What causes elevated Hemoglobin A1c (HbA1c) levels in children?

Common Causes of Elevated HbA1c in Children

The most common causes of elevated HbA1c in children include Type 1 diabetes, Type 2 diabetes, insulin resistance, poor glycemic control, obesity, stress, certain medications, and physiological factors related to growth and puberty. 1

Diabetes-Related Causes

Type 1 Diabetes

• Most common cause of elevated HbA1c in children
• Characterized by autoimmune destruction of pancreatic beta cells
• Typically presents with:
  • Polyuria and polydipsia
  • Weight loss
  • HbA1c values typically >6.5% at diagnosis (often between 6.6% and >14%) 2

Type 2 Diabetes

• Increasing in prevalence among children, especially in racial and ethnic minority populations 1
• Associated with:
  • Obesity (approximately 80% of youth with T2DM are obese) 1
  • Family history of diabetes
  • Sedentary lifestyle
  • Poor dietary habits

Insulin Resistance

• Common in both T1DM and T2DM
• In T1DM:
  • Normal-weight adolescents with T1DM have significantly lower glucose disposal rates than matched controls 1
  • Associated with more atherogenic lipid profiles and decreased cardiopulmonary fitness 1
• In T2DM:
  • Primary pathophysiological process underlying the disease 1
  • Strongly associated with obesity

Non-Diabetes Causes and Contributing Factors

Obesity and Weight-Related Factors

• Approximately 22% of children with T1DM are overweight 1
• Higher insulin doses used to improve glucose control are associated with greater increases in BMI over time 1
• Obesity is a pathogenetic factor contributing to T2DM development through its association with insulin resistance 1

Lifestyle Factors

• Poor dietary habits:
  • High fat intake 1
  • Consumption of sugar-sweetened beverages 1
  • Frequent fast food consumption 1
• Physical inactivity:
  • Youth with diabetes appear more sedentary and less fit than non-diabetic youth 1
  • Physical fitness is consistently associated with lower HbA1c 1

Psychosocial Factors

• Family stress and critical parenting 3
  • Youth perception of critical parenting predicts poorer adherence and higher HbA1c
• Externalizing behavior problems 3
  • Associated with poorer adherence and higher HbA1c
• Depression and anxiety:
  • Depressive symptoms associated with poorer blood glucose monitoring and diabetes control 1
  • May independently predict proteinuria 1

Physiological Factors

• Puberty:
  • Hormonal changes during puberty can increase insulin resistance
  • Distinct HbA1c trajectories occur during puberty in youth with established T1DM 4
• Growth:
  • Periods of rapid growth may affect insulin requirements and glycemic control

Hematologic Factors

• Anemia, particularly iron deficiency anemia:
  • Can falsely elevate HbA1c levels 5
  • Should be corrected before setting treatment goals for optimal HbA1c control

Patterns of HbA1c Elevation

Research has identified five distinct HbA1c trajectories in children with T1DM 4:

1. Low stable (good control maintained)
2. Intermediate stable (moderate control maintained)
3. High stable (consistently elevated HbA1c >8.0%)
4. Target increase (starting near target but increasing over time)
5. High increase (above target from diagnosis with worsening trajectory)

Clinical Approach to Elevated HbA1c

1. Determine if the elevation represents diabetes:

   • HbA1c ≥6.5% is diagnostic for diabetes 1
   • Values between 5.7-6.4% indicate prediabetes 6

2. Assess for contributing factors:

   • Evaluate weight status and BMI
   • Screen for psychosocial stressors
   • Review medication use
   • Consider hematologic testing if clinically indicated

3. Implement appropriate interventions:

   • For diagnosed diabetes: optimize insulin regimen and diabetes management
   • For prediabetes: intensive lifestyle modification
   • Address contributing factors (weight management, stress reduction)
   • Correct anemia if present before finalizing treatment goals

Age-Specific HbA1c Targets

For children with diagnosed diabetes, age-specific HbA1c targets should be considered 1:

• Toddlers/preschoolers (0-6 years): 7.5-8.5%
• School-age children (6-12 years): 8%
• Adolescents (13-19 years): 7.5%

These targets balance the need for glycemic control with the risks of hypoglycemia, particularly in younger children who may have hypoglycemic unawareness.