Treatment of Complications:

High Blood Pressure and Heart Disease

All patients with diabetes and high blood pressure should make lifestyle changes. These include losing weight (when needed), following the Dietary Approaches to Stop Hypertension (DASH) diet, quitting smoking, limiting alcohol intake, and limiting salt intake to no more than 1,500 mg of sodium per day.

Reducing Blood Pressure. Strict control of blood pressure is critical for preventing complications of diabetes and has proven to improve survival rates. Patients should strive for blood pressure levels of less than 130/80 mm Hg (systolic/diastolic).

Patients with diabetes and high blood pressure need an individualized approach to drug treatment, based on their particular health profile. Dozens of anti-hypertensive drugs are available. The most beneficial fall into the following categories:

• Diuretics rid the body of extra sodium (salt) and water. There are three main types of diuretics: Potassium-sparing, thiazide, and loop.
• Angiotensin-converting enzyme (ACE) inhibitors reduce the production of angiotensin, a chemical that causes arteries to narrow.
• Angiotensin-receptor blockers (ARBs) block angiotensin's action on arteries.
• Beta blockers block the effects of adrenaline and ease the heart� ' s pumping action.
• Calcium-channel blockers (CCBs) decrease the contractions of the heart and widen blood vessels.

Nearly all patients who have diabetes and high blood pressure should take an ACE inhibitor (or ARB) as part of their regimen for treating hypertension. These drugs help prevent kidney damage. [For more information, see In-Depth Report #14: High blood pressure.]

Improving Cholesterol and Lipid Levels. Abnormal cholesterol and lipid levels are common in diabetes. High LDL (“bad”) cholesterol should always be lowered, but people with diabetes also often have additional harmful imbalances, including low HDL (“good”) cholesterol and high triglycerides.

Adult patients should aim for LDL levels below 100 mg/dL, HDL levels over 50 mg/dL, and triglyceride levels below 150 mg/dL. Patients with diabetes and heart disease should strive for even lower LDL levels; the American Diabetes Association recommends LDL levels below 70 mg/dL for these patients.

Pediatric patients should be treated for LDL cholesterol above 160 mg/dL, or above 130 mg/dL if other cardiovascular risk factors are present.

For medications, statins are the best cholesterol-lowering drugs. They include atorvastatin (Lipitor), lovastatin (Mevacor and generics), pravastatin (Pravachol), simvastatin (Zocor and generics), fluvastatin (Lescol), and rosuvastatin (Crestor). These drugs are very effective for lowering LDL cholesterol levels.

The primary safety concern with statins has involved myopathy, an uncommon condition that can cause muscle damage and, in some cases, muscle and joint pain. A specific myopathy called rhabdomyolysis can lead to kidney failure. People with diabetes and risk factors for myopathy should be monitored for muscle symptoms.

Although lowering LDL cholesterol is beneficial, statins are not as effective as other medications -- such as niacin and fibrates -- in addressing HDL and triglyceride imbalances. This is a common problem in type 2 diabetes. Combining a statin with one of these drugs may be helpful for people with diabetes who have heart disease, low HDL levels, and near-normal LDL levels. Although combinations of statins and fibrates or niacin increase the risk of myopathy, both combinations are considered safe if used with extra care.

Fibrates, such as gemfibrozil (Lopid) and fenofibrate (Tricor), are usually the second choice after statins. Niacin has the most favorable effect on raising HDL and lowering triglycerides of all the cholesterol drugs. However, some patients who take high-dose niacin experience increased blood glucose levels. Moderate doses of niacin can achieve lipid control without causing serious blood glucose problems. [For more information, see In-Depth Report #23: Cholesterol.]

Aspirin for Reducing the Risk for Blood Clots. Taking a daily aspirin reduces the risk for blood clotting and may help protect against heart attacks. The recommended dose is 75 - 162 mg/day. Patients with diabetes for whom aspirin is recommended include those who have:

• Age over 40 years old
• History of heart problems
• Family history of heart disease
• High blood pressure or elevated cholesterol and
• Smokers

Prevention and Treatment of Retinopathy

Prevention of Retinopathy. Fortunately, severe and even moderate vision loss is largely preventable with tight control of blood glucose levels. (Intense glucose control can cause early worsening of retinopathy, although this is nearly always counterbalanced by long-term benefits.) Tight control of blood pressure can also help protect against retinopathy. Aspirin therapy does not help prevent retinopathy.

Treatment of Retinopathy. Patients with severe diabetic retinopathy or macular edema (swelling of the retina) should be sure to see an eye specialist who is experienced in the management and treatment of diabetic retinopathy. Once damage to the eye develops, laser or photocoagulation eye surgery may be needed. Laser surgery can help reduce vision loss in high-risk patients.

Treatment of Foot Ulcers

About a third of foot ulcers will heal within 20 weeks with good wound care treatments. Some treatments are as follows:

• Antibiotics are generally given. In some cases, hospitalization and intravenous antibiotics for up to 28 days may be needed for severe foot ulcers.
• In virtually all cases, wound care requires debridement, the removal of injured tissue until only healthy tissue remains. Debridement may be accomplished using chemical (enzymes), surgical, or mechanical (irrigation) means.
• Hydrogels (such as Nu-Gel), may help to soothe and heal ulcers.
• Felted foam may help heal ulcers on the sole of the foot. Felted foam uses a multi-layered foam pad over the bottom of the foot with an opening over the ulcer.

Other Treatments for Foot Ulcers. Doctors are also using or investigating other treatments to heal ulcers. These include:

• Administering hyperbaric oxygen (oxygen given at high pressure) is showing promise in promoting healing. It is generally reserved for patients with severe, full thickness diabetic foot ulcers that have not responded to other treatments, particularly when gangrene, or an abscess, is present.
• Total-contact casting (TCC) uses a cast that is designed to match the exact contour of the foot and to distribute weight along the entire length of the foot. It is usually changed weekly. It may be helpful for ulcer healing and for Charcot foot. Although it is very effective in healing ulcers, recurrence is common.

Treatment of Neuropathy

A number of different drugs are used for peripheral neuropathy pain relief: They include:

• Nonprescription analgesics, such as aspirin, acetaminophen, and non-steroidal anti-inflammatory drugs (NSAIDs). (Patients with stomach or kidney problems should check with their doctors before using these drugs.)
• Prescription painkillers, such as tramadol (Ultram). Tramadol is a drug that is similar to opioids. It can help relieve pain but has significant side effects, including nausea, constipation, and headache.
• Topical medications, particularly capsaicin (the active ingredient in hot peppers), are applied to the skin to relieve minor local pain. A 5% lidocaine patch has also shown good results in clinical trials.
• Tricyclic antidepressants, such as amitriptyline (Elavil) or doxepin (Sinequan), are effective in reducing pain from neuropathy for many patients. A combination of doxepin and capsaicin (applied to the skin) may also be helpful. Unfortunately, tricyclics may cause heart rhythm problems, so patients at risk need to be monitored carefully.
• Duloxetine (Cymbalta), a serotonin and norepinephrine reuptake inhibitor, is approved for treatment of pain associated with diabetic peripheral neuropathy.
• Anti-seizure drugs used for peripheral neuropathy pain relief include gabapentin (Neurontin), pregabalin (Lyrica), carbamazepine (Tegretol), and valproate (Depakote).

Although not proven to be beneficial, patients may also try transcutaneous electrostimulation (TENS), a treatment that involves administering mild electrical pulses to painful areas. Alternative treatments, such as hypnosis, biofeedback, relaxation techniques, and acupuncture, have also been reported to help some patients manage pain. Doctors also recommend lifestyle measures, such as walking and wearing elastic stockings.

Treatments for Other Complications of Neuropathy. Neuropathy also impacts other functions, and treatments are needed to reduce their effects. If diabetes affects the nerves in the autonomic nervous system, then abnormalities of blood pressure control and bowel and bladder function may occur. Erythromycin, domperidone (Motilium), or metoclopramide (Reglan) may be used to relieve delayed stomach emptying caused by neuropathy. Patients need to watch their nutrition if the problem is severe.

Erectile dysfunction is also associated with neuropathy. Studies indicate that phosphodiesterase type 5 (PDE-5) drugs, such as sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis), are safe and effective, at least in the short term, for many patients with diabetes. Typical side effects are minimal but may include headache, flushing, and upper respiratory tract and flu-like symptoms. Patients who take nitrate medications for heart disease cannot use PDE-5 drugs.

Treatment of Kidney Problems

Tight control of blood sugar and blood pressure is essential for preventing the onset of kidney disease. Strict control of these two conditions produces a reduction in new cases of nephropathy and a delay in progression of the disease.

ACE inhibitors are the best class of blood pressure medications for delaying kidney disease and slowing disease progression in patients with diabetes. Angiotensin-receptor blockers (ARBs) are also very helpful.

• For patients with diabetes who have microalbuminuria, the American Diabetes Association strongly recommends ACE inhibitors or ARBs. Microalbuminuria is an accumulation of protein in the blood, which can signal the onset of kidney disease (nephropathy).
• Nearly all patients who have diabetes and high blood pressure should take an ACE inhibitor (or ARB) as part of their regimen for treating their hypertension.

A doctor may recommend a low-protein diet for patients whose kidney disease is progressing despite tight blood sugar and blood pressure control. Protein-restricted diets can help slow disease progression and delay the onset of end-stage renal disease (kidney failure). However, patients with end-stage renal disease who are on dialysis generally need higher amounts of protein. [For more information, see In-Depth Report #42: Diabetes diet.]

Anemia. Anemia is a common complication of end-stage kidney disease. Patients on dialysis usually need injections of erythropoiesis-stimulating drugs to increase red blood cell counts and control anemia. However, these drugs -- darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit) -- can increase the risk of blood clots, stroke, heart attack, and heart failure in patients with end-stage kidney disease when they are given at higher than recommended doses.

The FDA recommends that patients with end-stage kidney disease who receive erythropoiesis-stimulating drugs should:

• Maintain hemoglobin levels between 10 - 12 g/dL.
• Receive frequent blood tests to monitor hemoglobin levels.
• Contact their doctors if they experience such symptoms as shortness of breath, pain, swelling in the legs, or increases in blood pressure.

[For more information, see In-Depth Report #57: Anemia.]