What is the pathophysiology of type IV hyperlipoproteinemia (HLP)?

Updated: Jun 27, 2019
  • Author: Henry J Rohrs, III, MD; Chief Editor: Stuart Berger, MD  more...
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In type IV HLP, a predominant increase in VLDL TGs is observed; however, levels are lower (eg, < 1000 mg/dL) than in HLP types I or V.

Hypertriglyceridemia (usually the type IV HLP phenotype) is frequently observed in children with obesity, diabetes, or both conditions. In type 1 diabetes mellitus, hypertriglyceridemia results from absolute insulin deficiency, whereas in children with obesity and type 2 diabetes mellitus, insulin resistance is the root cause, combined with relative insulin deficiency. Other causes of insulin resistance, including renal disease, liver disease, ethanol abuse, pregnancy, endocrinopathies (eg, Cushing disease, hypothyroidism, acromegaly), and drugs (eg, glucocorticoids, growth hormone, androgens, thiazides, beta blockers, estrogen, HIV protease inhibitors), may also lead to hypertriglyceridemia.

Similar to insulin, thyroid hormone regulates LPL activity; hypothyroidism can cause elevated TG levels by lowering LPL activity.

The combination of type IV HLP and low HDL-C (eg, hypoalphalipoproteinemia) are typical findings in the metabolic syndrome. The metabolic syndrome is a constellation of findings related to reduced insulin sensitivity most commonly caused by centripetal and abdominal obesity. Besides dyslipidemia, features of the metabolic syndrome include hyperinsulinism, dysglycemia (eg, impaired glucose tolerance, impaired fasting glucose or type 2 diabetes), hypertension, hyperuricemia, hyperandrogenism in women, polycystic ovary syndrome, propensity to thrombosis (because of increased plasminogen activator inhibitor levels), and elevated ferritin concentrations. Adults with the metabolic syndrome are at greatly increased risk for cardiovascular disease.

Two inherited causes of a type IV phenotype include familial hypertriglyceridemia and FCH. Familial hypertriglyceridemia is rarely expressed in childhood unless another underlying cause of hypertriglyceridemia is present. About 15% of patients with premature cardiovascular disease have hypertriglyceridemia.

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