What causes high triglycerides in children?

Causes of High Triglycerides in Children

Childhood obesity represents the major cause of pediatric hypertriglyceridemia, with approximately 1 in 5 children with BMI above the 95th percentile having hypertriglyceridemia, a rate 7-fold higher than for non-obese children. 1

Primary (Genetic) Causes

Genetic abnormalities affecting triglyceride metabolism can lead to hypertriglyceridemia in children, though these are relatively rare:

• Lipoprotein lipase (LPL) deficiency
• Apolipoprotein C-II (APOC2) deficiency
• Apolipoprotein A-V (APOA5) mutations
• Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) deficiency 1

These genetic disorders are typically diagnosed soon after birth and can cause severe hypertriglyceridemia (>1000 mg/dL).

Secondary Causes

Secondary causes are more common and include:

1. Obesity-Related Factors

• Adipose tissue dysfunction leading to impaired triglyceride storage and increased fatty acid release 2
• Insulin resistance, which precedes the development of hypertriglyceridemia in many children 1

2. Dietary Factors

• Excessive carbohydrate intake causing lipogenesis 1
• High sugar consumption, particularly sugar-sweetened beverages 1
  • Each additional daily serving of sugar-sweetened beverages is associated with a 2.25 mg/dL increase in triglyceride levels 1
• High fructose consumption 1

3. Metabolic Conditions

• Insulin resistance and impaired glucose tolerance 1
  • Mean triglyceride levels are 28% higher in adolescents with impaired glucose tolerance 1
• Type 2 diabetes mellitus 1
• Metabolic syndrome 2

4. Lifestyle Factors

• Physical inactivity 1
  • In boys, high physical activity combined with low intake of sugar-sweetened beverages is associated with lower triglyceride levels 1

5. Medical Conditions and Treatments

• Parenteral nutrition (especially with high glucose content) 1
• Sepsis 1
• Certain medications (estrogen therapy, thiazide diuretics, beta-blockers) 3
• Liver dysfunction 1

Risk Factors for Elevated Triglycerides

• Limited muscle and fat mass in preterm infants (decreased hydrolytic capacity) 1
• Malnourishment (slower clearance rates) 1
• Ethnic background (Mexican American adolescents have higher rates of impaired fasting glucose associated with hypertriglyceridemia) 1

Clinical Implications

Hypertriglyceridemia in children is concerning because:

• It's associated with other cardiometabolic risk factors 2
• The TG/HDL-C ratio is a marker of structural vascular changes and insulin resistance in obese youth 2
• Severe hypertriglyceridemia (>1000 mg/dL) increases risk for acute pancreatitis 4
• Early pathophysiological changes in arteries begin soon after birth and accelerate during adolescence 1

Management Approach

For mild to moderate hypertriglyceridemia:

1. Lifestyle modifications (primary approach) 2
2. Dietary changes with reduced carbohydrates (45-50%) and added sugars (<5%) 1
3. Increased physical activity 1
4. Weight management for obese children 5

For severe hypertriglyceridemia (>500 mg/dL):

1. Consider fibrates to prevent pancreatitis 5
2. Omega-3 fatty acids as adjunctive therapy 5
3. For hospitalized patients with very severe hypertriglyceridemia, consider fasting followed by fat-free diet until triglycerides decline below 1000 mg/dL 4

Important Considerations

• Universal lipid screening with non-fasting non-HDL-C is recommended in children aged 9-11 years 2
• Fasting lipid profiles should be measured in obese children and overweight adolescents 2
• When managing hypertriglyceridemia related to parenteral nutrition, reduce glucose intake first rather than lipid infusion 1
• Monitoring frequency should be increased in high-risk patients (those with high lipid or glucose dosage, sepsis, malnourishment, or extremely low birth weight) 1

Understanding the multifactorial nature of hypertriglyceridemia in children is essential for effective management and prevention of long-term cardiovascular complications.