WHAT ARE THE LONG-TERM COMPLICATIONS OF TYPE 1 DIABETES AND HOW ARE THEY TREATED?

Type 1 diabetes reduces the normal life span by an average of five to eight years. In general, however, survival rates are improving in all ethnic groups and both genders. Longer survival rates are probably due to improvements in monitoring and closer control of blood glucose. Intensive glucose control is critical in reducing many of these complications. Such complications in diabetes are due to vascular (blood vessel) abnormalities and nerve damage (neuropathy) that can cause major damage to organs, including the eyes, kidneys, and heart.

Complications of Heart and Circulation

Heart attacks account for 60% and strokes for 25% of deaths in all diabetics. Diabetes effects the heart in many ways:

• Both type 1 and 2 diabetes accelerate the progression of atherosclerosis (hardening of the arteries). This can lead to coronary artery disease, heart attack, or stroke.

• In type 1 diabetes, high blood pressure usually develops if the kidneys become damaged. High blood pressure is another major cause of heart attack, stroke, and heart failure. Children with diabetes are also at risk for hypertension.

• Impaired nerve function (neuropathy) associated with diabetes also causes heart abnormalities. And some experts estimate that the mortality rates from neuropathy-related heart conditions ranges between 15% and 53%. [ See also Neuropathy , below. ]

Preventing Coronary Artery Disease Cholesterol. Experts recommend intensive blood sugar control as the initial treatment of choice for unhealthy cholesterol levels in diabetes type 1, although it is still not known whether intensive control will have a major protective effect on the heart. A 2001 report from a major study was encouraging, however. Statins are other important agents in improving cholesterol and lipid levels and protecting the heart. They include pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol) atorvastatin (Lipitor), and rosuvastatin (Crestor) and many others). Studies suggest that they can reduce the risk for adverse heart events in people with diabetes, even if their cholesterol levels are normal or if their diabetes is mild. Another cholesterol-lowering drug, fenofibrate, may also be especially useful.

Reducing the Risk for Blood Clots. Taking a daily aspirin has also been shown to be protective because of its anti-clotting properties. Intensive glucose control may improve blood clotting factors.

Reducing Blood Pressure. Reducing blood pressure is very important for preventing complications of diabetes. Lowering systolic pressure (the higher and first number in a blood pressure measurement) many be particularly important for diabetics. (Diastolic pressure is the second number.) In general, the optimal blood pressure is less than 120/80 mm Hg (systolic/diastolic). Angiotensin-converting enzyme (ACE) inhibitors are proving to have remarkable benefits for people with diabetes, including reducing the risks of heart attack, stroke, and death. These drugs also delay the onset and progression of kidney disease by 30% to 60% and may even help prevent or limit progression of foot ulcers and retinopathy. Some experts recommend ACE inhibitors for all middle-aged type 2 diabetics. Newer agents called angiotensin-receptor blockers (ARBs) may have similar benefits. In one study a combination of an ACE inhibitor and candesartan, an ARB, reduced blood pressure and risk factors for kidney disease better than either agent alone. Children with diabetes are also at risk for hypertension and may need ACE inhibitors. Of concern are studies reporting an increase of type 2 diabetes in people who take beta blockers, which reduce blood pressure and are important heart protective agents. More research is needed, and experts do not discourage use of beta blockers based on any current evidence. [For more information, see the Well-Connected Report #23, Cholesterol, Other Lipids, and Lipoproteins ; Report #14, High Blood Pressure ; and Report #03, Angina and Coronary Artery Disease .]

Neuropathy

Diabetes reduces or distorts nerve function causing a condition called neuropathy. It particularly affects sensation. It is a common complication that affects nearly half of both type 1 and type 2 diabetics after 25 years. Neuropathy usually starts in the fingers and toes and moves up to the arms and legs (called a glove and stocking distribution). Symptoms include the following:

• Tingling.

• Weakness.

• Burning sensations.

• Loss of the sense of warm or cold.

• Numbness. (If the nerves are damaged sufficiently, the person may be unaware that even a blister or minor wound has become infected.)

• Deep pain.

• In some cases, neuropathy may block angina, the warning chest pain for heart disease and heart attack. Diabetic patients should be aware of other warning signs of a heart attack, including sudden fatigue, sweating, shortness of breath, nausea, and vomiting.

• If diabetes affects the nerves in the autonomic nervous system, then abnormalities of blood pressure control and bowel and bladder function may occur.

• Impotence in men is also associated with neuropathy.

• Charcot foot is a condition associated with neuropathy. It causes bone deformity, and can occur as an isolated complication or after foot or ankle surgery. Charcot foot may cause little pain, but should be suspected in cases of swelling and redness in a single leg or foot. It results in abnormal pressure on the foot and increases the risk for foot ulcers and amputation.

Treatment of Nerve Damage. Studies show that tight control of blood glucose levels also delays the onset and slows progression of neuropathy, although there is some concern that the increased incidence of hypoglycemia with intensive insulin control may actually cause nerve damage . A number of agents are used for neuropathy depending on its effects. Some include the following:

• Topical capsaicin (the active ingredient in hot peppers) is also commonly used for local neuropathy pain.

• Tricyclic antidepressants, such as amitriptyline (Elavil) or doxepin (Sinequan) are effective in reducing pain from neuropathy in up to 75% of patients. A combination of doxepin and capsaicin (applied to the skin) may be particularly beneficial. Unfortunately tricyclics carry some distressing side effects. Other, newer antidepressants with fewer side effects, including venlafaxine (Effexor), sertraline (Zoloft), and nefazodone (Serzone), are showing promise. In one 2000 report, for example, 56% of diabetic patients (who were not depressed) reported significant pain relief when venlafaxine was taken at high doses (150 to 225 mg per day).

• The anti-seizure drug gabapentin (Neurontin) may be effective, but it is expensive and patients report as many side effects.

• Tramadol (Ultram), a pain killer that is similar to opioids, achieved moderate pain reduction in one study and may have fewer side effects than anti-seizure drugs or tricyclics, although it carries a slight risk for addiction; nausea, headache, and constipation are common.

• If foot pain, numbness, or tingling is worse at night, diphenhydramine (Benadryl) may help.

• Vitamin E supplements may be helpful.

• Erythromycin or metoclopramide (Reglan) may relieve delayed stomach emptying caused by neuropathy.

• Sildenafil (Viagra) is proving to be an effective treatment for impotence in men with either type 1 or type 2 diabetes and has minimal side effects.

Investigators are testing a number of nerve-protective substances, particularly nerve-growth and insulin-like growth factor. In some clinical trials, patients taking nerve-growth factor experienced both greater sensation and reduced levels of pain and discomfort with few side effects.

Treating Injuries in the Feet and Legs Caused by Blood Vessel (Vascular) Injury

People with diabetes are at risk for problems resulting from blood vessel injury, which may be severe enough to cause tissue damage in the legs and feet. Numbness from neuropathy makes this a significant problem, since the patient may not be aware of injuries. Even minor infections can develop into deep tissue injury. Extensive surgery may be required, and, in extreme cases, amputation of the foot or leg may be necessary. Diabetes is responsible for about two-thirds of all the lower limb amputations performed in the US each year. Preventive foot care could reduce the risk of amputation in people with diabetes by 44% to 85%.

Home Prevention. Some tips for preventing problems include the following:

• Patients inspect their feet daily and watch for changes in color or texture, odor, and firm or hardened areas, which may indicate infection and potential ulcers.

• When washing the feet, the water should be warm (not hot) and the feet and areas between the toes should be thoroughly dried afterward. Check water temperature with the hand or a thermometer before stepping in.

• Moisturizers should be applied, but not between the toes.

• Corns and calluses should be gently pumiced and toenails trimmed short and the edges filed to avoid cutting adjacent toes.

• Patients should not use medicated pads or try to shave the corns or calluses themselves.

• They should avoid high heels, sandals, thongs, and going barefoot.

• Shoes should be changed often during the day.

• Wear socks, particularly with extra padding (which can be purchased).

• Patients should avoid tight stockings or any clothing that constricts the legs and feet.

A specialist in foot care should be consulted for any problems. There are several easily administered tests for checking for nerve damage. The doctor should administer one of these once per year.

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

• In virtually all cases, wound care requires debridement, which is the removal of injured tissue until only healthy tissue remains. Debridement may be accomplished using chemical (enzymes), surgical, or mechanical (eg. irrigation) means.

• Hospitalization and intravenous antibiotics for up to 28 days may be needed for severe foot ulcers.

• number of investigative measures include the following:

• A number of treatments (Dermagraft, Apligraf, Regranex) are now available that stimulate new cell growth and help heal skin ulcers or use cultures of human skin cells, although their benefits are still unproven.

• Granulocyte-colony stimulating factor, or G-CSF (filgrastim, Neupogen, Amgen) is showing promise as an effective alternative to antibiotics. Studies are reporting that G-CSF accelerates healing and significantly reduces the need for surgery.

• Total-contact casting (TCC). This approach uses a cast that is designed to contact the exact contour of the foot and distribute weight along the entire length of the foot. It is usually changed weekly. In one trial, it healed ulcers in nearly 90% of selected patients. It is also useful for Charcot foot.

• A device that compresses the foot (NuPulse) appears to increase the circulation, reduces edema (swelling), and improves wound healing.

• Charcot food is initially treated with strict immobilization of the foot and ankle; some centers use a cast that allows the patient to move and still protects the foot. When the acute phase has passed, patients usually need lifelong protection of the foot using a brace initially and custom footwear.

Retinopathy and Eye Complications

Diabetes accounts for 12,000 to 24,000 of new cases of blindness annually and is the leading cause of new cases of blindness in adults ages 20 to 74. The most common eye disorder in diabetes is retinopathy, abnormalities of the blood vessels in the retina. People with diabetes are also at higher risk for developing cataracts and certain types of glaucoma. [See also the Well-Connected Reports # 26, Cataracts or #25, Glaucoma.]

Description of Retinopathy. Given the long duration of the disease and low control of insulin administration, nearly all patients with type 1 diabetes will develop retinopathy. In fact, a major study suggested that over half of patients have some degree of the eye disease within five years of diagnosis and 89% have at least signs of retinopathy within nine years. Experts in the study recommend that all type 1 patients should be screened for the eye disorder within five years. (It should be noted, however, that only a minority of patients with retinopathy develops severe vision loss or blindness. )

Retinopathy generally occurs in one or two phases:

• The early and more common type of this disorder is called nonproliferative or background retinopathy . The blood vessels in the retina are abnormally weakened. They rupture and leak, and waxy areas may form. If these processes affect the central portion of the retina, swelling may occur, causing reduced or blurred vision. If the weak blood vessels become blocked and blood flow is cut off, soft, "woolly" areas may develop in the retina's nerve layer.

• These woolly areas may signal the development of proliferative retinopathy . Often there are no symptoms of progressing retinopathy, however. In this more severe condition, new, abnormal blood vessels form and grow on the surface of the retina. They may spread into the cavity of the eye or bleed into the back of the eye. Major hemorrhage or retinal detachment can result, possibly causing severe visual loss or blindness. The sensation of seeing flashing lights may indicate retinal detachment.

Prevention of Retinopathy. Tight insulin control is also proving to help prevent retinopathy in patients with either type 1 or 2 diabetes. It should be noted that intense glucose control can cause early worsening of retinopathy, although this is nearly always counterbalanced by long-term benefits. Reducing the risks for heart disease using blood pressure lowering medications (particularly ACE inhibitors) and drugs that improve cholesterol levels may also have protective benefits for the eyes.

Treatment of Retinopathy. Once damage to the eye develops, eye surgery may be needed.

• Argon or diode laser photocoagulation is proving to be particularly effective in reducing severe visual loss from retinopathy, and is useful for patients with macular edema when fluid build-up threatens the retina.

• A surgical technique called vitrectomy removes scarred tissue in the eye, helps flatten areas of detached retinal material, and can improve vision in patients with severe eye hemorrhage.

• Experts hope that an investigative agent called protease inhibitors may block the growth of blood vessels in the eye that lead to retinopathy.

Kidney Damage (Nephropathy)

Kidney disease is a very serious complication of diabetes. The risk for this complication is compounded by the presence of hypertension, coronary artery disease, and problems in the urinary tract. Symptoms include swelling in the feet and ankles, fatigue, and pale skin color.

Treatment and Prevention of Nephropathy. Strict blood glucose control may delay progression of kidney disease and other diabetic-related complications in type 2 diabetics as well as type 1. A number of studies have shown that tight blood glucose control using intensive insulin therapy delays progression of kidney disease. High hemoglobin A1c (glycolated hemoglobin) levels may relate directly to a risk for kidney dysfunction. One study indicated, in fact, that patients could reduce the risk for kidney disease by maintaining glycolated hemoglobin levels at 7% or below rather than trying to keep strict control of glucose levels. (Such a strategy might also help prevent retinopathy.) Controlling high blood pressure is also important for preventing kidney disease. The antihypertensive drugs ACE inhibitors and newer agents called angiotensin-II-receptor blockers (ARBs) may be especially important for both purposes. Studies suggest agents may help protect against progression of kidney disease independent of their effects on blood pressure. [For more detailed information, see above and also Well-Connected Report #14, High Blood Pressure .]

Mental Function and Dementia

Studies indicate that patients with type 2 diabetes face a higher than average risk of developing dementia caused either by Alzheimer's disease or problems in blood vessels in the brain. Problems in attention and memory can occur even in people under age 55 who have had diabetes for a number of years. In one study of people with type 1 diabetes, high glucose levels (hyperglycemia) were associated with slower brain function, including less verbal fluency and slow ability to do mental arithmetic.

Infections

Respiratory Infections. People with diabetes face a higher risk for influenza and its complications, including pneumonia, possibly because the disorder neutralizes the effects of protective proteins on the surface of the lungs. In fact, deaths among people with diabetes increase by 5% to 15% during flu epidemics and they are six times more likely to be hospitalized with complications from flu than nondiabetics who have flu. Everyone with diabetes should have influenza vaccinations annually and a vaccination against pneumococcal pneumonia.

Urinary Tract Infections. Women with diabetes face a significantly higher risk for urinary tract infections, which are likely to be more complicated and difficult to treat than in the general population.

Other Complications

Other complications including the following:

• Scaly and hardened skin may develop after a patient has had diabetes for many years. Such skin changes may be signs of other complications, including retinopathy.

• There has been some concern that type 1 diabetics are at risk for bone-density loss, although a recent two-year study found little basis for alarm. Longer studies are needed. One 2001 study found that diabetic women over the age of 65 had nearly twice the risk for hip or shoulder fracture as nondiabetics. Although these women had type 2, those on insulin therapy were more than twice as likely to suffer a foot fracture, suggesting a similar risk in type 1 diabetes. The risk was independent of bone density and body weight.

• Type 1 diabetes also appears to increase the risk for celiac disease, an allergy to gluten, found in wheat, barley, and rye.

• Both women and men with diabetes appear to have a higher risk for colon and rectal cancers.

• A 2001 study found diabetics have a slightly higher prevalence of hearing loss than non-diabetics.

Specific Complications in Women

Diabetes and Pregnancy. Both temporary diabetes that occurs during pregnancy (gestational diabetes) and pregnancy in a patient with existing diabetes can increase the risk for birth defects. Studies indicate that hyperglycemia may effect the developing fetus as soon as it is conceived.

Because glucose crosses the placenta, a woman with diabetes can pass high levels of blood glucose to the fetus. In response, the fetus secretes large amounts of insulin. This combination of high fetal blood levels of insulin and glucose can have significant effects:

• It leads to excessive fetal growth.

• It may also contribute to delayed maturation of the lungs or to the death of the fetus.

In addition to endangering the fetus, diabetes also presents risks to the pregnant woman, particularly preeclampsia, a potentially dangerous condition involving very high blood pressure. Pregnant women with diabetes are also at greater risk for retinopathy.

Some suggestions for preventing complications include the following:

• Controlling blood glucose levels before and during pregnancy. A 1999 study reported that when pregnant women with diabetes took insulin four times a day for intensive blood sugar control, their babies had better outcomes than women who took insulin only twice a day. Rates of hypoglycemia were similar in both groups of mothers.

• Aerobic exercise before and during pregnancy can lower glucose levels. (All pregnant women, particularly those with diabetes, should check with their physicians before embarking on a rigorous exercise regimen.)

• Women should have an eye examination during pregnancy and up to a year afterward.

Effect on Estrogen. Diabetes appears to affect female hormones. It seems to blunt the beneficial effects of estrogen, increasing the risk for heart disease. Women with diabetes have a higher risk for early menopause, which, in one study, occurred at an average age of about 41 years.

Reproductive Cancers. Women with type 1 diabetes often have lumps in the breast that are benign but which make mammograms difficult to interpret. It is not clear whether these lumps are risk factors for breast cancer. One study indicated that women with diabetes have a higher risk for endometrial cancer and possibly for breast cancer.

Self Destructive Behavior in Adolescents

Suicidal Fantasies. One study found that young people with diabetes have a higher than average rate of suicidal fantasies. Although the actual rate of suicide was no higher than that of their non-diabetic peers, such thoughts are strongly associated with self-destructive behavior.

Lack of Compliance with Insulin. Lack of blood sugar control is a major problem in adolescents with type 1 diabetes. Adolescents with diabetes are at higher risk than adults for ketoacidosis resulting from non-compliance. Young people who do not control glucose are also at high risk for permanent damage in small vessels, such as those in the eyes.

Eating Disorders. Up to one-third of young women with type 1 diabetes have eating disorders resulting in under use of insulin to lose weight. Anorexia and bulimia pose significant health dangers, particularly in people with diabetes.

Behavior Therapy. Behavioral-family systems therapy (BFST), a form of behavioral therapy that focuses on family relationships and conflict resolution, might prove to have beneficial effects on family communications and acceptance of diabetes and treatment compliance by the child. More research is needed.