Hypoglycemia in children and adolescents with type 1 diabetes mellitus

INTRODUCTION — Hypoglycemia is a common complication of type 1 diabetes mellitus (T1DM) in childhood [1]. It can occur in any child in whom the dose of administered insulin exceeds the insulin requirement. Avoiding severe and recurrent hypoglycemia is an important goal of diabetes management because these events can lead to acute and permanent neurologic complications. Fortunately, setting stringent targets for glycemic control generally does not increase the risk for severe hypoglycemic events and good glycemic control may improve cognitive development [2,3].

The symptoms, risk factors, prevention, and treatment of hypoglycemia in children and adolescents with T1DM are discussed in this topic review. Other issues in this population are discussed separately:

●(See "Epidemiology, presentation, and diagnosis of type 1 diabetes mellitus in children and adolescents".)

●(See "Overview of the management of type 1 diabetes mellitus in children and adolescents".)

●(See "Insulin therapy for children and adolescents with type 1 diabetes mellitus".)

●(See "Complications and screening in children and adolescents with type 1 diabetes mellitus".)

●(See "Management of exercise for children and adolescents with type 1 diabetes mellitus".)

●(See "Management of type 1 diabetes mellitus in children during illness, procedures, school, or travel".)

DEFINITIONS AND PATHOPHYSIOLOGY — An international consensus panel defined the following important thresholds for categorizing hypoglycemic episodes in children with T1DM [3,4]:

●Clinical hypoglycemia alert – Blood glucose <70 mg/dL (3.9 mmol/L); this is commonly used as a threshold for recognizing and initiating treatment for hypoglycemia.

●Clinically important or serious hypoglycemia – Blood glucose <54 mg/dL (3.0 mmol/L); values in this range tend to be associated with defective glucose counterregulation, impaired hypoglycemia awareness, and, sometimes, cognitive dysfunction.

●Severe hypoglycemia – An event associated with severe cognitive impairment (including coma and seizures), requiring assistance of another person to correct, including administration of carbohydrates or glucagon or intravenous (IV) dextrose.

Although these blood glucose thresholds are somewhat arbitrary because the clinical correlates vary among individuals and across age groups, they provide consistent definitions that can be applied to research and also match definitions proposed by an international consensus panel for hypoglycemia in adults [5].

Physiologic responses to hypoglycemia include increased secretion of the counterregulatory hormones glucagon, epinephrine, cortisol, and growth hormone. In individuals with T1DM, the counterregulatory hormone response often becomes blunted over time, so that the glucagon response is impaired and the epinephrine surge may be attenuated; this increases the risk of persistent hypoglycemia. Impairment of the epinephrine response occurs in 30 percent or more of children and adolescents whose diabetes is well controlled [6]. This is especially likely to occur in tightly controlled patients with frequent biochemical hypoglycemia. (See "Physiologic response to hypoglycemia in healthy individuals and patients with diabetes mellitus".)

RISK FACTORS — The risk of hypoglycemia is associated with the following:

Young age — Hypoglycemic episodes are more common and severe in younger children because food intake, activity, and adherence to treatment schedules are less predictable in younger compared with older children. Aiming for very tight glycemic control can further increase the risk of hypoglycemia in this age group, although this risk can be reduced with the use of a continuous glucose monitoring (CGM) device together with a pump that has a predictive low glucose insulin suspend feature [7]. (See "Overview of the management of type 1 diabetes mellitus in children and adolescents", section on 'Age-based care'.)

In a large multicenter registry, severe hypoglycemia occurred in 9.6 percent of children 2 to <6 years of age, as compared with 5.2 percent of those 6 to <13 years and 6.3 percent of those 13 to <18 years [8]. In a second observational study, the incidence of severe hypoglycemia decreased with age [9]. In girls <7 years of age, 7 to 12 years of age, and ≥13 years of age, the frequency of hypoglycemia was 24, 19, and 14 episodes per 100 patient-years, respectively. Frequent recurrences of hypoglycemia occurred in a minority of patients, with 20 percent of patients accounting for 80 percent of episodes.

Type of insulin regimen — Insulin dosing regimens are an important predictor of the risk of hypoglycemia. In general, intensive insulin therapy has the advantage of improved glycemic control and probably also reduces the risk for hypoglycemia when appropriately administered. (See "Insulin therapy for children and adolescents with type 1 diabetes mellitus", section on 'Value of an intensive regimen'.)

●Fixed-dose regimens – These insulin regimens consist of a fixed daily injection schedule using intermediate- and rapid- or short-acting insulins. The incidence of hypoglycemia in children treated with a fixed-dose regimen ranges between 20 and 60 episodes per 100 patient-years [9-11]. Such regimens are unlikely to achieve optimal glycemic control and have largely been replaced by intensive regimens in resource-abundant areas.

A fixed-dose insulin regimen typically includes NPH (neutral protamine hagedorn), an intermediate-acting insulin, which peaks several hours after administration. Hypoglycemia can occur if adequate glucose is not available at the time of peak insulin effect. As an example, if NPH is given with dinner or at bedtime, nocturnal hypoglycemia may occur between 12 AM to 4 AM, when NPH effect peaks (table 1 and figure 1). The risk is increased at night because sleep impairs the counterregulatory hormone responses to hypoglycemia. Similarly, a missed morning snack or delayed lunch may result in hypoglycemia as a consequence of the morning NPH insulin reaching its peak without concomitant food intake. Snacks between meals and at bedtime that contain complex carbohydrates (with fat to delay absorption) reduce the frequency and severity of hypoglycemic episodes in children receiving fixed-dose insulin regimens.

●Intensive regimens – In general, an insulin replacement regimen that delivers a basal insulin dose with intermittent boluses of rapid-acting insulin to cover food intake is associated with a lower risk of hypoglycemia than fixed-dose insulin regimens [12-21]. The risk for hypoglycemia has been examined for specific types of intensive insulin therapies:

•Multiple daily injections (MDI) – Most regimens use a long-acting insulin analog (insulin glargine, detemir, or degludec) to deliver insulin at a relatively consistent basal rate without a pronounced peak effect (table 1). Boluses of a rapid-acting insulin such as lispro, aspart, or glulisine are given before meals and snacks or, sometimes, immediately after the meal or snack (particularly in very young children or when it is uncertain whether or not the child will finish the meal/snack). Observational studies have shown that this approach reduces the incidence of severe hypoglycemic episodes in all age groups, including children <6 years of age, as compared with fixed insulin regimens. These data are discussed in a separate topic review. (See "Insulin therapy for children and adolescents with type 1 diabetes mellitus", section on 'Multiple daily injections'.)

•Insulin pump – Insulin pump therapy (also known as continuous subcutaneous insulin infusion) is an alternate form of intensive insulin therapy. The insulin pump provides a continuous subcutaneous infusion of rapid-acting insulin delivered at a basal rate, with boluses administered with meals and snacks. Controlled trials of insulin pump therapy in this age group generally suggest that it is similar to or somewhat better than MDI in achieving glycemic control and avoiding hypoglycemic episodes [22,23]. These data are discussed separately. (See "Insulin therapy for children and adolescents with type 1 diabetes mellitus", section on 'Insulin pump'.)

When using either MDI or insulin pump therapy, administration of boluses of rapid-acting or short-acting insulin before the glucose-lowering effect of each dose has completely dissipated is referred to as "stacking" and may precipitate hypoglycemia. To prevent "stacking," patients should be counseled to wait at least three hours before administering another dose of rapid-acting insulin to correct hyperglycemia.

●Glucose sensors and sensor-augmented pumps – Devices that may help to reduce rates of hypoglycemia include:

•CGM device

•Various types of sensor-augmented insulin pumps (open-loop systems), with low glucose suspension (suspend on low) or predictive low glucose management (suspend before low)

•Hybrid closed-loop insulin pump systems (sometimes called "artificial pancreases")

These devices are described in more detail in a separate topic, including their performances for reducing hypoglycemia in children. (See "Insulin therapy for children and adolescents with type 1 diabetes mellitus", section on 'Automated insulin delivery (hybrid closed-loop insulin pumps)' and "Insulin therapy for children and adolescents with type 1 diabetes mellitus", section on 'Insulin pumps with glucose sensors'.)

Exercise — Exercise is a well-established cause of hypoglycemia because exercise enhances insulin sensitivity, increases utilization of glucose, and increases insulin absorption from the injection site due to increased blood flow. The hypoglycemic effects of exercise can be delayed several hours and can vary among individuals and with the intensity and duration of exercise.

Recommendations to avoid hypoglycemia during and after exercise include:

●Monitoring blood glucose before, during, and after vigorous activity. If this is a new activity, monitoring should be done up to 12 hours after physical activity because of possible delayed effects.

●Consuming a snack before and/or during the time of increased activity.

●Reducing the last insulin dose before activity.

●Reducing the basal rate of the insulin pump (by setting a "temporary" basal rate) for the duration of exercise and for a variable period thereafter.

Automated systems to adjust insulin infusions may also reduce the risk of hypoglycemia during exercise. Preliminary studies suggest benefits from use of a predictive low glucose suspend system or a closed-loop control system [24-26]. (See "Insulin therapy for children and adolescents with type 1 diabetes mellitus", section on 'Insulin pumps with glucose sensors'.)

Exercise can cause paradoxical hyperglycemia under certain conditions, including high-intensity activity or competition, because of release of counterregulatory hormones from stress associated with the activity. Glycemic management during exercise is discussed in detail in a separate topic review. (See "Management of exercise for children and adolescents with type 1 diabetes mellitus".)

Alcohol ingestion — Alcohol ingestion is a common cause of hypoglycemic episodes in adolescents and young adults because it suppresses gluconeogenesis and glycogenolysis and acutely increases insulin sensitivity [1]. The combination of exercise with alcohol ingestion further increases the risk for severe hypoglycemia.

Other risk factors

●Acute illness – During acute illnesses associated with nausea, vomiting, and anorexia, hypoglycemia may occur because of poor oral intake if the doses of insulin with meal-associated peaks are not appropriately adjusted. Hyperglycemia can also occur during acute illnesses because of peripheral insulin resistance. Frequent blood glucose monitoring is mandatory for insulin dose adjustment based upon the blood glucose measurements. In many cases, the insulin dose may need to be reduced, but it should only rarely be omitted entirely because hyperglycemia and diabetic ketoacidosis can develop if basal insulin is not given. (See "Management of type 1 diabetes mellitus in children during illness, procedures, school, or travel", section on 'Sick-day management'.)

●Inconsistent carbohydrate intake – Variations in the timing and carbohydrate content of food intake result in erratic glycemic effects and an increased risk of hypoglycemia. Children who are on a fixed insulin regimen are particularly vulnerable if the schedule and carbohydrate content of meals are not consistent, because insulin doses will not match glycemic needs. (See "Nutritional considerations in type 1 diabetes mellitus".)

●Psychological and socioeconomic factors – Increased risk of hypoglycemia is associated with lower socioeconomic status [9] and psychiatric disorders. (See "Complications and screening in children and adolescents with type 1 diabetes mellitus", section on 'Psychiatric disorders'.)

●Coexisting autoimmune disorders – Celiac disease, Addison's disease, and autoimmune thyroiditis are associated with T1DM and may increase the risk of hypoglycemia. These disorders should be excluded in children with recurrent unexplained hypoglycemia. (See "Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus".)

PREVENTION AND ANTICIPATORY GUIDANCE

Targets for glycemic control — A target for hemoglobin A1c (A1C) of <7 percent (53 mmol/mol) is recommended for most children and adolescents who have access to comprehensive diabetes care, but a more or less stringent target may be appropriate for an individual patient [1,27]. These stringent A1C targets improve glycemic control without significantly increasing the risk for severe hypoglycemia. Considerations for setting an A1C target in individual patients are discussed separately. (See "Insulin therapy for children and adolescents with type 1 diabetes mellitus", section on 'Target for hemoglobin A1c'.)

Fear of hypoglycemia — Fear of hypoglycemia on the part of the child, caregiver, or provider can result in poor glycemic control. Some children and parents who are concerned about hypoglycemia may keep blood glucose values above recommended targets in an effort to avoid hypoglycemic episodes [28-31]. Counseling about this issue and careful attention to accurate insulin dose calculations should be an important part of diabetes management [32].

Neurologic sequelae

●Acute effects of hypoglycemia – Hypoglycemia clearly has short-term effects on cognitive function. Even mild hypoglycemia can affect critical activities, such as driving or performance in standardized school examinations, and reduce mental efficiency, including attention, memory, and performance on mathematical tasks [33-36].

Severe hypoglycemia is associated with neurologic impairment, which occasionally includes acute and transient cortical blindness [37,38]. Stroke-like hemiparesis can occur and persist for up to 24 hours after a severe episode. These functional changes are accompanied by altered findings on the electroencephalogram and increases in regional cerebral blood flow [39]. Prolonged severe hypoglycemia is responsible for 5 to 10 percent of deaths in patients with T1DM [40].

●Chronic effects of hypoglycemia – Concerns have been raised that severe or repeated episodes of hypoglycemia may have deleterious effects on brain development and learning, particularly in young children [41-44]. Therefore, avoidance of these episodes is an important goal of diabetes management, especially in young children. Fortunately, studies of children and adults using modern methods of diabetes management provide some reassurance that moderate episodes of hypoglycemia probably are not associated with long-term cognitive sequelae [40,45-47]. As an example, in a population-based study of children with T1DM in Denmark, there were no differences in standardized tests for reading and mathematics between children with and those without T1DM [47]. In addition, children with onset of T1DM before six years of age or those with diabetes duration of more than four years did not have significantly different test scores compared with children without T1DM. Sixty-four percent of the children used an insulin pump, and those with tight glucose control had better test scores than those with poor control. Similarly, among adults and adolescents enrolled in the Diabetes Control and Complications Trial (DCCT), neither tight glucose control (intensive therapy) nor recurrent severe hypoglycemia were associated with cognitive deficits after an average of 6.5 years of follow-up [48]. Long-term follow-up of the DCCT cohort after 18 years of therapy still revealed no association between cognitive function and frequency of episodes of hypoglycemia [49]. These findings contrast with earlier studies in which earlier onset of T1DM was associated with an increased risk for mild neuropsychological dysfunction [50-55].

Although early onset of T1DM may be associated with an increased risk for neuropsychological dysfunction and structural changes in the brain, it is not clear that these effects are mediated by chronic or acute severe episodes of hypoglycemia. Indeed, some studies suggest that chronic hyperglycemia may be responsible for cognitive dysfunction [43,56-58] and children with a history of diabetic ketoacidosis have lower rates of accurate memory on structured tasks than those without a history of diabetic ketoacidosis [59,60]. These observations led to the current clinical approach to glycemic management of T1DM, which recommends more stringent glycemic targets, provided that episodes of severe hypoglycemia can be avoided [3,27,57]. (See 'Targets for glycemic control' above.)

Hypoglycemia unawareness — "Hypoglycemia unawareness" is a condition characterized by a lack of warning symptoms of hypoglycemia because of blunting of the sympathetic neural activation and epinephrine response (see 'Definitions and pathophysiology' above). This is more commonly seen in children with long duration of diabetes and increases the risk of severe and/or recurrent hypoglycemia. Any episode of hypoglycemia can lower the glucose threshold at which adrenergic discharge and symptoms occur, increasing the risk for subsequent severe hypoglycemia. Prevention of hypoglycemia for a few weeks can restore hypoglycemia awareness.

Preparation for hypoglycemic episodes — Key precautions for all patients with T1DM are:

●Oral glucose – Always have ready access to a concentrated and rapidly absorbed simple carbohydrate food source, such as sweetened fruit juice, glucose tablets, or cake frosting. (See 'Mild and moderate hypoglycemia' below.)

●Glucagon – Have a glucagon kit at home, at school/daycare, and in the car during long journeys. Prescriptions should be refilled before the date of expiration. (See 'Glucagon' below.)

●Medical identification – Wear an identification band to ensure appropriate intervention by emergency personnel should such a situation arise. MedicAlert is a commonly used and excellent system.

SYMPTOMS AND SIGNS — Clinicians should inquire about symptoms of hypoglycemia during the routine care of a child with T1DM (table 2). Identification of nocturnal hypoglycemia is particularly important, given reported incidences on any given night of 30 percent or more in children on insulin pump or multiple daily injections (MDI) and higher rates in young children or those using fixed-dose insulin regimens [61-63]. Symptoms can be subtle and include nightmares, restless sleep, and, upon awakening, headache, confusion, or behavior changes. Decreased release of counterregulatory hormones during sleep and/or delayed hypoglycemic response to afternoon exercise may contribute to the risk for nocturnal hypoglycemia [64].

Nocturnal hypoglycemia is readily identified by continuous glucose monitoring (CGM) devices, and the frequency of episodes can be decreased in children using such devices, especially when linked to pumps with a suspend infusion function or partial closed loop.

Symptoms of hypoglycemia include:

●Adrenergic symptoms – Tremor, pallor, rapid heart rate, palpitations, and diaphoresis. These are caused by sympathetic neural activation and epinephrine release [65]. However, episodes of hypoglycemia can lower the threshold at which these symptoms occur, leading to "hypoglycemia unawareness" and increasing the risk for subsequent severe hypoglycemia. (See 'Hypoglycemia unawareness' above.)

●Neuroglycopenic symptoms – Fatigue, lethargy, headaches, behavior changes, drowsiness, unconsciousness, seizures, or coma. These symptoms result from direct effects of hypoglycemia on the central nervous system. The severity of neuroglycopenic symptoms increases with the severity of hypoglycemia and resultant central nervous system glucose deprivation.

●Behavioral symptoms – Behavioral symptoms include irritability, agitation, erratic behavior, unusual quietness, or tantrums and are most common in younger children. These behavioral symptoms are probably a consequence of adrenergic and neuroglycopenic responses [1].

MANAGEMENT — Hypoglycemia may be symptomatic or can be detected by a low blood glucose concentration in the absence of symptoms. If a patient is symptomatic, measure blood glucose to confirm the suspected hypoglycemia. Families of children monitoring glycemia with continuous glucose monitoring (CGM) devices need to know that these devices measure the levels of glucose in interstitial fluid. Circulating blood glucose levels equilibrate with the levels in interstitial fluid with a lag time of 15 minutes or more. Thus, if the child has a rapid drop in circulating blood glucose concentration, they may become symptomatic before hypoglycemia is detected by the CGM device. If confirmation is not possible, treat presumptively for hypoglycemia.

Classification of severity — The severity of hypoglycemia is classified by symptoms and the response needed for successful treatment [1,40]. Although these symptom patterns are common, children and their parents show poor ability to detect either high or low blood glucose levels based on symptoms alone. Therefore, regular and confirmatory blood glucose monitoring or CGM is important. (See 'Management' above and "Insulin therapy for children and adolescents with type 1 diabetes mellitus", section on 'Blood glucose monitoring'.)

●Mild symptoms – Symptoms of mild hypoglycemia include adrenergic and mild neuroglycopenic manifestations:

•Older children can generally recognize symptoms (headache, tremor, palpitations, diaphoresis) and adequately treat themselves with oral intake of a rapidly absorbed carbohydrate.

•For infants and very young children, symptoms of hypoglycemia include poor feeding, lethargy, jitteriness, and hypotonia; these symptoms may appear over a range of blood glucose concentrations. Young children are unable to communicate symptoms to caregivers and may not have the same adrenergic signs as older children. Thus, caregivers need to be trained to recognize and treat nonspecific symptoms associated with hypoglycemia in this age group. (See 'Definitions and pathophysiology' above.)

●Moderate symptoms – Moderate symptoms consist of sufficient neurologic impairment such that a second person is needed to administer oral therapy.

●Severe symptoms – Severe symptoms of hypoglycemia include neurologic impairment that precludes oral therapy, thus requiring intervention with intranasal, subcutaneous, or intramuscular glucagon or intravenous (IV) dextrose. Symptoms may progress to loss of consciousness, seizures, or coma.

Mild and moderate hypoglycemia — Patients with mild and moderate hypoglycemia (blood glucose <70 mg/dL [3.9 mmol/L] and/or adrenergic and neuroglycopenic symptoms described above) should be treated orally with a concentrated and rapidly absorbed simple carbohydrate food source (10 to 15 g glucose). Options include:

●Glucose tablets – 5 g per tablet

●Glucose gel – 15 g per tube

●Fruit juice – 12 g carbohydrate per 4 oz (120 mL)

●Regular soda (not diet) – 12 g carbohydrate per 4 oz (120 mL)

●Honey – 17 g carbohydrate per 1 tablespoon (15 mL)

●Table sugar (granulated sugar) – 12.5 g sucrose per 1 tablespoon

●Skittles – 10 g carbohydrate (sucrose) per 10 candies

Glucose and sucrose (which is rapidly broken down to glucose and fructose) are more effective than fructose alone in treating hypoglycemia [66]. These simple carbohydrates rapidly raise the blood glucose concentration. A weight-based dose (0.3 to 0.6 g/kg) may also be used, depending on the blood glucose level; one study reported that this was a more effective strategy to treat symptomatic hypoglycemia in children and adults compared with non-weight-based dosing of glucose [67].

In children who use an insulin pump to deliver insulin and/or use a CGM device, this treatment is usually sufficient. By contrast, in children receiving a fixed dose of insulin, it may be necessary to follow this treatment with a snack that contains a carbohydrate, protein, and fat in order to sustain blood glucose levels, such as a peanut butter sandwich or a bagel with cream cheese or other fat and protein. Blood glucose should be checked again in 15 to 20 minutes to confirm that glucose values have normalized and to determine whether further intervention is necessary. The patient may need to eat additional carbohydrates until blood glucose concentrations are sustained above 100 mg/dL (5.6 mmol/L). Children managed with an insulin pump or a hybrid closed-loop system rarely require an extra snack; indeed, ingesting more carbohydrate than necessary to treat the hypoglycemia often leads to rebound hyperglycemia.

In patients with poor oral intake during gastroenteritis or other illnesses, minidose glucagon has been used effectively to prevent impending hypoglycemia or to treat mild hypoglycemia at home.

Dosing is as follows, using a standard U100 insulin syringe:

●Children ≤2 years of age – 2 "units" (20 micrograms) of glucagon given subcutaneously

●Children 2 years and older – 1 "unit" of glucagon (10 micrograms)/year of age up to 15 "units" (150 micrograms)

A second dose (at double the initial dose) is given if blood glucose does not increase in 30 minutes [68,69].

Severe hypoglycemia — Patients with severe neurologic symptoms who are unable to take oral therapy require intervention with glucagon and/or IV dextrose.

Glucagon — Patients with significant neurologic impairment and/or who are unable to take oral glucose require urgent treatment with glucagon. Every person with T1DM should have a glucagon kit readily available at all times. (See 'Preparation for hypoglycemic episodes' above.)

Glucagon comes in several forms:

●Standard (lyophilized) glucagon – Glucagon may be administered subcutaneously or intramuscularly at the following doses:

•≤20 kg body weight – 0.5 mg (or 0.02 to 0.03 mg/kg)

•>20 kg body weight – 1 mg

The standard formulation of glucagon is unstable in solution; it is only available as a lyophilized powder that requires reconstitution with a diluent immediately before use.

These doses of glucagon are usually sufficient to increase blood glucose within a few minutes. The glucagon dose must be followed by oral intake of concentrated carbohydrates immediately upon awakening from the confused state. This is because both severe hypoglycemia and glucagon may cause nausea and vomiting within 45 minutes to an hour.

●Intranasal glucagon – Dosing for intranasal glucagon is:

•3 mg intranasally initially (for ages ≥4 years)

•Administer an additional 3 mg dose (using a new device) if there has been no glycemic response after 15 minutes

Intranasal glucagon is a unique powder formulation that is delivered through a device designed for one-time use.

The use of intranasal glucagon in children and adolescents is supported by results from a randomized trial and an observational study under "real-world" conditions [70,71]. The time course of the glycemic response is similar to that for intramuscularly administered glucagon. Data on intranasal glucagon in adults are discussed separately. (See "Hypoglycemia in adults with diabetes mellitus", section on 'Without IV access'.)

●Dasiglucagon – Dasiglucagon is a soluble glucagon analog that is available in a fixed-dose autoinjector, with dosing:

•0.6 mg (for ages ≥6 years), given subcutaneously via autoinjector

Because dasiglucagon does not require reconstitution, it should be easier to administer in the stressful circumstances associated with the emergency treatment of severe hypoglycemia (seizure or loss of consciousness). Dasiglucagon is approved in the United States for individuals six years and older; the safety profile of this fixed dose in children and adolescents is similar to that of glucagon [72].

●Stable liquid glucagon – A stable premixed liquid form of glucagon is available in the following doses:

•2 to 12 years – 0.5 mg

•≥12 years – 1 mg

This stable liquid form is available as an autoinjector or prefilled syringe (Gvoke), which is approved in the United States for individuals two years and older [73]. It does not require refrigeration, and the medication is administered subcutaneously.

Intravenous dextrose — For patients with severe hypoglycemia, IV dextrose should be given if IV access and appropriately trained medical personnel are available.

Dosing is 0.25 g/kg (maximum single dose 25 g). This is supplied by:

●2.5 mL/kg of 10% dextrose solution or

●1 mL/kg of 25% dextrose solution

An IV infusion sufficient to maintain glucose can be started if the child is still unable to take orally. An infusion of 10% glucose at a maintenance rate may be required and can be titrated up or down based upon the blood glucose, which should be checked every 30 minutes initially. Electrolytes should be included in the IV fluids if the infusion is prolonged (eg, one hour or more).

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: Hypoglycemia in infants and children".)

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 5^th to 6^th 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 10^th to 12^th 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: My child has diabetes: How will we manage? (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: Should I switch to an insulin pump? (The Basics)")

●Beyond the basics topics (see "Patient education: Type 1 diabetes: Overview (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Risk factors – Risk factors for hypoglycemia in children with type 1 diabetes mellitus (T1DM) include younger age, a split-mixed insulin regimen with a fixed daily insulin schedule, increased vigorous activity (exercise), alcohol ingestion, acute illnesses, and depression. (See 'Risk factors' above.)

●Blood glucose thresholds for categorizing hypoglycemia – In children with T1DM, an alert value for hypoglycemia is defined as blood glucose <70 mg/dL (3.9 mmol/L). Clinically important hypoglycemia is defined as blood glucose <54 mg/dL (3.0 mmol/L). (See 'Definitions and pathophysiology' above.)

●Prevention and anticipatory guidance – Counseling to children and families includes:

•Good glycemic control using modern methods for insulin administration, insulin analogs, and frequent blood glucose monitoring (including continuous glucose monitoring [CGM]) does not increase the risk for hypoglycemia or long-term cognitive sequelae. However, severe or repeated episodes of hypoglycemia may have deleterious effects on brain development and learning, particularly in young children, and should be avoided. (See 'Neurologic sequelae' above.)

•"Hypoglycemia unawareness" is a condition characterized by a lack of warning symptoms of hypoglycemia because of blunting of the sympathetic neural and epinephrine response to hypoglycemia. This is more commonly seen in children with long duration of diabetes and recurrent episodes of hypoglycemia and increases the risk of severe hypoglycemia. (See 'Hypoglycemia unawareness' above.)

•Important precautions for all individuals with T1DM include having ready access to a concentrated and rapidly absorbed simple carbohydrate food source, having a glucagon kit at home and wherever they spend time, and wearing a medical alert that identifies them as having T1DM. (See 'Preparation for hypoglycemic episodes' above.)

●Clinical classification of severity – Because the clinical response to hypoglycemia varies, hypoglycemia is further classified by severity of symptoms and the response needed for successful treatment of the patient. (See 'Classification of severity' above.)

•Mild symptoms of hypoglycemia include tremor, palpitations, diaphoresis, headaches, and behavior changes. There is little or no functional impairment, and older children can treat themselves with oral intake of a rapidly absorbed carbohydrate.

•Moderate neurologic symptoms consist of sufficient neurologic impairment such that a second person has to administer oral therapy.

•Severe neurologic symptoms consist of unresponsiveness, seizures, or coma, such that the patient is unable to take oral therapy and requires subcutaneous administration of glucagon or administration of intravenous (IV) dextrose.

●Management of hypoglycemia

•Patients who can take oral therapy – Patients with mild and moderate neurologic symptoms should be treated promptly with a concentrated and rapidly absorbed simple carbohydrate food source, such as fruit juice, glucose tablets, Skittles candy, or cake frosting. In children who use an insulin pump and/or a CGM device, this treatment is usually sufficient. However, children on a fixed-dose insulin regimen may require an additional longer-lasting snack containing carbohydrate, fat, and protein in order to sustain a normal blood glucose level. Blood glucose should be checked again in 15 to 20 minutes to confirm that glucose values have normalized and to determine whether further intervention is necessary. (See 'Mild and moderate hypoglycemia' above.)

•Patients who cannot take oral therapy – Patients with severe neurologic impairment require prompt treatment with glucagon or IV dextrose (see 'Severe hypoglycemia' above):

-For standard (lyophilized) glucagon, give 0.02 to 0.03 mg/kg (maximum dose 1 mg). Different doses are used for other formulations of glucagon (stable liquid form [fixed-dose], intranasal, or a soluble liquid analog [dasiglucagon]). (See 'Glucagon' above.)

-For IV dextrose, give 2.5 mL/kg of 10% dextrose solution or 1 mL/kg of 25% dextrose solution (both are equivalent to 0.25 g/kg; maximum single dose 25 g). (See 'Intravenous dextrose' above.)