Diabetes mellitus, type 1

INTRODUCTION — Type 1 diabetes mellitus is a chronic medical condition that occurs when the pancreas, an organ in the abdomen, produces very little or no insulin (show figure 1). Insulin is a hormone that helps the body to absorb and use glucose and other nutrients from food, store fat, and build up protein. Without insulin, blood glucose (sugar) levels become elevated.

Elevated blood glucose levels (called hyperglycemia) cause a person to urinate more frequently, causing loss of body water and dehydration. A person can also feel tired and lose weight. In addition, a serious and potentially life-threatening complication known as diabetic ketoacidosis can develop (see "Symptoms" below). Long term complications associated with hyperglycemia can affect the eyes, nerves, kidneys, and cardiovascular system, leading to blindness, loss of sensation in the feet, the need for amputation of toes or a foot, kidney failure, and an increased risk of heart attack and stroke.

Type 1 diabetes requires regular blood glucose monitoring and treatment with insulin. Treatment, lifestyle adjustments, and self-care can effectively control blood glucose levels and minimize a person's risk of ketoacidosis and other disease-related complications.

Type 1 diabetes usually begins in childhood or young adulthood, but can develop at any age. In the United States, Canada, and Europe, type 1 diabetes accounts for 5 to 10 percent of all cases of diabetes. It is relatively more common in people who are white compared to people of African or Asian descent.

THE IMPACT OF DIABETES — Being diagnosed with type 1 diabetes can be a frightening and overwhelming experience for some patients, 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 patients, the first few months after being diagnosed are filled with emotional highs and lows. Persons 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 insulin) becomes a "normal" part of the daily routine. (See "Patient information: Self-blood glucose monitoring").

In addition, persons 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 1 diabetes, most persons 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 persons with diabetes can enjoy exercise in almost any form.

CAUSES — Type 1 diabetes usually develops when a person's immune system destroys the insulin-producing cells (called the beta cells) in the pancreas. This is called an autoimmune response. This process occurs over many months or years, during which a person has no signs or symptoms of diabetes. Hyperglycemia and its associated symptoms (frequent urination, thirst) do not usually occur until more than 90 percent of the beta cells have been destroyed, which greatly reduces insulin secretion. The cause of the abnormal immune response that destroys the beta cells is being actively studied.

Type 1 diabetes may develop in persons with a family history of type 1 diabetes, but may also develop in persons with no family history of diabetes. In either case, the person has one or more genes that make them susceptible to the disease. Environmental factors, such as exposure to certain viruses and foods early in life, may trigger the autoimmune response.

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

Symptoms — Most people have symptoms of high blood glucose levels (hyperglycemia) before being diagnosed with type 1 diabetes. These symptoms may include excessive thirst, fatigue, frequent urination, weight loss, or blurred vision.

Less commonly, a person will develop signs and symptoms of diabetic ketoacidosis (DKA) at the time of diagnosis. DKA causes symptoms of high blood glucose levels (see above), as well as nausea and vomiting, abdominal pain, rapid breathing, lethargy, decreased alertness, and sometimes coma. DKA is a medical emergency and must be treated promptly.

Rarely, type 1 diabetes is diagnosed before symptoms develop.

Laboratory tests — Several blood tests are used to measure blood glucose levels; this is 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 a person who has the typical symptoms of hyperglycemia suggests a diagnosis of diabetes. Fasting blood glucose test — Fasting blood glucose testing involves measurement of blood glucose after not eating or drinking for 8 to 12 hours (usually overnight). Fasting blood glucose is normally less than 100 mg/dL (5.6 mmol/L); values of 126 mg/dL (7.0 mmol/L) or higher suggests diabetes. However, the test must be repeated on another day to confirm the diagnosis of diabetes. 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 used to diagnose the disease. Normal values for A1C are usually 6.1 percent or lower (indicating an average blood glucose of 120 mg/dL [6.6 mmol/L], show figure 2). Most healthcare providers recommend measuring A1C three to four times per year in people with type 1 diabetes.

Criteria for diagnosis — The following criteria are used to define blood glucose levels as normal or indicative of diabetes. Normal — Fasting plasma glucose (FPG) <100 mg/dL (5.6 mmol/L). Diabetes mellitus — A person is diagnosed with diabetes if he or she has one or more of the following criteria:

- Symptoms of diabetes (see "Symptoms" above) and a fasting blood glucose level of 126 mg/dL (7.0 mmol/L) or higher

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


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 patient has type 1 or type 2 diabetes based upon the need for insulin (which is 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 factors, such as age at diagnosis (generally younger for type 1), obesity (more common in type 2), and the presence of antibodies in the blood (present in type 1) can be used to distinguish between the two types. (See "Patient information: Diabetes mellitus, type 2").

However, there are situations where it is not clear if a person has type 1 or 2 diabetes. In this situation, a healthcare provider usually treats the patient as if they have type 1, since missing this diagnosis can result in DKA.

RISK FACTORS — A person whose parent or sibling has type 1 diabetes is at increased risk of developing the disease, compared to a person with no family history (5 to 6 percent versus 0.4 percent, respectively). To determine if a person with a family history of type 1 diabetes is at increased risk, genetic testing can be performed. Currently these tests are only available to those who participate in a clinical research trial. Persons who are found to be at risk for developing type 1 diabetes may be enrolled in further clinical trials aimed at preventing or delaying the disease from developing.

PREVENTION — Methods to prevent type 1 diabetes are still in the investigational stage. Currently, no treatment has been found to be effective in preventing type 1 diabetes for more than a brief period of time.

TREATMENT — Treatment of diabetes requires a team approach, including the patient and their family and healthcare providers (physician, nurse, diabetes educator, dietitian), and sometimes other clinicians (exercise physiologist, podiatrist, etc). The treatment of type 1 diabetes is discussed on a separate topic review. (See "Patient information: Diabetes type 1: Insulin treatment").

LONG-TERM OUTCOMES — Several studies have proven that persons with diabetes whose blood glucose levels are kept at near-normal levels can reduce their risk of long-term complications. In the Diabetes Control and Complications Trial, 1441 patients were followed for 6.5 years. Half the group used intensive insulin therapy (either with an insulin pump or three or more insulin injections daily) with the goal of maintaining glucose levels as close to the non-diabetic range as possible. The other half used conventional therapy (one to two insulin injections per day). Intensive therapy reduced the risk of retinopathy by 76 percent, nephropathy by 54 percent, and neuropathy by 60 percent [1]. Longer-term study of the DCCT population has shown that heart disease and strokes are also reduced with intensive diabetes therapy.

Thus, persons with diabetes can greatly reduce their risk of long-term complications by monitoring blood glucose levels frequently and using intensive insulin therapy. The goal A1C is as close to the non-diabetic range as possible and, at a minimum, should be less than 7 percent.

The life expectancy for persons with diabetes is based upon many factors, including the development of diabetes-related complications, lifestyle factors such as smoking, diet, exercise, and alcohol consumption, weight and other medical conditions.

COMPLICATIONS — Complications of type 1 diabetes are related to the disease itself as well as to the treatments that are necessary to manage diabetes. (See "Patient information: Preventing complications in diabetes mellitus").

Disease-related complications — Persons with type 1 diabetes are at increased risk of cardiovascular disease, which can cause myocardial infarction (heart attack), angina (chest pain), stroke, and death. The risk is estimated to be at least twice that of nondiabetics. However, persons with type 1 diabetes can substantially lower their risk of cardiovascular disease by not smoking, taking a low-dose aspirin every day (for adults only), and by managing high blood pressure and hyperlipidemia with diet, exercise, and medications, and by achieving an A1C level of 7 percent or lower. (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").

The more specific complications of type 1 diabetes include damage to small blood vessels (called microvascular damage) and nerves. This damage is the result of elevated blood glucose levels over a period of many years; improving blood glucose control can prevent or reduce the risk of these complications.

Microvascular damage affects the retina in the eyes (the light-sensitive film in the back of the eyes). This is called retinopathy, which can lead to decreased vision or blindness. Microvascular damage also affects the kidneys (called nephropathy, which can lead to kidney failure), and nerves (called neuropathy, which can cause pain and increases the risk of foot injury and infection). The risk of nephropathy, neuropathy, and retinopathy is related to the level of the A1C; the higher the A1C value, the greater the risk (show figure 3 and show figure 4). Other factors, especially high blood pressure, increase the risk of diabetic complications. (See "Patient information: Foot care in diabetes").

Treatment-related complications — Treatment-related complications of type 1 diabetes are more common in persons who use intensive insulin therapy. Intensive insulin therapy involves giving three or more insulin injections daily, or use of an insulin pump. Complications of this type of treatment can include hypoglycemia (low blood sugar) and weight gain. However, intensive insulin therapy has significant benefits despite these treatment-related risks. (See "Patient information: Diabetes type 1: Insulin treatment").

Results from a large trial demonstrated that the risk of hypoglycemia increased as the A1C was lowered. However, there is wide variability in the rate of hypoglycemia for a given A1C value. Thus, each patient must find his or her own level of tolerance. (See "Patient information: Hypoglycemia (low blood glucose) in diabetes").

Weight gain is also a common problem with intensive insulin regimens. Weight gain can be prevented or managed with regular exercise and careful attention to diet.

PREGNANCY AND DIABETES — Women with type 1 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. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329:977.
2. Alberti, KG, Zimmet, PZ for the WHO Consultation. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabet Med 1998; 15:539.
3. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997; 20:1183.
4. Nathan, DM, Cleary, PA, Backlund, JY, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005; 353:2643.
5. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. N Engl J Med 2000; 342:381.
6. LaGasse, JM, Brantley, MS, Leech, NJ, et al. Successful prospective prediction of type 1 diabetes in schoolchildren through multiple defined autoantibodies: an 8-year follow-up of the Washington State Diabetes Prediction Study. Diabetes Care 2002; 25:505.