What causes elevated triglycerides?

Causes of Elevated Triglycerides

Elevated triglycerides are primarily caused by overweight-obesity, diabetes mellitus, genetic factors, and alcohol consumption, with severely elevated levels often resulting from severely dysregulated diabetes mellitus, alcoholism, or rare genetic mutations. 1

Primary Causes

• Genetic factors:
  • Mutations in genes involved in triglyceride metabolism: LPL, APOC2, APOA5, LMF1, GPIHBP1, and GPD1 1
  • Polygenic inheritance - multiple genetic risk variants that cumulatively affect triglyceride levels 2
  • Familial hypertriglyceridemia - genetic predisposition to elevated triglycerides

Secondary Causes

Medical Conditions

• Diabetes mellitus - especially poorly controlled diabetes 1, 3
• Metabolic syndrome - characterized by abdominal obesity, insulin resistance, low HDL, high triglycerides, and hypertension 4
• Hypothyroidism - affects lipid metabolism 5, 4
• Obesity - particularly central/abdominal obesity 1, 3
• Chronic kidney disease - impairs triglyceride clearance

Lifestyle Factors

• Diet-related factors:

  • High intake of refined carbohydrates and added sugars 3
  • Excessive fat consumption (>30-35% of total daily calories) 3
  • Low fiber intake 3
  • High caloric intake 6

• Alcohol consumption - particularly excessive intake 1, 3, 5

  • Can convert moderate hypertriglyceridemia (Type IV) to severe hypertriglyceridemia (Type V) with fasting chylomicronemia 5

• Physical inactivity - contributes to metabolic syndrome and obesity 3

Medications

• Estrogen therapy - can cause massive rises in plasma triglycerides, especially in those with familial hypertriglyceridemia 5
• Thiazide diuretics - can elevate triglyceride levels 7
• Beta-blockers - may increase triglyceride levels 7
• Other medications:
  • Tamoxifen
  • Retinoids
  • Immunosuppressants 3

Classification of Hypertriglyceridemia

Triglyceride Level	Classification	Risk
<150 mg/dL	Normal	-
150-199 mg/dL	Borderline high	Increased cardiovascular risk
200-499 mg/dL	High	Increased cardiovascular risk
≥500 mg/dL	Very high	Risk of pancreatitis and cardiovascular disease
1,000-1,999 mg/dL	Severe	High risk of pancreatitis
≥2,000 mg/dL	Very severe	Extremely high risk for acute pancreatitis [3]

Clinical Significance

• Mild-to-moderately elevated triglycerides (2-10 mmol/L or 176-880 mg/dL) increase risk of atherosclerotic cardiovascular disease (ASCVD) 1
• Severely elevated triglycerides (>10 mmol/L or >880 mg/dL) increase risk of acute pancreatitis and possibly ASCVD 1
• Elevated triglycerides are often associated with other lipid abnormalities, particularly low HDL cholesterol 4, 8
• Hypertriglyceridemia is frequently a component of metabolic syndrome 4

Important Clinical Considerations

• Population distribution shows 27% of adults have mild-to-moderately elevated triglycerides, while only 0.1% have severely elevated levels (>10 mmol/L or 880 mg/dL) 1
• Triglycerides themselves may not directly cause atherosclerosis (unlike cholesterol), as they can be degraded by most cells in the body 1
• High triglycerides should be viewed as a marker of high levels of cholesterol in triglyceride-rich lipoproteins 1
• Remnant cholesterol (total cholesterol minus LDL cholesterol minus HDL cholesterol) may be a more clinically relevant measure than triglycerides alone 1
• Patients with triglyceride levels between 1000-2000 mg/dL with a history of pancreatitis or recurrent abdominal pain typical of pancreatitis should be considered for treatment 5

Understanding the specific cause of hypertriglyceridemia is essential for determining appropriate management strategies, which may include lifestyle modifications, dietary changes, and pharmacological interventions depending on the severity and underlying etiology.