Complications of Diabetes in Children and Adolescents

Hypoglycemia in children and adolescents

Hypoglycemia is a common but critical complication in children treated with an intensive insulin regimen. Hypoglycemia is defined as a plasma glucose < 70 mg/dL (< 3.9 mmol/L) regardless of symptoms, which may not be apparent to many patients (hypoglycemia unawareness) (1). A plasma glucose level < 54 mg/dL (< 3.0 mmol/L) is considered "serious" (level 2) hypoglycemia and carries risk of neurologic symptoms (2).

Hypoglycemia may be detected based on symptoms (eg, shakiness, irritability, anxiety, diaphoresis, tachycardia, lightheadedness) and confirmed by a routine blood glucose check. Real-time continuous glucose management devices can help children who have hypoglycemia unawareness because an alarm sounds when glucose is below a specified range or when glucose declines at a rapid rate (see Methods for monitoring glycemic control). Most children have several mild hypoglycemic events per week and manage them by self-treating with 15 g of fast-acting carbohydrates (eg, 4 oz of juice, glucose tablets, hard candies, graham crackers, or glucose gel).

Severe hypoglycemia (level 3) is defined as an episode requiring the assistance of another person to give carbohydrates or glucagon. Statistically, most children with type 1 diabetes will experience at least one such episode before age 18 years ((level 3) is defined as an episode requiring the assistance of another person to give carbohydrates or glucagon. Statistically, most children with type 1 diabetes will experience at least one such episode before age 18 years (3). Oral carbohydrates may be tried, but glucagon (1 mg IM or 3 mg intranasal spray) is usually used if neuroglycopenic symptoms (eg, behavioral changes, confusion, difficulty thinking) prevent eating or drinking. In the hospital or prehospital setting, hypoglycemia is treated with intravenous dextrose-containing solution (eg, 2 to 3 mL/kg 10% dextrose). If untreated, severe hypoglycemia can cause seizures or even coma or death. ). Oral carbohydrates may be tried, but glucagon (1 mg IM or 3 mg intranasal spray) is usually used if neuroglycopenic symptoms (eg, behavioral changes, confusion, difficulty thinking) prevent eating or drinking. In the hospital or prehospital setting, hypoglycemia is treated with intravenous dextrose-containing solution (eg, 2 to 3 mL/kg 10% dextrose). If untreated, severe hypoglycemia can cause seizures or even coma or death.

Ketones and sick-day management

Sick-day management refers to a program of measuring ketones and administering additional fluid and insulin during illness and/or hyperglycemia.Sick-day management refers to a program of measuring ketones and administering additional fluid and insulin during illness and/or hyperglycemia.

Ketonuria or ketonemia is most often caused by intercurrent illness but also can result from not taking enough insulin or from missing doses and can be a warning of impending diabetic ketoacidosis (DKA). Because early detection of ketones is crucial to prevent progression to DKA and minimize need for emergency department or hospital admission, children and families should be taught to check for ketones in the urine or capillary blood using ketone test strips. Blood ketone testing may be preferred in younger children, those with recurrent DKA, and insulin pump users or if a urine sample is difficult to obtain.

More frequent glucose monitoring and ketone testing should be performed whenever the child becomes ill (regardless of the blood glucose level) or when the blood glucose is high (typically > 240 mg/dL [13.3 mmol/L]) (4). The presence of moderate or large urine ketone levels or blood ketone levels > 1.5 mmol/L can suggest DKA. DKA is more likely if ketone levels are > 3 mmol/L, especially if children also have abdominal pain, vomiting, drowsiness, or rapid breathing. Trace or small urine ketone levels or blood ketone levels of 0.6 to 1.5 mmol/L must also be monitored.

Urine Ketone Test Strip

Image

DR P. MARAZZI/SCIENCE PHOTO LIBRARY

When ketones are present, children are given additional short-acting insulin, typically 10 to 20% of the total daily dose, every 2 to 3 hours until ketones are cleared (4). Also, additional fluid should be given to prevent dehydration. Parents and caregivers should be instructed to call a health care professional or go to the emergency department if ketones increase or do not clear after 4 to 6 hours, or if the clinical status worsens (eg, respiratory distress, continued vomiting, change in mental status).

Diabetic ketoacidosis (DKA)

In children and adolescents, DKA is common among patients with type 1 diabetes; it develops in approximately 1 to 10% of patients each year, usually because they have not taken their insulin. Other risk factors for DKA include prior episodes of DKA, difficult social circumstances, depression or other psychiatric disturbances, and improper management of insulin needs during intercurrent illness. Interrupted delivery of insulin in children using an insulin pump (because of a kinked or dislodged catheter, poor insulin absorption due to infusion site inflammation, or pump malfunction) can also lead to rapid progression to DKA. Clinicians can help minimize the effects of risk factors by providing education, counseling, and support.

Diagnostic criteria for DKA in children include (5):

• Venous pH < 7.30 or serum bicarbonate < 18 mEq/L (18 mmol/L)

• Presence of moderate to large urine ketones, or serum beta-hydroxybutyrate > 3 mmol/L

• Serum glucose > 200 mg/dL (11 mmol/L)

DKA can be further classified into (5):

• Mild DKA: pH < 7.3, serum bicarbonate < 18 mEq/L (18 mmol/L)

• Moderate DKA: pH < 7.2, serum bicarbonate < 10 mEq/L (10 mmol/L)

• Severe DKA: pH < 7.1, serum bicarbonate < 5 mEq/L (5 mmol/L)

For children, vascular access is secured and initial volume resuscitation is given with 0.9% saline 10 to 20 mL/kg over 20 to 30 minutes (5). For shock, 20-mL/kg boluses can be given more rapidly. Patients who are obtunded may require airway management. Once blood pressure and perfusion are adequate, the remaining fluid deficit is calculated (usually assumed to be 5 to 10%, with a higher degree of intravascular volume depletion [≥10%] suggested by a blood urea nitrogen [BUN] > 20 mg/dL (> 7.1 mmol/L), a pH < 7.1, hypotension, or oliguria) and replaced over 24 to 48 hours, with 0.45 to 0.9% saline, with dextrose added once blood glucose is nitrogen [BUN] > 20 mg/dL (> 7.1 mmol/L), a pH dextrose added once blood glucose is< 300 mg/dL (16.7 mmol/L). A large trial showed that neither fluid administration rate nor sodium concentration (between 0.45% and 0.9%) influenced the rate of cerebral edema in children (6). Replacement for ongoing losses must also be provided (see pediatric maintenance fluids).

Electrolytes, including potassium, should be checked initially and then frequently during treatment. Patients are typically deficient in total body potassium; insulin treatment will drive potassium intracellularly and may lower serum levels to dangerous concentrations. Generally, potassium replacement should start during initial volume expansion. Insulin therapy should be deferred if serum potassium is < 3.5 mEq/L (3.5 mmol/L).

Continuous IV insulin is given, initially at 0.05 to 0.1 Unit/kg/hour, without an initial bolus. Once ketoacidosis is resolved (pH > 7.3) and the patient is drinking and clinically improved, medication is transitioned to subcutaneous Continuous IV insulin is given, initially at 0.05 to 0.1 Unit/kg/hour, without an initial bolus. Once ketoacidosis is resolved (pH > 7.3) and the patient is drinking and clinically improved, medication is transitioned to subcutaneousinsulin.

Acute cerebral edema, a complication in less than 1% of patients with DKA (7, 8), occurs primarily in children and less often in adolescents and young adults. Headache and fluctuating level of consciousness herald this complication in some patients, but respiratory arrest is the initial manifestation in others. The cause is not well understood but may be related to excessively rapid reductions in serum osmolality or to brain ischemia. Children with the highest BUN levels and lowest PaCO2 at presentation appear to be at greatest risk. Age < 6 years, delays in correction of hyponatremia, and the use of bicarbonate during DKA treatment are other risk factors (9).

Clinical Calculators

Maintenance Fluid Calculation for Children

Hyperosmolar hyperglycemic state (HHS)

In children and adolescents, hyperosmolar hyperglycemic state (HHS), a serious diabetic emergency, typically occurs in patients with type 2 diabetes. HHS is characterized by very high blood glucose levels (> 600 mg/dL [33.3 mmol/L]), severe dehydration, and increased serum osmolality (> 320 mOsm/kg), with minimal or no ketosis and only mild acidosis (pH > 7.25) (10). It results from relative insulin deficiency that leads to osmotic diuresis and profound fluid loss, causing hyperosmolarity and neurologic impairment. Common triggers include infections, poor diabetes control, and medications. Management focuses on cautious fluid resuscitation, careful electrolyte replacement, low-dose insulin therapy, and treatment of causes, with close monitoring to prevent complications like cerebral edema and thrombosis. HHS is not common, but has higher morbidity and mortality than diabetic ketoacidosis, making early recognition and aggressive treatment essential.

Vascular complications

Vascular complications rarely are clinically evident in childhood. However, early pathologic changes and functional abnormalities may be present a few years after disease onset in type 1 diabetes; prolonged poor glycemic control is the greatest long-term risk factor for the development of vascular complications. Microvascular complications include diabetic kidney disease (nephropathy), retinopathy, and neuropathy. Microvascular complications are more common among children with type 2 diabetes than type 1 diabetes and in type 2 diabetes may be present at diagnosis or earlier in the disease course. Neuropathy is more common among children who have had diabetes for a long duration (≥ 5 years) with poor control (glycosylated hemoglobin [HbA1C] > 10%). Macrovascular complications include coronary artery disease, peripheral vascular disease, and stroke.

Patients with type 1 diabetes typically begin screening within 5 years of diagnosis (and once puberty has started or the child has reached 10 years of age), while patients with type 2 diabetes begin screening at diagnosis. Screening includes:

• Foot examination

• Fundoscopic examination

• Urine testing for albuminuria

• Measurement of serum creatinine and lipid profile

• Blood pressure measurement

Mental health issues

Mental health issues are very common among children with diabetes and their families. Up to half of children develop depression, anxiety, or other psychological issues. Eating disorders are a serious problem in adolescents, who sometimes also skip insulin doses in an effort to control weight. Psychological issues can also result in poor glycemic control by affecting children's ability to adhere to their dietary and/or medication regimens. Social workers and mental health professionals (as part of a multidisciplinary team) can help identify and alleviate psychosocial causes of poor glycemic control.

Other complications

Patients with type 1 diabetes are at risk for other autoimmune diseases, including celiac disease, autoimmune thyroid disease, and Addison disease. Screening for these disorders is recommended according to established guidelines such as those from the American Diabetes Association and other expert consensus statements(1, 3) (see table Screening Children for Complications of Diabetes and Associated Disorders).

Patients with type 2 diabetes are at risk for other metabolic-dysfunction and insulin-resistance associated complications, including obesity, obstructive sleep apnea, metabolic dysfunction-associated liver disease (MASLD), and polycystic ovary syndrome. Screening for these conditions is also recommended in accordance with established guidelines (1, 2,3) (see table Screening Children for Complications of Diabetes and Associated Disorders).

Long-term complications references

1. 1. American Diabetes Association Professional Practice Committee. 14. Children and Adolescents: Standards of Care in Diabetes-2025. Diabetes Care. 2025;48(1 Suppl 1):S283-S305. doi:10.2337/dc25-S014

2. 2. Shah AS, Barrientos-Pérez M, Chang N, et al. ISPAD Clinical Practice Consensus Guidelines 2024: Type 2 Diabetes in Children and Adolescents. Horm Res Paediatr. 2024;97(6):555-583. doi:10.1159/000543033

3. 3. Limbert C, Tinti D, Malik F, et al. ISPAD Clinical Practice Consensus Guidelines 2022: The delivery of ambulatory diabetes care to children and adolescents with diabetes. Pediatr Diabetes. 2022;23(8):1243-1269. doi:10.1111/pedi.13417