Cholesterol Drugs and Diabetes

Cholesterol Drugs and Diabetes

Summary

Cholesterol drugs improve levels of fats in the blood, including cholesterol and triglycerides. Unhealthy levels of fats in the bloodstream increase the risk of hardening of the arteries (atherosclerosis), heart attack, stroke, diabetes and other conditions.

Cholesterol drugs are frequently prescribed for diabetic individuals because diabetes increases the risk of developing cardiovascular disorders and many patients have abnormal levels of cholesterol.

There are five main categories of cholesterol medications: statins, bile acid resins, nicotinic acid, fibrates and cholesterol absorption inhibitors. Most are available only by prescription, except for nicotinic acid, a form of vitamin B3 (niacin), which is available over-the-counter. However, niacin still needs to be taken under the care of a physician to monitor possible side effects.

The American Diabetes Association (ADA) and the U.S. National Institutes of Health (NIH) recommend the following cholesterol and triglyceride target levels for people with diabetes:

  • LDL (“bad”) cholesterol: Lower than 100 mg/dL for men and women
  • HDL (“good”) cholesterol: Greater than 40 mg/dL for men and 50 mg/dL for women.
  • Triglycerides: Lower than 150 mg/dL for men and women

Some materials published by the ADA call for minimum HDL levels of 45 in diabetic men and 55 in diabetic women. Individuals should consult their physician about their cholesterol targets.

Some people can achieve target levels with diet and exercise. However, many require cholesterol medications to keep their levels within a healthy range and reduce the risk of cardiovascular disease.

About cholesterol drugs and diabetes

Cholesterol drugs improve the levels of fats (lipids) in the blood, which include cholesterol and triglycerides. Unhealthy levels of cholesterol increase the risk of cardiovascular diseases. People with diabetes have a higher risk for cardiovascular disease, and many have abnormal cholesterol counts. Patients are often prescribed these drugs to lower their chance of heart attack and stroke.

In people who do not have diabetes but are at risk, control of risk factors such as unhealthy cholesterol levels and high blood pressure can help prevent diabetes.

Cholesterol medications lower levels of LDL (“bad”) cholesterol and in some cases also increase levels of HDL (“good”) cholesterol.

Cholesterol is a waxy type of fat. Most is produced naturally by the body, and the rest comes from eating animal products such as meat, eggs and cheese. The body needs some cholesterol for functions such as making hormones and building cell walls.

Cholesterol is carried through the bloodstream in a package known as a lipoprotein. Researchers have identified a number of different lipoproteins, each of which interacts with the body in a different way. High-density lipoproteins (HDLs) are compact packages that can remove cholesterol from arteries, thus reducing the risk of heart attack and stroke. Other types of lipoproteins, including low-density lipoproteins (LDLs), very low-density lipoproteins (VLDLs) and intermediate-density lipoproteins (IDLs), are unstable packages that can deposit cholesterol into an artery, thus accelerating atherosclerosis and raising the risk of heart attack and stroke. Triglycerides are another type of fat associated with increased cardiovascular risk.

About 65 percent of deaths among people with diabetes are due to heart disease and stroke, according to the National Institutes of Health (NIH). Rates of fatal cardiovascular disease in diabetic adults are two to four times higher than in nondiabetic adults. The NIH estimates that improved control of blood lipids can reduce cardiovascular complications by 20 to 50 percent in diabetic patients.

People with diabetes can reduce their risk of health problems by maintaining the following cholesterol levels, according to the American Diabetes Association (all measurements are in milligrams per deciliter, mg/dL):

CategoryLDL CholesterolHDL Cholesterol
AcceptableLess than 100
(Less than 70 for high-risk patients)
MenOver 40
WomenOver 50
Borderline100 to 129Men35 to 40
Women45 to 50
High130 or greaterMenUnder 35
WomenUnder 45

Some materials published by the ADA and other experts call for minimum HDL levels of 45 mg/dL in diabetic men and 55 mg/dL in diabetic women. The National Cholesterol Education Program recommends total cholesterol levels of less than 200 mg/dL. Individuals should consult their physician about their cholesterol targets.

However, many diabetes patients are not taking the medications or other steps necessary to improve their cholesterol levels, according to recent research.

Types and differences

Patients with diabetes are often prescribed a combination of cholesterol medications. Different types of cholesterol drugs affect levels of fats in different ways:

  • Statins. Considered a first line of treatment for most patients with high cholesterol (hypercholesterolemia), including those with diabetes. Statins block the production of specific enzymes used by the body to make cholesterol. Statins have been shown to reduce the risk of a first heart attack, as well as recurrent heart attacks in patients with known disease. They are particularly effective at lowering levels of LDL (“bad”) cholesterol and, to a lesser degree, triglycerides. Though statins do increase levels of HDL (“good”) cholesterol, they do not seem to increase those levels as well as other cholesterol drugs do.

    Routine use of statins in people with diabetes may provide an extra measure of defense against a first heart attack or stroke. People with diabetes have an increased risk of developing cardiovascular disease in general. The risk of stroke also might be decreased with use of statins. Some researchers have recommended statins to help prevent cardiovascular problems in diabetic patients who have normal levels of cholesterol.

    Some studies have shown that statins may benefit heart disease patients who also have mild kidney failure and that kidney transplant patients who receive statins have a lowered risk of heart-related death after the procedure. However, the U.S. Food and Drug Administration (FDA) reported in 2005 that kidney failure has been reported in patients taking statins, though it could not conclude that recommended doses of statins caused or worsened renal failure. Patients should ask their physician about the possible effects of statins on their risk of diabetic nephropathy and end-stage renal failure.

Contrary to earlier claims, statins do not offer protection against macular degeneration, an eye disease that can occur with advancing age. However, statins appear to help prevent cataracts, according to the Beaver Dam Eye Study, possibly because they may have antioxidant properties.

Research has suggested that statins have varying effects on different racial groups. Scientists have found that statins may be less effective for black Americans, perhaps because of genetic variations. The FDA has warned that Asian patients taking the statin rosuvastatin (Crestor) had twice the blood levels of the drug that white patients had, though the risk of rhabdomyolysis (a serious form of muscle damage) did not appear to be higher.

  • Bile acid resins. Because the liver takes cholesterol out of the blood to make bile, bile acid resins (also known as bile acid sequestrants) prevent the recycling of bile acids in the intestine. As a result, the liver is forced to remove more cholesterol from the blood in order to manufacture more bile. Bile acid resins are usually taken in powder form or in a chewable bar. Many patients, however, have gastrointestinal discomfort with these drugs. Research has suggested that colesevelam might help lower glucose (blood sugar) in patients with type 2 diabetes.

  • Nicotinic acid (niacin), a form of vitamin B3. In large doses, nicotinic acid is very effective in lowering triglyceride levels and raising levels of HDL (“good”) cholesterol. Nicotinic acid can also lower levels of LDL (“bad”) cholesterol, but not as effectively as other cholesterol drugs.

When taking niacin, patients are advised to slowly build up to the high doses needed to treat high cholesterol. Taking too much niacin too quickly can lead to intense side effects that include flushing, palpitations, nausea and, in extreme cases, liver toxicity (especially when taken in “rapid-release” form). Even with proper buildup, as many as 50 percent of patients find the side effects of this medication too difficult to tolerate. Nicotinic acid is available over the counter, but physicians prefer to prescribe the medication in time-release pills. Because of the potentially intense side effects, patients are advised not to begin taking niacin without the supervision of a physician.

  • Fibrates (fibric acid derivatives). Fibric acid reduces the production of triglycerides and increases the rate at which they are removed from the bloodstream. Fibrates can significantly lower triglyceride levels and modestly increase HDL (“good”) cholesterol levels in most patients, but they are less effective at reducing LDL (“bad”) cholesterol levels. They are most commonly used in patients who have elevated triglycerides, usually in conjunction with low HDLs (many people with diabetes have this type of lipid profile). Simultaneous use of fibrates and statins should be carefully monitored.

Research reported by the American Heart Association has suggested that bezafibrate may prevent or delay the onset of diabetes in overweight patients with prediabetes and coronary artery disease.

  • Cholesterol absorption inhibitors. Ezetimibe (Zetia) is the first of a newer class of drug that directly blocks cholesterol absorption in the small intestine (in contrast to bile acid resins, which bind with bile acid in the intestine). Ezetimibe is most commonly used in addition to statins, whereby up to an additional 25 percent reduction in LDLs is achieved. It can also be used as a single agent, but whether or not it will have the same protective effect as statins when used as a single agent is not yet known. Side effects have shown to be similar to that of placebo, and there is minimal increase in liver enzymes when used with statins.

Examples of these medications:

Statins
atorvastatin (Lipitor)
fluvastatin (Lescol)
lovastatin (Advicor, Altoprev, Mevacor)
pravastatin (Pravachol, Pravigard)
rosuvastatin (Crestor)
simvastatin (Zocor)
Bile acid resins
cholestyramine (Prevalite; Questran, a powder)
colestipol (Colestid)
colesevelam (WelChol)
Nicotinic acid
niacin/vitamin B3 (Niacor, Niaspan)
Fibrates
clofibrate (Abitrate, Atromid-S)
fenofibrate (Lofibra, Tricor)
gemfibrozil (Lopid, Gemcor)
bezafibrate (Bezalip)
Cholesterol absorption inhibitors
ezetimibe (Zetia)

There are also combination drugs, such as Advicor (lovastatin and niacin), Vytorin (ezetimibe and simvastatin) and Caduet (atorvastatin and amlodipine, a calcium channel blocker used to lower high blood pressure).

Conditions of concern

Certain types of cholesterol-reducing drugs may not be recommended for patients with certain conditions. Liver disorders are a particular concern.

Most cholesterol-lowering drugs are not known to cause changes in the ability of patients with diabetes to control glucose (blood sugar). However, researchers have found that nicotinic acid can cause hyperglycemia.

Patients who have or are at risk of diabetic nephropathy or other kidney disease are advised to ask their physician about the possible effects of statins or other cholesterol drugs on their kidney function.

In addition, conditions that may affect use of statins include:

  • Alcohol abuse.
  • Electrolyte imbalance.
  • Deficient metabolism of enzymes.
  • Severe infection.
  • Low blood pressure (hypotension).
  • Organ transplant (e.g., heart transplant, kidney transplant or pancreas transplant).
  • Recent major surgery or trauma.

Conditions that may affect use of fibrates include:

  • Gastrointestinal ulcer.
  • Gallbladder stones or disease.
  • Hypothyroidism (underactive thyroid gland).
  • Heart transplant.
  • Increased levels of homocysteine (a metabolic byproduct that may raise cardiovascular risks).

In addition to diabetes, conditions that may affect use of nicotinic acid include:

  • Bleeding problems.
  • Glaucoma.
  • Gout.
  • Low blood pressure.
  • Stomach ulcer.

Conditions that may affect bile acid resins include:

  • Gallstones.
  • Bleeding problems.
  • Stomach problems (e.g., heartburn, ulcers).
  • Constipation and hemorrhoids.
  • Hypothyroidism.
  • Phenylketonuria (a disorder that makes it difficult for the body to break down certain types of food). Sugar-free versions of bile acid resins may contain phenylalanine, an ingredient in the artificial sweetener aspartame. Aspartame can cause problems in people with phenylketonuria.

Potential side effects

There are a number of side effects that could occur as a result of taking cholesterol drugs. Muscle aches can occur and must be immediately reported to a physician. These medicines can produce abnormal liver function in about 2 percent of the population, which can be diagnosed by periodic blood tests of liver enzymes. This liver dysfunction can rarely lead to liver failure. Patients with moderate or severe liver disease are generally advised not to take statins.

A rare but potentially fatal side effect of statins and certain fibrates is rhabdomyolysis, a severe muscle reaction in which muscle cells break down, releasing their contents into the bloodstream. Physicians can monitor patients for this complication by checking muscle enzyme levels (e.g., creatine phosphokinase, CPK) in the blood.

Rhabdomyolysis most often affects the muscles in the back or lower calves. Some patients report no symptoms. In rare cases rhabdomyolysis can lead to kidney failure or other organ failure and death. Patients should report any of the following symptoms of rhabdomyolysis to their physician immediately:

  • Muscle cramps
  • Pain
  • Swelling (edema)
  • Weakness
  • Stiffness
  • Tenderness
  • Fever
  • Dark urine
  • Nausea or vomiting
  • Malaise (a general feeling of illness or discomfort)

Risk of this severe complication appears to be higher in elderly patients, those taking high doses of statin and those taking statins in conjunction with a fibrate. In 2001, one statin, cerivastatin (Baycol), was voluntarily withdrawn from the market by its manufacturer because of reports that fatal cases of rhabdomyolysis had been significantly more common with cerivastatin than with other approved statin drugs. Statins carry a very low risk of side effects to the nervous system. Tingling, numbness and burning pain are some of the manifestations of peripheral neuropathy. Patients on any cholesterol-lowering drugs should also notify their physician if they experience any side effects such as:

  • Allergic reaction (new onset of wheezing, respiratory congestion, itching or skin rashes)
  • Abdominal pain, bloating, constipation, nausea, vomiting, heartburn or other gastrointestinal distress
  • Headache
  • Dizziness, lightheadedness or faintness
  • Flushing of the face or neck
  • Blurred vision
  • Drowsiness, weakness or fatigue
  • Fast or irregular heartbeat  
  • Jaundice (yellowing of the skin and the whites of the eyes)
  • Decreased sexual interest or sexual dysfunction
  • Hair loss

Drug or other interactions

Patients should consult their physician before taking any other medication (either prescription or over-the-counter) or nutritional supplements. Of particular concern to patients taking cholesterol drugs are other cholesterol medications. Taking more than one cholesterol reducer at a time may worsen side effects, unless a physician has prescribed a specially dosed combination of medications.

It is also important to consider the effects of over-the-counter and “herbal” remedies that purport to lower cholesterol. Because these preparations do not make explicit health claims, they do not undergo the same level of scrutiny by the U.S. Food and Drug Administration (FDA) as do prescription drugs. For example, the herbal substance guggul, derived from the mukul myrrh tree, has been advertised as a “cholesterol fighter.” Researchers found, however, that it actually increased levels of LDL (“bad”) cholesterol.

Other substances that may cause concern with some types of cholesterol-reducing drugs include:

  • Birth control pills
  • Immunosuppressives (drugs that suppress the body’s immune system, used with organ transplants and autoimmune disorders such as rheumatoid arthritis)
  • Inotropes (class of heart drugs)
  • Anticoagulants
  • Some antihypertensives (medications to treat high blood pressure) including diuretics, calcium channel blockers and certain beta blockers
  • Azole antifungals (used for conditions such as yeast infections)
  • Some antibiotics
  • Certain nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Thyroid hormones
  • Protease inhibitors (HIV drugs)

Patients taking cholesterol drugs may be instructed to avoid grapefruit juice. Grapefruit juice interferes with the liver’s ability to rid the body of some substances. This could lead to a buildup of medications to toxic levels in the body. Though the buildup is less likely if the juice is ingested four or more hours prior to the medicine, patients taking cholesterol drugs are usually advised to refrain from drinking grapefruit juice. Patients may also be instructed to avoid eating grapefruit, tangelos and Seville oranges. Some research suggests that pomegranate juice may have similar effects on medications.

Lifestyle considerations

Some cholesterol drugs can cause liver inflammation, which tends to resolve on its own after patients stop taking the medication. To monitor this and other complications, patients will undergo regular liver function tests and possibly other blood tests.

Some cholesterol drugs can affect the kidneys. Because kidney damage is a common consequence of diabetes, patients are advised to ask their physician about whether their medication can impair their kidney function and whether they should have regular monitoring, such as microalbuminuria testing.

Women taking cholesterol medication should inform their physician at once if they are or plan to become pregnant. Although it has been found that statins do not have a negative effect on female reproductive hormone levels, cholesterol is an important contributor to the development of the fetus. In addition, some cholesterol drugs are excreted in breast milk. Nursing mothers, therefore, should consult with their physician before taking or discontinuing these drugs.

Patients are advised not to abruptly stop taking their medications without first consulting their physician. It is also important that patients notify all physicians (including dentists) that they are taking statins before undergoing any surgical procedure. Patients should inform their physician immediately of any side effects or concerns.

Most patients on medication to treat high cholesterol (hypercholesterolemia) will be taking it for the rest of their lives, provided no serious side effects occur. Patients should remember that medications may control high cholesterol, but they do not cure it. Even if all their symptoms are relieved, patients should continue to take their medication exactly as directed, eat a heart–healthy diet that is low in saturated fats and has little or no artificial trans fats, and keep all scheduled follow-up appointments with their physician.

Cholesterol medications are not meant to serve as a substitute for a healthy lifestyle. People with diabetes are generally advised to eat a diet low in sugar and harmful fats, adequate in monounsaturated and omega-3 fats and protein, and high in fiber-rich vegetables, fruits and whole grains. In addition, they are advised to follow a physician-recommended exercise routine, avoid smoking and limit or avoid alcohol to help maintain normal levels of cholesterol, glucose and blood pressure.

Questions for your doctor

Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions and treatments. Patients may wish to ask their doctor the following questions about cholesterol drugs:

  1. Do you recommend cholesterol drugs for me?

  2. Can improvements in diet and exercise decrease or end my need for these drugs?

  3. Which drug am I being prescribed? What class of cholesterol drugs is it in? Does it reduce bad cholesterol, or does it reduce the bad and increase good cholesterol?

  4. What is my dosage and frequency?

  5. How and when should I take the drug?

  6. What should I do if I forget a dose or take an extra dose?

  7. What side effects might I experience from cholesterol drugs?

  8. At what point should I inform you of side effects?

  9. Can this drug affect my risk of kidney disease, kidney failure or other problems?

  10. Can this drug affect my blood sugar or have other effects on my diabetes?

  11. What sort of monitoring is needed for safety, and how often? Should I have microalbuminuria tests or other testing to detect kidney damage? How often do I need a blood test to monitor my liver function?

  12. A relative experienced pain and other problems after taking statins and had to be prescribed another treatment. Am I at risk of these side effects?

  13. Do statins or other cholesterol drugs have different effects on different racial groups? Am I in a group at increased risk?

  14. What other treatments might be used if I can’t tolerate this drug?

  15. Can this drug be safely used by pregnant women, nursing women, children or elders?
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