eMedicine Specialties > Endocrinology > Metabolic Disorders

Dysbetalipoproteinemia: Treatment & Medication

Author: Elena Citkowitz, MD, PhD, FACP, Clinical Professor of Medicine, Yale University School of Medicine; Director, Cholesterol Management Center, Director, Cardiac Rehabilitation, Department of Medicine, Hospital of St Raphael
Coauthor(s): Karen E Friday, MD, FACP, Clinical Core Director of Tulane Xavier National Center of Excellence, Associate Professor, Department of Internal Medicine, Section of Endocrinology, Tulane University School of Medicine
Contributor Information and Disclosures

Updated: Nov 10, 2009

Treatment

Medical Care

  • Patients first should be treated for the metabolic condition that is causing or exacerbating their hyperlipidemia.
    • If diabetes is present, glucose levels and glycosylated hemoglobin (HbA1c) should be normalized if possible.
    • If hypothyroidism is diagnosed, TSH should be normalized.
    • Obesity and inactivity should be addressed appropriately.
  • A careful history should be obtained to find other modifiable risk factors for atherosclerosis, such as smoking and hypertension, that can be addressed.
  • First-degree relatives should be screened for hyperlipidemia and the risks of cardiovascular disease.

Surgical Care

  • Surgical care is not indicated.

Consultations

  • A specialist in lipid disorders may be helpful in treating the hyperlipidemia that develops in these patients, which can be very severe and difficult to treat, often requiring multiple lipid-lowering agents.
  • Patients should receive nutrition counseling and should be advised to restrict calories if overweight. They also should reduce saturated and trans fats and cholesterol intake.

Diet

  • A dietitian or knowledgeable physician should counsel the patient.
  • Encourage the following behaviors:
    • Consume less than 20% of calories as fat.
    • Consume less than 7% of calories from saturated fat and 0% trans fats.
    • Consume less than 200 mg of cholesterol per day.
    • Restrict refined carbohydrates, particularly sugar and liquid calories.
    • Increase fiber intake.
    • Abstain or severely limit alcohol consumption. Consuming more than 1 standard alcoholic drink per day may worsen hypertriglyceridemia.
    • Attain and maintain a desirable weight, and caution that rapidly regaining weight may cause severe hypertriglyceridemia.

Activity

  • If patients have no known cardiovascular disease, they should be encouraged to begin an exercise program of graduated aerobics and toning.
  • Encourage no less than 30 minutes of brisk aerobic activity 4 days per week.
  • Frequent and sustained exercise lowers elevated triglyceride levels and may raise HDL cholesterol levels.
  • Before beginning an exercise program, consider giving a stress test to older patients and patients with multiple risk factors for coronary artery disease. These patients are at increased risk for cardiovascular disease.

Medication

The drugs of choice for severe hypertriglyceridemia include fibric acid derivatives (gemfibrozil or fenofibrate) and niacin. In patients with type 2 diabetes, glucose control should be carefully monitored, because niacin sometimes causes a modest increase in insulin resistance.6 In addition, because uncontrolled diabetes can lead to dysbetalipoproteinemia, patients with diabetes mellitus should be treated aggressively to normalize blood glucose levels and to reduce the HbA1c level to less than 7%.

While HMG CoA reductase inhibitors (statins) are not the drugs of choice to treat dysbetalipoproteinemia, their use may be necessary if the response to a fibrate and or niacin is inadequate. If a patient is taking gemfibrozil, the addition of a statin should prompt switching to fenofibrate, which has a lower risk of causing severe myopathy.

If triglycerides are inadequately controlled despite treatment with a fibrate and/or niacin, high-dose fish oil may be added.

Bile acid sequestrants are usually avoided, because they usually increase triglycerides.

Antilipemic agents

Can reduce triglyceride levels in blood.


Gemfibrozil (Lopid)

Fibric acid derivative that reduces blood triglyceride, VLDL cholesterol, and IDL cholesterol, but raises HDL cholesterol. Increases activity of lipoprotein lipase, which hydrolyzes triglycerides in triglyceride-rich lipoproteins. Gemfibrozil reduces synthesis of VLDL in liver and increases clearance of remnant lipoproteins from blood.

Adult

600 mg PO bid 30 min ac

Pediatric

Not established

May potentiate effects of warfarin (reduce warfarin dose to maintain prothrombin time at desired level); monitor closely for myositis/myalgia if coadministered with statin therapy

Documented hypersensitivity; gallbladder disease and renal or hepatic insufficiency

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Before beginning therapy in stable patients, attempt to control serum lipids with diet, exercise, weight loss, and glucose control unless triglyceride level is greater than 1000 mg/dL or patient has developed clinical pancreatitis
Not known if drug is excreted in human milk but should not be prescribed to nursing mothers
Evaluate patients reporting generalized muscle pain for myositis with a serum creatinine kinase level
Periodic blood counts are recommended during first 12 months of therapy
May cause liver function test abnormalities including elevations of AST, ALT, LDH, bilirubin, and alkaline phosphatase; liver abnormalities usually are reversible when gemfibrozil is discontinued; periodic liver function studies are recommended, and therapy should be discontinued if liver abnormalities persist
If baseline of plasma creatinine is >2 mg/dL, renal insufficiency may become worse with gemfibrozil therapy; consider alternative therapy against risks and benefits of a lower dose


Fenofibrate (Tricor, Lofibra, Triglide, Antara)

Fibric acid may reduce blood triglycerides, VLDL cholesterol, and IDL cholesterol. Increases activity of lipoprotein lipase, which helps clear triglycerides from the blood. Fenofibrate also reduces synthesis of VLDL in the liver and increases clearance of remnant lipoproteins from the blood.

Adult

Dosing variable depending on brand

Pediatric

Not established

Myositis, occasionally with rhabdomyolysis, has been reported when gemfibrozil (a fibric acid derivative related to fenofibrate) has been combined with statin therapy; increases effect of anticoagulants and nephrotoxic effects of cyclosporine; bile acid sequestrants may decrease absorption if given concurrently

Documented hypersensitivity; hepatic or severe renal dysfunction (including primary biliary cirrhosis); unexplained persistent liver function abnormalities; preexisting gallbladder disease

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Before beginning therapy in stable patients, attempt to control serum lipids with diet, exercise, weight loss, and glucose control unless triglyceride level is greater than 1000 mg/dL or patient has developed clinical pancreatitis; pancreatitis may occur possibly due to failure of triglyceride-lowering therapy or through biliary stone formation with biliary obstruction
Not for use in nursing mothers
Monitor hemoglobin, hematocrit, and WBC count during first 12 mo of therapy
Monitor liver function, and discontinue therapy if abnormal liver enzyme levels persist
Fibrates alone or in combination with statin therapy have been associated with development of myositis and rarely rhabdomyolysis; patients should be advised to report unexplained muscle pain, tenderness, or weakness (assess CK levels in patients with these symptoms)


Nicotinic acid/Niacin/Vitamin B3

Water-soluble vitamin B3 has several lipid-altering effects when taken at pharmacologic doses. Effectively lowers triglycerides and VLDL, IDL, and LDL cholesterol and raises HDL cholesterol. Available in immediate-release preparations that are extremely inexpensive. Several time-release niacin preparations are available but are more expensive. In general, time-release preparations have a higher incidence of niacin-induced hepatitis than do immediate-release preparations. Niacin may increase insulin resistance and worsen glucose control, but it is useful for the dyslipidemias common in patients with diabetes. Carefully monitor AST and ALT indefinitely in these patients.
Immediate-release niacin is best taken tid pc and slowly titrated from 100 mg tid to required maximum dose to reduce flushing and reduce risk of niacin-induced hepatitis.

Adult

1.5-3 g PO qd; higher doses may be necessary to control dyslipidemia

Pediatric

Not established; successfully used in some trials

Cutaneous vasodilation may be a problem if high dose used with peripheral dilators such as nitroglycerin
Taking aspirin 30-60 min before first dose of day may help alleviate adverse prostaglandin-mediated effects (flushing, itching); clonidine may inhibit niacin-induced flushing

Coadministration with MAOIs may precipitate hypertensive crisis; with anesthetics, may precipitate arrhythmias; dextroamphetamine may increase toxicity of phenobarbital, propoxyphene, meperidine, TCAs, phenytoin, and norepinephrine

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in gallbladder disease or diabetes and those predisposed to gout; monitor blood glucose; may elevate uric acid levels; pregnancy category C when used at doses greater than RDA

More on Dysbetalipoproteinemia

Overview: Dysbetalipoproteinemia
Differential Diagnoses & Workup: Dysbetalipoproteinemia
Treatment & Medication: Dysbetalipoproteinemia
Follow-up: Dysbetalipoproteinemia
References
Further Reading
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References

  1. Feussner G, Piesch S, Dobmeyer J. Genetics of type III hyperlipoproteinemia. Genet Epidemiol. 1997;14(3):283-97. [Medline].

  2. Mahley RW, Huang Y, Rall SC Jr. Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia). Questions, quandaries, and paradoxes. J Lipid Res. Nov 1999;40(11):1933-49.

  3. Mahley RW, Rall SC Jr. Type III hyperlipoproteinemia (dysbetalipoproteinemia): The role of apolipoprotein E in normal and abnormal metabolism, in The Metabolic and Molecular Bases of Inherited Disease, 8th ed. Edited by Scriver CR, Beaudet AR, Sly WS, Valle D. New York, McGraw-Hill. 2001, pp 2835–2862.

  4. Smelt AH, de Beer F. Apolipoprotein E and familial dysbetalipoproteinemia: clinical, biochemical, and genetic aspects. Semin Vasc Med. Aug 2004;4(3):249-57.

  5. Holmes DT, Long P, Frohlich J. Dysbetalipoproteinemia and clomipramine. Am J Psychiatry. Jul 2005;162(7):1384-5. [Medline]. [Full Text].

  6. [Best Evidence] Goldberg RB, Jacobson TA. Effects of niacin on glucose control in patients with dyslipidemia. Mayo Clin Proc. Apr 2008;83(4):470-8. [Medline].

  7. Blom DJ, O'Neill FH, Marais AD. Screening for dysbetalipoproteinemia by plasma cholesterol and apolipoprotein B concentrations. Clin Chem. May 2005;51(5):904-7.

  8. Brummer D, Evans D, Berg D. Expression of type III hyperlipoproteinemia in patients homozygous for apolipoprotein E-2 is modulated by lipoprotein lipase and postprandial hyperinsulinemia. J Mol Med. Apr 1998;76(5):355-64. [Medline].

  9. Civeira F, Cenarro A, Ferrando J. Comparison of the hypolipidemic effect of gemfibrozil versus simvastatin in patients with type III hyperlipoproteinemia. Am Heart J. Jul 1999;138(1 Pt 1):156-62. [Medline].

  10. Civeira F, Pocovi M, Cenarro A. Apo E variants in patients with type III hyperlipoproteinemia. Atherosclerosis. Dec 20 1996;127(2):273-82. [Medline].

  11. Devaraj S, Vega G, Lange R. Remnant-like particle cholesterol levels in patients with dysbetalipoproteinemia or coronary artery disease. Am J Med. May 1998;104(5):445-50. [Medline].

  12. Evans D, Seedorf U, Beil FU. Polymorphisms in the apolipoprotein A5 (APOA5) gene and type III hyperlipidemia. Clin Genet. Oct 2005;68(4):369-72.

  13. Feussner G, Kurth B, Lohrmann J. Comparative effects of bezafibrate and micronised fenofibrate in patients with type III hyperlipoproteinemia. Eur J Med Res. Apr 21 1997;2(4):165-8. [Medline].

  14. Hopkins PN, Wu LL, Hunt SC, Brinton EA. Plasma triglycerides and type III hyperlipidemia are independently associated with premature familial coronary artery disease. J Am Coll Cardiol. Apr 5 2005;45(7):1003-12. [Medline].

  15. Wang T, Nakajima K, Leary ET. Ratio of remnant-like particle-cholesterol to serum total triglycerides is an effective alternative to ultracentrifugal and electrophoretic methods in the diagnosis of familial type III hyperlipoproteinemia. Clin Chem. Nov 1999;45(11):1981-7. [Medline].

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Keywords

dysbetalipoproteinemia, hypercholesterolemia, familial hypercholesterolemia, low-density lipoprotein, LDL, very low-density lipoprotein, VLDL, intermediate-density lipoprotein, IDL, xanthomatosis, hyperlipidemia, hypercholesteremia, hypertriglyceridemia

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Contributor Information and Disclosures

Author

Elena Citkowitz, MD, PhD, FACP, Clinical Professor of Medicine, Yale University School of Medicine; Director, Cholesterol Management Center, Director, Cardiac Rehabilitation, Department of Medicine, Hospital of St Raphael
Elena Citkowitz, MD, PhD, FACP is a member of the following medical societies: American College of Physicians, American Heart Association, National Lipid Association, and Sigma Xi
Disclosure: Nothing to disclose.

Coauthor(s)

Karen E Friday, MD, FACP, Clinical Core Director of Tulane Xavier National Center of Excellence, Associate Professor, Department of Internal Medicine, Section of Endocrinology, Tulane University School of Medicine
Karen E Friday, MD, FACP is a member of the following medical societies: American College of Physicians, American Diabetes Association, American Heart Association, American Society for Clinical Nutrition, and Endocrine Society
Disclosure: AstraZeneca own AstraZeneca stock None; Merck own Merck stock None; Schering Plough own Schering Plough stock None; Medco Health own Medco Health stock None

Medical Editor

Robert A Gabbay, MD, PhD, Associate Professor of Medicine, Division of Endocrinology, Diabetes and Metabolism, Laurence M Demers Career Development Professor, Penn State College of Medicine; Director, Diabetes Program, Penn State Milton S Hershey Medical Center; Executive Director, Penn State Institute for Diabetes and Obesity
Robert A Gabbay, MD, PhD is a member of the following medical societies: American Association of Clinical Endocrinologists, American Diabetes Association, and Endocrine Society
Disclosure: Novo Nordisk Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Romesh Khardori, MD, Chief, Division of Endocrinology, Metabolism and Molecular Medicine, Professor, Department of Internal Medicine, Southern Illinois University School of Medicine
Romesh Khardori, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Medical Association, American Society of Andrology, Endocrine Society, and Illinois State Medical Society
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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