According to the U.S. Centers for Disease Control and Prevention’s (CDC) National Diabetes Fact Sheet, nearly 26 million American adults and children have diabetes. About 79 million Americans aged 20 years and older have pre-diabetes, a condition that increases the risk for developing diabetes.
Type 2 Diabetes Risk Factors
Risk factors for type 2 diabetes and pre-diabetes include:
The FDA is investigating whether incretin mimetics may increase the risk for pre-cancerous changes in the pancreas (pancreatic duct metaplasia). These drugs’ prescribing labels already include warnings about possible increased risk for pancreatitis (inflammation of the pancreas). Incretin mimetics include the GLP-1 inhibitors exenatide (Byetta, Bydureon) and liraglutide (Victoza), and the DPP-4 inhibitors sitagliptin (Januvia, Janumet, Juvisync), saxagliptin (Onglyza, Kombiglyze), linagliptin (Tradjenta, Jentadueto) and alogliptin (Nesina, Kazano, Oseni). .
New Drug Approvals
The CDC now recommends that adults ages 19 - 59 years diagnosed with diabetes should receive vaccination to prevent hepatitis B. The hepatitis B virus is transmitted through blood. Unvaccinated patients 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 maturity-onset diabetes).
Both type 1 and type 2 diabetes share one central feature: elevated blood sugar (glucose) levels 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 behind the liver and is where the hormone insulin is produced. Insulin is used by the body to store and use glucose.
Type 2 diabetes is the most common form of diabetes, accounting for 90 - 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:
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. Patients 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 delivery complications 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 obesity, poor diet, high alcohol intake, and being sedentary.
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 some people’s chances of developing type 2 diabetes. Some types of drugs can also cause temporary diabetes including corticosteroids, beta blockers, and phenytoin.
Nearly 26 million American children and adults have diabetes. Up to 95% of these cases are type 2. In addition, 79 million American adults have pre-diabetes, a condition that increases the risk for developing diabetes.
Risk factors that strongly increase the risk for diabetes or pre-diabetes include:
Obesity and Metabolic Syndrome. Obesity is the number one risk factor for type 2 diabetes. 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 insulin resistance and diabetes, heart disease, high blood pressure, stroke, and unhealthy cholesterol levels. 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 abdominal obesity, unhealthy cholesterol and triglyceride levels, high blood pressure, and insulin resistance.
Polycystic Ovary Syndrome. Polycystic ovary syndrome (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 PCOS patients 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 may elevate blood glucose levels. Patients taking antipsychotic medications (such as 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 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. They should be screened for diabetes 6 - 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:
Patients 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 patients. 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 levels, 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 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 swelling in the feet and ankles, itching, fatigue, and pale skin color.
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 who 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.
About 15% of patients with diabetes have serious foot problems. They are the leading cause of hospitalizations for these patients.
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 peripheral neuropathy, peripheral artery disease, foot deformities, and a history of ulcers.
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 patient 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 sensation in the foot and are not aware of an existing injury. Instead of resting an injured foot or seeking medical help, the patient often continues normal activity, causing further damage.
Diabetes accounts for thousands of new cases of blindness annually and is the leading cause of new cases of blindness in adults age 20 - 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:
Some studies indicate that patients 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. Patients 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 finger-stick 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 levels (hyperglycemia) and 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 levels fall below normal. It is generally defined as blood sugar level below 70 mg/dL, although this level may not necessarily cause symptoms in all patients. 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 patient 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, all patients who intensively control blood sugar (glucose) levels should be aware of warning symptoms.
Hypoglycemia Symptoms. Mild symptoms usually occur at moderately low and easily correctable levels of blood glucose. They include:
Severely low blood glucose levels 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) 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 patients with type 2 diabetes, usually due to a serious infection or another severe illness.
Hyperglycemic hyperosmolar nonketonic syndrome (HHNS) is a serious complication of diabetes that involves a cycle of increasing blood sugar levels 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 high blood sugar levels, dry mouth, extreme thirst, dry skin, and high fever. HHNS can lead to loss of consciousness, seizures, coma, and death.
Diabetes increases the risk for developing other conditions, including:
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 levels. For example, birth control pills can raise blood glucose levels. 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. Both temporary diabetes that occurs during pregnancy (gestational diabetes) and pregnancy in a patient with existing diabetes can increase the risk for birth defects. High blood sugar levels (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 - 6 months before pregnancy. It is also important for women to closely monitor their blood sugar levels 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 levels. 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. Patients 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.
Pre-diabetes precedes the onset of type 2 diabetes. People who have pre-diabetes have fasting blood glucose levels that are higher than normal, but not yet high enough to be classified as diabetes. (Pre-diabetes used to be referred to as “impaired glucose tolerance.”) Pre-diabetes greatly increases the risk for diabetes.
There are three tests that can be used to diagnose diabetes or identify pre-diabetes:
The fasting plasma glucose (FPG) test has been the standard test for diabetes. It is a simple blood test taken after 8 hours of fasting. FPG levels indicate:
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.
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 patient has symptoms or risk factors of diabetes. The test uses the following procedures:
OGTT levels indicate:
The patient cannot eat for at least 8 hours prior to the FPG and OGTT tests.
This test examines blood levels of glycosylated hemoglobin, also known as hemoglobin A1C (HbA1c, A1c). The results are given in percentages and indicate a person’s average blood glucose levels over the past 2 - 3 months. (The 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 patients 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 levels indicate:
A1C tests are also used to help patients with diabetes monitor how well they are keeping their blood glucose levels under control. For patients with diabetes, A1C is measured periodically every 2 - 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 patients with diabetes should aim for A1C levels of around 7%. Your doctor may adjust this goal depending on your individual health profile.The American Diabetes Association recommends that results from the A1C test be used as to calculate estimated Average Glucose (eAG). EAG is a relatively new term that patients may see on lab results from their A1C tests. It converts the A1C percentages into the same mg/dL units that patients 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 patients to better interpret the results of their A1C tests and make it easier to correlate A1C with results from home blood glucose monitoring.The American Diabetes Association recommends screening for gestational diabetes:
Screening for Heart Disease. All patients with diabetes should be tested for high blood pressure (hypertension) and unhealthy cholesterol and lipid levels and given an electrocardiogram. Other tests may be needed in patients with signs of heart disease.
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 patients with type 2 diabetes who have high blood pressure.
The American Diabetes Association recommends that people with diabetes receive an annual urine test for albumin. Patients 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. High levels of creatinine may indicate kidney damage. A doctor uses the results from a creatinine blood test to calculate the glomerular filtration rate (GFR). The GFR is an indicator of kidney function; it estimates how well the kidneys are cleansing the blood.
Screening for Retinopathy. The American Diabetes Association recommends that patients 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 - 3 years.) The eye exam should include dilation 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. All patients should be screened for nerve damage (neuropathy), including a comprehensive foot exam. Patients who lose sensation in their feet should have a foot exam every 3 - 6 months to check for ulcers or infections. Patients should also be screened for intermittent claudication and peripheral artery disease (PAD) using the ankle-brachial index for diagnosis.
Good nutrition and regular exercise can help prevent or manage medical complications of diabetes (such as heart disease and stroke) and help patients live longer and healthier lives.
There is no such thing as a single diabetes diet. Patients should meet with a professional dietitian to plan an individualized diet within the general guidelines that takes into consideration their own health needs.
Healthy eating habits along with good control of blood glucose are the basic goals, and several good dietary methods are available to meet them. General dietary guidelines for diabetes recommend:
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. Patients should lose weight if their body mass index (BMI) is 25 - 29 (overweight) or higher (obese).
The American Diabetes Association recommends that patients aim for a small but consistent weight loss of ½ - 1 pound per week. Most patients should follow a diet that supplies at least 1,000 - 1,200 kcal/day for women and 1,200 - 1,600 kcal/day for men.
Obese patients 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, are associated with significantly higher risks for obesity and type 2 diabetes. Regular exercise, even of moderate intensity (such as brisk walking), improves insulin sensitivity and may play a role in preventing type 2 diabetes -- regardless of weight loss.
Aerobic Exercise. Aerobic exercise 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 patients have no risk factors for heart disease other than diabetes itself.
For improving blood sugar control, the American Diabetes Association recommends at least 150 minutes per week of moderate-intensity physical activity (50 - 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 American Diabetes Association recommends performing resistance exercise three times a week. Build up to three sets of 8 - 10 repetitions using weight that you cannot lift more than 8 - 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:
Patients who are taking medications that lower blood glucose, particularly insulin, should take special precautions before starting a workout program:
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 patients with diabetes not to be duped by bogus and unproven remedies.
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.
The major treatment goals for people with type 2 diabetes are to control blood glucose levels and to treat all conditions that place patients 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 levels before meals
Less than 100 mg/dL
70 - 130 mg/dL for adults
100 - 180 mg/dL for children under age 6
90 - 180 mg/dL for children 6 - 12 years old
90 - 130 mg/dL for children 13 - 19 years old
Bedtime blood glucose levels
Less than 120 mg/dL
Less than 180 mg/dL for adults
110 - 200 mg/dL for children under age 6
100 - 180 mg/dL for children 6 - 12 years old
90 - 150 mg/dL for children 13 - 19 years old
Hemoglobin A1C levels
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 – 12 years old
Less than 7.5% for children 13 – 19 years old
Major source: Standards of Medical Care In Diabetes -- 2013, American Diabetes Association.
Different goals may be necessary for specific individuals, including pregnant women, very old and very young people, and those with accompanying serious medical conditions. 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 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.
All patients with diabetes and high blood pressure should make lifestyle changes. These include losing weight (when needed), following the Dietary Approaches to Stop Hypertension (DASH) diet, quitting smoking, limiting alcohol, and limiting salt to no more than 1,500 mg of sodium per day.
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 patients, a systolic blood pressure goal of less than 130 mm Hg may be appropropriate.
Patients 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 patients who have diabetes and high blood pressure should take an ACE inhibitor (or ARB) as part of their regimen for treating hypertension. These drugs help prevent kidney damage.
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.
Adult patients should aim for LDL levels below 100 mg/dL, HDL levels over 50 mg/dL, and triglyceride levels below 150 mg/dL. Patients with diabetes and heart disease should strive for even lower LDL levels. The American Diabetes Association recommends LDL levels below 70 mg/dL for these patients.
Pediatric patients 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 patients with diabetes focus on:
For medications, statins are the best cholesterol-lowering drugs. They include atorvastatin (Lipitor, generic), lovastatin (Mevacor, generic), pravastatin (Pravachol, generic), simvastatin (Zocor, Simcor, Vytorin, and generics), fluvastatin (Lescol, generic), rosuvastatin (Crestor), and pitavastatin (Livalo). 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 patients, especially when taken in high doses. They may also increase the risk for developing type 2 diabetes in patients who have risk factors. Still, statin drugs are considered generally safe and the best first choice for managing high cholesterol. If one statin drug does not work, 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.
Occasionally, patients do not respond to statins and need a different type of medication such as a fibrate (gemfibrozil, fenofibrate, or fenofibric acid) or niacin drug. This is especially true for patients who have very low HDL levels or severe triglyceride imbalances. Combination therapy of a statin with a fibrate or niacin drug is not recommended due to increased risk for rhabdomolysis and other serious side effects.
Aspirin for Heart Disease Prevention. For patients 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 patients at lower risk.) The recommended dose is 75 - 162 mg/day. Aspirin as primary prevention is recommended for men who are older than age 50 or women who are older than age 60 who have at least one additional heart risk factor. These risk factors include a family history of heart disease, high blood pressure, smoking, unhealthy cholesterol levels, or excessive urine levels of the protein albumin. Talk to your doctor, particularly if you are at risk for aspirin side effects such as gastrointestinal bleeding and ulcers.
Surgery for Heart Disease. Patients 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 patients with diabetes who have multiple blockages in their arteries.
Patients 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 patients. Drug therapy with anti-vascular endothelial growth factor (VEGF ) is also recommended for treatment of diabetic macular edema.
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:
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 patients. 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. Patients 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 patients with diabetes. Patients who take nitrate medications for heart disease cannot use PDE-5 drugs.
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 patients 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.
A doctor may recommend a low-protein diet for patients whose kidney disease is progressing despite tight blood sugar and blood pressure control. Protein-restricted diets can help slow disease progression and delay the onset of end-stage renal disease (kidney failure). However, patients with end-stage renal disease who are on dialysis generally need higher amounts of protein.
Anemia.Anemia is a common complication of end-stage kidney disease. Patients on dialysis usually need injections of erythropoiesis-stimulating drugs to increase red blood cell counts and control anemia. However, these drugs -- darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit) -- can increase the risk of blood clots, stroke, heart attack, and heart failure in patients with end-stage kidney disease when they are given at higher than recommended doses.
The FDA recommends that patients with end-stage kidney disease who receive erythropoiesis-stimulating drugs should:
Many types of anti-hyperglycemic drugs are available to help patients with type 2 diabetes control their blood sugar levels. Most of these drugs are aimed at using or increasing sensitivity to the patient'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, 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 patients 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 obese patients 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. Side effects 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, generic), tolazamide (Tolinase, generic), glipizide (Glucotrol, generic), tolbutamide (Orinase, generic), glyburide (Micronase, generic), and glimepiride (Amaryl, generic). For adequate control of blood glucose levels, the drugs should be taken 20 - 30 minutes before a meal.
Most patients can take sulfonylureas for 7 - 10 years before they lose effectiveness. Combinations with small amounts of insulin or other oral anti-hyperglycemic drugs (such as 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 by individuals who are allergic to sulfa drugs should not use sulfonylureas. Side effects may include:
Sulfonylureas interact with many other drugs, and patients 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, generic). These drugs are rapidly metabolized and short-acting. If taken before every meal, they mimic the normal effects of insulin after eating. Patients, 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, 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 patients. Combinations with insulin increase the risk. Patients with heart failure should not use them. People with risk factors for heart failure should use these drugs with caution.
In particular, rosiglitazone has been associated with increased risks for heart attack and heart failure. The FDA advises that due to its cardiovascular risks, rosiglitazone should only be used by patients who are already taking the drug or patients whose blood sugar is not well controlled by other diabetes medications and who do not wish to take pioglitazone. Patients who take rosiglitazone, especially those who have heart failure, heart disease, or who are at high risk for heart attack, should talk to their doctor about their treatment options.
Thiazolidinediones may cause more weight gain than other diabetes medications or insulin. Any patient who has sudden weight gain, water retention, or shortness of breath should immediately call their doctor. These drugs have also been linked to increased risks for bone fracture. The FDA is currently investigating whether pioglitazone may increase the risk for bladder cancer.
There have been rare reports of rosiglitazone causing or worsening diabetic macular edema. This is an eye condition associated with diabetic retinopathy that causes swelling in the macular area of the retina. Symptoms include blurred vision and decreased color sensitivity. Most patients who had this side effect also had swelling in the feet and legs (peripheral edema). The condition resolved or improved when patients stopped taking the drug.
Thiazolidinediones can also cause liver damage. Patients who take these drugs should have their liver enzymes checked regularly.
Alpha-glucosidase inhibitors, including acarbose (Precose, 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 patients 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 patient receive 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.
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 patients 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.
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, vomiting, and diarrhea.
Exenatide and liraglutide have been associated with cases of acute pancreatitis, which is sudden inflammation of the pancreas. Symptoms of acute pancreatitis include severe abdominal pain that may radiate to the back. The pain may or may not be accompanied by nausea and vomiting. Patients who feel severe stomach pain that does not go away should seek prompt medical attention.
The FDA is investigating whether incretin mimetics may increase the risk for pre-cancerous changes in the pancreas called pancreatic duct metaplasia. These drugs may also increase the risk for thyroid cancer.
Exenatide may cause new or worse problems with kidney function, including kidney failure. Patients with severe kidney problems should not use this drug.
Dipeptidyl peptidase-4 (DPP-4) inhibitors, also called gliptins, are the second class of incretin drugs. They include sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), and alogliptin (Nesina).
DPP-4 inhibitors work in a similar way to GLP-1 inhibitors. However, unlike exenatide, which is 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. The most common side effects include upper respiratory tract infection, sore throat, and diarrhea.
These drugs may increase the risk of acute pancreatitis (inflammation of the pancreas). Patients should be monitored for signs of pancreatitis after treatment begins or if the dosage is increased. The FDA is investigating whether incretin mimetics, which include GLP-1 inhibitors and DPP-4 inhibitors, may increase the risk for pre-cancerous changes in the pancreas (pancreatic duct metaplasia).
Sodium-glucose co-transportor 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. The drug helps lower blood glucose levels by blocking the kidney’s reabsorption of glucose.
Canagliflozin can be used alone or in combination with other types of diabetes drugs (metformin, sulfonylurea, pioglitazone, insulin). It should not be used by patients who have diabetic ketoacidosis or severe kidney impairment.
Common side effects include vaginal yeast infection and urinary tract infections. During the initial months of treatment, this drug may cause decreased blood pressure and dizziness when standing up (orthostatic hypotension).
Pramlintide (Symlin) is an injectable drug that may help patients 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.
Bromocriptine mesylate (Cycloset) is an oral drug that may help improve blood sugar control in addition to diet and exercise. Bromocriptine helps boost levels of dopamine, a nerve chemical (neurotransmitter). Bromocriptine is used in other formulations, and usually in higher doses, for treatment of Parkinson’s disease. Common side effects may include nausea, vomiting, headache, dizziness, and fatigue.
Insulin replacement may be necessary when natural insulin reserves are depleted. It is typically started in combination with an oral drug (usually metformin).
Because type 2 diabetes is progressive, many patients 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 patients 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. There are two main insulin types:
In general, there is no advantage to dosing insulin more than two times a day for patients with type 2 diabetes.
Both low blood sugar (hypoglycemia) and high blood sugar (hyperglycemia) are of concern, especially for patients who take insulin. Blood glucose levels are generally more stable in type 2 diabetes than in type 1, so doctors usually recommend measuring blood levels only once or twice a day. For patients who have become insulin-dependent, more intensive monitoring is necessary. Patients should aim for the following measurements:
Different goals may be required for specific individuals, including pregnant women, very old and very young people, and those with accompanying serious medical conditions.
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. However, they are usually accurate enough to indicate when blood sugar is too low.
Some simple procedures may improve accuracy:
For patients who have trouble controlling hypoglycemia (low blood sugar) or fluctuating blood sugar levels, 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.
Family and friends should be aware of the symptoms and be prepared:
Patients are encouraged to wear at all times a medical alert ID bracelet or necklace that states they have diabetes. If patients 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, Genuth S, Ismail-Beigi F, Buse JB, et al. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011 Mar 3;364(9):818-28.
ACCORD Study Group, Ginsberg HN, Elam MB, Lovato LC, Crouse JR 3rd, Leiter LA, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010 Apr 29;362(17):1563-74. Epub 2010 Mar 14.
Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008 Jun 12;358(24):2545-59. Epub 2008 Jun 6.
Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, 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 Oct 20;120(16):1640-5. Epub 2009 Oct 5.
American Diabetes Association. Standards of medical care in diabetes -- 2013. Diabetes Care. 2013 Jan;36 Suppl 1:S11-66..
Bril V, England J, Franklin GM, Backonja M, Cohen J, Del Toro D, 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 May 17;76(20):1758-65. Epub 2011 Apr 11.
Carlsson LM, Peltonen M, Ahlin S, Anveden Å, Bouchard C, Carlsson B, et al. Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. N Engl J Med. 2012 Aug 23;367(8):695-704.
Centers for Disease Control and Prevention. National Diabetes Fact Sheet: National Estimates and General Information on Diabetes and Prediabetes in the United States, 2011. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2011.
Centers for Disease Control and Prevention (CDC). Use of hepatitis B vaccination for adults with diabetes mellitus: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2011 Dec 23;60(50):1709-11.
Copeland KC, Silverstein J, Moore KR, Prazar GE, Raymer T, Shiffman RN, et al. Management of newly diagnosed type 2 Diabetes Mellitus (T2DM) in children and adolescents. Pediatrics. 2013 Feb;131(2):364-82. Epub 2013 Jan 28.
Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study Research Group, Jacobson AM, Musen G, Ryan CM, Silvers N, Cleary P, et al. Long-term effect of diabetes and its treatment on cognitive function. N Engl J Med. 2007 May 3;356(18):1842-52.
Farkouh ME, Domanski M, Sleeper LA, Siami FS, Dangas G, Mack M, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med. 2012 Dec 20;367(25):2375-84. Epub 2012 Nov 4.
Garber AJ, Handelsman Y, Einhorn D, Bergman DA, Bloomgarden ZT, Fonseca V, 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 Oct;14(7):933-46.
Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, et al. Diabetes and cancer: a consensus report. CA Cancer J Clin. 2010 Jul-Aug;60(4):207-21. Epub 2010 Jun 16.
Graham DJ, Ouellet-Hellstrom R, MaCurdy TE, Ali F, Sholley C, Worrall C, et al. Risk of acute myocardial infarction, stroke, heart failure, and death in elderly Medicare patients treated with rosiglitazone or pioglitazone. JAMA. 2010 Jul 28;304(4):411-8. Epub 2010 Jun 28.
Gross JL, Kramer CK, Leitão CB, Hawkins N, Viana LV, Schaan BD, et al. Effect of antihyperglycemic agents added to metformin and a sulfonylurea on glycemic control and weight gain in type 2 diabetes: a network meta-analysis. Ann Intern Med. 2011 May 17;154(10):672-9.
Holman RR, Thorne KI, Farmer AJ, Davies MJ, Keenan JF, Paul S, et al. Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes. N Engl J Med. 2007 Oct 25;357(17):1716-30. Epub 2007 Sep 21.
Inzucchi SE, Bergenstal RM, Buse JB, Diamant, M, Ferrannini E, Nauck M, 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 Jun;35(6):1364-79. Epub 2012 Apr 19.
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 Feb 23. [Epub ahead of print]
Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ, Armstrong DG, et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012 Jun;54(12):e132-73.
Nathan DM, Kuenen J, Borg R, Zheng H, Schoenfeld D, Heine RJ; A1C-Derived Average Glucose Study Group. Translating the A1C assay into estimated average glucose values. Diabetes Care. 2008 Aug;31(8):1473-8. Epub 2008 Jun 7.
Pignone M, Alberts MJ, Colwell JA, Cushman M, Inzucchi SE, Mukherjee D, 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 Jun 22;121(24):2694-701. Epub 2010 May 27.
Preiss D, Seshasai SR, Welsh P, Murphy SA, Ho JE, Waters DD, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011 Jun 22;305(24):2556-64.
Qaseem A, Humphrey LL, Sweet DE, Starkey M, Shekelle P; Clinical 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 Feb 7;156(3):218-31.
Rosenzweig JL, Ferrannini E, Grundy SM, Haffner SM, Heine RJ, Horton ES, 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 Oct;93(10):3671-89. Epub 2008 Jul 29.
Skyler JS, Bergenstal R, Bonow RO, Buse J, Deedwania P, Gale EA, 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 Jan;32(1):187-92. Epub 2008 Dec 17.
Springer SC, Silverstein J, Copeland K, Moore KR, Prazar GE, Raymer T, et al. Management of type 2 diabetes mellitus in children and adolescents. Pediatrics. 2013 Feb;131(2):e648-64. Epub 2013 Jan 28.
U.S. Preventive Services Task Force. Screening for gestational diabetes mellitus: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008 May 20;148(10):759-65.
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 Jun 3;148(11):846-54.
Waters DD, Ho JE, DeMicco DA, Breazna A, Arsenault BJ, Wun CC, et al. Predictors of new-onset diabetes in patients treated with atorvastatin: results from 3 large randomized clinical trials. J Am Coll Cardiol. 2011 Apr 5;57(14):1535-45.