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Simeon Margolis, M.D.
09-02-2010
- Elevated blood levels of lipids (cholesterol and triglycerides) and/or abnormalities in the blood concentrations of lipoproteins including: increased low density lipoprotein cholesterol (LDL-C), decreased high density lipoprotein cholesterol (HDL-C), and increased lipoprotein(a) (Lp(a)).
- Normal fasting triglyceride levels are <150 mg/dL. Triglycerides >500 mg/dL are considered very high.
- Desirable levels of LDL-C in patients with diabetes are <100 mg/dL and probably <70 mg/dL.
- HDL-C levels are considered too low when <40 mg/dL in men and <50 mg/dL in women. Non-HDL cholesterol = total cholesterol - HDL-C.
- Normal levels of Lp(a) vary with the laboratory methods used to measure them.
- Diabetic dyslipidemia: most common lipid abnormality is elevated triglycerides. Almost equally common is low levels of HDL-C(Howard).
- On average LDL-C and Lp(a) levels are no higher in individuals with diabetes compared to those without diabetes.
- Diabetic dyslipidemia is associated with greater amounts of atherogenic, small dense LDL-C.
- Severe insulin deficiency can be associated with very high triglycerides and the risk of acute pancreatitis.
- Cardiovascular disease, the most common cause of death in diabetes, is already present in about half of patients with type 2 diabetes at the time of diagnosis and is the most important long-term sequela of untreated diabetic dyslipidemia (Haffner).
- Obtain a fasting lipid panel (cholesterol, triglycerides, and HDL-C) at time of diagnosis and at least annually if normal during follow-up.
- Small dense LDL-C and number of LDL-C particles can be determined by measuring apolipoprotein B or by NMR spectroscopy, measuring lipoprotein subfractions.
- In patients with hypertriglyceridemia, presence of chylomicrons can be detected by observing a lipid layer on top of plasma after overnight refrigeration.
- In patients with triglycerides over 1000 mg/dL, serum amylase and lipase may be normal with attacks of acute pancreatitis.
- No signs or symptoms are associated with modestly elevated triglycerides or with abnormal levels or LDL-C, HDL-C, or Lp(a).
- Tendon xanthomas and xanthelasma palpebra may indicate familial hypercholesterolemia, but about 50% of people with xanthelasmas have normal cholesterol levels.
- Yellow appearance of palmar creases in dysbetalipoproteinemia.
- Eruptive xanthomas (maculopapular with white "head" containing triglyceride), tuberous xanthomas around the elbows and knees, and lipemia retinalis in severe hypertriglyceridemia.
- Extremely high triglycerides may cause pancreatitis, with severe abdominal pain, nausea and vomiting.
- Aims: Prevention of cardiovascular disease (Colhoun). A second goal is to prevent acute pancreatitis.
- Always begin with lifestyle measures to manage dyslipidemias. To lower LDL-C: diet containing <35% total fat calories, <7% saturated fat, <200 mg cholesterol per day.
- Weight loss and glycemic control most effective in lowering triglycerides.
- Exercise can lower triglycerides and raise HDL-C, but relatively ineffective in lowering LDL-C.
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Statins are most effective drugs to lower LDL-C and are usually starting drug for diabetic dyslipidemia.
- Fibrates, Lovaza (omega-3-acid ethyl esters), and over-the-counter fish oil capsules are most effective treatments for very high triglycerides.
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Niacin preparations are most effective drugs to raise HDL-C and generally do not significantly worsen glycemic control(Grundy).
- Pioglitazone is more effective than rosiglitazone in lowering triglycerides, raising HDL-C, and lowering LDL-C (Goldberg).
- The bile acid sequestrant, colesevelam, improves glycemic control, lowers LDL-C by about 15%, and decreases small dense LDL(Fonseca).
- If triglycerides remain >200 mg/dL during statin treatment, consider adding a fibrate or niacin.
- If lifestyle measures do not achieve targets after 4 to 6 weeks, add a cholesterol-lowering drug(Brunzell).
- Do lipid panel and liver enzymes 4 to 6 weeks after starting drug to determine its effectiveness.
- After 4-6 weeks, if LDL-C targets are not achieved and liver enzymes are normal, raise statin dose or add ezetimibe.
- Targets of statin treatment: LDL-C <100mg/dL or total cholesterol/HDL-C < 2.0
- If a fibrate is added to lower triglycerides, choose fibric acid rather than gemfibrozil for lower risk of myositis. Target is non HDL cholesterol < 100 mg/dL.
- Second line therapy for hypertriglyceridemia is niacin for modestly elevated triglycerides, and either over-the-counter fish oil capsules or the prescription drug Lovaza for triglycerides > 500 mg/dL.
- Many experts recommend adding Niaspan if HDL-C remains < 40 mg/dL in men or < 50 mg/dL in women (Grundy).
- Measure CK if any complaints of muscle pain or weakness (need not measure at baseline). Stop statins if troublesome muscle symptoms to see if muscle symptoms go away and/or reduce statin dose. Stop statins if CK is >1000 mg/dL. If symptoms disappear within 2 weeks and CK was less than 1000, can restart same statin at a lower dose or choose a different statin. Use statin cautiously if CK was >1000 mg/dL.
- Stop statin if liver enzymes 3 times or more higher than upper limits of normal.
- Ask about muscle pain and weakness at every patient visit.
- Must increase statin dose or add another drug if follow-up results do not meet target.
- Initiate a statin cautiously in patients at higher risk of myositis (i.e. those on drugs like gemfibrozil, antifungal agents, or cyclosporin).
- Even modest weight loss (5 to 19% of body weight) in people who are either mildly overweight or more obese can dramatically reduce triglycerides.
- To determine effect of weight loss on triglycerides, wait until weight has stabilized; triglyceride levels may be falsely low during periods of weight loss.
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