2型糖尿病

INTRODUCTION
Type 2 diabetes (also called type 2 diabetes mellitus) is a disorder that is known for disrupting the way your body uses glucose (sugar); it also causes other problems with the way your body stores and processes other forms of energy, including fat.

All the cells in your body need sugar to work normally. Sugar gets into the cells with the help of a hormone called insulin. If there is not enough insulin or if your body stops responding to insulin, sugar builds up in the blood. This is what happens to people with diabetes. High blood sugar levels can lead to problems if untreated.

There are two different types of diabetes, type 1 and type 2:

●In type 1 diabetes, the problem is that the pancreas (an organ in the abdomen) stops making insulin

●In type 2 diabetes, the body stops responding to normal or even high levels of insulin, and over time, the pancreas does not make enough insulin

In the United States, Canada, and Europe, approximately 90 percent of all people with diabetes have type 2 diabetes. This is a chronic medical condition that requires regular monitoring and treatment throughout your life in order to keep your blood sugar levels as close to normal as possible. This involves lifestyle changes (including your diet and exercise habits), self-care measures, and sometimes medications. Fortunately, these treatments can keep your blood sugar levels under control and minimize your risk of developing complications.

This topic provides a general overview of type 2 diabetes.

THE IMPACT OF DIABETES
Being diagnosed with type 2 diabetes can be a frightening and overwhelming experience, and you likely have questions about why it developed, what it means for your long-term health, and how it will affect your everyday life. Your doctor or nurse can help answer your questions and talk to you about what to expect. They can also direct you to resources for medical, as well as psychological, support. These may include group classes; meetings with a registered dietitian, social worker, or nurse educator; and other educational resources such as books, websites, or magazines. Several of these resources are listed below. (See 'Where to get more information' below.)

For most people, the first few months after being diagnosed are filled with emotional highs and lows. If you have just been diagnosed with diabetes, you and your family should use this time to learn as much as possible so that caring for your diabetes (including testing your blood sugar, going to medical appointments, and taking your medications) becomes a part of your daily routine. (See "Patient education: Glucose monitoring in diabetes (Beyond the Basics)".)

Type 2 diabetes can lead to health complications, some of which can be serious. However, there are things you can do to reduce your risk of developing these problems (see "Patient education: Preventing complications from diabetes (Beyond the Basics)"). Most people with diabetes lead active lives and continue to enjoy many of the foods and activities that they previously enjoyed. Diabetes does not mean an end to "special occasion" foods like birthday cake, and most people with diabetes can (and should) enjoy exercise in almost any form. (See "Patient education: Type 2 diabetes and diet (Beyond the Basics)" and "Patient education: Exercise and medical care for people with type 2 diabetes (Beyond the Basics)".)

TYPE 2 DIABETES CAUSES
Type 2 diabetes is thought to be caused by a combination of genetic and environmental factors.

Genetic causes — Many people with type 2 diabetes have a family member with either type 2 diabetes or other medical problems associated with diabetes, such as high cholesterol and triglyceride levels, high blood pressure, or obesity.

The lifetime risk of developing type 2 diabetes is 5 to 10 times higher in first-degree relatives (ie, sibling or child) of a person with diabetes compared with a person with no family history of diabetes. The likelihood of developing type 2 diabetes is greater in certain ethnic groups, such as people of Hispanic, African, and Asian descent.

Lifestyle factors — Eating an unhealthy diet and not getting enough exercise can lead to weight gain, which increases your risk of developing type 2 diabetes.

Pregnancy — A small number of pregnant women develop diabetes during pregnancy, called "gestational diabetes." Gestational diabetes is similar to type 2 diabetes, but it usually resolves after the woman delivers her baby. Women who develop gestational diabetes during pregnancy are at increased risk for developing type 2 diabetes later in life. (See "Patient education: Gestational diabetes (Beyond the Basics)".)

TYPE 2 DIABETES DIAGNOSIS
The diagnosis of diabetes is based upon your symptoms and the results of blood tests.

Symptoms — Before being diagnosed with type 2 diabetes, most people have no symptoms at all. In those who do have symptoms, the most common include:

●Needing to urinate frequently

●Feeling thirsty

●Blurred vision

Laboratory tests — The main test doctors use to diagnose diabetes is a blood glucose (sugar) test. This can be done in several different ways:

●Random blood sugar test – For a random blood sugar test, you can have blood drawn at any time throughout the day, regardless of when you last ate. A normal random blood sugar level is between 70 and 140 mg/dL (3.9 to 7.8 mmol/L).

●Fasting blood sugar test – A fasting blood sugar test is a blood test done after not eating or drinking for 8 to 12 hours (usually overnight). A normal fasting blood sugar level is less than 100 mg/dL (5.6 mmol/L).

●Hemoglobin A1C test – The "A1C" blood test measures your average blood sugar level over the past two to three months. Normal values for A1C are 4 to 5.6 percent. The A1C test can be done at any time of day (before or after eating).

●Oral glucose tolerance test – Oral glucose tolerance testing (OGTT) is a test that involves drinking a special glucose solution (usually orange or cola flavored). Your blood sugar level is tested before you drink the solution and then again one and two hours after drinking it. Because of its inconvenience, OGTT is not commonly used for testing, except in pregnant women.

Criteria for diagnosis — The following criteria are used to classify your blood sugar levels as normal, increased risk (blood sugar levels that are higher than normal and indicate a risk of future diabetes), or diabetes.

Normal — Fasting blood sugar less than 100 mg/dL (5.6 mmol/L) is considered normal, that is, it does not indicate an increased risk for diabetes.

Increased risk — Some test results put a person in the category of "increased risk," meaning they are at risk of going on to develop diabetes:

●"Impaired fasting glucose" – This is defined as a fasting blood sugar level between 100 and 125 mg/dL (5.6 to 6.9 mmol/L).

●"Impaired glucose tolerance" – This is defined as a blood sugar level of 140 to 199 mg/dL (7.8 to 11 mmol/L) two hours after an OGTT.

●A1C – People with an A1C of 5.7 to 6.4 percent (39 to 46 mmol/mol) are considered at increased risk; the likelihood of developing type 2 diabetes is higher with A1C levels closer to the upper limit of this range.

These categories of increased risk are sometimes called "prediabetes." Approximately one in three American adults can be classified as having prediabetes. If your test results suggest you are at increased risk, your doctor or nurse can talk to you about changes you can make to reduce your risk of developing diabetes. These include improving your diet and exercise habits, losing weight, and quitting smoking (if you smoke). Blood sugar testing is repeated every year.

Although the rate of progression varies, approximately 25 percent of people with either impaired fasting glucose or impaired glucose tolerance will go on to develop type 2 diabetes over three to five years.

Diabetes — Doctors diagnose diabetes if a person has one or more of the following:

●Symptoms of diabetes (see 'Symptoms' above) and a random blood sugar of 200 mg/dL (11.1 mmol/L) or higher

●A fasting blood sugar level of 126 mg/dL (7 mmol/L) or higher

●A blood sugar of 200 mg/dL (11.1 mmol/L) or higher two hours after an OGTT

●An A1C of 6.5 percent (48 mmol/mol) or higher

If your results suggest diabetes, your doctor will repeat one of these tests on another day to confirm the diagnosis.

Type 1 versus type 2 diabetes — Doctors can usually tell whether a person has type 1 or type 2 diabetes, but there are situations in which the diagnosis is difficult to determine. Type 1 diabetes should be suspected in a person without a strong family history of type 2 diabetes who has the following combination of risk factors:

●A family history of certain autoimmune diseases such as hypothyroidism, hyperthyroidism, or celiac sprue

●Symptoms such as frequent urination and weight loss

●High blood sugar levels even after starting type 2 diabetes treatments

In such cases, doctors often run additional blood tests to determine which type the person has.

TYPE 2 DIABETES TREATMENT
The treatment of type 2 diabetes is discussed in detail separately. (See "Patient education: Type 2 diabetes: Treatment (Beyond the Basics)" and "Patient education: Type 2 diabetes: Insulin treatment (Beyond the Basics)" and "Patient education: Hypoglycemia (low blood glucose) in people with diabetes (Beyond the Basics)".)

More information about lifestyle changes for people with diabetes is also available. (See "Patient education: Type 2 diabetes and diet (Beyond the Basics)" and "Patient education: Exercise and medical care for people with type 2 diabetes (Beyond the Basics)".)

TYPE 2 DIABETES COMPLICATIONS
Complications of type 2 diabetes can be related to the disease itself or to the treatments used to manage diabetes. (See "Patient education: Preventing complications from diabetes (Beyond the Basics)".)

PREGNANCY AND DIABETES
Women with type 2 diabetes are usually able to become pregnant and have a healthy baby. A full discussion of diabetes in pregnancy is available separately. (See "Patient education: Care during pregnancy for patients with type 1 or 2 diabetes (Beyond the Basics)".)

TYPE 2 DIABETES OVERVIEWType 2 diabetes mellitus is a disorder that is known for disrupting the way your body uses glucose (sugar); it also causes other problems with the way your body stores and processes other forms of energy, including fat.

All the cells in your body need sugar to work normally. Sugar gets into the cells with the help of a hormone called insulin. In type 2 diabetes, the body stops responding to normal or even high levels of insulin, and over time, the pancreas (an organ in the abdomen) does not make enough insulin to keep up with what the body needs. Being overweight, especially having extra fat stored in the liver and abdomen, even if weight is normal, increases the body's demand for insulin. This causes high blood sugar (glucose) levels, which can lead to problems if untreated. (See "Patient education: Type 2 diabetes: Overview (Beyond the Basics)".)

People with type 2 diabetes require regular monitoring and ongoing treatment to maintain normal or near-normal blood sugar levels. Treatment includes lifestyle changes (including dietary changes and exercise to promote weight loss), self-care measures, and sometimes medications, which can minimize the risk of diabetes and cardiovascular (heart-related) complications.

This topic review will discuss the medical treatment of type 2 diabetes.

DIABETES CARE DURING THE COVID-19 PANDEMICCOVID-19 stands for "coronavirus disease 2019." It is an infection caused by a virus called SARS-CoV-2. The virus first appeared in late 2019 and has since spread throughout the world.

People with certain underlying health conditions, including diabetes, are at increased risk of severe illness if they get COVID-19. COVID-19 infection can also lead to severe complications of diabetes, including diabetic ketoacidosis (DKA).

Getting vaccinated lowers the risk of severe illness; experts recommend COVID-19 vaccination for anyone with cancer or a history

TYPE 2 DIABETES TREATMENT GOALSThe main goals of treatment in type 2 diabetes are to keep your blood sugar levels within your goal range and treat other medical conditions that go along with diabetes (like high blood pressure); it is also very important to stop smoking if you smoke. These measures will reduce your risk of complications.

Blood sugar control — It is important to keep your blood sugar levels at goal levels. This can help prevent long-term complications that can result from poorly controlled blood sugar (including problems affecting the eyes, kidney, nervous system, and cardiovascular system).

Home blood sugar testing — Your doctor may instruct you to check your blood sugar yourself at home, especially if you take certain oral diabetes medicines or insulin. Home blood sugar testing is not usually necessary for people who manage their diabetes through diet only or with diabetes medications that do not cause low blood sugar.

A random blood sugar test is based on blood drawn at any time of day, regardless of when you last ate. A fasting blood sugar test is a blood test done after not eating or drinking for 8 to 12 hours (usually overnight). A normal fasting blood sugar is more than 70 mg/dL (3.9 mmol/L) but less than 100 mg/dL (5.6 mmol/L), although people with diabetes may have a different goal. Your doctor or nurse can help you set a blood sugar goal and show you exactly how to check your level. (See "Patient education: Glucose monitoring in diabetes (Beyond the Basics)".)

A1C testing — Blood sugar control can also be estimated with a blood test called glycated hemoglobin, or "A1C." The A1C blood test measures your average blood sugar level over the past two to three months. The goal A1C for most young people with type 2 diabetes is 7 percent (53 mmol/mol) or less, which corresponds to an average blood sugar of approximately 150 mg/dL (8.3 mmol/L) (table 1). Lowering your A1C level reduces your risk for kidney, eye, and nerve problems. For some people, a different A1C goal may be more appropriate. Your health care provider can help determine your A1C goal.

Reducing the risk of cardiovascular complications — The most common, serious, long-term complication of type 2 diabetes is cardiovascular disease, which can lead to problems like heart attack, stroke, and even death. On average, people with type 2 diabetes have twice the risk of cardiovascular disease as people without diabetes.

However, you can substantially lower your risk of cardiovascular disease by:

●Quitting smoking, if you smoke

●Managing high blood pressure and high cholesterol with diet, exercise, and medicines

●Taking a low-dose aspirin every day, if you have a history of heart attack or stroke or if your health care provider recommends this

Some studies have shown that lowering A1C levels with certain medications may also reduce your risk for cardiovascular disease. (See 'Type 2 diabetes medicines' below.)

A detailed discussion of ways to prevent complications is available separately. (See "Patient education: Preventing complications from diabetes (Beyond the Basics)".)

DIET AND EXERCISE IN TYPE 2 DIABETESDiet and exercise are the foundation of diabetes management.

Changes in diet can improve many aspects of type 2 diabetes, including helping to control your weight, blood pressure, and your body's ability to produce and respond to insulin. The single most important thing most people can do to improve diabetes management and weight is to avoid all sugary beverages, such as soft drinks or juices, or if this is not possible, to significantly limit consumption. Limiting overall food portion size is also very important. Detailed information about type 2 diabetes and diet is available separately. (See "Patient education: Type 2 diabetes and diet (Beyond the Basics)".)

Regular exercise can also help control type 2 diabetes, even if you do not lose weight. Exercise is related to blood sugar control because it improves your body's response to insulin. (See "Patient education: Exercise and medical care for people with type 2 diabetes (Beyond the Basics)".)

TYPE 2 DIABETES MEDICINESA number of medications are available to treat type 2 diabetes.

Metformin — Most people who are newly diagnosed with type 2 diabetes will immediately begin a medicine called metformin (sample brand names: Glucophage, Glumetza, Riomet, Fortamet). Metformin improves how your body responds to insulin to reduce high blood sugar levels.

Metformin is a pill that is usually started with a once-daily dose with dinner (or your last meal of the day); a second daily dose (with breakfast) is added one to two weeks later. The dose may be increased every one to two weeks thereafter.

Side effects — Common side effects of metformin include nausea, diarrhea, and gas. These are usually not severe, especially if you take metformin along with food. The side effects usually improve after a few weeks.

People with severe kidney, liver, and heart disease and those who drink alcohol excessively should not take metformin. There are certain situations in which you should stop taking metformin, including if you develop acute or unstable heart failure, get a serious infection causing low blood pressure, become dehydrated, or have severely decreased kidney function. You will also need to stop your metformin before having surgery of any kind.

Adding a second medicine — Your doctor or nurse might recommend a second medication in addition to metformin. This may happen within the first two to three months if your blood sugar and A1C levels are still higher than your goal; otherwise, many people need to add a second glucose-lowering medication later (after several years of having diabetes). There are many available classes of medication that can be used with metformin or in combination with each other if metformin is contraindicated or not tolerated. (See "Patient education: Type 2 diabetes: Insulin treatment (Beyond the Basics)".)

If your blood sugar levels are still high after two to three months but your A1C is close to the goal (generally between 7 and 8.5 percent), a second oral medicine might be added. If your A1C is higher than 9 percent, however, your doctor might recommend insulin (usually as a single daily injection) or a glucagon-like peptide-1 (GLP-1) or dual receptor agonist (a daily or weekly injection). The most appropriate second medicine depends upon several different factors, including your weight, risk of low blood sugar, other medical problems, and preferences, in addition to the efficacy, side effects, and cost of the medication.

Sulfonylureas — Sulfonylureas have been used to treat type 2 diabetes for many years. They work by increasing the amount of insulin your body makes and can lower blood sugar levels by approximately 20 percent. However, over time they gradually stop working. They are reasonable second agents because they are inexpensive, effective, universally available, and have a long-term track record. Most patients can take sulfonylureas even if they have an allergy to "sulfa" drugs. You should be very cautious taking a sulfonylurea if you have kidney failure.

A number of short-acting sulfonylureas are available (sample brand names: Glucotrol, Amaryl), and the choice between them depends mainly upon cost and availability.

If you take a sulfonylurea, you can develop low blood sugar, known as hypoglycemia. Low blood sugar symptoms can include:

●Sweating

●Shaking

●Feeling hungry

●Feeling anxious

●Feeling confused

Low blood sugar must be treated quickly by eating 10 to 15 grams of fast-acting carbohydrate (eg, fruit juice, hard candy, glucose tablets). It is possible to pass out if you do not treat low blood sugar quickly enough. To reduce the risk of low blood sugar when you are not eating, if you know you are going to miss a meal, you can skip the sulfonylurea tablet you would usually take before eating. A full discussion of low blood sugar is available separately. (See "Patient education: Hypoglycemia (low blood glucose) in people with diabetes (Beyond the Basics)".)

DPP-4 inhibitors — This class of medicines, dipeptidyl peptidase-4 (DPP-4) inhibitors, includes sitagliptin (brand name: Januvia), saxagliptin (brand name: Onglyza), linagliptin (brand name: Tradjenta), alogliptin (brand name: Nesina), and vildagliptin (brand name: Galvus). Vildagliptin is available in some countries but not in the United States. These medicines lower blood sugar levels by increasing insulin release from the pancreas in response to a meal. They can be given alone in people who cannot tolerate the first-line medicine (metformin) or other medicines, or they can be given together with other oral medicines if blood sugar levels are still higher than the goal. These medicines do not cause hypoglycemia or changes in body weight. There have been rare reports of joint pain, pancreatitis, and severe skin reactions.

SGLT2 inhibitors — The sodium-glucose co-transporter 2 (SGLT2) inhibitors, canagliflozin (brand name: Invokana), empagliflozin (brand name: Jardiance), dapagliflozin (brand name: Farxiga), and ertugliflozin (brand name: Steglatro), lower blood sugar by increasing the excretion of sugar in the urine. They are variably effective, but on average, they are similar in potency to the DPP-4 inhibitors (see 'DPP-4 inhibitors' above). SGLT2 inhibitors may be a good choice for people with heart failure or chronic kidney disease because they have been shown to have some cardiovascular, renal, and mortality benefits.

SGLT2 inhibitors do not cause low blood sugar. They promote modest weight loss and blood pressure reduction. Side effects include genital yeast infections in men and women, urinary tract infections, and dehydration. Some medicines in this class have been associated with an increased risk of bone fracture or amputation. An uncommon but deadly infection of the tissue in the perineum (the area between the genitals and the anus) has also been reported in men and women.

SGLT2 inhibitors can increase the risk of diabetic ketoacidosis (DKA); this is a serious problem that can happen when acids called "ketones" build up in the blood. DKA can happen even when blood sugar is only mildly elevated. Blood ketones should be checked if symptoms of nausea and/or vomiting develop while taking SGLT2 inhibitors.

GLP-1 receptor agonists — The glucagon-like peptide-1 (GLP-1) receptor agonists are medications given by injection that increase insulin release in response to a meal and slow digestion. They include exenatide, dosed twice daily (brand name: Byetta); exenatide extended release, dosed weekly (brand name: Bydureon); liraglutide, dosed daily (brand name: Victoza); dulaglutide, dosed weekly (brand name: Trulicity); lixisenatide, dosed daily (brand name: Adlyxin); and semaglutide, dosed weekly as an injection (brand name: Ozempic) or daily as a tablet (brand name: Rybelsus). These medications are useful for people whose blood sugar is not controlled on the highest dose of one or two oral medicines. They may be especially helpful for overweight people who are gaining weight or struggling to lose weight on other diabetes medicines. Liraglutide, dulaglutide, or semaglutide injections are recommended for people who have, or are at high risk for, cardiovascular disease, as they have been shown to have cardiovascular benefits in these groups.

GLP-1 receptor agonists do not usually cause low blood sugar when used without other medications that cause low blood sugar. They promote loss of appetite and a sense of feeling full after eating a smaller amount of food, which helps with weight loss, but can also cause bothersome side effects, including nausea, vomiting, and diarrhea. Gastrointestinal side effects usually improve with time. Pancreatitis (inflammation of the pancreas) has been reported rarely in people taking GLP-1 receptor agonists, but it is not known if the medications caused the pancreatitis. They have also been associated with gall bladder disease. You should stop taking these medications if you develop severe abdominal pain. Exenatide and lixisenatide should not be used in people with abnormal kidney function, and liraglutide and dulaglutide should be used with caution in this situation. These drugs are generally expensive.

Meglitinides — Meglitinides include repaglinide (brand name: Prandin) and nateglinide (brand name: Starlix). They work to lower blood sugar levels, similar to the sulfonylureas, but they act more quickly than sulfonylureas and should be taken right before a meal; they might also be recommended in people who are allergic to sulfonylureas. They are taken in pill form. Meglitinides are not generally used as a first-line treatment, because they are more expensive than sulfonylureas. Repaglinide can be used in patients with kidney failure.

Thiazolidinediones — This class of medicines includes pioglitazone (brand name: Actos) and rosiglitazone (brand name: Avandia), which work to lower blood sugar levels by increasing the body's sensitivity to insulin. They are taken in pill form and usually in combination with other medicines such as metformin, a sulfonylurea, or insulin.

Common side effects of thiazolidinediones include:

●Weight gain.

●Swelling of the feet and ankles, which sometimes can be a sign of new or worsening heart failure. The risk of heart failure is small but serious. An early sign of heart failure is swelling of the feet and ankles. People who take thiazolidinediones should monitor for swelling.

●A small but serious increased risk of developing fluid retention at the back of the eyes (macular edema).

●A possible risk of developing certain types of cancer (like bladder cancer).

●An increased risk of bone fractures.

Alpha-glucosidase inhibitors — These medicines, which include acarbose (brand name: Precose) and miglitol (brand name: Glyset), work by interfering with the absorption of carbohydrates in the intestine. This helps to lower blood sugar levels but not as well as metformin or the sulfonylureas. They can be combined with other medicines if the first medicine does not lower blood sugar levels enough.

The main side effects of alpha-glucosidase inhibitors are gas (flatulence), diarrhea, and abdominal pain; starting with a low dose may minimize these side effects. The medicine is usually taken three times per day with the first bite of each meal.

Insulin — In the past, insulin treatment was reserved for patients with type 2 diabetes whose blood sugar was not controlled with oral medicines and lifestyle changes (ie, diet and exercise). However, there is increasing evidence that insulin treatment at earlier stages may improve overall diabetes management over time. Side effects include low blood sugar, if you take more insulin than your body needs, and weight gain. Adjusting the dose of insulin to the body's needs can minimize the risk of these side effects. It may be necessary to readjust your dose frequently.

In some situations, insulin injections (shots) can be used as a first-line treatment for type 2 diabetes. In other cases, insulin can be added to or substituted for oral medicines. If you take insulin, you will need to get comfortable giving yourself the injections or have a family member or housemate learn how to do it for you. More detailed information about insulin treatment is available separately. (See "Patient education: Type 2 diabetes: Insulin treatment (Beyond the Basics)".)

LIVING WITH TYPE 2 DIABETESLiving with type 2 diabetes can be stressful. It is a lot of responsibility to have to monitor your blood sugar (if you need to do this), watch your diet, exercise regularly, keep all your appointments, and take your medications every day. It can also be scary to think about the potential complications of diabetes. It can help to involve your family and friends and make sure you have a solid support system in place to provide encouragement, reminders, and help as you need it.

It is not uncommon for stress to lead to burnout or even depression, and this can make taking care of yourself more difficult. Having an open and honest discussion with your doctor, nurse, or other health care provider can help you to understand your diagnosis, treatment plan, and what to do if you are overwhelmed. Some people also benefit from talking with a counselor or social worker to help them cope with their responsibilities and worries.