Version July 2025
INTRODUCTION —
Insulin therapy is the mainstay of treatment for type 1 diabetes mellitus (T1DM), which is characterized by insulin deficiency. The goal of treatment is to maintain blood glucose within age-appropriate glycemic targets to minimize short- and long-term complications of chronic hyperglycemia. However, this goal remains elusive because of the difficulty in replicating the minute-to-minute variations of endogenous (physiologic) insulin secretion directly into the portal vein versus delivery of exogenous insulin, which is absorbed from the site of subcutaneous injection or infusion into the systemic circulation.
Many different insulin preparations and delivery systems are available. The specific insulin regimen selected for any child and family/caregiver is based on their individual lifestyle needs, cost considerations, local medication availability, and provider preference, while also optimizing the ability to maintain the child's blood glucose within target ranges. As a result, the preferred insulin formulation and regimen will vary among children and can change for any individual child over time.
This topic review will focus on the details of insulin therapy, including dosing, dose adjustment based on blood glucose monitoring, and options for insulin administration.
Other aspects of childhood-onset T1DM are discussed separately:
●Routine management:
•(See "Overview of the management of type 1 diabetes mellitus in children and adolescents".)
•(See "Epidemiology, presentation, and diagnosis of type 1 diabetes mellitus in children and adolescents".)
•(See "Type 1 diabetes mellitus in children and adolescents: Management of exercise".)
•(See "Management of type 1 diabetes mellitus in children during illness, procedures, school, or travel".)
●Prevention and management of acute glycemic emergencies:
•(See "Type 1 diabetes in children and adolescents: Prevention and management of hypoglycemia".)
•(See "Diabetic ketoacidosis in children: Clinical features and diagnosis".)
•(See "Diabetic ketoacidosis in children: Treatment and complications".)
•(See "Diabetic ketoacidosis in children: Cerebral injury (cerebral edema)".)
SELECTING AN INITIAL INSULIN REGIMEN
General principles — Patients with T1DM may present with hyperglycemic complications at the time of diagnosis (eg, ketosis, diabetic ketoacidosis [DKA]). After the resolution of medical complications, patients with T1DM are transitioned to a maintenance insulin regimen selected based on the needs of the patient and their family/caregivers, cost considerations, local medication availability, and clinician preferences [1]. Patients/caregivers must receive training in the safe use of insulin from the diabetes clinical team. Because of the potential for severe complications if insulin is used inappropriately, all insulin treatment for children and adolescents with diabetes should be initiated and supervised by an experienced pediatric diabetes team. (See "Overview of the management of type 1 diabetes mellitus in children and adolescents".)
The goal of insulin therapy is to replace insulin as physiologically as possible. This is best achieved with "intensive" management, which involves frequent monitoring of glucose levels and adjustment of insulin doses based on carbohydrate intake, activity status, and blood glucose concentration. (See "Glycemic management and vascular complications in type 1 diabetes mellitus", section on 'Benefits of intensive glycemic control' and "General principles of insulin therapy in diabetes mellitus".)
Basal-bolus MDI regimens (most patients) — Our practice is to initiate therapy with a regimen that includes multiple daily subcutaneous insulin injections (MDI): a long-acting "basal" insulin analog (eg, insulin glargine, insulin degludec) and variable doses or "boluses" of rapid-acting insulin analogs (eg, insulin aspart, insulin lispro) given with meals (table 1).
In randomized trials in adults and children with T1DM, intensive management has been associated with lower hemoglobin A1C (A1C) and a reduced risk of microvascular complications compared with older regimens [2-5]. For most patients with T1DM, intensive regimens are the standard of care for glycemic management and long-term outcomes compared with older fixed-dose regimens of neutral protamine Hagedorn (NPH) insulin and short-acting (regular) insulin [6].The data supporting intensive diabetes management are reviewed separately. (See "Glycemic management and vascular complications in type 1 diabetes mellitus", section on 'Benefits of intensive glycemic control' and "Type 1 diabetes mellitus in children and adolescents: Screening and management of complications and comorbidities", section on 'Measures to reduce risk of all vascular complications'.)
●Basal insulins – Long-acting "basal" insulins are given once (or, rarely, twice) daily to maintain blood glucose in the target range throughout the day, including between meals.
•Basal insulin analogs (preferred) – Insulin glargine is a long-acting insulin analog and is the basal insulin most commonly used in pediatric patients (table 1). Insulin glargine is approved by United States regulatory agencies for use in children ≥6 years but is commonly used off-label in younger children. Insulin glargine has a duration of action of up to 24 hours and is administered once per day. However, the half-life is shorter in some patients, requiring division of the daily dose into two injections per day. (See 'Step 2: Calculate the basal insulin dose' below.)
Although insulin glargine has a modified structure similar to insulin-like growth factor 1 (IGF-1), no increased risk of adverse effects associated with IGF-1 (eg, malignancy) has been demonstrated in patients with T1DM using insulin glargine [7,8]. (See "General principles of insulin therapy in diabetes mellitus", section on 'Safety'.)
Several other long-acting insulin analogs are available for pediatric patients, such as insulin degludec, which has a longer duration of action than glargine (>40 hours). Insulin detemir is a basal insulin analog that is no longer available in some countries, including the United States. (See "General principles of insulin therapy in diabetes mellitus", section on 'Basal insulin analogs'.)
•Basal NPH – NPH is an alternative option for basal therapy that is less costly than insulin analogs. It is used infrequently in high-resource settings because it requires twice-daily dosing as well as consistent timing and carbohydrate intake from day to day to prevent hypo- and hyperglycemia. A systematic review of studies comparing long-acting insulins (eg, glargine, detemir, degludec) with NPH insulin in pediatric and adult patients did not demonstrate clear differences in hypoglycemia risk between glargine and NPH. However, data were limited by variable definitions of hypoglycemia among studies [9]. (See "General principles of insulin therapy in diabetes mellitus", section on 'NPH insulin'.)
●Bolus insulin – Doses of shorter-acting insulin are given before each meal or snack and to manage mealtime hyperglycemia.
•Rapid-acting insulin analogs (preferred) – Rapid-acting insulin analogs (eg, lispro, aspart) are preferred over short-acting preparations (ie, regular insulin). Rapid-acting insulins have a rapid onset of action and shorter duration of action, allowing for optimal coverage of mealtime glycemic excursions while minimizing the risk of postmeal hypoglycemia. To achieve this, boluses of rapid-acting insulin are given 15 minutes before eating whenever possible. Because the carbohydrate content of meals varies, the amount of insulin given at a particular meal will often vary from day to day. Dosing is calculated based on the estimated amount of carbohydrates to be consumed, the premeal blood glucose level, and recent or anticipated exercise. (See 'Step 3: Calculate the bolus insulin dose' below and "General principles of insulin therapy in diabetes mellitus", section on 'Rapidly acting insulin analogs'.)
•Short-acting (regular) insulin – Regular insulin is not routinely used for mealtime coverage because its duration of action exceeds the duration of the postmeal rise in glucose, increasing the risk of hypoglycemia. However, if rapid-acting insulin analogs (aspart, lispro) are not locally available, short-acting insulins may be used for mealtime carbohydrate coverage. When this is done, the bolus should be given 30 minutes before the meal to mitigate blood glucose elevations resulting from carbohydrate intake.
In addition, regular insulin may be quite useful for patients with diabetes receiving enteral feeds or parenteral nutrition, in whom carbohydrates are delivered over several hours. (See 'Alternative regimens in selected patients' below.)
Dosing of basal and bolus insulin and insulin injection techniques are discussed below. (See 'Insulin dosing' below and 'Insulin injection technique' below.)
Alternative regimens in selected patients — In situations where standard basal-bolus regimens might not be optimal for a patient and their family/caregivers, bolus insulin may be administered using a predetermined written insulin chart containing precalculated insulin doses. In other cases, fixed doses of insulin are given at mealtimes. The selection of an alternative insulin regimen should be based on the specific needs of the family/individual.
●Patients and families/caregivers with low numeracy – In cases where the patient or caregiver is unable to calculate the bolus insulin dose for variable mealtime carbohydrate coverage, clinicians may provide a written grid with insulin doses calculated based on the insulin-to-carbohydrate ratio (ICR) as well as the estimated amount of carbohydrates per meal and the insulin sensitivity factor (ISF; or "correction" factor) for a range of blood glucose concentrations. To accommodate low numeracy, such a grid could be prepared to provide insulin coverage for "small," "medium," and "large" meals based on the estimated amount of carbohydrates for such meals.
Alternately, clinical teams may opt to set fixed insulin doses for mealtimes. Such regimens require patients to eat only a predetermined amount of carbohydrates at each meal. This may be particularly difficult for children, whose diets vary considerably depending on context. Fixed mealtime insulin dose regimens are associated with high risk of hypoglycemia when food intake is not timed to match the peak of insulin action or if patients eat less carbohydrates than prescribed for a specific meal. In addition, the timing of vigorous physical activity must occur on a relatively fixed daily schedule. Finally, applications for mobile devices are available to facilitate calculating insulin doses based on prepopulated insulin regimens.
●Enteral feeds – Intermediate-acting (NPH insulin) and/or short-acting insulin (regular insulin) may be used in combination with long-acting basal insulin in patients utilizing enteral feeds. In cases where enteral feeds are run over several hours (eg, overnight enteral feeds or extended enteral bolus feeds), the longer half-life of intermediate- and short-acting insulins may be preferable to rapid-acting insulin, which peaks 1 to 1.5 hours after administration (figure 1). Such regimens are used frequently to manage patients with cystic fibrosis-related diabetes. (See "Cystic fibrosis-related diabetes mellitus", section on 'Insulin dose and administration'.)
●Limited ability to administer daytime insulin – Fixed doses of intermediate-acting NPH insulin combined with short- or rapid-acting insulin for twice-daily administration along with fixed carbohydrate intake can be used in patients who are unable to receive insulin for a midday meal (eg, during school days in the absence of a school nurse).
For such regimens, intermediate-acting insulin (eg, NPH) is typically given twice a day (at breakfast and a second dose either at dinner or bedtime), with a rapid-acting (ie, lispro, aspart, or glulisine) or short-acting (regular) insulin given two or three times per day. For example, NPH insulin given before breakfast will cover lunch, which may be useful for young children who do not have a school nurse to administer rapid-acting insulin before lunch. This regimen may also be used for patients with T1DM in whom a twice-daily injection regimen is preferred, although this must be balanced with the greater risk of hyper- and hypoglycemia than basal-bolus regimens. Mixed-insulin pens containing NPH plus a rapid-acting insulin are available for patients using such regimens but are not generally recommended. (See "General principles of insulin therapy in diabetes mellitus", section on 'Pre-mixed insulins'.)
Insulin dosing — For a child with newly diagnosed T1DM, the initial dosing of exogenous insulin is estimated as follows (algorithm 1):
Step 1: Calculate total daily insulin needs — The first step is to estimate the total daily insulin requirement. This is based on the body weight, age, and pubertal stage of the child and whether the child presents in DKA or is on medications that may increase insulin resistance (such as glucocorticoids).
In general, pediatric patients with T1DM require an initial total daily insulin dose of 0.3 to 1 units/kg/day. However, the dose is individualized based on patient needs. Specifically:
●Upon resolution of the ketosis and dehydration often associated with new onset diabetes, prepubertal children usually require initial insulin doses of 0.3 to 0.7 units/kg/day.
●Higher doses (eg, 0.7 to 1.5 units/kg/day and sometimes higher) may be needed in patients who are pubertal, present in DKA, have a body mass index (BMI) >95th percentile, or receive glucocorticoid therapy.
●This estimated dose is adjusted up or down as needed depending on the child's response to the initial regimen. After adjustment, the total insulin dose may be as low as 0.25 units/kg/day (or even lower) for some children during the "honeymoon" phase.
●Following the "honeymoon" phase, prepubertal and pubertal children typically require 0.7 to 1 units/kg/day and 1 to 1.5 units/kg/day, respectively. (See 'During the "honeymoon" phase' below.)
Step 2: Calculate the basal insulin dose — The next step is to calculate the basal insulin dose.
●For regimens using basal insulin analogs (eg, glargine, degludec) – The initial basal insulin dose for MDI regimens using basal glargine or degludec is approximately 50 percent of the total daily dose (TDD). The initial dose may be lower (eg, 30 to 40 percent) in young children who are very insulin sensitive and higher (up to 60 percent) in those who are more insulin resistant. Insulin glargine is usually given once daily in the evening. However, some children do better with a morning dose (eg, those who tend to have nocturnal hypoglycemia) or with two divided doses (eg, when a single daily dose of insulin glargine does not have a 24-hour duration of action). Insulin degludec has a longer duration of action than insulin glargine, with a low peak-to-trough ratio, and is given once daily. Similarly, concentrated insulin glargine (U-300 [insulin glargine 300 units/mL]) is administered once daily.
●For regimens using basal NPH – For patients with regimens using NPH, basal insulin doses are calculated differently. Two-thirds of the TDD is administered before breakfast (two-thirds as NPH and one-third as rapid- or short-acting insulin), and one-third is administered before dinner or at bedtime (two-thirds to one-half as NPH and one-third to one-half as rapid- or short-acting insulin). The evening dose of NPH can also be split such that a portion is delivered before dinner and the remainder at bedtime. This allows for the effect to be spread out over a longer duration and avoids a larger peak with associated hypoglycemia risk in the middle of the night.
Step 3: Calculate the bolus insulin dose — In patients using basal-bolus regimens with insulin analog basal insulins (eg, glargine, degludec), a dose of rapid-acting insulin should be given each time patients eat. Rapid-acting insulin analogs are preferred in patients with T1DM.
In newly-diagnosed pediatric patients with T1DM, bolus insulin usually makes up approximately 50 percent of the total dose. The bolus insulin dose may be adjusted based on patient nutrition and review of glycemic trends (algorithm 1). (See 'Based on daily glucose monitoring' below.)
The dose of insulin given at a particular meal depends on the anticipated amount of carbohydrates to be consumed and the premeal blood glucose concentration as well as exercise activity that has either occurred or is anticipated to occur during the period of peak insulin action. The total premeal bolus is the sum of the dose calculated based on the ICR plus the dose adjustment (if needed) to correct premeal hyperglycemia. In young children with unpredictable food intake during meals and snacks, mealtime insulin is often administered immediately after the meal or snack so that the dose can be adjusted to reflect the actual amount of carbohydrates consumed. This strategy is not optimal for blood glucose control and should be converted to premeal boluses as soon as is developmentally possible.
In settings where calculations are not possible, accommodations may be made, including use of fixed mealtime insulin or dose calculation applications for mobile devices. (See 'Alternative regimens in selected patients' above.)
●Carbohydrate coverage (also called the ICR) is based on the patient's total insulin dose (algorithm 1). It is calculated as follows:
Amount of carbohydrate (grams) covered by 1 unit of insulin = 500 ÷ total daily insulin dose (assuming that rapid-acting insulin is used).
The equation used to calculate the ICR is an estimate, and the actual ICR depends on several factors. Some endocrinologists prefer to use a factor of 450 rather than 500 for younger children, and toddlers and very young children may require a factor of 250 or 330. Many children require a different ICR (relatively more insulin) for breakfast than for meals later in the day. Obesity and associated insulin resistance may lead to greater insulin requirements. If short-acting (regular) insulin (rarely used in MDI or pump regimens) is used, a factor of 450 should be used rather than 500.
Example:
•If a patient's total daily insulin dose is 50 units, then 1 unit of rapid-acting insulin is estimated to cover 10 grams of carbohydrate (500 ÷ 50). This patient's ICR is 1:10.
•If this patient plans to ingest 40 grams of carbohydrates at the meal, the bolus insulin dose for carbohydrate coverage is 40 ÷ 10 = 4 units.
Many mobile device applications for carbohydrate counting and simplified systems for assessing the carbohydrate content of meals are available. (See "Nutritional considerations in type 1 diabetes mellitus", section on 'Medical nutrition therapy' and "Nutritional considerations in type 1 diabetes mellitus", section on 'Carbohydrate intake'.)
●Dose adjustment for premeal hyperglycemia – For patients with premeal blood glucose above a target range, the premeal dose of insulin is further adjusted based on the following calculation by using a "correction" factor or ISF, which is individualized to the patient:
(Premeal glucose − target glucose) ÷ ISF
ISF = 1500 or 1800 ÷ patient's total daily insulin dose
The ISF describes how much one unit of rapid- or short-acting insulin is expected to lower blood glucose for the individual patient; it is usually expressed as a ratio (eg, 1:30 or 1:50 [1 unit of insulin is expected to lower blood glucose by 30 or 50 mg/dL, respectively]).
For younger children, some endocrinologists use a factor of 1800 to calculate the ISF. For older children who are more insulin resistant and when short-acting insulin is used for correction boluses, a factor of 1500 is preferred.
The total correction dose of insulin is based on the ISF as well as a target blood glucose. The target blood glucose is usually between 100 to 120 mg/dL for most children, although a higher target is sometimes used for younger children, particularly for evening insulin doses. Obesity and associated insulin resistance may lead to greater insulin requirements.
A smaller-than-calculated correction bolus may be given if the child is expected to be very physically active.
Example:
•If a patient's total daily insulin dose is 50 units, then 1 unit of rapid-acting insulin is estimated to bring down the blood glucose by 30 mg/dL (1500/50). This patient's ISF is 1:30.
•If this patient (with ISF 1:30) has a premeal blood glucose of 220 mg/dL and the target blood glucose is 100 mg/dL, the blood glucose correction bolus is (220 − 100) ÷ 30 = 4 units.
•The total premeal bolus is the sum of the "correction dose" plus the dose calculated from the ICR. If the anticipated carbohydrate intake is 40 g, the total premeal bolus is 4 units for the premeal glycemic status + 4 units for the anticipated carbohydrate consumption = 8 units.
Insulin concentrations — (table 1)
●U-100 insulin (most common) – Most insulin preparations use a concentration of 100 units of insulin per mL (U-100). Although these U-100 preparations are appropriate for most school-aged children and adolescents with T1DM, some patients require very low or very high doses of insulin. These patients may benefit from either less or more concentrated insulin formulations. (See "General principles of insulin therapy in diabetes mellitus", section on 'Insulin preparations'.)
●Dilute rapid-acting insulin – In infants and toddlers, the required doses of rapid-acting insulin may be so small that precise dosing with U-100 insulin is challenging. The smallest dose of U-100 insulin that can be accurately administered without dilution using a syringe is 0.5 units. Dilution to concentrations such as 1 unit of insulin per 10 mL (U-10) or 1 unit of insulin per 20 mL (U-20) allows for more precise administration of doses <0.5 units. Individual institutions have their own dilute insulin protocols, and these must be followed closely to prevent medication error. Insulin can be diluted either at a specialized pharmacy or at home with proper training. Specific diluent for many insulin preparations is available from the insulin manufacturer.
Although some insulin pumps are able to deliver small doses of U-100 insulin, dilute insulin may also be needed to avoid excessive insulin doses in very young children whose insulin requirements are less than the specific pump's lowest rate of insulin delivery. This strategy has been shown to be safe and effective in small trials and case series but should be initiated only after intensive family/caregiver training in the use of diluted insulin by qualified pediatric diabetes clinicians [10,11]. (See 'Initiating insulin pump therapy' below.)
●Concentrated insulin glargine (U-300) – Severe insulin resistance may occur in adolescent patients taking glucocorticoids and/or with a high BMI. In such patients, insulin doses may exceed 200 units of insulin per day. More concentrated basal insulin formulations permit equivalent dosing in a smaller volume than U-100 insulin without the need for MDI.
Glargine U-300, a concentrated form of glargine, has a longer duration of action than glargine U-100 and is helpful for those with high insulin needs and those in whom a single daily dose of insulin glargine U-100 does not last 24 hours. The smaller volume of insulin required for equivalent doses of U-300 also improves the absorption kinetics. More concentrated formulations of rapid- and short-acting insulins are also commercially available and may be used in pediatric patients with T1DM requiring high doses of insulin. These are discussed elsewhere. (See "Insulin therapy in type 2 diabetes mellitus", section on 'Insulin resistance'.)
Insulin injection technique — Insulin is administered by needle and syringe, pen, or, after acclimatization to the diagnosis, insulin pump. (See 'Initiating insulin pump therapy' below.)
●Needle and syringe – Most patients diagnosed with T1DM in the United States are first treated with subcutaneous insulin injections using syringes, subcutaneous needles, and insulin vials because of the widespread availability of these items. In addition, learning the technique of injecting insulin is important for patients who utilize insulin pump therapy; they must be able to administer insulin as injections in the event of mechanical failure of the insulin pump. (See 'Complications' below.)
The smallest needle available for use with an insulin syringe is 31 gauge and 15/64" (6 mm) in length. This small size is used for most patients and is particularly helpful for younger children. Syringes are available in 30 (0.3 mL), 50 (0.5 mL), and 100 (1 mL) unit sizes. Thirty-unit syringes with one-half unit markings are available. (See "General principles of insulin therapy in diabetes mellitus", section on 'Insulin delivery' and "General principles of insulin therapy in diabetes mellitus", section on 'Injection technique'.)
Most insulins cannot be mixed (eg, insulin glargine cannot be mixed with short-acting insulin formulations). However, NPH and short- or rapid-acting insulins can be mixed in a single injection, thereby reducing the number of injections. (See 'Alternative regimens in selected patients' above.)
●Insulin pen – Pens are supplied prefilled with insulin and are available for most insulin preparations. Advantages of insulin pens include ease of use, portability, and the ability to use smaller needles. The smallest needle available is 32 gauge and 4 mm in length; smaller needles are preferred for younger children. Pens that deliver insulin aspart and lispro are available; these offer the flexibility of one-half unit delivery (figure 2 and figure 3).
Although mixed insulin preparations are available in pens, these are usually reserved for adults who require fixed insulin dosing.
INSULIN DOSE ADJUSTMENT
Based on daily glucose monitoring — Monitoring of blood glucose is performed several times daily to detect short-term glycemic excursions and determine optimal insulin dosing. Monitoring can be done with a home glucose meter using fingerstick sampling or, more commonly, a continuous glucose monitor (CGM). If available, we offer CGM as soon as possible after diagnosis with T1DM. (See "Overview of the management of type 1 diabetes mellitus in children and adolescents", section on 'Overview of insulin therapy'.)
The planned insulin regimen should be adjusted based on fingerstick blood glucose measurements (and/or CGM metrics) as well as episodes of hyperglycemia and hypoglycemia. Frequent review and adjustment of the regimen is essential because the insulin dose varies substantially between individuals and also changes over time [12]. Artificial intelligence-based decision support tools have been used to safely adjust insulin doses in conjunction with clinician judgment [13].
●Insulin dose adjustments are usually made in increments or decrements of 10 to 20 percent at a time based on fingerstick blood glucose readings or CGM output. The diabetes medical team will often need to recommend frequent (eg, daily) dose adjustments during the first few weeks after diagnosis.
●As the child enters the "honeymoon" phase of diabetes (typically a few weeks after initiation of insulin therapy), rapid reductions in basal and bolus insulin regimens are typically required to avoid hypoglycemia. (See 'During the "honeymoon" phase' below.)
●The total daily insulin dose and the ratio of the basal-to-total insulin dose should be reviewed at each visit to assure that they are within the expected ranges.
•The total daily insulin dose after the "honeymoon" phase is between 0.7 and 1.5 units/kg/day. A typical range for prepubertal children is 0.7 to 1 units/kg/day [12], though very young children may need lower doses. During puberty, the daily insulin requirement rises (typically to 1 to 1.5 units/kg/day) because of an increase in insulin resistance from high growth hormone concentrations.
•Basal insulin should be approximately 30 to 60 percent of the total daily dose (TDD); the lower target is appropriate for young (preschool age) children who are growing rapidly, and the higher target is appropriate for those on a low-carbohydrate diet.
●The basal regimen may be adjusted with different rates at different times of the day. As an example, some children require a higher basal rate in the early morning hours because of an increase in counterregulatory hormones and between breakfast and lunch (when they are sedentary at school) and a lower rate during and for a variable period after exercise (depending on the duration and nature of exercise).
●Some children may also require different insulin-to-carbohydrate ratios (ICRs), different correction factors (or insulin sensitivity factors [ISFs]), and different target blood glucose concentrations at different times of the day depending on activity levels or as a strategy to reduce the risk of hypoglycemia overnight.
Based on long-term glycemic trends (A1C) — Hemoglobin A1C (A1C) or "time in range" (as measured by CGMs) are used to assess chronic glycemia and glycemic trends.
Glycemic targets should be tailored to the individual patient. For most children and adolescents, a target A1C of <7 percent (53 mmol/mol) is recommended in order to minimize microvascular and macrovascular complications; this is consistent with guidelines from the American Diabetes Association (ADA) and the International Society for Pediatric and Adolescent Diabetes (ISPAD) [14,15]. However, targets may be adjusted based on individual patient-level factors. (See "Type 1 diabetes mellitus in children and adolescents: Screening and management of complications and comorbidities", section on 'Risk factors for all vascular complications'.)
The insulin regimen should be adjusted if patients are adherent to treatment and have frequent blood glucose measurements outside the target range(s) (higher variability in blood glucose) over a period of several weeks. An A1C above 7 percent indicates sustained blood glucose levels above target range and should also prompt increased insulin dosing in adherent patients. (See "Overview of the management of type 1 diabetes mellitus in children and adolescents", section on 'Overview of insulin therapy'.)
Several clinical situations may lead to increased or decreased sensitivity to insulin, which requires close monitoring to ensure patients are able to maintain blood glucose within target ranges.
During the "honeymoon" phase — A few weeks after the diagnosis and initiation of insulin therapy, a period of decreasing exogenous insulin requirement occurs, commonly referred to as the "honeymoon" or remission phase of diabetes. During this period, the remaining functional beta cells secrete some insulin, resulting in reduced exogenous requirements. The total insulin dose may be as low as 0.25 units/kg/day (or even lower) for some children during this period. Close monitoring of blood glucose is mandatory since hypoglycemic episodes are likely if the insulin dose is not appropriately and quickly adjusted.
The duration of this phase is variable and may last several months or, uncommonly, one to two years. Rising blood glucose levels, A1C, and increasing exogenous insulin requirements indicate the end of this phase.
For growth and puberty — Follow-up visits with the diabetes medical team at least every three months are required to adjust for the increasing insulin requirement with continued growth of the child and increasing insulin deficiency with duration of diabetes. The family/caregivers can be taught to make interim adjustments via telephone consultation or telemedicine visits. As a child enters puberty, daily insulin requirements may increase to 1 to 1.5 units/kg because puberty is associated with increased insulin resistance [12,16].
For insulin resistance — In patients with severe insulin resistance, the TDD of insulin may exceed 1.5 or even 2 units/kg/day. Concentrated insulin preparations may be used in such patients to minimize the volume of subcutaneous insulin injections. In trials in pediatric patients with T1DM and a TDD <1.44 units/kg, insulin glargine 300 units/mL (U-300) was shown to have efficacy and safety similar to standard glargine 100 units/mL (U-100) [17,18]. Trials in adults with T1DM demonstrated improvements in A1C with use of concentrated insulins. (See "Management of blood glucose in adults with type 1 diabetes mellitus", section on 'Basal insulin options' and 'Insulin concentrations' above.)
INITIATING INSULIN PUMP THERAPY
Patient selection — We suggest offering insulin pump therapy (also known as continuous subcutaneous insulin infusion [CSII]) to all patients with established T1DM for whom this technology is accessible and can be used safely [1,14]. There is no specific hemoglobin A1C (A1C) threshold for pump initiation. This is consistent with American Diabetes Association (ADA) and International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines [19]. The timing of offering pump therapy is discussed below. (See 'Timing' below.)
●Rationale for use in most patients – Use of pumps to administer insulin and of continuous glucose monitors (CGMs) is increasingly the standard of care for pediatric T1DM in resource-abundant settings. This is based on evidence that insulin pumps (with or without CGM) modestly improve glycemic management compared with multiple daily injections (MDI) and may reduce hospitalizations [20-24]. As an example, in a 2019 meta-analysis of randomized trials involving children and adolescents, insulin pump therapy modestly reduced A1C compared with MDI (-0.23 percent; 95% CI -0.56 to -0.11 percent) [22]. Severe hypoglycemia occurred less frequently in the insulin pump group, but the finding was not statistically significant (15 versus 22 percent; odds ratio [OR] 0.70, 95% CI 0.44-1.12). Episodes of diabetic ketoacidosis (DKA) were uncommon in both groups (2 versus 1 percent, respectively). In a subsequent diabetes registry study including more than 100,000 children with T1DM, there was an association between achievement of glycemic outcomes and use of insulin pump therapy [25].
●Benefits for patients with unpredictable insulin requirements – Because of the flexibility of insulin dosing and ease with which insulin pump regimens can be adjusted, these devices may be particularly valuable for youth with T1DM who have variable or unpredictable insulin requirements, such as:
•Very young children (including infants) [26-30]
•Children and adolescents engaged in frequent, intense exercise (eg, competitive athletes) [19]
●Benefits for patients with A1C above target – Patients with A1C above target may benefit from insulin pump therapy, assuming there is adequate education, supervision, and support from parents/caregivers and the diabetes team [31]. Regardless of A1C, use of insulin pumps has been associated with improved quality of life in multiple observational studies and randomized trials in children and adolescents with T1DM [29,30,32-36].
However, in some patients, decreased adherence to pump protocols is associated with deterioration in glycemic management over time. Parental/caregiver involvement may help offset this risk in adolescents [37].
Timing — We offer insulin pump therapy to patients with T1DM after a period of acclimatization to the diagnosis and after patients/caregivers are comfortable with the use of MDI. This is based on data suggesting that starting pump therapy at T1DM diagnosis does not preserve beta cell function or improve glycemic outcomes. In a trial in the United Kingdom, 294 children (aged 7 months to 15 years) with newly diagnosed T1DM were randomly assigned to either insulin pump therapy or MDI. A1C was above target in both treatment groups and did not differ between groups [38]. Moreover, children treated with an insulin pump had higher resource utilization, including emergency department visits and annual total costs, compared with MDI. However, this strategy may change over time with availability of more sophisticated insulin pump algorithms and of the bihormonal (insulin and glucagon) pump.
Meta-analyses have demonstrated the benefit of insulin pump therapy in children who have had diabetes for a longer duration [22], suggesting that after a period of acclimatization to diagnosis and management, adopting insulin pump therapy is consistent with optimal management. Furthermore, the impact of insulin pump therapy on A1C reduction may be greater later in the course of diabetes, particularly past the "honeymoon" phase. (See "Continuous subcutaneous insulin infusion (insulin pump)".)
Types of insulin pumps — All insulin pumps deliver rapid-acting insulin via a subcutaneous catheter. They automatically deliver a basal rate (small boluses of insulin infused every few minutes continuously throughout the day) and user-initiated bolus doses for mealtimes or to correct elevated blood glucose. In the United States, several different types of pumps have been used successfully in children and adolescents. The mechanics of the different insulin pump systems are discussed elsewhere. (See "Continuous subcutaneous insulin infusion (insulin pump)", section on 'Types of insulin pumps'.)
For most children and adolescents, we suggest use of an automated insulin delivery (AID) system rather than sensor-augmented insulin pumps. Hybrid closed-loop (HCL) devices are the most widely available kind of AID systems. HCL devices are partially automated, which means that they use an algorithm to automatically adjust insulin delivery based on CGM data but do not automatically deliver premeal boluses. Compared with sensor-augmented pumps (ie, pumps that display CGM glucose data but do not automate insulin delivery in response to blood glucose), HCL systems have been associated with greater time in glucose target range in children of all ages [39-45]. Trials have shown more variable results for hypoglycemia prevention. (See "Continuous subcutaneous insulin infusion (insulin pump)", section on 'Insulin only, partially automated systems'.)
As examples:
●In a six-month randomized trial in patients with T1DM aged 14 to 71 years, use of an HCL system compared with a sensor-augmented insulin pump increased time in glycemic target range (71 versus 59 percent; risk-adjusted difference 11 percent, 95% CI 9-14), improved A1C levels, and modestly reduced time spent in a hypoglycemic state (eg, <54 mg/dL, 0.29 versus 0.35 percent) [39]. However, the HCL group had more hyperglycemic adverse reactions (including one episode of DKA) compared with the sensor-augmented group (14 versus 2 patients), primarily due to infusion set failures.
●A randomized trial that primarily enrolled adolescents compared HCL with standard therapy (insulin pump or other) and found that the HCL system modestly improved time in range, time spent in hypoglycemic range, glycemic variability, several other secondary glycemic outcomes, a standardized diabetes-specific measure of quality of life, and treatment satisfaction [42].
●A 16-week randomized crossover trial in 74 children two to seven years of age with well-controlled T1DM (baseline mean A1C 7.3 percent) compared a different HCL insulin delivery system (Cambridge closed-loop algorithm) with a sensor-augmented insulin pump [43]. The HCL insulin delivery system increased time in glycemic target range (71.6 versus 62.9 percent; mean adjusted difference 8.7 percentage points, 95% CI 7.4-9.9); the greatest improvement was at night. The system also modestly decreased A1C by 0.4 percent and reduced time spent above the target range but did not alter the overall time in the hypoglycemic range. One serious hypoglycemic event occurred, attributable to user error.
●In a 16-week randomized trial in 101 children aged 6 to 13 years, use of an HCL system increased time in target range (67 versus 55 percent; mean adjusted difference 11 percentage points, 95% CI 7-14) [40]; this study used the same HCL system as the adolescent study described above [39]. The percentage of time below the target range (<70 mg/dL) was low for both systems (1.6 and 1.8 percent, respectively), and there were no episodes of severe hypoglycemia or DKA.
An AID system that simplifies delivery of premeal insulin boluses is also available. The pump's algorithm requires minimal inputs by the user (only body weight and qualitative descriptions of carbohydrate intake). This may be a simpler option than the partially automated AID system and has shown promise for attainment of improved blood glucose targets in pediatric patients with T1DM. In a 13-week unblinded randomized trial including 112 participants age <18 years, use of this device led to greater reduction in A1C compared with standard care (mean adjusted difference -0.5 percent, 95% CI -0.7 to -0.2), with a 10 percent improvement in time in range [46,47]. Standard of care was any insulin delivery method combined with CGM. (See "Continuous subcutaneous insulin infusion (insulin pump)", section on 'More fully automated system' and "Continuous subcutaneous insulin infusion (insulin pump)", section on 'Sensor-augmented insulin pump'.)
Converting from MDI to insulin pump therapy — When converting a patient from multiple daily injections (MDI) or regimens using neutral protamine Hagedorn (NPH) with short or rapid-acting insulin to an insulin pump, the initial insulin doses given by the pump are determined by current glycemic management (eg, time within target blood glucose range on CGM, A1C) and total daily insulin dose (algorithm 2).
●Total daily dose (TDD) – For patients with blood glucose generally within target range, the initial total daily insulin dose (daily insulin pump dose) is 10 to 20 percent less than the MDI dose. In patients with chronic hyperglycemia, the previous total daily insulin dose should be used. (See "Continuous subcutaneous insulin infusion (insulin pump)", section on 'Dosing'.)
●Basal insulin – To determine the hourly basal rate, the total basal dose given as part of the calculated basal-bolus regimen is divided by 24 hours.
Basal insulin dose ÷ 24.
This is given as a continuous infusion of rapid-acting insulin (lispro, aspart, or glulisine).
●Mealtime insulin – Generally, patients using basal-bolus regimens may program their preexisting insulin to carbohydrate ratio (ICR) into the insulin pump. Some devices can be programmed to prolong the mealtime insulin ("extended") bolus to improve control of postmeal hyperglycemia. The bolus can be administered in a "dual-wave" or "square-wave" pattern [48,49]. For dual-wave administration, the mealtime insulin dose is divided into a bolus followed by a continuous infusion (higher than the basal rate) over two hours; this is useful for meals with varied glycemic content (and especially high fat content). For square-wave administration (also known as extended bolus), the dose of insulin is given as a continuous infusion over two hours; this is useful for patients who plan to snack over an extended period of time, as might occur in social settings.
Complications — Potential complications of pump use include infusion set failure and dermatologic effects such as contact dermatitis/skin irritation and lipohypertrophy.
●Risk of infusion set failure – All insulin pumps run the risk of failure to infuse insulin. This may be related to occlusion or bending of the tubing, displacement of the catheter from the subcutaneous site, or, less likely, failure of the pump mechanism. Failure of insulin delivery can quickly lead to hyperglycemia, ketosis, and DKA because only rapid- or short-acting insulin is used in insulin pumps, and patients do not have a long-acting subcutaneous depot of insulin on board. As a result, CGM and/or frequent blood glucose checking with a glucose meter is essential for children on insulin pump therapy [50]. Younger children who tend to be very active may be at a higher risk of infusion site failure. In our experience, steel infusion sets may be preferred in this population as they are less prone to bending/occlusion.
Education of patients and caregivers regarding the recognition and management of infusion set failures is essential. If persistent hyperglycemia occurs and does not respond to bolus insulin administration through the pump, the initial correction dose of insulin should be administered by syringe or insulin pen, and the infusion set should be replaced and checked before resuming use of the pump. Patients should be taught to check blood or urine ketones in these circumstances, as ketone elevations indicate insulin deficiency. If there is ongoing concern about pump malfunction (eg, persistent hyperglycemia and/or ketonuria/ketonemia), insulin injections should be continued. Management of insulin pump failure with insulin injections is reviewed in detail separately. (See "Continuous subcutaneous insulin infusion (insulin pump)", section on 'Pump failure'.)
●Skin irritation and contact dermatitis – Rashes are common in areas exposed to adhesives used to secure insulin pumps and CGM; they may lead to discontinuation of device use [51]. Rashes may be caused by contact dermatitis or allergic dermatitis [52,53]. Treatment usually involves pump site rotation and use of topical glucocorticoids. Some patients report improvement with use of hydrocolloid or silicone adhesives [54].
●Lipohypertrophy – Accumulation of adipose tissue at the site of insulin infusion commonly occurs in pediatric and adolescent patients with T1DM [55]. To minimize the risk of this complication, patients should be instructed to rotate the placement of insulin pumps and/or insulin injection sites.
INSULIN MANAGEMENT FOR SPECIAL SITUATIONS
Illness or ketosis — When patients are ill, insulin needs often change. Insulin resistance may occur, necessitating higher doses of insulin to maintain blood glucose in the target range as well as prevent ketosis and diabetic ketoacidosis (DKA). Management of diabetes during illness is reviewed in detail elsewhere. (See "Management of type 1 diabetes mellitus in children during illness, procedures, school, or travel", section on 'Sick-day management'.)
Patients with persistent hyperglycemia and moderate or severe ketosis (blood beta-hydroxybutyrate [BOHB] ≥1.5 mmol/L or moderate-large urine ketones) should urgently consult with their diabetes clinician or seek emergency care for evaluation and management of impending DKA. Many of these patients can be managed in the home setting as long as they are in close communication with a diabetes clinician until ketosis has resolved. Patients with BOHB >5 mmol/L should immediately seek medical attention in an emergency department, as this degree of ketosis is a strong predictor of DKA [56]. (See "Diabetic ketoacidosis in children: Clinical features and diagnosis".)
Hospitalization — Insulin pumps may be safely used in hospital settings, assuming hospital staff are appropriately trained in pump management and patients do not have other contraindications to use of pumps (eg, impaired consciousness, critical illness, or other factors limiting ability to safely self-manage the pump) [57,58]. In a retrospective cohort study of children with T1DM hospitalized for reasons other than DKA, patients treated with an insulin pump (either their own or a pump supplied by the hospital) had more blood glucose readings within target blood glucose range and fewer episodes of hyperglycemia than those managed with subcutaneous injections [59].
Exercise — Exercise usually requires insulin adjustments to prevent hypoglycemia. This is discussed in detail elsewhere. (See "Type 1 diabetes mellitus in children and adolescents: Management of exercise", section on 'Severe hypoglycemia, hyperglycemia, or ketosis'.)
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Diabetes mellitus in children" and "Society guideline links: Hyperglycemic emergencies".)
INFORMATION FOR PATIENTS —
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Type 1 diabetes (The Basics)" and "Patient education: Type 1 diabetes in children (The Basics)" and "Patient education: Managing blood sugar in children with diabetes (The Basics)" and "Patient education: Carb counting for children with diabetes (The Basics)" and "Patient education: Managing diabetes in school (The Basics)" and "Patient education: Giving your child insulin (The Basics)" and "Patient education: Checking your child's blood sugar level (The Basics)" and "Patient education: Insulin pumps (The Basics)")
●Beyond the Basics topics (see "Patient education: Type 1 diabetes: Overview (Beyond the Basics)" and "Patient education: Type 1 diabetes: Insulin treatment (Beyond the Basics)")
●The American Diabetes Association (ADA) maintains a consumer guide of insulins, insulin pumps, continuous glucose monitors (CGMs) and other tools used for patients with T1DM [60].
SUMMARY AND RECOMMENDATIONS
●Initial insulin regimen – In all cases, insulin therapy should be managed by clinicians experienced in the care of pediatric patients with type 1 diabetes mellitus (T1DM).
After acute medical concerns (eg, diabetic ketoacidosis [DKA]) have resolved, patients with newly diagnosed T1DM are treated with subcutaneous insulin regimens for outpatient management. The goal of outpatient insulin management is to maintain glucose levels within target ranges in order to reduce the risk of short- and long-term complications of T1DM. (See 'General principles' above.)
Our preferred initial insulin regimen for patients with T1DM utilizes multiple daily subcutaneous injections (MDI) delivered as a combination of long-acting "basal" insulin analogs (eg, insulin glargine, insulin degludec) and "boluses" of rapid-acting insulin analogs (eg, insulin aspart, insulin lispro). (See 'Basal-bolus MDI regimens (most patients)' above.)
Alternative insulin preparations may be used when insulin analogs are not available (table 1).
Alternative insulin regimens may be used when patients and their families/caregivers cannot perform the required calculations for basal-bolus regimens and in the management of diabetes in patients who cannot eat by mouth. (See 'Alternative regimens in selected patients' above.)
●Insulin dosing for MDI regimens using insulin analogs – An individual patient's insulin regimen is determined as follows (algorithm 1):
•Step 1: Calculate the total daily insulin requirement. The insulin requirement is determined by age, pubertal stage, and whether the child presents in DKA or is being treated with glucocorticoids. (See 'Step 1: Calculate total daily insulin needs' above.)
•Step 2: Calculate the basal insulin dose. In regimens using insulin analogs (glargine, degludec), the basal insulin dose is approximately 50 percent of the estimated total insulin requirement but can range from 30 to 60 percent. (See 'Step 2: Calculate the basal insulin dose' above.)
•Step 3: Calculate the bolus insulin dose. The dose of bolus insulin consists of:
-Mealtime (premeal/presnack) doses, which are calculated based on anticipated carbohydrate intake and the patient's individual insulin dose per gram of carbohydrate (expressed as their insulin-to-carbohydrate ratio [ICR]).
-Doses used to treat blood glucose above the target range, which are based on the "correction" or insulin sensitivity factor (ISF). (See 'Step 3: Calculate the bolus insulin dose' above.)
Doses are calculated differently for patients using less common MDI regimens composed of basal neutral protamine Hagedorn (NPH) and either short-acting (ie, regular insulin) or immediate-acting insulin analogs (eg, insulin aspart or insulin lispro). (See 'Step 3: Calculate the bolus insulin dose' above.)
●Adjusting insulin – Insulin therapy is adjusted to achieve a target hemoglobin A1C (A1C) of <7 percent for most children and adolescents with T1DM. While this target has been shown to reduce microvascular complications in patients with T1DM, glycemic targets should be tailored to the individual patient.
Insulin doses may need to be adjusted to account for increased insulin sensitivity (eg, during the "honeymoon" phase) and decreased insulin sensitivity (eg, during rapid growth and puberty or in association with weight gain). Insulin must also be adjusted to account for changes in carbohydrate delivery (eg, the initiation of enteral feeds or parenteral nutrition). (See 'Insulin dose adjustment' above.)
Insulin adjustments are often needed during illness/hospitalization and exercise. (See 'Insulin management for special situations' above.)
●Insulin pump therapy for long-term T1DM management – After a period of acclimatization to the T1DM diagnosis, we offer insulin pump therapy (continuous subcutaneous insulin infusion [CSII]) for all patients with T1DM whose parents/caregivers can safely utilize an insulin pump. The selection of a particular pump system is based on the functional characteristics of the pump, the needs and preferences of the patient and family/caregivers, cost considerations, and clinician preferences. (See 'Patient selection' above.)
•Automated insulin delivery (AID) systems for most patients – For most patients, we suggest a hybrid closed-loop (HCL) system (in which the insulin pump automatically adjusts insulin based on continuous glucose monitor [CGM] data) rather than MDI regimens or sensor-augmented insulin pumps (Grade 2C). In clinical trials, these systems improved glycemic outcomes compared with sensor-augmented insulin pumps and MDI regimens. In our clinical experience, most children and families/caregivers have high satisfaction with HCL devices and can learn to use them effectively with appropriate training and support. (See 'Types of insulin pumps' above.)
•Converting to an insulin pump – When converting from an MDI regimen to insulin pump therapy, the starting insulin dose depends on the patient's current blood glucose management (algorithm 2). For patients with blood glucose measurements largely within the target range on an MDI regimen, the initial total daily dose (TDD) used to program the insulin pump should be 10 to 20 percent less than the TDD used in the MDI regimen. For patients with chronic hyperglycemia, the TDD used in the MDI regimen should be used to program the insulin pump. (See 'Converting from MDI to insulin pump therapy' above.)
Special training is required for the safe use of any insulin pump system, including management of mechanical failures, which can rapidly lead to DKA. (See 'Complications' above.)
