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Diabetes: Type 2


An in-depth report on the causes, diagnosis, treatment, and prevention of type 2 diabetes.

Alternative Names

Maturity Onset Diabetes; Noninsulin-dependent Diabetes Mellitus

Long-Term Complications

Patients with diabetes have higher mortality rates than nondiabetics regardless of sex, age, or affluence. Heart disease and stroke are the leading causes of death in these patients. All life-style and medical efforts should be made to reduce the risk for these conditions.

People with type 2 diabetes are also subject to nerve damage (neuropathy) and abnormalities in both small and large blood vessels (vascular injuries) that occur as part of the diabetic disease process. Such abnormalities produce complications over time in many organs and structures in the body. Although these complications tend to be more serious in type 1 diabetes, they still are of concern in type 2 diabetes. People with diabetes should aim for fast blood glucose levels of less than 110 mg/dl and hemoglobin A1C or less than 7%.

The impact of these multiple health problems are of great concern, particularly with the dramatic increase in diabetes. Experts now estimate that over a third of people born in 2002 will eventually develop diabetes.

There are two important approaches to preventing complications from diabetes:

  • Intensive control of blood glucose and keeping glycosylated hemoglobin (HbA1c) levels below 7.0. This is proving to prevent complication due to vascular (blood vessel) abnormalities and nerve damage (neuropathy) that can cause major damage to organs, including the eyes, kidneys, and heart.
  • Managing risk factors for heart disease. Evidence is increasing that control of blood glucose also helps the heart, but its benefits most likely occur over time. It is very important that people with diabetes control blood pressure, cholesterol levels, and other factors associated with heart disease.

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%.

Intensive blood sugar control may help protect blood vessels and reduce the risk for blood clotting. It is still not known whether intensive control will have a major protective effect on the heart, however. People with diabetes must be sure to use other measures as well to protect the heart.

Aspirin for Reducing the Risk for Blood Clots. Taking a daily aspirin reduces the risk for blood clotting and has been shown to be protective against heart attacks. In one 2000 study, low-dose aspirin was associated with a 30% lower risk for death from heart disease in adults with type 2 diabetes. Of note: people who are at risk for retinopathy should discuss the possible benefits of high-dose aspirin with their physician.

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). (Controlling systolic pressure may be especially important for reducing the risk for kidney complications.)

Anti-hypertensive agents that block angiotensin are the first option for may people with diabetes. Angiotensin is natural chemical that influences all aspects of blood pressure control and also interferes with insulin's normal metabolic signaling. In fact, angiotensin may be the common factor linking diabetes and high blood pressure. Drugs that block them are ACE inhibitors and ARBs:

  • Angiotensin-converting enzyme (ACE) inhibitors are the standard agents for people with diabetes and hypertension. They include captopril (Capoten), enalapril (Vasotec), quinapril (Accupril), benazepril (Lotensin), ramipril (Altace), perindopril (Aceon), and lisinopril (Prinivil, Zestril). These agents have remarkable benefits for people with diabetes, including reducing the risks of heart attack, stroke, and death. ACE inhibitors also delay the onset and progression of kidney disease. In many cases, however, combinations are required to achieve blood pressure goals. In such cases, low-dose diuretics or calcium-channel blockers are added as needed.
  • Angiotensin-receptor blockers (ARBs), also known as angiotensin II receptor antagonists, are newer drugs that are similar to ACE inhibitors in effectiveness. They may have fewer side effects. Brands include losartan (Cozaar, Hyzaar), olmesartan (Benicar) candesartan (Atacand), telmisartan (Micardis), eprosartan (Teveten), irbesartan (Avapro), and valsartan (Diovan). In one study, ARBs appeared to reduce the risk of developing diabetes. Other studies have also reported protection against kidney disease even in people with normal blood pressure, making them particularly beneficial for people with diabetes.

Combinations of the two are under investigation, and studies suggest such combinations may be beneficial for people with diabetes and kidney disease.

Other anti-hypertensive agents may be important for specific groups. Diuretics appear to be more beneficial than ACE inhibitors for African Americans with diabetes. In one major study, these patients had lower rates of stroke and heart failure than those taking ACE inhibitors. Beta blockers, another group of anti-hypertensive agents, may have more benefits for patients with existing heart disease, although more research is needed to confirm this.

[For more information, seeWell-Connected Report #14 High Blood Pressure.]

Improving Cholesterol and Lipid Levels. Abnormal cholesterol and lipid levels are common in diabetes. High LDL cholesterol should always be lowered, but people with diabetes also often have additional harmful imbalances--low-HDL cholesterol and high triglycerides. Patients should aim for LDL levels below 100 mg/dl, HDL levels over 60 mg/dL and triglyceride levels below 150 mg/dL.

Statins are currently the best cholesterol-lowering agents for people with diabetes. They include pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), and atorvastatin (Lipitor). These agents are very effective for lowering LDL cholesterol levels. In addition, evidence suggests that statins reduces the risk for adverse heart events in people with even mild diabetes and in those with normal cholesterol levels. Furthermore, in one study, a statin was shown to reduce the risk by 30% of developing diabetes in people with high cholesterol. (Statins, however, do not appear to have any effect on blood vessel inflexibility in diabetes, which is an important risk factor for heart disease in these patients.) The primary safety concern with statins in people with diabetes 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 is beneficial, statins are not as effective as other medications, such as fibrates or niacin, in addressing HDL and triglyceride imbalances--a common problem in type 2 diabetes.

Combinations of statins with one these agents, then, may be important in people with diabetes. 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 fenofibrate (Tricor) and bezafibrate (Bezalip), are usually the first choice. Niacin has the most favorable effect on HDL and triglycerides of all the cholesterol drugs. However, about 30% of patients who take niacin experience elevated blood glucose levels. On the positive side, some studies have reported that diabetics who use niacin had little trouble with glucose control. In addition, niacin-statin therapy reduces the progression of heart disease. Some experts believe it now may be used as an alternative to or in combination with statins. Combinations with a new agent ezetimibe (Zetia) may also be beneficial. Ezetimibe inhibits the absorption of cholesterol in the intestines and is proving to be a very useful adjunct to statins for lowering LDL levels.

[For more information, seeWell-Connected Report #23 Cholesterol, Other Lipids, and Lipoproteins.]

Kidney Damage (Nephropathy)

Kidney disease (nephropathy) is a very serious complication of diabetes. With this condition, the tiny filters in the kidney (called glomeruli) become damaged and leak protein into the urine. Over time this can lead to kidney failure. Urine tests showing microalbuminuria (small amounts of protein in the urine) are important markers for kidney damage.

Treatment and Prevention of Nephropathy. Long-term studies are now reporting a 60% reduction in new cases of nephropathy with strict blood glucose control and a delay in progression of the disease. Targeting specific preventive measures may especially protect against kidney disease. They include maintaining glycolated hemoglobin levels at 7% or below, controlling blood pressure--particularly systolic pressure, and lowering not only LDL cholesterol but also triglycerides.

Click the icon to see an image of the pancreas and kidneys.

The antihypertensive drugs ACE inhibitors are proving to protect against progression of kidney disease even in people with normal blood pressure. They are now the agents of choice for both preventing and managing nephropathy in type 1 diabetes. Newer agents called angiotensin-IIreceptor blockers (ARBs), such as losartan (Cozaar) and irbesartan (Avapro), are also helpful for both conditions.

Sulodexide is an agent based on a natural substance called a glycosaminoglycan, which helps reduce blood clotting. Studies are suggesting that it may help prevent nephropathy with few side effects. (It also may be helpful for foot ulcers.)

If the kidneys fail, the patient will need to go on dialysis. Symptoms of kidney failure may include swelling in the feet and ankles, itching, fatigue, and pale skin color.


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 stocking-glove 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 a blister or minor wound has become infected.)
  • Deep pain.

The most serious consequences of neuropathy affect the legs and feet and pose a risk for ulcers and, in very severe cases, amputation. In some cases, neuropathy may mask 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.

Neuropathy Pain and its Treatment. 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 used for neuropathy pain include the following:

  • Topical medications, particularly capsaicin (the active ingredient in hot peppers), are commonly used for local neuropathy pain. One study reported that a spray containing isosorbide dinitrate, which helps open blood vessels, was helpful in reducing burning and pain in about half of patients.
  • Alpha lipoic acid dramatically improved neuropathy in one study when administered intravenously to a group of patients with diabetes. Animal studies suggest that this potent antioxidant may have nerve-protective properties. Alpha lipoic acid is available over-the-counter. However, this substance is not regulated in the US and, as with all natural remedies, the safety and effectiveness of over-the-counter supplements cannot be guaranteed.
  • 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 may have adverse effects on heart rhythm, which make them problematic for many patients, particularly elderly ones.
  • Anti-seizure drugs, such as gabapentin (Neurontin) or valproate, may prove to an effective alternative for treating painful neuropathy.
  • Transcutaneous electrostimulation involves administering mild electrical pulses to painful areas. Some evidence suggests this procedure may help reduce pain, particularly in combination with a tricyclic.
  • Tramadol (Ultram), a painkiller that is similar to opioids, achieved moderate pain reduction in one study and may have fewer side effects than anti-seizure drugs or tricyclics. It carries a slight risk for addiction. Nausea, headache, and constipation are common.

Other Complications of Neuropathy. Neuropathy also affects other functions and treatments are needed to reduce their effects as well. 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.

Impotence in men is also associated with neuropathy. Sildenafil (Viagra), vardenafil (Levitra, Nuviva, and tadalafil (Cialis)) are proving to be effective treatments for impotence in about half of the men with either type 1 or type 2 diabetes. Side effects and usually minimal.

Foot Ulcers and Amputations. Perhaps the most serious consequences of diabetic neuropathy occur in the lower limbs. An estimated 15% of diabetics experience serious foot problems. They are the leading cause of hospitalizations for these patients.

Diabetes is responsible for more than half of all the lower limb amputations performed in the U.S. Each year there are about 88,000 non-injury amputations and between 50% to 75% of them are due to diabetes. Worse, the number is increasing as the prevalence in diabetes type 2 rises. About 85% of amputations start with foot ulcers, which develop in about 12% of people with diabetes.

In general, foot ulcers develop from infections, such as those resulting from blood vessel injury. Even minor infections can develop into severe complications. Numbness from nerve damage, which is common in diabetes, compounds the danger since the patient may not be aware of injuries. About one-third of foot ulcers occur on the big toe.

According to a 2003 government survey, those at higher risk for foot ulcers tend to be people with diabetes who are overweight, smokers, and those with a long history of diabetes. People who had had the disease for more than 20 years and were insulin-dependent were at the highest risk. Related conditions that put people at risk include peripheral neuropathy, peripheral arterial disease, foot deformities, and a history of ulcers.

Charcot Foot. Charcot foot or Charcot joint (medically referred to as neuropathic arthropathy) occurs in up to 2.5% of people with diabetes. Early changes appear like an infection, with the foot becoming swollen, red, and warm. A seriously affected foot can become deformed. The bones may crack, splinter, and erode, and the joints may shift, change shape, and become unstable. It typically develops in people who have neuropathy to the extent that they cannot feel sensation in the foot and are not aware of an existing injury. Instead of resting an injured foot or seeking medical help, the patient often continues to normal activity, causing further damage.

Charcot foot 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. A 2001 study in the U.K. concluded that a single dose of pamidronate, a bisphosphonate, reduces bone turnover, symptoms, and disease activity. When the acute phase has passed, patients usually need lifelong protection of the foot using a brace initially and custom footwear.

Measures to Prevent Foot Ulcers. Preventive foot care could significantly reduce the risk of ulcers and amputation. Some tips for preventing problems include the following:

  • Patients should 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.
  • Well-fitting footwear is very important. People should be sure the shoe is wide enough; according to a 2001 study, 30% of diabetic patients wear shoes that are too narrow. Patients should also avoid high heels, sandals, thongs, and going barefoot. Shoes with a rocker sole (e.g., LucRo) reduce pressure under the heel and front of the foot by 35% to 65% and may be particularly helpful. Custom-molded boots (e.g., Conformer Diabetic Boot) increase the surface area over which foot pressure is distributed. This reduces stress on the ulcers and allows them to heal.
  • 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.
  • Foot pain, numbness, or tingling is worse at night; diphenhydramine (Benadryl) may help.
  • A specialist in foot care should be consulted for any problems.
Diabetic foot care
People with diabetes are prone to foot problems because the disease can cause damage to the blood vessels and nerves, which may result in decreased ability to sense a trauma to the foot. The immune system is also altered, so that the diabetic cannot efficiently fight infection.

Treating Foot Ulcers in Diabetes. About one-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, which is the removal of injured tissue until only healthy tissue remains. Debridement may be accomplished using chemical (enzymes), surgical, or mechanical (e.g. irrigation) means.
  • Hydrogels (Nu-Gel, Intrasite Gel, Scherisorb, Clearsite, Duoderm, Geliperm) are helpful in healing ulcers and are noninvasive and soothing.
  • Felted foam appears to be helpful in healing ulcers on the sole of the foot.

Investigative Agents for Treating Foot Ulcers. A number of recent investigative agents and procedures for treating foot ulcers include the following:

  • Cultures of human skin cells or human skin equivalent (HSE) (e.g., Dermagraft, Apligraf, or Regranex) stimulate new cell growth and help heal skin ulcers. Studies are showing that HSE promotes healing and the risk for rejection of such grafts is low. Adverse effects include infections at other sites.
  • Administering hyperbaric oxygen (oxygen given at high pressure) is showing promise in promoting healing. In one study, for example, patients who had had ulcers that had not responded to treatment for over three months received daily treatments that lasted 90 minutes for two weeks. About 15 days after completion, patients who received oxygen had significant reduction in ulcers, sometimes with complete healing. Other studies are also demonstrating good results.
  • Sulodexide is an agent based on a natural substance called a glycosaminoglycan, which helps reduce blood clotting. Studies are suggesting that it may be helpful for treating foot ulcers but improving blood flow.
  • Granulocyte-colony stimulating factor, or G-CSF (filgrastim, Neupogen, Amgen) has accelerated healing and significantly reduced the need for surgery in some studies. A 2003 study, however, indicated that offered no additional advantages compared with antibiotics and bed rest.
  • Low-molecular weight heparin, which is a blood thinner, is being investigated for treating foot ulcers.
  • Monochromatic near-infrared photo energy (MIRE) uses light therapy to improve sensation in the feet of patients with peripheral neuropathy.

Devices to Heal Ulcers and Protect the Foot. Researchers are also using or investigating various devices to heal or prevent ulcers. The following are some examples:

  • 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 is useful for ulcer healing and for Charcot foot. Although it is very effective in healing ulcers, recurrence is common.
  • Noncontact normothermic wound therapy (Warm-UP) uses a unit that applies infrared radiant heat for an hour three times a day. In one study, 70% of the wounds treated were healed compared to 40% that received standard gauze treatments. More research is needed to determine if this approach has any advantages over other measures.
  • Felted foam uses a multi-layered foam pad over the bottom of the foot with an opening over the ulcer. Small studies have suggested that it is effective in healing ulcers in this area.

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. People with diabetes are also at higher risk for developing cataracts and certain types of glaucoma. [For more information, seeWell-Connected Report #26 Cataractsor Report #25 Glaucoma.]

Description of Retinopathy. Retinopathy is a condition in which the retina becomes damaged. The two primary abnormalities that occur are a weakening of the blood vessels in the retina and the obstruction in the capillaries--probably from very tiny blood clots. Retinopathy generally occurs in one or two phases:

Click the icon to see an image of diabetic retinopathy.
  • 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 capillaries 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.
Diabetes mellitus - retinal conditions Click the icon to see an animation on diabetic retinopathy.

According to a 2003 study, about 40% of young adults with type 1 diabetes had developed retinopathy within 10 years of diagnosis. (Although this rate is high, it is significantly lower than in previous years when blood glucose control was not as strict.) The risk is lower in patients with type 2, although in one study over 20% had signs of retinopathy six years after diagnosis. Any patient on insulin or who has had diabetes for more than 20 years should have a yearly eye examination. Patients with no signs of retinal damage or risk factors for retinopathy may only require screening every three years.

Prevention of Retinopathy. Fortunately, severe and even moderate vision loss is largely preventable with intensive control of blood glucose levels. (Note: intense glucose control can cause early worsening of retinopathy, although this is nearly always counterbalanced by long-term benefits.) Measures for reducing risks to the heart (e.g., ACE inhibitors for lower blood pressure and drugs that improve cholesterol) may also have protective benefits for the eyes. Whereas low-dose aspirin is used to prevent heart disease, high doses may prevent retinopathy. Patients at risk for retinopathy should discuss this therapy with their physicians.

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.

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.


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.


Diabetes doubles the risk for depression. Furthermore, according one study, depression, in turn, increases the risk for hyperglycemia and complications of diabetes. Restoring mental health, both through medication and psychotherapy, not only improves quality of life but also helps patients control their blood sugar levels.

Changes in Bone Quality

Diabetes changes bone quality and density, but the effects differ depending on type:

  • Type 1 diabetes is associated with a slightly reduced bone density, putting patients at risk for osteoporosis and possibly fracture. The best medications for bone loss in patients with diabetes may be the bisphosphonates, such as alendronate (Fosamax) and risedronate (Actonel). They not only help prevent bone loss but may even reduce daily insulin requirements in patients taking insulin. [SeeWell-Connected Report #18 Osteoporosis.]
  • Type 2 diabetes, on the other hand, is associated with an increased bone density but is also associated with fractures. In such cases, the bone quality itself may be impaired.

Older patients with either type are at risk for falling, which compounds the risk for fracture.

Other Complications

Other complications of diabetes include the following:

  • Diabetics have a slightly higher prevalence of hearing loss than nondiabetics.
  • Up to half of people with diabetes are at risk for nonalcoholic fatty liver disease, also called nonalcoholic steatohepatitis (NASH). It is a particular danger in people who are obese.
  • Women with type 2 diabetes face a higher risk for uterine cancer, although only if they are obese. Both women and men with diabetes appear to have a higher risk for colon and rectal cancers.
  • Much evidence exists on the link between type 1 and type 2 diabetes and periodontal disease. People with these diseases have 15 times the risk of the nondiabetic population.

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