Dysbetalipoproteinemia – a condition with many names
What is dysbetalipoproteinemia?
Dysbetalipoproteinemia (DBL), also called remnant removal disorder, or type III hyperlipidemia, is an inherited lipid disorder characterized by elevated levels of triglycerides and remnant lipoproteins, and an increased risk of cardiovascular disease. DBL is caused by having two copies of the E2 isoform of the APOE gene. This genetic variant leads to reduced binding of lipoprotein particles to their receptors on the surface of the liver, and thereby a reduction in their clearance from the bloodstream. One of the clinical clues to DBL is a discrepancy between the level of total cholesterol in blood and the level of apoB. ApoB is a blood test used to predict cardiovascular risk, and typically correlates with the levels of LDL cholesterol and total cholesterol. DBL is an exception to this, as the apoB is disproportionally low, but there is still an increased risk of cardiovascular disease. Homozygosity for the E2 isoform of APOE is a necessary but not sufficient condition for DBL, as this genotype is present in approximately 1% of the population, whereas the prevalence of DBL is thought to be approximately 0.2 – 0.8%, depending on the diagnostic criteria used.
What is the criteria for dysbetalipoproteinemia?
A number of different diagnostic criteria for DBL have been proposed. In general, these consist of elevated levels of total cholesterol and triglycerides, and often elevated levels of the ratio of non-HDL cholesterol to apoB. One set of criteria proposed by Dr. Sniderman and colleagues is a total cholesterol/apoB ratio >6.2 and a triglyceride/ApoB ratio of <10, where total cholesterol and triglcyerides are measured in mmol/L and apoB in g/L. The agreement between the various criteria is modest.
How is dysbetalipoproteinemia diagnosed?
DBL should be suspected in a patient with elevated total cholesterol and triglycerides, especially if the apoB is low. Clinical features that suggest DBL include the presence of palmar xanthomas, which are yellow/orange discolouration of the palm creases in the hand. Eruptive xanthomas on the extensor surface of elbows and knees can also occur. The diagnosis can be confirmed by genetic testing showing the presence of the E2/E2 genotype of APOE. Specialized testing using lipoprotein electrophoresis can demonstrate the presence of β-VLDL particles; however, such testing is rarely performed in clinical practice.
What lifestyle modifications are recommended for patients?
DBL tends to be responsive to lifestyle modification, more so than other forms of inherited dyslipidemias. As such, careful attention to a healthy lifestyle is essential for patients with DBL. Traditionally, dietary recommendations for DBL have consisted of restricting dietary cholesterol to <300 mg/day, limiting alcohol use, limiting carbohydrates to <40% of calories, avoiding simple carbohydrates, and promoting the consumption of marine-derived omega-3 fatty acids, and overall calorie restriction to promote weight loss. Other general health measures include regular physical activity and maintaining a healthy body weight.
What treatment options are available for patients with dysbetalipoproteinemia?
For patients with DBL who did not experience an adequate response to lifestyle modification, treatment with lipid lowering therapy is recommended. The most commonly used classes of lipid lowering therapy in patients with DBL are statins and fibrates, which can be helpful to lower the elevated cholesterol and triglyceride levels seen in these patients. Other classes of lipid lowering therapies, such as ezetimibe, bempedoic acid, icospent ethyl, PCSK9 inhibitors, or inhibitors of apoCIII or ANGPTL3, are less well studied in DBL but may also be considered.
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Clinical Trials, if applicable
| NCT Number | Study Title | Study URL | Acronym | Conditions | Interventions | Primary Outcome Measures |
|---|---|---|---|---|---|---|
| NCT01760265 | DARK STUDY "DysbetalipoproteinemiA and atheRoma Risk" | View Study | DARK | Dysbetalipoproteinemia | – | Computed tomographic measurements for coronary-artery calcium, Comparison with eventual previous examinations. Day one: the coronary calcium score is assessed on the date of measurement |
| NCT03811223 | Effects of Evolocumab Versus Placebo Added to Standard Lipid-lowering Therapy on Fasting and Post Fat Load Lipids in Patients With Familial Dysbetalipoproteinemia | View Study | EVOLVE-FD | Familial Dysbetalipoproteinemia | Hyperlipoproteinemia Type III | DRUG: Evolocumab Auto-Injector [Repatha] | DRUG: Placebos | AUC (area under the curve) non-HDL-cholesterol, 12 weeks |