Diabetes mellitus, type 2

INTRODUCTION — Type 2 diabetes mellitus occurs when the pancreas (an organ in the abdomen) produces insufficient amounts of the hormone insulin and/or the body's tissues become resistant to normal or even high levels of insulin (show figure 1). This causes high blood glucose (sugar) levels, which can lead to a number of complications if untreated.

Type 2 diabetes is a chronic medical condition that requires regular monitoring and treatment. Treatment, which includes lifestyle adjustments, self-care measures, and sometimes medications, can control blood glucose levels in the near-normal range and minimize the risk of diabetes-related complications.

In the United States, Canada, and Europe, type 2 diabetes accounts for about 90 percent of all cases of diabetes. More than 6 percent of all people between the ages of 20 and 74 years and more than 12 percent of persons over age 40 have type 2 diabetes; these numbers continue to increase.

THE IMPACT OF DIABETES — Being diagnosed with type 2 diabetes can be a frightening and overwhelming experience for some people, and it is common to have questions about why it developed, what it means for long-term health, and how it will affect everyday life. For most people, the first few months after being diagnosed are filled with emotional highs and lows. People with newly-diagnosed diabetes, as well as their families, can use this time to learn as much as possible so that diabetes-related care (eg, self-blood glucose testing, medical appointments, daily medications) becomes a "normal" part of the daily routine.

In addition, people who are newly diagnosed should talk to their healthcare provider about resources that are available for medical as well as psychological support. This may include group classes, meetings with a nutritionist, social worker, or nurse educator, and other educational resources such as books, web sites, or magazines. Several of these resources are listed in this topic review (see "Where to get more information" below).

Despite the risks associated with type 2 diabetes, most people can lead active lives and continue to enjoy the foods and activities that they previously enjoyed. Diabetes does not mean an end to special occasion foods like birthday cake, and with a little advanced planning, most people with diabetes can enjoy exercise in almost any form.

CAUSES — Type 2 diabetes is probably caused by a complex interaction of environmental factors and predisposing genetic factors.

Genetic causes — Many people with type 2 diabetes have a family member with type 2 diabetes or conditions commonly associated with diabetes, such as high blood lipid levels, high blood pressure, or obesity. As an example, 39 percent of patients with type 2 diabetes have at least one parent with the disease. The lifetime risk that a first-degree relative (sister, brother, son, daughter) will develop diabetes is five to ten times higher than that of a person of a similar age and weight who has no family history of diabetes. Several common genetic variants have been identified. However, genetic testing is not currently recommended.

The likelihood of developing type 2 diabetes is greater in certain ethnic groups; for example, people of Hispanic, African, and Asian descent are at greater risk of developing diabetes compared to people who are white.

Environmental conditions — Environmental factors such as diet and activity levels interact with genetic causes to influence the development of type 2 diabetes. The incidence of type 2 diabetes has increased dramatically in the United States over the last 20 years as the percentage of people who are obese increases.

Pregnancy — About 3 to 5 percent of pregnant women develop gestational diabetes, usually after 24 to 28 weeks of pregnancy. Gestational diabetes is similar to type 2 diabetes, but generally resolves after a woman delivers her baby. Hormones cause an increase in insulin resistance during pregnancy, which can lead to gestational diabetes. Women who develop gestational diabetes during pregnancy are at high risk for developing type 2 diabetes later in life. (See "Patient information: Care during pregnancy for women with type 1 or 2 diabetes").

Other causes — Other, less common causes of diabetes include endocrine conditions that indirectly change the production and action of insulin and lead to diabetes. These include Cushing's syndrome, acromegaly, pheochromocytoma, hyperthyroidism and polycystic ovarian syndrome (PCOS). (See "Patient information: Cushing's syndrome" and see "Patient information: Acromegaly (somatotroph adenomas)" and see "Patient information: Hyperthyroidism" and see "Patient information: Polycystic ovary syndrome (PCOS)").

DIAGNOSIS — The diagnosis of diabetes is based upon a person's symptoms and the results of laboratory tests.

Symptoms — Before being diagnosed with diabetes, some people have symptoms of high blood glucose, including frequent urination, excessive thirst, and blurred vision. Sometimes, diabetes is discovered when a person seeks medical help for another problem (such as erectile dysfunction or pain and numbness in the feet). However, most people with type 2 diabetes have no symptoms at all, and the diagnosis is often delayed for five or more years.

Because family history is a factor in the development of type 2 diabetes, people with family members with diabetes or conditions commonly associated with diabetes, such as hypertension, high blood lipid levels, and obesity, should mention this to their healthcare provider. There are usually few signs of diabetes on a physical examination early in the course of the disease.

Laboratory tests — Several blood tests are used to measure blood glucose levels, the primary test for diagnosing diabetes. Additional tests can determine the type of diabetes and its severity. Random blood glucose test — For a random blood glucose test, blood can be drawn at any time throughout the day, regardless of when the person last ate. A random blood glucose level of 200 mg/dL (11.1 mmol/L) or higher in persons who have symptoms of high blood glucose (see "Symptoms" above) suggests a diagnosis of diabetes. Fasting blood glucose test — Fasting blood glucose testing involves measuring blood glucose after not eating or drinking for 8 to 12 hours (usually overnight). A normal fasting blood glucose level is less than 100 mg/dL. A fasting blood glucose of 126 mg/dL (7.0 mmol/L) or higher indicates diabetes. The test is done by taking a small sample of blood from a vein or fingertip. It must be repeated on another day to confirm that it remains abnormally high (see "Criteria for diagnosis" below). Hemoglobin A1C test (A1C) — The A1C blood test measures the average blood glucose level during the past two to three months. It is used to monitor blood glucose control in people with known diabetes, but is not normally used to diagnose diabetes. Normal values for A1C are 4 to 6 percent (show figure 3). The test is done by taking a small sample of blood from a vein or fingertip. Oral glucose tolerance test — Oral glucose tolerance testing (OGTT) is the most sensitive test for diagnosing diabetes and pre-diabetes. However, the OGTT is not routinely recommended because it is inconvenient compared to a fasting blood glucose test.

The standard OGTT includes a fasting blood glucose test. The person then drinks a 75 gram liquid glucose solution (which tastes very sweet, and is usually cola or orange-flavored). Two hours later, a second blood glucose level is measured.

Oral glucose tolerance testing is routinely performed at 24 to 28 weeks of pregnancy to screen for gestational diabetes; this requires drinking a 50 gram glucose solution with a blood glucose level drawn one hour later. For women who have an abnormally elevated blood glucose level, a second OGTT is performed on another day after drinking a 100 gram glucose solution. The blood glucose level is measured before, and at one, two, and three hours after drinking the solution.

Criteria for diagnosis — The following criteria are used to define a person's blood glucose levels as normal, suggestive of pre-diabetes (defined as an abnormal blood glucose level which is not high enough to be considered diabetic, but with an increased risk of diabetes in the future), or as diagnostic for diabetes. Normal — Fasting plasma glucose (FPG) <100 mg/dL (5.6 mmol/L). Pre-diabetes — Pre-diabetes can be diagnosed based upon a fasting blood glucose test or an OGTT.

- Impaired fasting glucose is defined as a fasting plasma glucose between 100 and 125 mg/dL (5.6 to 6.9 mmol/L).

- Impaired glucose tolerance is defined as a glucose level of 140 to 199 mg/dL, measured two hours after a 75 gram oral glucose tolerance test.

At least 50 percent of people with impaired glucose tolerance eventually develop type 2 diabetes, and they have an increased risk of heart disease even if diabetes does not develop. Impaired glucose tolerance is very common; about 11 percent of all people between the ages of 20 and 74 years have impaired glucose tolerance. Diabetes mellitus — A person is considered to be diabetic if he or she has one or more of the following criteria:

- Symptoms of diabetes (see "Symptoms" above) and a random blood glucose of 200 mg/dL (11.1 mmol/L) or higher

- A fasting blood glucose level of 126 mg/dL (7.0 mmol/L) or higher


- A blood glucose of 200 mg/dL (11.1 mmol/L) or higher two hours after a 75 gram oral glucose tolerance test.

The blood tests must be repeated on another day to confirm that they remain abnormally high.

Type 1 versus type 2 diabetes — A healthcare provider is usually able to determine whether a person has type 1 or type 2 diabetes, based upon the person's need for insulin (needed from the beginning in type 1, and less commonly early in type 2), and the presence of ketones in the urine when blood glucose levels are elevated (common in type 1, uncommon in type 2). Other characteristics such as older age and higher weight suggest, but do not prove, type 2 diabetes.

However, there are situations where it is less clear if a person has type 1 or 2 diabetes. In this situation, additional blood testing may be needed. When the type of diabetes is in doubt, the clinician will usually treat the patient with insulin, as if they have type 1, since it is critical to avoid a potentially dangerous condition known as diabetic ketoacidosis (DKA). People with type 2 diabetes do not usually develop DKA. (See "Patient information: Diabetes mellitus, type 1").

TREATMENT — A full discussion of the treatment for type 2 diabetes is available separately. (See "Patient information: Diabetes type 2: Treatment" and see "Patient information: Diabetes type 2: Insulin treatment").

COMPLICATIONS — Complications of type 2 diabetes may be related to the disease itself or to the treatments necessary to manage diabetes. (See "Patient information: Preventing complications in diabetes mellitus").

Diabetes-related complications — The most common long-term complication of type 2 diabetes is cardiovascular (heart) disease, which can cause heart attack, angina (chest pain), stroke, and even death. The risk of heart disease in people with diabetes is estimated to be at least twice that of people without diabetes.

However, people with type 2 diabetes can substantially lower their risk of cardiovascular disease by quitting smoking, taking a low-dose aspirin every day, and by managing their high blood pressure and hyperlipidemia with diet, exercise, and medications (show figure 2). (See "Patient information: High cholesterol and lipids (hyperlipidemia)" and see "Patient information: High blood pressure treatment" and see "Patient information: Smoking cessation" and see "Patient information: Aspirin and heart disease").

People with type 2 diabetes are also at increased risk of developing eye, kidney, and nerve complications that can result in blindness, kidney failure, foot ulcers requiring amputation, and impotence in men. These complications occur after many years of diabetes and are related to elevated blood glucose levels over time. These complications can be prevented or delayed by keeping blood sugar levels as close to normal as possible and by carefully controlling blood pressure. Diabetes remains the greatest cause of blindness, kidney failure, and amputations in the United States and in much of the world.

Treatment-related complications — The most common treatment-related complication of type 2 diabetes is weight gain. This occurs most commonly in people who use certain oral diabetes medications and in those who take insulin. The oral medication metformin is not associated with weight gain.

Weight gain can be prevented or managed with regular exercise and careful attention to diet. Some patients with type 2 diabetes who are significantly overweight benefit from medications or surgery to improve their chances of losing weight. (See "Patient information: Weight loss treatments" and see "Patient information: Weight loss surgery").

PREGNANCY AND DIABETES — Women with type 2 diabetes are usually able to become pregnant and have a healthy baby. However, it is important to tightly control blood glucose levels before and during pregnancy to minimize the risk of complications. A full discussion of this topic is available separately. (See "Patient information: Care during pregnancy for women with type 1 or 2 diabetes").

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine

(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Institute of Diabetes and Digestive and Kidney Diseases

(www.niddk.nih.gov)
American Diabetes Association (ADA)

(800)-DIABETES (800-342-2383)
(www.diabetes.org)
The Endocrine Society

(www.endo-society.org)
The Hormone Foundation

(www.hormone.org/public/diabetes.cfm, available in English and Spanish)


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Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Knowler, WC, Barrett-Connor, E, Fowler, SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346:393.
2. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352:854.
3. Kjos, SL, Peters, RK, Xiang, A, et al. Predicting future diabetes in Latino women with gestational diabetes: Utility of early postpartum glucose tolerance testing. Diabetes 1995; 44:586.
4. Selvin, E, Coresh, J, Golden, SH, et al. Glycemic control, atherosclerosis, and risk factors for cardiovascular disease in individuals with diabetes: the atherosclerosis risk in communities study. Diabetes Care 2005; 28:1965.
5. Meigs, JB, Singer, DE, Sullivan, LM, et al. Metabolic control and prevalent cardiovascular disease in non-insulin-dependent diabetes mellitus (NIDDM): the NIDDM Patient Outcomes Research Team. Am J Med 1997; 102:38.
6. Selvin, E, Wattanakit, K, Steffes, MW, et al. HbA1c and Peripheral Arterial Disease in Diabetes: The Atherosclerosis Risk in Communities study. Diabetes Care 2006; 29:877.
7. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352:837.