According to the U.S. Centers for Disease Control and Prevention's (CDC) 2014 National Diabetes Fact Sheet, more than 29 million American adults and children have diabetes. 86 million Americans aged 20 years and older have pre-diabetes, a condition that increases the risk for developing diabetes. About 1 in 4 Americans have diabetes but do not know it.
Diabetes rates are increasing among both adults and children. In 2010, 26 million Americans had diabetes and 79 million had prediabetes.
TYPE 2 DIABETES RISK FACTORS
Risk factors for type 2 diabetes and pre-diabetes include:
NEW NUTRITION GUIDELINES
In 2013, the American Diabetes Association (ADA) released updated nutritional guidelines. Key recommendations include:
NEW DRUG APPROVALS
In 2014, the FDA approved several new drugs for type 2 diabetes:
The CDC now recommends that adults ages 19 to 59 years diagnosed with diabetes should receive vaccinations to prevent hepatitis B. The hepatitis B virus is transmitted through blood. Unvaccinated people with diabetes can become infected with hepatitis B through sharing fingerstick or blood glucose monitoring devices.
The two major forms of diabetes are type 1 (previously called insulin-dependent diabetes mellitus, IDDM, or juvenile-onset diabetes) and type 2 (previously called noninsulin-dependent diabetes mellitus, NIDDM, or adult-onset diabetes).
In type 2 diabetes, the body is insulin resistant: it does not make or use insulin very well. In type 1 diabetes, the body does not make any insulin or does not produce enough of it.
Both type 1 and type 2 diabetes share one central feature of elevated blood sugar (glucose) level due to insufficiencies of insulin, a hormone produced by the pancreas. Insulin is a key regulator of the body's metabolism. It works in the following way:
The pancreas is located below and behind the stomach and is where the hormone insulin is produced. Insulin is used by the body to store and use glucose.
TYPE 2 DIABETES
Type 2 diabetes is the most common form of diabetes, accounting for 90 to 95% of cases. In type 2 diabetes, the body does not respond properly to insulin, a condition known as insulin resistance. The disease process of type 2 diabetes involves:
TYPE 1 DIABETES
In type 1 diabetes, the pancreas does not produce insulin. Type 1 diabetes is considered an autoimmune disorder. The condition is usually first diagnosed in childhood or adolescence but can occur at any age. People with type 1 diabetes need to take daily insulin for survival.
Gestational diabetes is a form of type 2 diabetes, usually temporary, that first appears during pregnancy. It usually develops during the third trimester of pregnancy. After delivery, blood sugar (glucose) levels generally return to normal, although some women develop type 2 diabetes within 15 years.
Because glucose crosses the placenta, a pregnant woman with diabetes can pass high levels of blood glucose to the fetus. This can cause excessive fetal weight gain, which can cause complications during delivery as well as increased risk of breathing problems.
Children born to women who have gestational diabetes have an increased risk of developing obesity and type 2 diabetes. In addition to endangering the fetus, gestational diabetes can also cause serious health risks for the mother, such as preeclampsia, a condition that involves high blood pressure during pregnancy.
Type 2 diabetes is caused by insulin resistance, in which the body does not properly use insulin. Type 2 diabetes is thought to result from a combination of genetic factors along with lifestyle factors, such as:
Genetic mutations likely affect parts of the insulin gene and various other physiologic components involved in the regulation of blood sugar. Some rare types of diabetes are directly linked to genes.
DIABETES SECONDARY TO OTHER CONDITIONS
Conditions that damage or destroy the pancreas, such as pancreatitis (inflammation), pancreatic surgery, or certain industrial chemicals, can cause diabetes. Certain genetic and hormonal disorders are associated with or increase the risk of diabetes.
High doses of statin drugs, which are used to lower cholesterol levels, may increase the risk of developing type 2 diabetes. Some types of drugs can also cause temporary diabetes, including:
More than 29 million American children and adults have diabetes. Up to 95% of these cases are type 2. In addition, 86 million American adults have pre-diabetes, a condition that increases the risk for developing diabetes. About 1 in 4 Americans have diabetes but do not know it. Diabetes rates have been increasing among both adults and children.
Risk factors that strongly increase the risk for diabetes or pre-diabetes include:
MEDICAL CONDITIONS ASSOCIATED WITH INCREASED RISK OF DIABETES
Obesity and Metabolic Syndrome: Obesity is the number one risk factor for type 2 diabetes. 85% of people with type 2 diabetes are overweight or obese. Excess body fat plays a strong role in insulin resistance, but the way the fat is distributed is also significant.
Weight concentrated around the abdomen and in the upper part of the body (apple-shaped) is associated with:
Waist circumferences greater than 35 inches in women and 40 inches in men are specifically associated with a greater risk for heart disease and diabetes. People with a "pear-shape", fat that settles around the hips and flank, appear to have a lower risk for these conditions. However, obesity does not explain all cases of type 2 diabetes.
Metabolic syndrome is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. The syndrome consists of:
Polycystic Ovary Syndrome (PCOS): PCOS is a condition that affects about 6% of women and results in the ovarian production of high amounts of androgens (male hormones), particularly testosterone. Women with PCOS are at higher risk for insulin resistance, and about half of the people with PCOS also have diabetes.
Depression: Severe clinical depression may modestly increase the risk for type 2 diabetes.
Schizophrenia: While no definitive association has been established, research has suggested an increased background risk of diabetes among people with schizophrenia. In addition, many of the new generation of antipsychotic medications can elevate the blood glucose level. People taking atypical antipsychotic medications (clozapine, olanzapine, risperidone, aripiprazole, quetiapine fumarate, and ziprasidone) should receive a baseline blood glucose level test and be monitored for any increases during therapy.
GESTATIONAL DIABETES RISK FACTORS
Gestational diabetes mellitus (GDM) is a type of diabetes that develops during the last trimester of pregnancy. A pregnant woman's risk factors include:
Women who have gestational diabetes are at increased risk of developing type 2 diabetes after their pregnancy. Guidelines recommend that women without diabetes symptoms should be screened for gestational diabetes at 24 to 28 weeks of pregnancy.
Women with risk factors for diabetes may be screened for GDM earlier in the pregnancy. They should also be tested for undiagnosed type 2 diabetes at the first prenatal visit.
Women diagnosed with GDM should be screened for persistent diabetes 6 to 12 weeks after giving birth and should be sure to have regular screenings at least every 3 years afterward.
Type 2 diabetes usually begins gradually and progresses slowly. Symptoms in adults include:
Symptoms in children are often different:
People with diabetes have higher death rates than people who do not have diabetes regardless of sex, age, or other factors. Heart disease and stroke are the leading causes of death in these people. All lifestyle and medical efforts should be made to reduce the risk for these conditions.
People with type 2 diabetes are also at risk for 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.
There is an association between high blood pressure (hypertension), unhealthy cholesterol level, and diabetes. People with diabetes are more likely than non-diabetics to have heart problems, and to die from cardiovascular complications, including heart attack and stroke.
Diabetes affects the heart in many ways:
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.
Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD). If the kidneys fail, dialysis is required. Symptoms of kidney failure may include:
NERVE DISORDERS (NEUROPATHY)
Diabetes reduces or distorts nerve function, causing a condition called neuropathy. Neuropathy refers to a group of disorders that affect nerves. The two main types of neuropathy are:
Peripheral neuropathy particularly affects sensation. It is a common complication for nearly half of people that have lived with type 1 or type 2 diabetes for more than 25 years. The most serious consequences of neuropathy occur in the legs and feet and pose a risk for ulcers and, in unusually severe cases, amputation. Peripheral neuropathy usually starts in the fingers and toes and moves up to the arms and legs (called a stocking-glove distribution). Symptoms include:
Autonomic neuropathy can cause:
Heart disease risk factors may increase the likelihood of developing neuropathy. Lowering triglycerides, losing weight, reducing blood pressure, and quitting smoking may help prevent the onset of neuropathy.
FOOT ULCERS AND AMPUTATIONS
About 15% of people with diabetes have serious foot problems. They are the leading cause of hospitalizations for these people.
Diabetes is responsible for more than half of all lower limb amputations performed in the U.S. Most amputations start with foot ulcers.
Those most at risk are people with a long history of diabetes, and people with diabetes who are overweight or who smoke. People who have the disease for more than 20 years and are insulin-dependent are at the highest risk. Related conditions that put people at risk include:
Foot ulcers usually develop from infections, such as those resulting from blood vessel injury. Foot infections often develop from injuries, which can dramatically increase the risk for amputation. Even minor infections can develop into severe complications. Numbness from nerve damage, which is common in diabetes, compounds the danger since the person may not be aware of injuries. About a third of foot ulcers occur on the big toe.
Charcot Foot: Charcot foot or Charcot joint (medically referred to as neuropathic arthropathy) is a degenerative condition that affects the bones and joints in the feet. It is associated with the nerve damage that occurs with neuropathy. Early changes appear similar to an infection, with the foot becoming swollen, red, and warm. Gradually, the 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 sensations in their foot and are not aware of an existing injury. Instead of resting an injured foot or seeking medical help, the person often continues normal activity, causing further damage.
People with diabetes are prone to foot problems because the disease can cause damage to the nerves and blood vessels, which may result in decreased ability to sense trauma to the foot. The immune system is also altered, so that the person cannot efficiently fight infection.
RETINOPATHY AND EYE COMPLICATIONS
Diabetes accounts for thousands of new cases of blindness annually and is the leading cause of new cases of blindness in adults age 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, such as primary-open angle glaucoma (POAG). The risk for POAG is especially high for women with type 2 diabetes.
Retinopathy is a condition in which the retina in the eye becomes damaged. Retinopathy generally occurs in one or two phases:
MENTAL FUNCTION AND DEMENTIA
Some studies indicate that people with type 2 diabetes, especially those who have severe instances of low blood sugar, face a higher than average risk of developing dementia. Diabetes can also cause problems with attention and memory.
Respiratory Infections: People with diabetes face a higher risk for influenza and its complications, including pneumonia. Everyone with diabetes should have annual influenza vaccinations 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.
Hepatitis: People with diabetes are at increased risk for contracting the hepatitis B virus, which is transmitted through blood and other bodily fluids. Exposure to the virus can occur through sharing fingerstick devices or blood glucose monitors. Adults newly diagnosed with type 1 or type 2 diabetes should get hepatitis B vaccinations.
Diabetes doubles the risk for depression. Depression, in turn, may increase the risk for high blood sugar level (hyperglycemia) and the complications of diabetes.
Tight blood sugar (glucose) control increases the risk of low blood sugar (hypoglycemia). Hypoglycemia, also called insulin shock, occurs if blood glucose level falls below normal. It is generally defined as a blood sugar level below 70 mg/dL, although this level may not necessarily cause symptoms in all people.
Hypoglycemia may also be caused by insufficient intake of food, or excess exercise or alcohol. Usually the condition is manageable, but occasionally, it can be severe or even life-threatening, particularly if the person fails to recognize the symptoms, especially while continuing to take insulin or other hypoglycemic drugs.
Mild hypoglycemia is common among people with type 2 diabetes, but severe episodes are rare, even among those taking insulin. Still, people who intensively control their blood sugar (glucose) level should be aware of warning symptoms.
Hypoglycemia Symptoms: Mild symptoms usually occur at moderately low and easily correctable level of blood glucose. They include:
Severely low blood glucose level can cause neurologic symptoms, such as:
[For information on preventing hypoglycemia or managing an attack, see Home Management section of this report.]
DIABETIC KETOACIDOSIS (DKA)
Diabetic ketoacidosis (DKA) is a life-threatening complication caused by a complete (or almost complete) lack of insulin. In DKA, the body produces abnormally high levels of blood acids called ketones. Ketones are byproducts of fat breakdown that build up in the blood and appear in the urine. They are produced when the body burns fat instead of glucose for energy. The buildup of ketones in the body is called ketoacidosis. Extreme stages of diabetic ketoacidosis can lead to coma and death.
DKA is usually a complication of type 1 diabetes. In such cases, it is nearly always due to noncompliance with insulin treatments. However, in rare cases DKA can also occur in people with type 2 diabetes, usually due to a serious infection or another severe illness.
HYPERGLYCEMIC HYPEROSOMOLAR NONKETONIC SYNDROME (HHNS)
Hyperglycemic hyperosmolar nonketonic syndrome (HHNS) is a serious complication of diabetes that involves a cycle of an increasing blood sugar level and dehydration, without ketones. HHNS usually occurs with type 2 diabetes, but it can also occur with type 1 diabetes. It is often triggered by a serious infection or another severe illness, or by medications that lower glucose tolerance or increase fluid loss; especially in people who are not drinking enough fluids.
Symptoms of HHNS include:
HHNS can lead to loss of consciousness, seizures, coma, and death.
Diabetes increases the risk for developing other conditions, including:
SPECIFIC COMPLICATIONS IN WOMEN
Diabetes can cause specific complications in women. Women with diabetes have an increased risk of recurrent yeast infections. In terms of sexual health, diabetes may cause decreased vaginal lubrication, which can lead to pain or discomfort during intercourse.
Women with diabetes should be aware that certain types of medication can affect their blood glucose level. For example, birth control pills can raise their blood glucose level. Long-term use (more than 2 years) of birth control pills may increase the risk of health complications. Thiazolidinedione drugs such as rosiglitazone (Avandia) and pioglitazone (Actos) can prompt renewed ovulation in premenstrual women who are not ovulating, and can weaken the effect of birth control pills.
Diabetes and Pregnancy: Diabetes that occurs during pregnancy (gestational diabetes) and pregnancy in a person with existing diabetes can increase the risk for birth defects. A high blood sugar level (hyperglycemia) can affect the developing fetus during the critical first 6 weeks of organ development.
Women with diabetes (either type 1or type 2) who are planning on becoming pregnant should strive to maintain good glucose control for 3 to 6 months before pregnancy. Those who are overweight or obese should try to lose weight before becoming pregnant. It is also important for women to closely monitor their blood sugar level during pregnancy. For women with type 2 diabetes who take insulin, pregnancy can affect their insulin dosing needs. Insulin dosing may also need to be adjusted following delivery.
Diabetes and Menopause: The changes in estrogen and other hormonal levels that occur during perimenopause can cause major fluctuations in blood glucose level. Women with diabetes also face an increased risk of premature menopause, which can lead to higher risk of heart disease.
Healthy adults age 45 and older should get tested for diabetes every 3 years. People who have certain risk factors should ask their doctors about testing at an earlier age and more frequently. These risk factors include:
Children age 10 and older should be tested for type 2 diabetes (even if they have no symptoms) every 3 years if they are overweight and have at least two risk factors.
TESTING FOR DIABETES AND PRE-DIABETES
Pre-diabetes precedes the onset of type 2 diabetes. People who have pre-diabetes have a fasting blood glucose level that is higher than normal, but not yet high enough to be classified as diabetes. Pre-diabetes greatly increases the risk for diabetes.
There are three tests that can be used to diagnose diabetes or identify pre-diabetes:
FASTING PLASMA GLUCOSE TEST
The fasting plasma glucose (FPG) test is the standard test for diabetes. It is a simple blood test taken after 8 hours of fasting. FPG level indicates:
The FPG test is not always reliable, so a repeat test is recommended if the initial test suggests the presence of diabetes, or if the test is normal in people who have symptoms or risk factors for diabetes.
ORAL GLUCOSE TOLERANCE TEST
The oral glucose tolerance test (OGTT) is more complex than the FPG and may over-diagnose diabetes in people who do not have it. Some doctors recommend it as a follow-up after FPG, if the latter test results are normal but the person has symptoms or risk factors of diabetes. The test uses the following procedures:
OGTT level indicates:
The person cannot eat for at least 8 hours prior to the FPG and OGTT tests.
HEMOGLOBIN A1C TEST
This test examines blood levels of glycosylated hemoglobin, also known as hemoglobin A1C (HbA1c or A1C). The results are given in percentages and indicate a person's average blood glucose level over the past 2 to 3 months. FPG and OGTT show a person's glucose level for only the time of the test. The A1C test is not affected by recent food intake so people do not need to fast to prepare for the blood test.
In addition to providing information on blood sugar control and diabetes treatment, the A1C test may also be used as an alternative test for diagnosing diabetes and identifying pre-diabetes.
A1C level indicates:
A1C tests are also used to help people with diabetes monitor how well they are keeping their blood glucose levels under control. For people with diabetes, A1C is measured periodically every 2 to 3 months, or at least twice a year. While fingerprick self-testing provides information on blood glucose for that day, the A1C test shows how well blood sugar has been controlled over the period of several months. In general, most people with diabetes should aim for an A1C level of around 7%. Your doctor may adjust this goal depending on your individual health profile.
The American Diabetes Association (ADA) recommends that results from the A1C test be used to calculate the estimated average glucose (eAG). eAG is a term that people may see on lab results from their A1C tests. It converts the A1C percentages into the same mg/dL units that people are familiar with from their daily home blood glucose tests. For example, an A1C of 7% is equal to an eAG of 154 mg/dL. The eAG terminology can help people to better interpret the results of their A1C tests and make it easier to correlate A1C with results from home blood glucose monitoring.
SCREENING FOR GESTATIONAL DIABETES MELLITUS (GDM)
The ADA recommends screening for gestational diabetes:
SCREENING TESTS FOR COMPLICATIONS
Screening for Heart Disease: People with diabetes should be:
Other tests may be needed for people with signs of heart disease.
The electrocardiogram (ECG or EKG) is used extensively in the diagnosis of heart disease, from congenital heart disease in infants to myocardial infarction and myocarditis in adults. Several different types of electrocardiogram exist.
Screening for Kidney Damage: The earliest manifestation of kidney damage is microalbuminuria, in which tiny amounts of a protein called albumin are found in the urine. Microalbuminuria typically shows up in people with type 2 diabetes who also have high blood pressure.
The ADA recommends that people with diabetes receive an annual urine test for albumin. People should also have their blood creatinine tested at least once a year. Creatinine is a waste product that is removed from the blood by the kidneys. A high level of creatinine may indicate kidney damage. A doctor uses the results from a creatinine blood test to calculate the glomerular filtration rate (GFR). GFR is an indicator of kidney function; it estimates how well the kidneys are cleansing the blood.
Screening for Retinopathy: The ADA recommends that people with type 2 diabetes get an initial comprehensive eye exam by an ophthalmologist or optometrist shortly after they are diagnosed with diabetes, and once a year thereafter. People at low risk may need follow-up exams only every 2 to 3 years.
The eye exam should include dilation of the pupil to check for signs of retinal disease (retinopathy). In addition to a comprehensive eye exam, fundus photography may be used as a screening tool. Fundus photography uses a special type of camera to take images of the back of the eye.
Screening for Neuropathy: People should be screened for nerve damage (neuropathy), including a comprehensive foot exam. People who lose sensation in their feet should have a foot exam every 3 to 6 months to check for ulcers or infections. People should also be screened for intermittent claudication and peripheral artery disease (PAD) using the ankle-brachial index for diagnosis.
Good nutrition and regular physical activity can help prevent or manage medical complications of diabetes (heart disease and stroke) and help people live longer and healthier lives.
There is no such thing as a single diabetes diet. People should meet with a professional dietitian to plan an individualized diet within the general guidelines that takes into consideration their own health needs. Diabetes self-management education programs can also provide valuable nutritional advice.
The American Diabetes Association (ADA) no longer advises a uniform ideal percentage of daily calories for carbohydrates, fats, or protein for all people with diabetes. Rather, these amounts should be individualized, based on your unique health profile.
Healthy eating habits along with good control of blood glucose are the basic goals, and several good dietary methods are available to meet them. Recommended eating plans include Mediterranean, vegetarian, and lower-carbohydrate diets. What is most important is to find a healthy eating plan that works best for you and your lifestyle and food preferences. Whatever eating plan you follow, try to eat a variety of nutrient-rich food in appropriate portion sizes.
The ADA's most recent nutritional guidelines for recommendations include:
Being overweight is the number one risk factor for type 2 diabetes. Even modest weight loss can help prevent type 2 diabetes from developing. It can also help control or even stop progression of type 2 diabetes in people with the condition and reduce risk factors for heart disease. People should lose weight if their body mass index (BMI) is 25 to 29 (overweight) or higher (obese).
The American Diabetes Association recommends that people aim for a small but consistent weight loss of ½ to 1 pound per week. Most people should follow a diet that supplies at least 1,000 to 1,200 kcal/day for women and 1,200 to 1,600 kcal/day for men.
People who are obese with type 2 diabetes who have a BMI greater than 35 may consider having bariatric surgery to help improve their blood glucose levels.
Sedentary habits, especially watching TV and sitting in front of a computer, are associated with significantly higher risks for obesity and type 2 diabetes. Regular exercise and physical activity, even of moderate intensity (brisk walking), improves insulin sensitivity and may play a role in preventing type 2 diabetes, regardless of weight loss.
Aerobic Exercise: Aerobic activity has significant and particular benefits for people with diabetes. Regular aerobic exercise, even of moderate intensity, improves insulin sensitivity. The heart-protective effects of aerobic exercise are also important, even if people have no risk factors for heart disease other than diabetes itself.
For improving blood sugar control, the ADA recommends at least 150 minutes per week of moderate-intensity physical activity (50 to 70% of maximum heart rate) or at least 90 minutes per week of vigorous aerobic exercise (more than 70% of maximum heart rate). Exercise at least 3 days a week, and do not go more than 2 consecutive days without physical activity.
Strength Training: Strength training, which increases muscle and reduces fat, is also helpful for people with diabetes who are able to do this type of exercise. The ADA recommends performing resistance exercise three times a week. Build up to three sets of 8 to 10 repetitions using weight that you cannot lift more than 8 to 10 times without developing fatigue. Be sure that your strength training targets all of the major muscle groups.
Exercise Precautions: The following are precautions for all people with diabetes; both type 1 and type 2:
People who are taking medications that lower blood glucose, particularly insulin, should take special precautions before starting a workout program:
WARNING ON DIETARY SUPPLEMENTS
Various fraudulent products are often sold on the Internet as "cures" or treatments for diabetes. These dietary supplements have not been studied or approved. The FDA warns people with diabetes not to be duped by bogus and unproven remedies.
According to the ADA, there is no evidence to support herbal remedies or dietary supplements (including fish oil supplements) for the treatment of diabetes. There is no evidence that vitamin or mineral supplements can help people with diabetes who do not have underlying nutritional deficiencies.
MANAGEMENT OF PRE-DIABETES
Treatment of pre-diabetes is very important. Lifestyle changes and medical interventions can help prevent, or at least delay, the progression to diabetes, as well as lower their risk for heart disease.
MANAGEMENT OF TYPE 2 DIABETES
The major treatment goals for people with type 2 diabetes are to control blood glucose level and to treat all conditions that place people at risk for heart disease, stroke, kidney disease, and other major complications.
Approaches to controlling blood glucose levels include:
Approaches for reducing complications include:
Glucose Goals for Patients with Diabetes
Blood glucose level before meals
Less than 100 mg/dL
70 to 130 mg/dL for adults
100 to 180 mg/dL for children under age 6
90 to 180 mg/dL for children 6 to 12 years old
90 to 130 mg/dL for children 13 to 19 years old
Bedtime blood glucose level
Less than 120 mg/dL
Less than 180 mg/dL for adults
110 to 200 mg/dL for children under age 6
100 to 180 mg/dL for children 6 to 12 years old
90 to 150 mg/dL for children 13 to 19 years old
Hemoglobin A1C level
Less than 5.7%
Less than or around 7% for adults
Less than 8.5% for children under age 6
Less than 8% for children 6 to 12 years old
Less than 7.5% for children 13 to 19 years old
Major source: Standards of Medical Care In Diabetes -- 2014, American Diabetes Association.
TREATING SPECIAL POPULATIONS
Different goals may be necessary for specific individuals, including:
Treating children with type 2 diabetes depends on the severity of the condition at diagnosis. Metformin is approved for children. Formerly, only insulin was approved for treating children with diabetes.
The American Diabetes Association (ADA) does not recommend tight blood glucose control for children because glucose is necessary for brain development. Elderly people should not generally be placed on tight control as low blood sugar can increase the risk of stroke or heart attack.
HIGH BLOOD PRESSURE AND HEART DISEASE
People with diabetes and high blood pressure should make lifestyle changes. These include:
Reducing Blood Pressure: In general, people with diabetes should strive for blood pressure levels of less than 140/80 mm Hg (systolic/diastolic). For some people, especially younger people, a systolic blood pressure goal of less than 130 mm Hg may be appropriate.
People with diabetes and high blood pressure need an individualized approach to drug treatment, based on their particular health profile. Dozens of anti-hypertensive drugs are available. The most beneficial fall into the following categories:
Nearly all people who have diabetes and high blood pressure should take an ACE inhibitor as part of their regimen for treating hypertension. These drugs help prevent heart and kidney damage, and are recommended as the best first-line drugs for people with diabetes and hypertension. An angiotensin-receptor blocker (ARB) is recommended for patients who cannot tolerate ACE inhibitors.
Improving Cholesterol and Lipid Levels: Abnormal cholesterol and lipid levels are common in diabetes. High LDL (bad) cholesterol should always be lowered, but people with diabetes also often have additional harmful imbalances, including low HDL (good) cholesterol and high triglycerides.
Adults should aim for LDL levels below 100 mg/dL, HDL levels over 50 mg/dL, and triglyceride levels below 150 mg/dL. People with diabetes and heart disease should strive for even lower LDL levels. The American Diabetes Association (ADA) recommends LDL levels below 70 mg/dL for these people.
Children should be treated for LDL cholesterol above 160 mg/dL, or above 130 mg/dL if other cardiovascular risk factors are present.
Lifestyle changes for cholesterol management in people with diabetes focus on:
For medications, statins are the best cholesterol-lowering drugs. They include:
Juvisync is a two-in-one pill that combines the statin simvastatin with the diabetes drug sitagliptin (Juvisync).
These drugs are very effective for lowering LDL cholesterol levels. However, they may increase blood glucose levels in some people, especially when taken in high doses. They may also increase the risk for developing type 2 diabetes in people who have risk factors. Still, statin drugs are considered generally safe. If one statin drug does not work or has side effects, the doctor may recommend switching to a different statin.
The primary safety concern with statins 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.
Aspirin for Heart Disease Prevention: For people with diabetes who have additional heart disease risk factors, taking a daily aspirin can reduce the risk for blood clotting and may help protect against heart attacks. There is not enough evidence to indicate that aspirin prevention is helpful for people at lower risk. These risk factors include:
The recommended dose is 75 to 162 mg/day. Talk to your doctor, particularly if you are at risk for aspirin side effects such as gastrointestinal bleeding and ulcers.
Surgery for Heart Disease: People with heart disease that has caused blockage in the arteries, angina (chest pain), and other symptoms may require surgery. The two main types of surgical procedures are percutaneous coronary intervention (commonly called PCI or angioplasty) with stenting and coronary artery bypass grafting (CABG). Although PCI and stenting is less invasive than CABG, recent research indicates that CABG is safer and works better for people with diabetes who have multiple blockages in their arteries.
TREATMENT OF RETINOPATHY
People with severe diabetic retinopathy or macular edema (swelling of the retina) should be sure to see an eye specialist who is experienced in the management and treatment of diabetic retinopathy. Once damage to the eye develops, laser or photocoagulation eye surgery may be needed. Laser surgery can help reduce vision loss in high-risk people. Drug therapy with anti-vascular endothelial growth factor (VEGF) is also recommended for treatment of diabetic macular edema.
TREATMENT OF FOOT ULCERS
About a third of foot ulcers will heal within 20 weeks with good wound care treatments. Some treatments are as follows:
Other Treatments for foot ulcers: Doctors are also using or investigating other treatments to heal ulcers. These include:
TREATMENT OF DIABETIC NEUROPATHY
The only FDA-approved drugs for treating neuropathy are pregabalin (Lyrica) and duloxetine (Cymbalta). Other drugs and treatments are used on an off-label basis.
The American Academy of Neurology's (AAN) guidelines for treating painful diabetic neuropathy recommend:
Non-drug treatments: Percutaneous electrical nerve stimulation (PENS) may help some people. PENS uses electrodes attached to precisely placed acupuncture-type needles to deliver electrical current to peripheral sensory nerves. Doctors also recommend lifestyle measures, such as walking and wearing elastic stockings.
Treatments for other complications of neuropathy: Neuropathy also impacts other functions, and treatments are needed to reduce their effects. 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. People need to watch their nutrition if the problem is severe.
Erectile dysfunction is also associated with neuropathy. Studies indicate that phosphodiesterase type 5 (PDE-5) drugs, such as sildenafil (Viagra), vardenafil (Levitra), tadalafil (Cialis), and avanafil (Stendra) are safe and effective, at least in the short term, for many people with diabetes. People who take nitrate medications for heart disease cannot use PDE-5 drugs.
TREATMENT OF KIDNEY PROBLEMS
Good control of blood sugar and blood pressure is essential for preventing the onset of kidney disease and for slowing the progression of the disease.
ACE inhibitors are the best class of blood pressure medications for delaying kidney disease and slowing disease progression in people with diabetes. Angiotensin-receptor blockers (ARBs) are also very helpful. The calcium channel blockers diltiazem and verapamil can also reduce protein excretion by diabetic kidneys.
Anemia: Anemia is a common complication of end-stage kidney disease. People on dialysis usually need injections of erythropoiesis-stimulating drugs to increase red blood cell counts and control anemia. However, these drugs, including darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit), can increase the risk of blood clots, stroke, heart attack, and heart failure in people with end-stage kidney disease when they are given at higher than recommended doses.
The FDA recommends that people with end-stage kidney disease who receive erythropoiesis-stimulating drugs should:
Many types of anti-hyperglycemic drugs are available to help people with type 2 diabetes control their blood sugar levels. Most of these drugs are aimed at using or increasing sensitivity to the person's own natural stores of insulin.
Older oral hypoglycemic drugs, particularly metformin, are less expensive and generally work as well as newer diabetes drugs. Metformin is usually recommended as the first-line drug.
Adding a second oral hypoglycemic drug may be recommended if adequate control is not achieved with the first medication. For the most part, doctors should add a second drug rather than trying to push the first drug dosage to the highest levels.
Metformin (Glucophage and generic) is a biguanide, which works by reducing glucose production in the liver and by making tissues more sensitive to insulin. Doctors recommend it as a first choice for most people with type 2 diabetes. Metformin may also be used in combination with other drugs.
Metformin does not cause hypoglycemia or add weight, so it is particularly well-suited for people who are obese with type 2 diabetes. Metformin also appears to have beneficial effects on cholesterol and lipid levels and may help protect the heart. It is also the first choice for children who need oral drugs.
Side effects may include:
Certain people should not use this drug, including anyone with heart failure or kidney or liver disease. It is rarely suitable for adults over age 80.
Sulfonylureas are oral drugs that stimulate the pancreas to release insulin. A number of brands are available including chlorpropamide (Diabinese and generic), tolazamide (Tolinase and generic), glipizide (Glucotrol and generic), tolbutamide (Orinase and generic), glyburide (Micronase and generic), and glimepiride (Amaryl and generic). For adequate control of blood glucose levels, the drugs should be taken 20 to 30 minutes before a meal.
Most people can take sulfonylureas for 7 to 10 years before they lose effectiveness. Combinations with small amounts of insulin or other oral anti-hyperglycemic drugs (metformin or a thiazolidinedione) may extend their benefits. A combination of glyburide and metformin in one pill (Glucovance) is available.
Side effects and complications: In general, women who are pregnant or nursing or individuals who are allergic to sulfa drugs should not use sulfonylureas. Side effects may include:
Sulfonylureas interact with many other drugs, and people must inform their doctor of any medications they are taking, including over-the-counter drugs or herbal supplements.
Meglitinides stimulate beta cells to produce insulin. They include repaglinide (Prandin) and nateglinide (Starlix and generic). These drugs are rapidly metabolized and short-acting and therefore have a lower risk of hypoglycemia. If taken before every meal, they tend to mimic the normal effects of insulin after eating. People, then, can vary their meal times with this drug. These drugs often used in combination with metformin or other drugs.
Side effects: Side effects include diarrhea and headache. As with the sulfonylureas, repaglinide poses a slightly increased risk for cardiac events. Newer drugs, such as nateglinide, may pose less of a risk. People with heart failure or liver disease should use them with caution and be monitored.
Thiazolidinediones, also known as peroxisome proliferator-activated receptor (PPAR) agonists, include pioglitazone (Actos and generic) and rosiglitazone (Avandia). Thiazolidinediones are taken as pills, usually in combination with other oral drugs or insulin. Thiazolidinediones available as 2-in-1 pills include rosiglitazone and metformin (Avandamet), rosiglitazone and glimepiride (Avandaryl), pioglitazone and metformin (ACTOPLUS MET), and pioglitazone and glimepiride (Duetact).
Side Effects: Thiazolidinediones can have serious side effects. They can increase fluid build-up, which can cause or worsen heart failure in some people and often leads to water retention and swelling (edema) in the feet and legs. Combinations with insulin increase the risk. People with heart failure should not use them. People with risk factors for heart failure should use these drugs with caution.
In particular, there have been concerns that rosiglitazone increases the risks for heart attack and heart failure and should be restricted to only certain people. In 2013, the FDA lifted these restrictions, citing studies that indicated the drug posed no heightened risk for heart attack or death.
Thiazolidinediones may cause more weight gain than other diabetes medications or insulin. Any person who has sudden weight gain, water retention, or shortness of breath should immediately call their doctor. Thiazolidinediones can also cause liver damage. People who take these drugs should have their liver enzymes checked regularly.
Other health concerns associated with thiazolidinediones included possible increased risks for:
Alpha-glucosidase inhibitors, including acarbose (Precose and generic) and miglitol (Glyset), reduce glucose levels by interfering with the absorption of starch in the small intestine. Acarbose tends to lower insulin levels after meals, a particular advantage, since higher levels of insulin after meals are associated with an increased risk for heart disease.
Side effects: These medications need to be taken with meals. Unfortunately, about a third of people stop taking the drug because of flatulence and diarrhea, particularly after high-carbohydrate meals. The drug may also interfere with iron absorption.
Alpha-glucosidase inhibitors do not cause hypoglycemia when used alone, but combinations with other drugs do. In such cases, it is important that the person receives a solution that contains glucose or lactose, not table sugar. This is because acarbose inhibits the breakdown of complex sugar and starches, which includes table sugar.
GLP-1 INHIBITORS (EXENATIDE, LIRAGLUTIDE, AND ALBIGLUTIDE)
Incretin mimetics belong to a new class of drugs that help improve blood sugar control. Incretins include glucagon-like peptide-1 (GLP-1) inhibitors and DDP-4 inhibitors.
GLP-1 inhibitors are given by injection and are prescribed for people with type 2 diabetes who have not been able to control their glucose with metformin or a sulfonylurea drug. They can be taken in combination with these drugs or alone.
Exenatide (Byetta) was the first GLP-1 inhibitor drug. It is a synthetic version of the hormone found in the saliva of the Gila monster, a venomous desert lizard. Exenatide is injected twice a day, 1 hour before morning and evening meals. Bydureon is an extended-release version of Byetta that requires injection only once a week. Liraglutide (Victoza) is another GLP-1 inhibitor that is injected once a day. Albiglutide (Tanzeum) is the newest approved GLP-1 inhibitor.
Side effects: These drugs stimulate insulin secretion only when blood sugar levels are high and so have less risk for causing low blood sugar (hypoglycemia) when they are taken alone. However, the risk for hypoglycemia increases when GLP-1 inhibitors are taken along with a sulfonylurea drug. There does not appear to be a risk for hypoglycemia when they are used along with metformin.
Other side effects may include nausea, and reduced appetite. Exenatide may cause new or worse problems with kidney function, including kidney failure. People with severe kidney problems should not use this drug.
There have been safety concerns that incretin mimetics may be associated with pancreatitis (inflammation of the pancreas) and pancreatic cancer. In 2014, the U.S. FDA and the European Medicines Agency released a joint assessment that these drugs do not appear to cause pancreatic conditions.
DPP-4 INHIBITORS (GLIPTINS)
Dipeptidyl peptidase-4 (DPP-4) inhibitors, also called gliptins, are the second class of drugs that work through the incretin pathway. They include sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), and alogliptin (Nesina).
DPP-4 inhibitors work in a similar way to GLP-1 mimetics except they use the body's own incretins. However, unlike GLP-1 mimetics, which are given by injection, DPP-4 inhibitor drugs are taken as pills. They can be used alone or in combination with another oral diabetes drug (metformin, thiazolidinediones, or sulfonylureas).
These drugs are also available as two-in-one pills:
Like GLP-1 inhibitors, DPP-4 inhibitors do not cause weight gain, have low risks for hypoglycemia, and have few severe side effects. Side effects are uncommon, but may include upper respiratory tract infection, sore throat, and diarrhea.
In 2014, the FDA announced it was reviewing possible heart failure risks associated with saxagliptin.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of diabetes drugs. In 2013, the FDA approved the first of these drugs, canagliflozin (Invokana) for treatment of adults with type 2 diabetes. A second SGLT2 inhibitor, dapagliflozin (Farxiga) was approved in early 2014. These drugs help lower blood glucose levels by blocking the kidney's reabsorption of glucose.
SGLT2 inhibitors can be used alone or in combination with other types of diabetes drugs (metformin, sulfonylurea, pioglitazone, and insulin). They should not be used by people who have diabetic ketoacidosis or moderate-to-severe kidney impairment. The FDA is reviewing possible heart risks associated with dapagliflozin and whether this drug increases the risk for bladder cancer.
Common side effects include vaginal yeast infection and urinary tract infections. During the initial months of treatment, this drug may cause dehydration, which can lead to decreased blood pressure and dizziness when standing up (orthostatic hypotension).
Pramlintide (Symlin) is an injectable drug that may help people who take insulin but still need better blood sugar control. Pramlintide is a synthetic form of amylin, a hormone that is related to insulin. Pramlintide is used in combination with insulin to lower blood sugar levels in the 3 hours after meals.
DOPAMINE AGONISTS (CYCLOSET)
Bromocriptine mesylate (Cycloset) is an oral drug that may help improve blood sugar control in addition to diet and exercise. Bromocriptine helps boost the level of dopamine, a nerve chemical (neurotransmitter). Bromocriptine is used in other formulations, and usually in higher doses, for treatment of Parkinson disease. Common side effects may include nausea, vomiting, headache, dizziness, and fatigue.
Insulin replacement may be necessary when natural insulin reserves are depleted or insulin resistance cannot be overcome with oral medications. It is typically started in combination with an oral drug (usually metformin).
Because type 2 diabetes is progressive, many people eventually need insulin. However, when a single oral drug fails to control blood sugar it is not clear whether it is better to add insulin replacement or a second or third oral drug.
Some doctors advocate using insulin as early as possible for optimal control. However, in people who still have insulin reserves, there is concern that extra natural insulin will have adverse effects. Low blood sugar (hypoglycemia) and weight gain are the main side effects of insulin therapy. It is still not clear if insulin replacement improves survival rates compared to oral drugs, notably metformin.
Forms of Insulin -- The two main insulin types are rapid-acting insulin and basal insulin:
In general, there is no advantage to dosing insulin more than two times a day for people with type 2 diabetes.
MONITORING BLOOD GLUCOSE (BLOOD SUGAR) LEVEL
Both low blood sugar (hypoglycemia) and high blood sugar (hyperglycemia) are of concern, especially for people who take insulin. Blood sugar (glucose) level is generally more stable in type 2 diabetes than in type 1, so most people with type 2 diabetes need to check blood sugar level only once or twice a day. People with well-controlled blood sugar may need to test only a few times a week. For people with less stable blood sugar or those who have become insulin-dependent, more intensive monitoring is necessary.
People should aim for the following measurements:
Different goals may be required for specific individuals, including:
Finger-Prick Test -- A typical blood sugar test includes the following:
Home monitors are less accurate than laboratory monitors and many do not meet the standards of the American Diabetes Association (ADA.) However, they are usually accurate enough to indicate when blood sugar is too low.
Some simple procedures may improve accuracy:
For people who have trouble controlling hypoglycemia (low blood sugar) or a fluctuating blood sugar level, continuous glucose sensor monitors are also available. Continuous glucose sensor monitors do not replace fingerstick glucose meters and test strips, but are used in combination with them.
To monitor the amount of glucose within the blood a person with diabetes should test their blood regularly. The procedure is quite simple and can often be done at home.
The following tips may help avoid hypoglycemia or prepare for attacks:
Family and friends should be aware of the symptoms and be prepared:
People are encouraged to wear at all times a medical alert ID bracelet or necklace that states they have diabetes. If people take insulin, that information should be included as well.
Measures to prevent foot ulcers: Preventive foot care can significantly reduce the risk of ulcers and amputation. Some tips for preventing problems include:
ACCORD Study Group, Gerstein HC, Miller ME, et al. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011;364(9):818-828.
ACCORD Study Group, Ginsberg HN, Elam MB, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1563-1574.
Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545-2559.
Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640-1645.
American Diabetes Association. Standards of medical care in diabetes -- 2014. Diabetes Care. 2014;37(Suppl 1):S14-S80.
Blumer I, Hadar E, Hadden DR, et al. Diabetes and pregnancy: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(11):4227-4249.
Bril V, England J, Franklin GM, et al. Evidence-based guideline: treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology. 2011;76(20):1758-1765.
Carlsson LM, Peltonen M, Ahlin S, et al. Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. N Engl J Med. 2012;367(8):695-704.
Centers for Disease Control and Prevention. National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States, 2014. Atlanta, GA: U.S. Department of Health and Human Services; 2014.
Centers for Disease Control and Prevention. Use of hepatitis B vaccination for adults with diabetes mellitus: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 2011;60(50):1709-1711.
Cheng J, Zhang W, Zhang X, et al. Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on all-cause mortality, cardiovascular deaths, and cardiovascular events in patients with diabetes mellitus: a meta-analysis. JAMA Intern Med. 2014;174(5):773-785.
Copeland KC, Silverstein J, Moore KR, et al. Management of newly diagnosed type 2 diabetes mellitus (T2DM) in children and adolescents. Pediatrics. 2013;131(2):364-682.
Egan AG, Blind E, Dunder K, et al. Pancreatic safety of incretin-based drugs -- FDA and EMA assessment. N Engl J Med. 2014;370(9):794-797.
Evert AB, Boucher JL, Cypress M, et al. Position statement: Nutrition therapy recommendations for the management of adults with diabetes. Diabetes Care. 2013 Nov;36(11):3821-3842.
Farkouh ME, Domanski M, Sleeper LA, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med. 2012;367(25):2375-2384.
Garber AJ, Handelsman Y, Einhorn D, et al. Diagnosis and management of prediabetes in the continuum of hyperglycemia: when do the risks of diabetes begin? A consensus statement from the American College of Endocrinology and the American Association of Clinical Endocrinologists. Endocr Pract. 2008;14(7):933-946.
Giovannucci E, Harlan DM, Archer MC, et al. Diabetes and cancer: a consensus report. CA Cancer J Clin. 2010;60(4):207-221.
Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014; 63(25 Pt B):2935-2959.
Holman RR, Thorne KI, Farmer AJ, et al. Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes. N Engl J Med. 2007;357(17):1716-1730.
Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35(6):1364-1379.
Kaul S, Bolger AF, Herrington D, Giugliano RP, Eckel RH. Thiazolidinedione drugs and cardiovascular risks.a science advisory from the American Heart Association and American College of Cardiology Foundation. Circulation. 2010;121(16):1868-1877.
Lipsky BA, Berendt AR, Cornia PB, et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012;54(12):e132-e173.
Moyer VA; U.S. Preventive Services Task Force. Screening for gestational diabetes mellitus: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;160(6):414-420.
Nathan DM, Kuenen J, Borg R, et al; A1C-Derived Average Glucose Study Group. Translating the A1C assay into estimated average glucose values. Diabetes Care. 2008;31(8):1473-1478.
Pignone M, Alberts MJ, Colwell JA, et al. Aspirin for primary prevention of cardiovascular events in people with diabetes: a position statement of the American Diabetes Association, a scientific statement of the American Heart Association, and an expert consensus document of the American College of Cardiology Foundation. Circulation. 2010;121(24):2694-2701.
Qaseem A, Humphrey LL, Guidelines Committee of the American College of Physicians. Oral pharmacologic treatment of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2012;156(3):218-231.
Rosenzweig JL, Ferrannini E, Grundy SM, et al. Primary prevention of cardiovascular disease and type 2 diabetes in patients at metabolic risk: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2008;93(10):3671-3689.
Shen L, Shah BR, Reyes EM, et al. Role of diuretics, ß blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study. BMJ. 2013;347:f6745.
Skyler JS, Bergenstal R, Bonow RO, et al. Intensive glycemic control and the prevention of cardiovascular events:implications of the ACCORD, ADVANCE, and VA diabetes trials: a position statement of the American Diabetes Association and a scientific statement of the American College of Cardiology Foundation and the American Heart Association. Diabetes Care. 2009;32(1):187-192.
Springer SC, Silverstein J, Copeland K, et al. Management of type 2 diabetes mellitus in children and adolescents. Pediatrics. 2013;131(2):e648-e664.
Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/american Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25 Pt B):2889-2934.
U.S. Preventive Services Task Force. Screening for type 2 diabetes mellitus in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;148(11):846-854.