What causes elevated triglycerides?

Causes of Elevated Triglycerides

Elevated triglycerides result from both primary genetic disorders and secondary causes, with the most common secondary factors being obesity, excessive alcohol intake, poorly controlled diabetes, certain medications (thiazides, beta-blockers, estrogen, corticosteroids, antipsychotics), and dietary factors including high refined carbohydrate intake. 1

Secondary Causes (Most Common)

Lifestyle and Metabolic Factors

• Obesity and weight gain are the predominant contributors to mild-to-moderate hypertriglyceridemia (176-880 mg/dL), with much of the increase in adults directly caused by weight gain and lack of exercise 2, 1
• Physical inactivity significantly contributes to elevated triglycerides 1
• Diet high in simple/refined carbohydrates increases triglyceride production, while high saturated-fat intake combined with alcohol exacerbates elevations 2, 1
• Excessive alcohol intake, particularly when combined with high saturated-fat diet, is a major modifiable cause 2, 1

Endocrine and Metabolic Disorders

• Untreated or poorly controlled diabetes mellitus can cause severely elevated triglycerides 2, 1
• Hypothyroidism affects lipid metabolism leading to elevated triglycerides 2, 1
• Metabolic syndrome is frequently associated with hypertriglyceridemia 2, 1

Medications (Critical to Identify)

The following medications commonly elevate triglycerides and should be evaluated in all patients 2, 1:

• Thiazide diuretics (commonly prescribed antihypertensives) 2, 1
• Beta-blockers, especially atenolol 2, 1
• Estrogen therapy, particularly oral formulations 2, 1
• Corticosteroids 2, 1
• Atypical antipsychotics, particularly clozapine and olanzapine 1
• Antiretroviral protease inhibitors used in HIV treatment 2, 1
• Immunosuppressants (sirolimus) 2, 1
• Isotretinoin (retinoic acid drugs) 2, 1
• Bile acid-binding resins can significantly raise triglycerides in predisposed individuals 2, 1
• Tamoxifen 1

Other Medical Conditions

• Renal disease including chronic kidney disease and nephrotic syndrome affects lipid metabolism 2, 1
• Liver disease or hepatic dysfunction 2
• Pregnancy, especially in the third trimester 2, 1
• Autoimmune disorders such as systemic lupus erythematosus 2, 1

Primary (Genetic) Causes

Common Genetic Disorders

• Familial hypertriglyceridemia presents with triglyceride levels of 200-1000 mg/dL and is not typically associated with coronary heart disease unless metabolic syndrome features are present 1
• Familial combined hyperlipidemia (FCHL) affects 1-2% of white populations with increased production of apolipoprotein B lipoproteins 1

Rare Genetic Disorders (Severe Hypertriglyceridemia)

• Lipoprotein lipase deficiency causes severely elevated triglycerides and increased pancreatitis risk 1
• Apolipoprotein CII deficiency causes severe hypertriglyceridemia 1
• Apolipoprotein AV deficiency affects triglyceride metabolism 1
• Dysbetalipoproteinemia is a rare autosomal recessive disorder with defective apolipoprotein E, requiring a second "hit" for clinical expression 1

Clinical Evaluation Approach

When evaluating elevated triglycerides, systematically assess for secondary causes first, as these are treatable and often reversible 2, 1:

1. Review medications and consider alternatives when possible for drugs known to elevate triglycerides 1
2. Assess dietary intake focusing on alcohol consumption, refined carbohydrate intake, and saturated fat 2, 1
3. Screen for metabolic conditions including diabetes control, thyroid function, and renal/liver function 2, 1
4. Evaluate for metabolic syndrome components: abdominal obesity, hypertension, low HDL-C, elevated fasting glucose 1
5. Consider genetic testing only in cases of severe hypertriglyceridemia (≥1,000 mg/dL) without obvious secondary causes, especially with positive family history 1

Common Pitfalls

• Failing to discontinue or substitute causative medications before initiating drug therapy—estrogen therapy, thiazides, and beta-blockers can cause massive rises in plasma triglycerides, especially in subjects with familial hypertriglyceridemia, and discontinuation may obviate the need for specific drug therapy 2, 3
• Not addressing excess body weight and alcohol intake prior to drug therapy, as these are often the primary contributors 2, 3
• Missing undiagnosed or poorly controlled diabetes as a reversible cause 2, 1