Hypertriglyceridemia: Causes

Pathogenesis (disease development)

There are several factors that can lead to hypertriglyceridemia:

  • Genetic burden (see below).
  • Excessive stress due to lifestyle and diet
  • Diseases
  • Drug side effects

Excessive alcohol consumption (> 30 g/day) inhibits the oxidation of fatty acids in the liver. As a result, more fats are synthesized (→ steatosis hepatis/fatty liver) and released, increasing VLDL production. Furthermore, alcohol consumption leads to an increase in fatty acid synthesis in the intestine and liver, increases lipolysis (dissolution of fat stores), and simultaneously inhibits the enzyme lipoprotein lipase, which prevents effective breakdown of triglycerides. In familial hypertriglyceridemia, the disorder is due to a genetic defect that causes increased VLDL production and/or decreased VLDL catabolism.In familial lipoprotein lipase deficiency (type I hyperlipoproteinemia), there is a defect in lipoprotein lipase (LPL) or apoprotein CII (cofactor of LPL). This leads to an increase in chylomicrons in serum.

Etiology (Causes)

Biographic causes

  • Genetic burden from parents, grandparents, ie, primary hypertriglyceridemia/editary hypertriglyceridemia (triglycerides (TG) elevated, HDL cholesterol lowered, and LDL cholesterol normal):
    • Familial hypertriglyceridemia (type IV hyperlipoproteinemia; autosomal dominant inheritance (1: 500)).
    • Familial lipoprotein lipase deficiency (type I hyperlipoproteinemia; mostly autosomal recessive defect of lipoprotein lipase (LPL) or of apoprotein CII (see below ): very rare disease (2-4: 1,000,000)).
    • Familial apoprotein CII deficiency (apo C-II deficiency); autosomal recessive inherited metabolic defect characterized by extremely elevated serum concentrations of triglycerides (up to 30,000 mg/dl) and chylomicrons (milky creamy serum) (type I hyperlipoproteinemia).
    • Familial apoprotein A-V deficiency (apo-A-V deficiency; chylomicronemia syndrome); here, chylomicrons and VLDL are typically elevated; plasma is lipemic (milky-white) and triglycerides are usually highly elevated (> 850 mg/dl)
    • Chylomicronemia syndrome; rare, autosomal recessive disorder of chylomicron metabolism with extremely high triglyceride levels (type I hyperlipidemia); life-threatening disease.
  • Hormonal factors – menopause (menopause in women).

Behavioral causes

  • Nutrition
    • Increased intake of:
      • Calories (as fat or rapidly metabolized carbohydrates).
      • Triglycerides (neutral fats, dietary fat) – animal fats.
      • Trans fatty acids (10-20 g/day; e.g., baked goods, chips, fast food products, convenience foods, fried foods such as French fries, breakfast cereals with added fat, snacks, confectionery, dry soups).
      • Carbohydrates (including fructose, glucose), this causes an increased de novo lipogenesis (“new fatty acid synthesis”); the ingestion of fructose leads postprandially (after a meal) within 24 hours to an increase in triglyceride concentration
    • Micronutrient deficiency (vital substances) – see micronutrient therapy.
  • Pleasure food consumption
    • Alcohol (woman: > 20 g/day; man > 30 g/day); esp. alcohol abuse → increase in secretion of VLDL particles and inhibition of lipases.
    • Tobacco (smoking)
  • Physical activity
    • Physical inactivity
  • Psycho-social situation
    • Stress
  • Overweight (BMI ≥ 25; obesity).

Disease-related causes that increase triglycerides:

Blood-forming organs – immune system (D50-D90).

Endocrine, nutritional and metabolic diseases (E00-E90).

Infectious and parasitic diseases (A00-B99).

  • Sepsis (blood poisoning)

Liver, gallbladder, and bile ducts-pancreas (pancreas) (K70-K77; K80-K87).

  • Cholestasis (biliary stasis)
  • Hepatitis (inflammation of the liver), unspecified

Musculoskeletal system and connective tissue (M00-M99).

Psyche – nervous system (F00-F99; G00-G99).

  • Alcohol abuse (alcoholism)
  • Anorexia nervosa (anorexia)
  • Stress

Pregnancy, childbirth and puerperium (O00-O99)

  • Pregnancy

Genitourinary system (kidneys, urinary tract – reproductive organs) (N00-N99)

  • Nephrotic syndrome – collective term for symptoms that occur in various diseases of the glomerulus (renal corpuscles); symptoms include: Proteinuria (increased excretion of protein in urine) with protein loss greater than 1 g/m²/body surface area per day; hypoproteinemia, peripheral edema due to serum hypalbuminemia of < 2.5 g/dL, hyperlipoproteinemia (dyslipidemia).
  • Renal insufficiency (kidney weakness).

Laboratory diagnoses – laboratory parameters that are considered independent risk factors.

Medication

Other causes

  • Gravidity (pregnancy) [physiological triglyceride concentrations can double during the third trimester].