ACE Inhibitors and Diabetes

ACE Inhibitors and Diabetes

Summary

ACE inhibitors are a class of drugs that lower blood pressure. These medications are prescribed to many diabetic patients to prevent kidney damage and reduce cardiovascular risks.

ACE inhibitors can be prescribed in the form of a tablet, capsule, liquid or intravenous injection. In some cases, they are prescribed with another antihypertensive, such as a calcium channel blocker or angiotensin II receptor blocker (ARB).

People taking ACE inhibitors or any other antihypertensive need to be careful about spending too much time in the heat. They are encouraged to drink plenty of liquids during exercise or while outside in hot weather. The physician’s directions about exercise, activity levels and diet should also be followed. People taking ACE inhibitors should consult their physician before taking certain medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs).

The most common side effect of ACE inhibitors is cough, which is usually not serious. Regular blood tests are needed to screen for a potentially serious side effect called hyperkalemia, an abnormally high level of potassium in the blood.

About ACE inhibitors

ACE inhibitors are a group of drugs that reduce high blood pressure and treat other conditions including kidney disease and heart failure.

Though ACE inhibitors are much more expensive than some other antihypertensives, some physicians routinely prescribe them to diabetic patients, even those without cardiovascular risk factors, because of several potential benefits. Some but not all studies have found that they may be superior to other drugs in preventing or controlling diabetic nephropathy (kidney disease) and cardiovascular disease, and may lower the risk of type 2 diabetes in people with prediabetes.

ACE stands for angiotensin-converting enzyme. As the name suggests, these enzymes help the body “convert” a substance called angiotensin I into another substance called angiotensin II. ACE inhibitors are non-habit-forming medications that block the effects of angiotensin-converting enzymes, leading to reduced levels of angiotensin II in the body. Angiotensin II contributes to constriction of the blood vessels and fluid retention, both of which can increase blood pressure.

Because angiotensin II is a substance that causes the constriction of blood vessels, lower levels in the body have the opposite effect – blood vessels relax and blood requires less force (pressure) to flow through. ACE inhibitors are a type of vasodilator, medications that result in the opening or relaxing of blood vessels. As a result, such medications lower blood pressure and reduce the workload of the heart.

Recent research indicates that use of ACE inhibitors may improve the health of people with type 2 diabetes. These medications benefit diabetes patients by:

  • Controlling high blood pressure
  • Protecting the kidneys from damage
  • Possibly helping to prevent or reduce severity of stroke

People with diabetes have high rates of cardiovascular disease. Though the cause-and-effect relationship between diabetes and high blood pressure is not clear, research indicates that high blood pressure is a major culprit in sharply increasing cardiovascular risks in diabetes patients. Because of these risks, the American Diabetes Association has set more stringent goals for blood pressure control for diabetes patients:

  • Lower than 130 millimeters of mercury (mmHg) for systolic (upper number) blood pressure

  • Lower than 80 mmHg for diastolic (lower number) blood pressure.

  • For diabetes patients with kidney disease, target blood pressure should be 125/75 mmHg, according to the National Kidney Foundation.

ACE inhibitors also slow the progression of kidney disease, such as diabetic nephropathy. Studies have indicated that ACE inhibitors may directly protect the kidneys’ glomeruli (cluster of blood vessels within the kidneys), and have been shown to lower proteinuria (protein in the urine) and slow kidney deterioration, even in diabetes patients who do not have high blood pressure.

ACE inhibitors reduce hyperfiltration (abnormal increase in filtration rate) and constriction of blood vessels in the kidneys. Constriction can hamper the kidneys’ ability to filter waste products, water and chemicals from the blood. ACE inhibitors can arrest or even reverse such constriction.

In 2008, ACE inhibitors and a related group of drugs called angiotensin II receptor blockers (ARBs) made headlines as a potential obesity treatment because of research indicating they helped mice lose body fat and weight. However, it cannot be assumed that this finding extends to humans.

Types and differences of ACE inhibitors

ACE inhibitors are widely used in the treatment of high blood pressure (hypertension), as well as other conditions, such as kidney problems and heart failure. They are generally taken in the following forms:

  • Tablet
  • Capsule
  • Liquid
  • Intravenous (I.V.) injection

The medication generally begins to affect the body within one to two hours after each oral dose (e.g., tablet, capsule or liquid) and almost instantly after I.V. injection.

ACE inhibitors include medications such as:

benazepril (Lotensin)captopril (Capoten, Capozide)
cilazapril (Inhibace)enalapril (Vaseretic, Vasotec)
enalaprilat (Vasotec IV)fosinopril (Monopril)
lisinopril (Prinivil, Zestril)moexipril (Univasc)
perindopril (Aceon)quinapril (Accupril)
ramipril (Altace)trandolapril (Mavik)

In addition to standard ACE inhibitors, a number of combination therapies may be used to reduce blood pressure levels. For example, in some cases, ACE inhibitors are prescribed with another antihypertensive, such as a calcium channel blocker or an alpha blocker. This may enhance treatment results in those with diabetes.

A closely related group of drugs called angiotensin II receptor blockers also has been shown to prevent kidney disease in patients with diabetes. Studies are exploring whether diabetes patients can benefit from taking both ACE inhibitors and angiotensin receptor blockers.

Conditions treated with ACE inhibitors

ACE inhibitors are prescribed for a variety of conditions, including:

  • High blood pressure (hypertension). A condition in which blood is pumped with excessive force against the artery walls. ACE inhibitors cause blood vessels to relax, or widen, reducing blood pressure. They may be used alone or in combination with other antihypertensives (e.g., angiotensin-II receptor blockers, calcium channel blockers).

  • Diabetic nephropathy (kidney disease). Certain ACE inhibitors have been found to slow the process that leads to kidney damage in many patients with type 2 diabetes. They have also been found to help protect kidney function in type 1 diabetes.

  • Diabetes. Research has indicated that ACE inhibitors may even improve survival rates in diabetes patients without heart disease. Though use of ACE inhibitors after a heart attack has been found to be beneficial in general, people with diabetes may benefit even more than nondiabetics from these medications.

  • Coronary artery disease. A condition in which one or more of the blood vessels supplying the heart muscle (coronary arteries) become narrowed because of a buildup of plaque (atherosclerosis).

  • Heart attack. An event that results in permanent heart damage or death. A heart attack occurs when one of the coronary arteries becomes severely or totally blocked, usually by a blood clot. When the heart muscle does not obtain the oxygen-rich blood that it needs, it will begin to die. When given shortly after a heart attack, certain ACE inhibitors may prevent some of the damage to the heart and improve the survival rate of heart attack patients.

  • Heart failure. A condition in which one or more of the heart’s chambers is not pumping well enough to meet the body’s demands. ACE inhibitors bring the heart’s heavy workload back down toward a normal level.


  • Stroke. Patients take an ACE inhibitor, statin cholesterol drug and antiplatelet such as aspirin may have a decreased risk of having a stroke and increased chance of surviving a stroke, according to recent research.

  • Lower-extremity PAD. A type of peripheral arterial disease (PAD) in which one or more of the blood vessels supplying the legs become narrowed because of atherosclerosis.

Conditions of concern with ACE inhibitors

Patients may be advised by their physician not to take ACE inhibitors if they have been diagnosed with any of the following conditions:

  • Hyperkalemia. Because ACE inhibitors often cause an increase in potassium levels in the body, they may not be advised for patients who already have abnormally high levels of potassium in their blood (hyperkalemia).

  • Low blood pressure (hypotension). ACE inhibitors may lower blood pressure to dangerous levels in hypotensive patients, especially after the initial dose. However, physicians will often prescribe ACE inhibitors for certain patients with heart failure despite relatively low blood pressure.

  • Some types of kidney disease. In certain kinds of kidney disease (e.g., renal artery stenosis), ACE inhibitors could interfere with blood flow to the kidneys and worsen the condition. Also, some forms of kidney disease may cause this medication to be removed from the body at a slower rate, increasing the risk of overdose and/or side effects.

  • Liver disease. Some diseases of the liver can slow the removal of ACE inhibitors from the body. This can lead to an increased risk of side effects or overdose.

  • Lupus (systemic lupus erythematosus). Patients with this chronic disorder have an increased risk of blood-related side effects from ACE inhibitors. People with type 1 diabetes have an increased risk of lupus and other autoimmune diseases.

  • Previous allergic reaction to an ACE inhibitor.

  • Pregnancy. ACE inhibitors may be harmful to the fetus.

Potential side effects of ACE inhibitors

By far, the most common side effect associated with ACE inhibitors is a dry, persistent cough. This side effect is usually not serious, but it may lead the physician to change the patient to a different class of medications. Rarely, stridor (swelling within the airway) may occur, requiring prompt hospital treatment.

A potentially serious side effect is hyperkalemia, an abnormally high level of potassium in the blood. Patients usually have regular blood tests to check potassium levels and to avoid any serious consequences. This test is essential because most people will not experience symptoms or be aware of a rise in potassium.

People should seek medical attention immediately if they experience any side effects that could indicate an allergic or other severe reaction to ACE inhibitors. These side effects include:

  • Fainting (syncope)
  • Difficulty swallowing or breathing
  • Edema (swelling) of the head or face
  • Abdominal pain or swelling (with or without nausea or vomiting)
  • Skin rash, with or without itching

Rarely, stridor (swelling within the airway) may occur, requiring prompt hospital treatment. Other side effects of ACE inhibitors include:

  • Tachycardia (abnormally fast heartbeat)
  • Swelling in the face, mouth, hands or feet
  • Headache
  • Drowsiness, weakness or fatigue
  • Loss of taste (especially with captopril)
  • Diarrhea
  • Nausea or upset stomach
  • Vomiting
  • Abdominal cramps, pain or distention
  • Joint pain
  • Chest pain
  • Jaundice (rare, but serious)

When first taking ACE inhibitors, or after any increase in dosage, there is a possibility of a “first-dose effect.” During this effect, the patient’s blood pressure drops rapidly, which may cause dizziness, nausea and fainting. To avoid experiencing the first-dose effect, it may be recommended that the first dose of this medication be taken at bedtime.

In addition, ACE inhibitors rarely cause a decrease in white blood cells in some patients, making them more prone to infection. Patients should report any signs of infection to their physician immediately, which include fever, sore throat, nausea or vomiting.

Drug or other interactions with ACE inhibitors

Patients should consult their physician before taking any other medication (either prescription or over-the-counter), herbal remedies or nutritional supplements. Of particular potential danger to individuals taking ACE inhibitors are:

  • Potassium supplements. Use increases the risk of hyperkalemia (too much potassium in the body).

  • Some diuretics. Medications that stimulate the kidneys to produce more urine, flushing excess fluids and minerals (e.g., sodium) from the body. Most diuretics cause the body to lose potassium, as well as sodium and fluids. One type (potassium-sparing diuretics) actually preserves potassium while flushing other minerals from the body. Because of this, using potassium-sparing diuretics in conjunction with ACE inhibitors may increase the risk of hyperkalemia (too much potassium in the blood).

In patients taking both types of medications, risk of hyperkalemia increases with age and the dosage of diuretic prescribed (greater that 25 milligrams). People with kidney disease or diabetes are also more likely to develop hyperkalemia when taking these medications in combination.

  • Salt substitutes. Many of them contain potassium chloride, which increases the risk of hyperkalemia.

  • Alcohol. Drinking alcoholic beverages may produce a drop in blood pressure. Patients taking ACE inhibitors should consult their physician before drinking alcohol, as should anyone with diabetes.

  • Nonsteroidal anti-inflammatory drugs (NSAIDs), including COX-2 inhibitors. These can decrease the effectiveness of the ACE inhibitors, worsen high blood pressure or increase the risk of kidney problems. Patients should consult with their physician before using them.

  • Grapefruit juice. Grapefruit juice interferes with the liver’s ability to rid the body of some substances. This could lead to a buildup of ACE inhibitors 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 ACE inhibitors are advised to refrain from drinking grapefruit juice.

  • Over-the-counter (OTC) medications that increase blood pressure. Patients taking ACE inhibitors for high blood pressure should avoid OTC products that may increase blood pressure, such as those used for appetite control, asthma, flu, colds, cough, sinus problems or hay fever.

  • Other substances that may adversely react with ACE inhibitors include opioids (prescription narcotic painkillers), tobacco and marijuana or other illegal drugs.

Lifestyle considerations with ACE inhibitors

When first taking ACE inhibitors, patients should avoid driving or operating other heavy machinery until they know how the medication will affect them.

Many patients taking ACE inhibitors for high blood pressure (hypertension) will be on the medication for the rest of their lives, provided no serious side effects occur. Patients should remember that ACE inhibitors control high blood pressure but do not cure it. Even though they may not have any symptoms (which is common among those with high blood pressure), patients should continue to take their medication exactly as directed and to keep all scheduled follow-up appointments with their physician.

Patients should take and record their blood pressure readings regularly if ordered to do so, reporting anything unusual to their physician.

Patients on ACE inhibitors should inform their physician if they become ill, especially with severe vomiting or diarrhea. These conditions can cause the body to lose too much water and potassium, leading to low blood pressure (hypotension).

Patients are more likely to have side effects from ACE inhibitors if they spend too much time in the heat. Patients should be certain to drink enough liquids during exercise or in hot weather and to follow physician recommendations about activity levels, diet and ways to avoid dehydration.

Symptoms of ACE inhibitor overdose

Signs and symptoms of overdose can be similar to the medication’s side effects, but are usually more severe. A patient’s physician should be called immediately if the patient shows any of the following:

  • Low blood pressure (hypotension)
  • Edema (swelling) in the face, mouth, throat, hands or feet
  • Fainting (syncope)
  • Fever or chills
  • Sore throat
  • Convulsions or seizures
  • Coma (prolonged unconsciousness)

Swelling within the throat may lead to stridor (swelling within the airway, making it difficult to breathe). This condition, though rare, requires prompt hospital treatment.

Pregnancy use issues with ACE inhibitors

Women are advised against taking ACE inhibitors during pregnancy, including the first trimester. The medication can cause low blood pressure, severe kidney failure, hyperkalemia (too much potassium in the blood) or death or deformity of the newborn. Patients taking ACE inhibitors should inform their physician immediately if they become pregnant or are planning to become pregnant, so that they can start alternative therapy to ACE inhibitors.

When breastfeeding, some ACE inhibitors will pass into breast milk. Though this has not been found to cause problems in nursing infants, an alternative feeding method is recommended when ACE inhibitors are being used.

Child use issues with ACE inhibitors

Because children are more sensitive to the effects of ACE inhibitors on blood pressure, they are at higher risk of having side effects and of having more severe side effects. Parents are encouraged to discuss the potential risks and benefits with a physician, before children begin taking ACE inhibitors. In addition, use of certain ACE inhibitors may not be recommended in children under 6 years old.

Elderly use issues with ACE inhibitors

Certain types of ACE inhibitors may not be recommended for use in older adults. In general, older adults may be more sensitive to the effects of ACE inhibitors and at higher risk of side effects. Dosages tend to begin on the lower end of acceptable ranges for this population. In addition, elderly patients are more likely to have impaired kidney function, which can increase the risk of hyperkalemia (too much potassium in the blood). Elderly patients may undergo blood or other testing to determine kidney function before being prescribed ACE inhibitors.

Questions for your doctor

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

  1. Are ACE inhibitors safe for me to use?
  2. Are you recommending that I take an ACE inhibitor for high blood pressure or for another condition?
  3. How will taking an ACE inhibitor help my condition?
  4. What is the name of my ACE inhibitor, the dosage and frequency?
  5. How and when should I take the drug?
  6. Will I also need another type of antihypertensive drug?
  7. Can ACE inhibitors reduce my risk of kidney disease, heart disease, stroke or other complications?
  8. Do I have low blood pressure or a type of kidney disease or liver disease that an ACE inhibitor could worsen?
  9. Are there any symptoms that might indicate my ACE inhibitor is not working properly?
  10. What side effects might I experience?
  11. At what point should I notify you of side effects?
  12. What should I do if I miss a dose or take too much?
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