT I N CH I L D R EN WI T H EA R L Y related quality of life (HRQoL).
O N S E T T1 D ISPAD 2022 Consensus guidelines Chapter 8 on Glycemic Con-
trol Targets has recommended glycemic targets for hemoglobin A1c
Multiple risk factors have been associated with potential suboptimal (HbA1c <7.0%, <53 mmol/mol). This target is applicable to all pediat-
cognitive and fine motor development in children and adolescents ric age groups and the aim is to optimize glycemia for each individual
with T1D. These factors include early onset of disease (typically child. Children younger than 7 years with access to high quality diabe-
defined as <5 years of age),12 disease duration, history of moderate to tes care, including modern technology can achieve HbA1c 6.5%
severe ketoacidosis (including those at diagnosis),13 severe hypoglyce- [48 mmol/L] or lower without a high risk of hypoglycemia.20,21
14
mia (including seizures or unconsciousness) and cumulative expo- Optimizing glycemia is important in preschool age children diag-
sure to hyperglycemia.15 A meta-analysis showed that the risk of nosed with T1D due to their higher risk of diabetes complications and
cognitive disruption is largest for children with early-onset diabetes premature death than persons diagnosed with diabetes later in life.1
and the effect is detectable after a mean diabetes duration of 6 years. There is also evidence that hyperglycemia during childhood raises the
The mean effect size is moderate but might not be large enough to risk of long-term complications even if substantial improvement is
affect school performance.8 Clinicians should be concerned about dia- achieved later during young adulthood.22 This evidence underscores
betic ketoacidosis (DKA), severe hypoglycemia and hyperglycemia all the NICE guidelines, which encourage an HbA1c target ≤6.5%
being detrimental for the health of the preschool child.7 (≤48 mmol/mol)23 and may fuel urgency within all guidelines to strive
During toddler and preschool years, the brain is highly sensitive to for HbA1c levels that are as low as safely achievable for preschool
metabolic disturbances; potential abnormalities, particularly affecting age children to reduce the risk of long-term complications of T1D. It is
white matter, have been identified in several neuroimaging studies of important that the diabetes team and family share the same glycemic
young brains exposed to glycemic extremes, as occurs in T1D.16–18 The targets; hence they should be set and evaluated together with the
 13995448, 2022, 8, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/pedi.13427 by Egyptian National Sti. Network (Enstinet), Wiley Online Library on [25/12/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
SUNDBERG ET AL. 1499

child's family. Likewise, the glycemic targets need to be communi- specific emotional distress (both for the child and the caregivers) as
cated to other caregivers (i.e., at preschool) to guide the child's treat- well as metabolic aspects need to be considered.
ment. From the onset, it is important for the entire diabetes team to Although insulin pump use is recommended, injection therapy is
communicate that near normoglycemia is achievable through diabetes used in many centers for preschool children with T1D, especially in
education and clearly set glycemic targets.4–6 the following situations:
A CGM study in healthy children aged 2–8 years showed that glu-
cose is in the range 4–7.8 mmol/L (72–140 mg/dL) 89% of the day.24 • when insulin pump treatment is not available or affordable.
A reasonable treatment goal after the initial remission period in insulin • children who were using pumps have experienced pump failures or
treated children younger than 7 years can be >50% of time in target “skin reactions” that are difficult to adequately treat
(TIT) 3.9–7.8 (70–140 mg/dL) or >70% time in range (TIR) 3.9– • when the local diabetes team is inexperienced with using pumps in
10 mmol/L (70–180 mg/dL). Soon after diagnosis, during the remis- this age group. If so, advice should be sought from a more experi-
sion period, a higher TIT or TIR is preferable. enced center to provide the child with pump treatment and to opti-
It is important that both the diabetes team and families of young mize quality of care.
children use a language that tells the child that a glucose value can be
high, low or in range, and that the glucose level is never “good” or For safety reasons, all primary caregivers of very young children
“bad”. The knowledge of a glucose value often calls for action, but treated with an insulin pump need to be practically skilled in treat-
never for blame or punishment. Rather than asking a child “Your glu- ment with insulin injections in case of technical pump problems.
cose is high—what did you do?” or “what did you eat?,” which can imply Pain and fear associated with insulin delivery can be reduced by
that the child has done something wrong, caregivers can be taught to behavioral strategies (i.e., distraction, deep breathing).25 The usage of
“think out loud” and involve even young children in problem-solving subcutaneous catheters such as Insuflon (Unomedical, Lejre,
(i.e., “The glucose is high. What do we do when the glucose is high? Exer- Denmark) or I-port (Medtronic MiniMed, Northbridge CA, USA) and
cise and insulin can help. This time you will get insulin.”) This process changed every third day can be helpful.26 Topical lidocaine can be
can be started well before the child has an expressive verbal language, administered before insertion of s.c. insulin ports for infusion or
since the child's receptive language development starts early. This injections.
means that introducing diabetes related problem-solving gets inte-
grated into the child's global development from diagnosis. It is impor-
tant to be proactive when discussing glucose data and problem- 7.1 | Insulin dosing
solving in the clinic and to analyze positive examples together with
the caregivers versus only reacting to glucose excursions. Preschool children with optimal glycemic control usually need less
insulin on a body weight basis 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)
7 | INSULIN THERAPY IN PRESCHOOL in preschool children with well controlled T1D after the remission
C HI LD R E N phase.27 Preschool children have higher day-to-day variation in insulin
needs than older children.28 Insulin sensitivity varies with both age-
Insulin treatment guidelines for preschool children are essentially simi- appropriate activities and with age-appropriate napping. Preschool
lar to older children and adolescents, with age-dependent aspects children may have higher insulin needs during day-time napping.
taken into consideration. Insulin treatment always needs to be tailored
for the individual child and planned together with their caregivers.
Approval of insulin analogs for different age groups is regulated by 7.2 | Basal insulin
authorities. See the ISPAD 2022 Consensus Practice Guidelines on
Chapter 9 on Insulin treatment for further reading on insulin and insu- When using injections for insulin treatment, the unique diurnal pat-
lin analogs in pediatric use. Worldwide, most preschool children with tern of insulin requirements in preschool children should be taken into
diabetes use insulin injections to manage their diabetes. consideration in designing an individualized basal dosing scheme.29–32
Insulin pumps offer both greater flexibility in insulin dosing and a The low insulin requirement and tendency toward low glucose levels
better means to deliver very small, precise doses of insulin than are often most obvious during the night and especially between 3 and
injections and are thus considered the preferred method for insulin 6 AM. Preschool children often need much more insulin late in the
delivery in infants, toddlers, and preschoolers. A pump with high evening between 9 PM and 12 AM and the overnight insulin needs
precision in delivering very small basal rates should be chosen for a are variable from night to night.28 This creates typical patterns when
preschool child. If pump therapy is not available or affordable, multiple designing basal insulin dosing plans. If basal analogs are used one
daily injections (MDIs), with consideration of an injection port to should consider their action profile in relationship to insulin
reduce the number of injections, can be used. requirements.
When evaluating cost effectiveness and affordability of insulin The low body weight and thus low total insulin dose demands
pumps, psychosocial issues, such as quality of life and diabetes- special consideration when using commercially available insulin pumps
 13995448, 2022, 8, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/pedi.13427 by Egyptian National Sti. Network (Enstinet), Wiley Online Library on [25/12/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
1500 SUNDBERG ET AL.

and insulin preparations, especially in children with a body weight observe and calculate the correct proportion between insulin and
below 5–10 kg. Sometimes very small doses necessitate dilution of U- CHO from real life meals.
100 insulin, or an intermittent basal rate of 0 U/h for limited periods, The need for insulin at breakfast is often very high, and one might
i.e. every second hour during the night.33,34 These approaches may consider using 150/TDD in the calculation, and then evaluate and cal-
help to meet the needs of the young child's insulin treatment and culate from real life meals as above. At breakfast preschool children
must be carefully discussed (with advantages and disadvantages) with often have some degree of insulin resistance, and it is common to
the primary caregivers so that they are informed of the benefits and experience a marked glucose peak after breakfast despite an adequate
risks of the chosen strategy. Insulin should always be prescribed and insulin dose taken before the meal. For further reading, please see the
documented in normal units to avoid hazardous misunderstandings ISPAD 2022 guidelines chapter 10 on Nutritional Management in
regarding insulin dosing, especially if the child using diluted insulin is Children and Adolescents with Diabetes. Increasing the insulin dose
admitted to hospital. Any pump containing diluted insulin should be (lower insulin-to-CHO ratio) too much can risk hypoglycemia before
labeled with information regarding the currently contained concentra- lunch. In this situation, it may be helpful to give the prandial insulin
tion of insulin. 10 to 20 min before breakfast, lower the carbohydrate amount if it is
A glucose and meal-adjusted basal-bolus insulin regimen (deliv- high, and switch the carbohydrate type to a lower glycemic index
ered by injections or pump) requires that basal insulin delivery be (GI) carbohydrate. The need for a large bolus dose of insulin to cover
fine-tuned by the caregivers in accordance with the child's current breakfast might necessitate a very low basal rate during the following
insulin sensitivity. Preschool children have a higher day-to-day varia- 3 hours.
tion in insulin needs than older children.28 Insulin sensitivity can be The lower insulin requirement between 3 and 6 AM and higher
increased after very active days, such as a days at the beach or in the insulin requirement between 9 PM and 12 midnight can affect the
snow, or after a day playing with friends. The overnight long-acting individual insulin sensitivity/correction factor for treating hyperglyce-
insulin or basal rate might then be reduced by 10% to 30%. Insulin mia. The usual 100/ TDD for mmol/l (or 1800 for mg/dL) often needs
sensitivity can be markedly reduced (increased insulin resistance), for to be adjusted to give smaller correction doses during late night/early
example, during fever when the long- acting insulin or basal rate might morning and larger doses in the evening.
need to be increased by 20% to 100% according to glucose levels. Prandial bolus timing is important, regardless of mode of insulin
Under these circumstances, glucose levels must be carefully moni- delivery (pump or MDI). Pre-prandial bolus insulin given 15 min before
tored and caregivers need constant (24 hour per day/365 days per the meal is preferable to insulin administered during or after the meal
year) access to support from the diabetes team. and should be routinely advised for all toddlers and preschoolers, even
the most unpredictable eaters and when using formulations of insulin
designed for faster uptake (faster aspart).38 It is also important in
7.3 | Bolus dosing hybrid-closed loop systems (see below).
Given the difficulties in anticipating carbohydrate intake in very
A glucose and meal-adjusted basal-bolus insulin regimen (delivered by young children, if needed the dose can be split with an insulin pump: a
injections or pump) can be adapted to the preschool child's daily activ- portion of the insulin dose is delivered before the meal and the
ities and is the preferred type of insulin treatment. Twice daily insulin remainder during the meal when eating is erratic or new foods are
dosing in this age group does not give the flexibility needed to adapt offered. Another possibility with a pump, is that a combination bolus
doses to varying situations in daily life and requires a rigid pattern of (also called combo or dual wave bolus) can be used; that is, part of the
eating to match insulin peaks, which is challenging in this age group bolus is given before the meal and the remainder over 20–40 min. If
and is associated with poor glycemic outcomes.35,36 In settings with the child stops eating before the meal is finished, the remainder of the
limited resources or when struggling with severe socioeconomic dep- bolus can be canceled.
rivation, including problems with insulin availability and administra- Small inaccuracies in calculation of up to 5–7 g CHO will usually
tion, sometimes the only option is to give NPH insulin in the morning not be problematic. Larger inaccuracies may result in hypoglycemia or
together with rapid-acting insulin at the time of the first meal of the hyperglycemia 2–3 h after eating, but not immediately. These can be
day to provide some insulin for daytime meals. However, this regimen anticipated and treated with additional CHO or a small correction
should be avoided if at all possible. dose of insulin at least 2 h after the meal.
Preschool children often need proportionally larger bolus doses When giving relatively large bolus doses, one must remember that
than older children, often constituting 60% to 80% of the total daily they interact with the need for basal insulin in the following hours.
insulin dose (TDD). The often used rule of 500 (500/TDD = how Thus, the total basal rate can be relatively low, around 20%–40% of
many grams of carbohydrate [CHO] is covered by 1 U of insulin) for TDD. In preschool children, it is often estimated that the effect of a
bolus calculations, as detailed in the ISPAD 2022 Consensus Guide- subcutaneous bolus of a rapid-acting insulin analog (lispro, aspart, or
lines Chapter 9 on Insulin treatment rarely fits the youngest children glulisine) lasts for only 2–3 h (active insulin time in pumps).37
37
as it often underestimates the insulin dose. One can use a 330 or When using MDIs with frequent glucose checks and meal-
250 rule (gives 50%–100% more insulin) instead of 500. To evaluate adjusted insulin dosing, one possible strategy is to give a rapid-acting
and further tailor the child's insulin dosing it is necessary to repeatedly insulin analog for all meals, except for the last meal of the day when
 13995448, 2022, 8, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/pedi.13427 by Egyptian National Sti. Network (Enstinet), Wiley Online Library on [25/12/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
SUNDBERG ET AL. 1501

short-acting regular insulin can be used to ameliorate the increase in small insulin doses needed, often well below 10 U per day,44 the large
glucose before midnight. Part of the dose can be given as rapid-acting differences in physiological insulin needs during different parts of the
analog insulin, the insulins can be mixed in a syringe or given as sepa- day, significant day-to-day variation in insulin needs, and safety con-
rate injections (if an injection aid is used). cerns to avoid accidental insulin dosing.
When first implementing HCL-systems there may be a need for
some “re-learning” among diabetes teams and caregivers of young
8 | PRAC TIC A L A S P EC TS ON USE OF children. They should avoid late bolus dosing for carbohydrates, which
I N SU LI N P UM P S WI T H A N D WI T H OU T C GM on an automated system results in “basal” increases by the algorithm
IN PRESCHOOL CHILDREN when the glucose is rising without adequate insulin on board. A subse-
quent late bolus to cover the carbohydrate intake combined with the
Over the last few years pump size has decreased, pumps can deliver “basal” increase may precipitate hypoglycemia. Additionally, if basal
smaller doses, and CGM devices have become more accurate and insulin is suspended due to impending hypoglycemia, the amount of
more widely available making these therapies acceptable for pre- carbohydrate needed to treat hypoglycemia may be less than is usu-
school children. The safety of insulin pump and CGM use in this popu- ally required with standard pump therapy. The need to trust the sys-
lation appears to be similar to that seen in other age groups. tem's capacity to correct glycemic excursions is a new challenge for
Yet, frequency of insulin pump and CGM use varies between cen- caregivers.
ters.39 Barriers to the use of these treatment options in pre-school With some diabetes centers employing advanced technologies
children need to be explored and systems better adapted to this for patients from the time of diagnosis, healthcare providers now
patient group. sometimes encounter families of young children with T1D who have
For s.c. infusion of insulin in preschool children it is possible to never experienced any other mode of insulin treatment. Nonetheless,
use either flexible catheters or steel catheters. Both have advantages for safety reasons, all families need to be equipped, experienced and
and disadvantages. Considerations include risk of pain, risk of kinking, skilled in insulin injections and capillary glucose monitoring (“finger-
number of adhesive points, insertion technique and skin reactions. prick”) in case of technical problems with the devices or algorithms.
The choice of infusion set needs to be re-evaluated during childhood
as the child grows and subcutaneous fat distribution changes.
There are few data on special considerations regarding skin care 9 | P R A CT I C A L A S P E C T S O N U S E OF
in preschool children with T1D but CGM-related skin problems seem M U L T I P L E D A I L Y I N S U LI N I N J E C T I O N S I N
to be frequent in very young users.40 In general, recommendations for P RE S C H O O L C HI LD R E N
site use (including site selection, site preparation, and site rotation)
are similar as for older children. Many preschool children receive insu- When an insulin pump is not affordable or available, MDI is a treat-
lin injections and insert infusion sets and CGM sensors in their but- ment that can be used safely and effectively.
tocks, an area often covered by a diaper. The abdomen, upper arm, High precision insulin dosing adjusted by carbohydrate counting
and upper thigh are also commonly used. For children under the age is difficult when using insulin pens or syringes filled with insulin U-
of 6 years using insulin pumps, rates of scarring and lipohypertrophy 100. Syringes with ½ unit markings and pens with at least ½ unit dos-
40
are high but not different than in older children. ing increments should be used. Diluting insulin to 10 U/ml increases
the possibility to dose in small steps and to adjust insulin dosing to
anticipated carbohydrate intake and current glucose levels.
8.1 | Hybrid closed loop with automated insulin Giving insulin pre-meal is also necessary when insulin is adminis-
delivery systems in preschool children with T1D tered via injections. Giving all the insulin in one injection necessitates
a skilled caregiver estimation of the child's anticipated eating. This can
While hybrid closed loop insulin pumps (HCL) with automated insulin be achieved by encouraging eating practices that make it easier to
delivery (AID) are now relatively widely used in older children with predict intake (see Nutrition section below).
T1D, during the past few years, their use in infants, toddlers and pre- An individually programmed bolus calculator (i.e., a phone app or
school children has largely been restricted to clinical trials.28 Notably, a paper-and-pen scheme) can simplify calculation of bolus doses.
the evidence from clinical trials suggests that HCL with AID can It is important to create a calm situation when injecting insulin.
increase TIR, especially overnight, among very young children.41 HCL Insulin can be injected in the buttocks with the child sitting face-to-
with AID can reduce parental burden for managing diabetes-related face on the lap of a caregiver. Some children need to see what is hap-
care and reduce perceptions of parenting stress.42,43 Making certified pening and injecting in the abdominal region can make this possible.
systems with this technology available for children younger than Upper arms and legs can also be used for injection but may risk the
7 years, tailoring the algorithms to the age-specific needs of this child moving their limb and require the caregiver to hold the child, cre-
patient group, and further developing clinical and research experience ating an unpleasant injection experience.
using this treatment modality in preschool children will be important. The major challenge for many caregivers of toddlers and pre-
Age-specific challenges to address in automated systems include the schoolers on MDI is how to handle the complicated situation of more
 13995448, 2022, 8, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/pedi.13427 by Egyptian National Sti. Network (Enstinet), Wiley Online Library on [25/12/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
1502 SUNDBERG ET AL.

or less simultaneously cooking, calculating the insulin dose, injecting 10.2 | Continuous glucose monitoring
the child and then transferring focus to eating together with the fam-
ily. Cooperation between two caregivers is often a necessity in this CGM provides an effective mode of monitoring for low and high glu-
complex situation. cose levels. Qualitative reports from caregivers suggest CGM can pro-
mote a sense of safety, decreased worry, and greater comfort with
other caregivers when used as part of remote monitoring.49 When
10 | GLUCOSE MONITORING available and affordable, CGM should be used as a tool for adjusting
insulin doses. With use of newer systems, real-time CGM use is high
In this chapter, blood glucose (SMBG) values refer to glucose values and sustained in young children with T1D and significantly reduces
measured by capillary blood check (“finger prick” and “blood glucose hypoglycemia.50 Reduced glycemic variability was observed in real
monitoring”) although meters generally display plasma glucose concen- world use of CGM among a multinational cohort of young children.51
trations. Since plasma glucose is 11% higher than whole blood glucose, Health care providers should counsel caregivers on how to reduce
this term is used when exact numbers are mentioned. The term “glucose CGM-related challenges, which can include pain from insertion, dis-
value” refers to a glucose value from either continuous glucose monitor- ruptive alarms, limited areas to place a sensor, skin and adhesive prob-
ing (CGM) or a capillary blood check. The use of CGM (rtCGM or isCGM) lems, and data overload. Health care providers fill an important role in
is recommended in all insulin treated children younger than 7 years. educating families of young children about diabetes technologies,
including CGM, and need to help families to establish realistic expec-
tations of the benefits and challenges of CGM use.52
10.1 | Blood glucose checking The ability of some CGM devices to remotely transmit glucose
values to a phone can be of benefit for caregivers who rely on others
Families should be taught how to measure and interpret capillary for care of their child, for example, while at day care or preschool.53
blood glucose values (SMBG). The limited capacity of the preschool
child to verbally communicate necessary information related to self-
care increases the need for high quality and frequency of glucose 11 | N U T R I T I O N A L N E E D S OF TH E
monitoring. It is important for the preschool child that the caregivers P RE S CH OOL C HI LD WI T H T1 D
can perform the monitoring in a way that gives the child a sense of
security and trust. Accuracy in everyday monitoring situations should Optimal nutrition is required to provide sufficient energy and nutri-
be ensured by follow up with the diabetes team. The child should be ents to meet the rapidly changing needs of children at this stage of
introduced to glucose monitoring and interpretation according to age life. Relative to their body weight, children's nutrient and energy
appropriate and individual capabilities, as the development of the requirements are greater up to around 4–5 years of age, after which
mathematical understanding of numbers and time is gradual. their growth rate slows and their nutrient needs decrease relative to
While independent self-care can never be expected from any pre- their body size.54
school child with T1D, most typically-developing children with diabe- Breastfeeding should be encouraged for all infants,55 including
tes can perform blood glucose checks and perform some basic infants with diabetes. Complementary foods, preferably iron-rich,
interpretation by age 7 years. However, this should always be over- should be introduced from 4 to around 6 months of age. If breastfeed-
seen by a caregiver. ing is not possible, an iron-fortified infant formula should be given as
General advice on SMBG monitoring is available in the ISPAD the main milk drink until 12 months of age.
guidelines on Glucose monitoring. In children younger than 7 years- A routine regarding breast- or formula-feeding is important for
old, the recommended checking frequency of 4–6 times per day is infants with diabetes as this enables appropriate interpretation of glu-
rarely sufficient to achieve target glucose and HbA1c levels. A high cose levels and basal and bolus insulin adjustments. This may involve
proportion of time is spent out of glycemic target range.45 Even with 3–4 hourly feeds (of approximately 150–240 ml) during the day with
a higher monitoring frequency of 7 or 10 checks per day, undetected complementary solids. Continuous or hourly breastfeeding is discour-
hypoglycemia and hyperglycemic events in insulin treated preschool aged as this makes insulin dosing difficult while bolusing every third
children are common.46 to fourth hour during day-time works practically. Breast milk has
Nighttime SMBG is recommended by many diabetes teams and approximately 7.4 g CHO per 100 ml, so for infants 6 months and
performed by many families with pre-school children with T1D.47 Pre- older it is possible to bolus before the feed for at least 5–7 g CHO
school children with diabetes can spend a long time in the hypoglyce- and 15 g CHO in older babies (>9 months).
mic range without detection,36,48 despite nighttime monitoring of Dietary recommendations are based on healthy eating principles
SMBG.46 The normal activities of the child must be interrupted to suitable for all preschool children, with the aim of establishing family-
measure a blood glucose value during daytime. based meal-time routines that promote glycemic control and reduce
Thus, relying on SMBG as the only way of monitoring glucose has cardiovascular risk factors. Carbohydrate counting is important to per-
several limitations but is a necessary tool to master for all caregivers mit the matching of insulin dose to carbohydrate intake on intensive
of a preschool child with T1D. insulin regimens and should be taught to the family at the onset of
 13995448, 2022, 8, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/pedi.13427 by Egyptian National Sti. Network (Enstinet), Wiley Online Library on [25/12/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
SUNDBERG ET AL. 1503

diabetes (See nutrition chapter 10). Nutritional advice must be individ- vegetables (2½ servings) and 150 g fruit (1 serving) daily from 2 years
ualized and adapted to cultural and family traditions. of age; or 1½ serving of fruit and vegetables daily between 1 and
A pediatric diabetes dietitian should provide education, monitor- 3 years. 400 g of fruits/vegetables are recommended each day from
ing, and support at regular intervals throughout the preschool years, 4 years of age.
as caregivers of preschool children with diabetes report meal-times as The dietary quality of preschool children with diabetes is similar
one of the most difficult components of their child's care.56 Pre- to or poorer than their peers without diabetes.62 Preschool children
schoolers require more frequent dietetic review than older children, with T1D consume less fruit and vegetables and have higher saturated
with a suggestion for reassessment at least twice annually until the fat intakes than peers63 and then recommendations would advise.64,65
age of 6 years (See ISPAD 2022 Consensus Guidelines Chapter 10 on This may increase the risk of future cardiovascular disease. Eating
Nutritional Management in in Children and Adolescents with Diabe- habits in young children influence food choices later in life,66 so early
tes). It is important to provide caregivers guidance for appropriate intervention with increased attention to an increase in fruit and vege-
food quantities for age, including minimum and maximum carbohy- table intake and decrease in saturated fat is needed. It is helpful to
drate amounts, particularly as food intake may drop off during the counsel caregivers that young children with or without diabetes may
second year of life and following weight regain after a T1D require up to 10 exposures to a new food before it is accepted67 and
20
diagnosis. to educate caregivers on how to make appropriate adjustments to
There is international agreement that carbohydrate should not be pre-prandial insulin dosing or meal planning (e.g., pairing a new food
restricted in children with T1D as it may result in deleterious effects with a familiar food) to avoid dosing during or after the meal. It can
on growth and brain development.57,58 Care should be taken when also be helpful to remind caregivers that miscalculations of carbohy-
giving dietary education, so that methods of quantifying carbohy- drate content <5 g rarely affects the postprandial glucose levels.
drates do not increase saturated or trans-fat intake. Although care- More children with T1D have an overweight body mass index
givers may prefer high- fat snacks to avoid affecting glucose levels, compared to children in the general population,21,64,68,69 and this is
this should be discouraged as they will provide unnecessary calories, most pronounced in the youngest children (<6 years).70,71 It is impor-
an unhealthy fat intake, and negatively impact dietary quality. Studies tant to plot the growth chart including assessments of weight for
suggest that consistency in children's intake59 and balanced meals length or height at least at 3-month intervals to identify excessive
containing protein, fat and carbohydrate60 may be helpful methods weight gain, in order to commence interventions that involve the
for reducing post-prandial glycemic variation. whole family. Diabetes associated risks of extra caloric intake as over-
Preschool children with T1D should consume a diet that empha- treatment of hypoglycemia or excessive feeding before bed because
sizes vegetables, fruit, whole grain bread and cereals, dairy foods and of parental fear of hypoglycemia need to be explored if the child
appropriate types and amounts of fats. Low fat diets are not suitable develops overweight/obesity. Encouraging participation in family
for children under 2 years of age. Lower glycemic index (GI) choices, meals has been recommended to promote dietary quality and social
can be introduced as substitutes for higher GI food choices. Iron defi- interaction.
ciency can be a concern in this age group; adequate consumption of Age-appropriate finger foods should be encouraged for self-
lean meat or alternatives is important and should not be overlooked feeding, and the reintroduction of a bottle as an easy method of
because of the increased focus on carbohydrate. carbohydrate intake discouraged. Bottles can lead to overconsump-
A guide to the macronutrient distribution of the total daily energy tion of fluids, increasing carbohydrate intake and placing other nutri-
intake in preschool children is shown below. However, this should be ents at risk.
based on an individualized assessment and with respect to the family's
eating pattern prior to the child's diabetes diagnosis and day-to-day
variations in the child's appetite. 12 | E ST A BL IS HI NG POSI TIVE F OOD
Carbohydrates: 40–50 Energy (E) %. Average intakes 110– BEHAVIORS AND MEAL-TIME ROUTINES
140 g/d in children aged – 5 years; 200 g/d in children 6 to
10 years.57 Establishing positive food behaviors and meal-time routines are
Protein: 15–20 E % (decreasing with age from approximately important for preschool children with T1D, as these behaviors impact
1.5 g/kg body weight/day in 6-month-old infants to 1 g/kg body glycemic control56,72 and set the stage for life-long appropriate nutri-
weight/day in preschoolers). tion practices.66 It is important that caregivers model eating practices
Fat: 30–35 E % (less than 10 E% saturated fat, less than 10 E% and the preschool child is exposed to new foods in the context of
polyunsaturated fat, and more than 10 E% mono-unsaturated fat). family meals. Early childhood developmental traits, including seeking
Infants less than 12 months may consume up to 40% energy from fat. independence, transient food preferences, variable appetite, food
Fruit and vegetable intake remain of particular concern and ways refusal, and behavioral resistance often make mealtimes challenging
to incorporate these into the whole family's diet, including the pre- for caregivers of children with diabetes. Caregivers of children
59,61
school child's, should be discussed. Examples of recommenda- with T1D report more disruptive meal behaviors, including longer
tions from Australia, United States, and the Nordic countries are meal duration and more frequent food refusal compared with
expressed in different ways but consistent in content: 180 g controls69,73,74; even for children using insulin pumps.75 Research has
 13995448, 2022, 8, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/pedi.13427 by Egyptian National Sti. Network (Enstinet), Wiley Online Library on [25/12/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
1504 SUNDBERG ET AL.

demonstrated positive correlations between suboptimal dietary that are established in childhood often persist into adulthood. Thus,
adherence and higher glucose levels.56,63,75,76 Caregivers' fear of lifestyle factors in early childhood have a dual impact on later cardio-
hypoglycemia associated with food refusal or unpredictable dietary vascular risk, observable both as early markers of atherosclerosis dur-
patterns can result in force feeding, grazing continually over the day, ing adolescence83 and as a set of behaviors that influence the child's
and postprandial insulin administration, causing prolonged periods of risk of cardiovascular disease as an adult and even into senescence.
hyperglycemia. Children tend to follow the lifestyle habits of their caregivers and
To assist the reliable intake of carbohydrate at mealtimes and to entire family regarding physical activity,84 TV watching85 and food
minimize food refusal, the following strategies should be offered: choices61,86,87 in childhood and then subsequently throughout their
adult lives.66 Lifestyle supporting interventions should thus be
• structured mealtimes directed toward the caregivers and entire family and not the individual
• avoidance of continuous eating habits as this has been associated child with T1D.
with poorer glycemic outcomes in young children59
• small snacks including limits on low carbohydrate foods as these fill
the child up 13.1 | Physical activity
• limits on the time spent at the table; for small children, mealtimes
should be limited to approximately 20 minutes per meal.77 Physical activity and sleep confer many health benefits for all children.
• avoidance of force feeding Physical activity has a strong, graded, inverse cross-sectional relation-
• team members should reassure caregivers that hypoglycemic epi- ship to insulin resistance88,89 and body fat.90 High-intensity physical
sodes related to inadequate carbohydrate consumption are usu- activity is the most effective type of activity to reduce cardiovascular
ally mild. risk.91 Engaging in regular physical activity is also necessary to acquire
and improve gross motor skills.92 Many countries recommend at least
Caregivers should be advised that postprandial bolus insulin can 60 min/day of moderate and vigorous physical activity for all
become an established habit and reinforce anxiety about the child children,93 and WHO recommends this at least from 5 years of age.94
under-eating. Fear of hypoglycemia can lead to under-bolusing for Preschool-age children engage in patterns of physical activity that
meals, resulting in inadequate bolus doses given over the day and sub- are different from older children and characterized by multiple small
sequent hyperglycemia. Continuous eating (grazing) makes interpreta- bursts of activity.95 This difference can complicate how to quantify
tion of glucose levels and insulin dose adjustments difficult. A regular the physical activity of a preschooler. Asking caregivers about how,
meal pattern with one small snacking episode between meals (7–15 g where, and how often (vs. how long) their preschooler plays may be a
carbohydrate preceded by an appropriate insulin dose) may reduce way to help quantify their physical activity.
food refusal as the child may be hungrier at main meals. Unreasonable General facilitators of physical activity for preschoolers include
expectations of a child's intake may result in food refusal and subse- access to safe play environments and organized activities, their own
quent hypoglycemia. Food refusal should generally be dealt with preference for being physically active, positive parent modeling of
effectively and similarly to toddlers without diabetes. It is important physical activity, spending time outdoor and peer interaction.96,97
to emphasize parental patience and to encourage caregivers not to Data suggest that both having diabetes and being a girl represent
use food bribes. risk factors for greater physical inactivity in preschool-age children.98
All diabetes team members should provide the family with clear
and consistent messages regarding food and mealtime behaviors.78
Distractions such as the television and toys should be removed at 13.2 | Sleep
65
mealtimes. Research has demonstrated that disruptive child behav-
iors can be reduced by establishing specific rules and consequences Sufficient and high-quality sleep plays an important role in overall
for mealtimes and teaching caregivers behavioral strategies for health and may also be associated with hyperglycemia and glycemic
meals.79 Stepwise, the child needs to establish an age-appropriate variability in children with T1D.99,100 The American Academy of Sleep
positive connection between insulin, food and health (i.e., “I get insulin, Medicine recommends infants sleep between 12 and 16 h per day,
I eat and thus I can jump this high and feel great”). toddlers sleep between 11 and 14 h per day, and preschoolers sleep
between 10 and 13 h per day including naps.101,102 However, recent
studies in young children with T1D report much shorter than average
1 3 | L I F E S TY L E F A C T O R S I N P R E S C H O O L sleep durations (8 h per night) based on parent-report and actigra-
C HI LD R E N phy.100,103 Both children and caregivers experience sleep disruptions
and restriction because of nighttime caregiving and caregivers com-
The American Heart Association (AHA) has identified that T1D is monly report fear of nighttime hypoglycemia.11,104,105 Infants and
associated with extremely high risk of cardiovascular disease, calling toddlers sleeping pattern during the day needs to be taken into con-
for treatments to minimize this risk.80 Lifestyle habits, such as nutri- sideration when programming the insulin pump. There is emerging
tional preferences,66 physical activity,81 and time spent sedentary,82 evidence suggesting automated insulin delivery systems can reduce
 13995448, 2022, 8, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/pedi.13427 by Egyptian National Sti. Network (Enstinet), Wiley Online Library on [25/12/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
SUNDBERG ET AL. 1505

the number of parental awakenings and fear during the night and making it very difficult for caregivers to detect these symptoms. There
improve parental perceptions of sleep quality.42 is an additional risk due to prolonged nocturnal hypoglycemia, com-
mon in children younger than 7 years with T1D.46,108–110 HCL studies
indicate that preschool children have a high day-to-day variation in
14 | KETONE MONITORING insulin need,28 which may also contribute to risk.
Data suggest the frequency of severe hypoglycemia has
Ketoacidosis is a life-threatening acute complication of diabetes. Six decreased over time in all children with T1D and that there is no lon-
percent of children younger than 6 years in the United States and 4% ger a clear association between lower HbA1c and higher risk of hypo-
of children in Germany/Austria (data from the T1D Exchange clinic glycemia.111,112 Moreover, specific to preschoolers, Germany and
registry and the Prospective Diabetes Follow-up Registry: DPV) have Austria (DPV), USA (T1DX)106 and Sweden all report that no more
106
suffered from ketoacidosis during the past year. Education of fami- than 3% of children younger than 6 or 7 years with T1D have experi-
lies on prevention of ketoacidosis is an essential part of diabetes care, enced a severe hypoglycemic event with seizures/unconsciousness
especially as young children are physiologically prone to develop keto- during the previous year.21 These data suggest the use of insulin
sis. See the ISPAD Guidelines on Diabetic Ketoacidosis chapter 13 for pumps, hybrid closed loop systems, insulin pumps with a suspend
further advice. before low algorithm can reduce the time spent in hypoglycemia.
The high incidence of gastroenteritis with vomiting and risk of Access to CGM and predictive alarms for upcoming hypoglycemia
misinterpreting vomiting due to insulinopenia makes monitoring of appear to increase the probability of early detection and prevention
ketones important in this age group. Measuring ketone bodies in of hypoglycemia.
blood (betahydroxybutyrate, BOHB) should be the primary method of These technologies represent an opportunity to turn the corner in
detecting and monitoring ketosis in preschool children with T1D; see reducing the risk of severe hypoglycemia in preschool-age children
the ISPAD Guidelines chapter 12 on Sick days. Blood ketone checking with T1D. Caregivers who lack the knowledge or confidence to use
gives the caregivers and health care professionals timely information these technologies effectively in their child's daily management may
regarding ketone levels and their rise or fall to provide advice over the benefit from advanced diabetes education to understand glucose pat-
phone or in the emergency room. terns and how to use alerts on their child's CGM to recognize and
Ketones should be monitored when there is a suspicion of lack of treat potentially dangerous glucose trajectories (e.g., rate of glucose
insulin raised either by high blood glucose (2 values above 14 mmol/L decrease shown by arrows pointing downward).
[252 mg/dL] within 2 h that do not decline with an extra insulin dose) The fear of a hypoglycemic event, rather than the frequency of
or when the child shows symptoms suggestive of ketosis (vomiting, hypoglycemic events, is associated with higher HbA1c and lower
nausea, abdominal pain or unclear illness). It is important to educate HRQoL,107,113 suggesting the role of fear cannot be underestimated for
and remind caregivers of young children that insulin always should be caregivers of young children with T1D. Fear of nocturnal hypoglycemia
given by s.c. injection (with a syringe or a pen) when treating ketone- is a particular challenge. Emerging evidence supports that behavioral
mia (without DKA) even if the child usually is treated with an insulin interventions may reduce caregivers fear and there is evidence that con-
pump. See the ISPAD Guidelines chapter 12 on Sick days for further sistent CGM use can reduce time in hypoglycemia in young chil-
advice on treatment. dren.50,114 Asking in a clinic visit about typical frequency and severity of
Measurement of acetoacetate in urine with a dipstick can be used hypoglycemia is encouraged. It may also be helpful to use validated sur-
as an alternative to blood ketone measurement but gives different veys that ask about thoughts and feelings during and after the hypogly-
information. As preschool children do not urinate on command, results cemic event to identify caregivers who might benefit from treatment.
from blood ketone monitoring will be more easily available for the
caregiver parent unless the child uses diapers. Cotton balls can be put
in the diaper to absorb urine which can then be applied to the 15.1 | Treatment of mild hypoglycemia in infants
dipstick. and preschool children

Oral glucose as tablets, gel, or a drink is the preferred method of

15 | HYPOGLYCEMIA hypoglycemia treatment. The dose of glucose should be easily
accepted and quickly ingested by the child. The recommended dose
Hypoglycemia, including caregiver fear of hypoglycemia, is a limitation (0.3 g glucose/kg bodyweight) will raise plasma glucose approximately
to striving for normoglycemia in preschool children, see ISPAD guide- 2.5–3.6 mmol/L (45–64 mg/dL) (guidelines chapter 12 on hypoglyce-
lines chapter 12 on hypoglycaemia.47,105,107 Young age has tradition- mia).115 In young children 5–7 g carbohydrate is usually adequate, and
ally been regarded as a marker of high risk of severe hypoglycemia it is important not to give too much carbohydrate when treating hypo-
during insulin treatment. Inherent in this risk, is the observation that glycemia to avoid subsequent hyperglycemia. This risk is high in young
preschoolers are erratic in their daily life (food intake, activity levels, children with a small body size.
sleep, and sick days) predispoding to hypoglycemia. Many preschool To treat hypoglycemia in breast- or formula-fed infants, carbohy-
children are also unable to identify and articulate their symptoms, drate gel, diluted juice, or a glucose polymer from a spoon or bottle
 13995448, 2022, 8, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/pedi.13427 by Egyptian National Sti. Network (Enstinet), Wiley Online Library on [25/12/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
1506 SUNDBERG ET AL.

can be offered. Honey should not be given to infants younger than increased vigilance to dietary intake, symptom monitoring, and frus-
1 year due to risk of botulism. trations with glucose excursions. For caregivers of preschool children
Giving something that contains fat (i.e., milk and chocolate) will with T1D, additional complexities are encountered, including the
slow gastric emptying and cause a slower rise in plasma glucose.116 necessity to adapt to developmental changes to ensure adequate psy-
Sucrose sweetened confectionary should not be routinely used to chological adjustments for the child and themselves, and to facilitate
treat hypoglycemia, as it can lead to increased risk of dental caries. care in the context of other care providers such as preschool staff. Cli-
nicians need to be aware of the overwhelming sense of responsibility
and worry which parents of preschool children with T1D can feel.121
1 6 | C A R E O F T H E N E W LY D I A G N O S E D Caregivers who have access to a supportive network (relatives and/or
I N F A N T , T O D D L E R , OR P R E S C HO O L E R W I T H friends) have lower risk of diabetes-related stress and burnout.10 It is
DIABETES important to educate secondary caregivers about T1D and insulin
treatment. Attention should be given to the needs of the siblings of a
The care of the newly diagnosed child with T1D is a key opportunity young child with T1D.
for successful diabetes treatment. The diabetes team needs to have As children grow up, they understand more about health and ill-
clear routines regarding treatment initiation for newly diagnosed ness. When appropriate, it needs to be explained that diabetes is not
infants, toddlers and preschool children with diabetes and be ready to caused by eating too much sugar, and that you cannot catch diabetes
tailor these further to fit the individual child and family. from another person. This needs to be intentionally taught to friends
Preschool children, especially toddlers, have a high risk of rapidly and relatives to avoid common misconceptions about diabetes.
developing ketoacidosis at diabetes onset. Early detection and fast Caregivers are an integral part of the diabetes team and have the
referral to a hospital with competence in management of DKA in very most important supportive role to play over the years as their children
young children is lifesaving. Please see ISPAD 2022 guidelines Chap- eventually learn to self-manage their diabetes. Providing this support
ter 13 on Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar can be difficult when caregivers have their own stressors to deal with,
State. and struggle with the constant vigilance needed to ensure the safety
After DKA has resolved, or directly following diagnosis, if DKA is of their child. During young childhood, caregivers take responsibility
avoided, the immediate treatment goal should be to restore and main- for all diabetes-related tasks. It is important that they do this in a way
tain normoglycemia. that is neither threatening nor frightening for their child. Involving the
Carbohydrate counting, meal-time routines and nutrition need to child in aspects of diabetes management as soon as possible
be taught and discussed during the first days with insulin treatment. (e.g., using think aloud strategies when performing diabetes manage-
The education needs to be tailored to the individual family's crisis ment, incorporating choice options when appropriate “What side of
reaction upon diagnosis and preexisting understanding. The education your bottom for your pump site? Pick one or I will”) is recommended,
needs to be given in a culturally sensitive manner and with a high so the child can begin to develop a sense of ownership/management
respect of parental integrity. of their own health. A supportive and emotionally warm parenting
Very young children with T1D may benefit from introduction of style is important for promoting improved quality of life for children
an insulin pump and CGM at or soon after diagnosis. Both devices can with T1D.
offer families greater ability to fine-tune insulin delivery when navi- Establishing good habits in the early years may form the basis for
gating the partial remission period.117–120 optimal life-long diabetes self-management. The way that caregivers
The professional diabetes team needs to get acquainted with the model diabetes-related tasks will have a direct impact on the way
family's structure, habits and beliefs regarding lifestyle and upbringing their children learn. Supporting caregivers toward a positive adjust-
of young children to develop individualized diabetes care plans that ment to living with diabetes will help them to effectively model those
promote optimal habits and insulin treatment routines or can inform a tasks and assignments involved in daily life with diabetes as preschool
rationale for habits that need to be changed. children learn from examples.
The diabetes team should have programs and resources available It is important to engage all primary caregivers in diabetes care
to promote caregivers resilience and long-term capacity to provide from the onset, and to keep them involved in everyday diabetes care
developmentally appropriate levels of daily diabetes management as throughout the childhood years and to avoid that responsibility for
the child grows. diabetes self-care is carried by only one primary caregiver.

17 | LIVING WITH DIABETES IN THE 18 | S C R E E N I N G CH I L D R E N F O R

FAMILY PSYCHOSOCIAL DISTRESS

For people living with T1D and their families, the management of the Regular screening of children for psychosocial distress is important to
disease is complex and individual. Daily challenges imposed by T1D ensure that difficulties are identified early, and appropriate support
include cognitive and emotional burdens that can take the form of and treatment plans established as soon as possible. Most children are
 13995448, 2022, 8, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/pedi.13427 by Egyptian National Sti. Network (Enstinet), Wiley Online Library on [25/12/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
SUNDBERG ET AL. 1507

not able to complete questionnaires or report on their own level of caregivers and the diabetes team need to share the responsibility for
emotional distress in a reliable manner until they are approximately educating the preschool institution, especially when the child is newly
7–8 years of age. Therefore, both talking with them directly about diagnosed with diabetes or when an additional diagnosis such as
how they feel, and asking their caregivers to report on their children's celiac disease occurs. Working with the preschool staff on carbohy-
psychosocial well-being is recommended. Including the child in the drate counting enables the appropriate doses of insulin to be given in
discussion is important and asking the child direct questions is essen- relation to the food intake and glucose levels.
tial. What do you do for your diabetes that you are proud of? What parts In countries where there are no regulations to support the child
of diabetes are easy for you? What parts of diabetes are annoying for with diabetes, the diabetes team together with the parent organiza-
you? Who are your biggest helpers in caring for your diabetes? If you tions should advocate for improved regulations.
could change something about your diabetes, what would it be?
Members of diabetes teams need to develop clinical skills in talk-
ing directly with the very young child. This is sometimes a time con- 20 | C A R E F O R T H E P R E S C H O O L CH I L D
suming but necessary task. WI TH T1 D I N L I M I TE D R E SOUR C ES
Repeated meetings together with the child and caregivers are SETTI N GS
often needed to establish and continue an ongoing dialogue with the
very young child. Telemedicine can contribute new challenges in car- Whenever possible, the guidelines described in the preceding sections
ing for the preschool-age child (e.g., very young children may be shy should be followed. Treatment strategies and targets (such as HbA1c)
or become distracted by the telemedicine equipment/setting). There- need to be individualized and adapted to local circumstances.
fore, when using video-based telemedicine with families, it may be Treatment of preschool children with T1D in contexts with gener-
necessary for diabetes teams to allot additional time to re-establish ally high under-5 mortality-rates is an extreme challenge. Adding dia-
rapport with the child. Some strategies to try may include normalizing betes to general threats to health and survival such as infectious
the telemedicine experience by asking the child to share a treasured diseases and accidents puts the child in a hazardous position. Young
item (e.g., toy or game) or to introduce the practitioner to their pet children have a high risk of life-threatening ketoacidosis, which can be
and to encourage interaction between the caregiver and child. misinterpreted as gastroenteritis unless a high level of awareness and
There are several pediatric measures of depressive symptoms monitoring capabilities are available.
that are validated and reliable for use with children as young as If possible, priority should be given to the youngest patients to
7 years of age, varying in length and depth of detail. get best possible access to monitoring of glucose and ketones. Flexi-
Parental anxiety and fears can have a direct and negative effect ble insulin regimens are preferred as the insulin needs of the young
on diabetes management and health outcomes. It can be associated child is variable from day-to-day.
with depression; however, these are two separate conditions and Breast-feeding should be recommended for children with diabe-
should be treated separately. They can have an opposite effect on dia- tes on the same basis as other children in accordance with local tradi-
betes management and control, supporting the recommendation to tions and recommendations. Preschool children with diabetes should
assess them separately. follow the same guidelines for vaccination as healthy peers. Monitor-
ing of weight and height/length is essential.
For further advice see the ISPAD Guidelines chapter 25 on lim-
19 | PRESCHOOL CARE ited resources.

Legislation protects children with T1D in many countries. Schools

must make reasonable adjustments to ensure that children with dis- 21 | F U T U R E N E E D S OF P R E S C H O O L
abilities are not put at a substantial disadvantage compared with their CH I L D RE N WI T H T 1 D
peers. For diabetes, this means that preschools should have enough
staff trained to allow the child with diabetes to take part in all aspects “Diabetes during early childhood creates a psychosocial challenge to
of preschool and school life without loss of quality in insulin treat- the families of these children. Successful management of infants and
ment. Contingency plans must be in place to quickly train replacement toddlers with diabetes depends on a well-functioning and educated
staff. family, the availability of a diabetes health care team experienced in
In addition to ensuring the rights of the child with diabetes, it is the treatment of these youngsters, and the involvement of the
important to create trust and cooperation between the preschool, the extended family, child care personnel and others who play a role in
family, and the diabetes team. An individual diabetes management their daily care.”122
plan is needed in this collaboration and should include information Children younger than 7 years with T1D constitute only approxi-
about and practical training in the use of diabetes-related technolo- mately 10% of the population of all children (below 18 years) with
gies. The child's young age and limited capacity to verbally discuss T1D, but in many countries the incidence in this subgroup is increas-
aspects of self-care need to be offset by well trained staff, written ing.123 Collaboration among centers is thus necessary to conduct
plans and an ongoing dialogue with the primary caregivers. Both the pathophysiological, epidemiological and clinical studies regarding
 13995448, 2022, 8, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/pedi.13427 by Egyptian National Sti. Network (Enstinet), Wiley Online Library on [25/12/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
1508 SUNDBERG ET AL.

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