Diabetes mellitus is a chronic condition in which insulin production or responses to insulin are inadequate, causing high blood sugar (glucose) levels (hyperglycemia). Type 2 diabetes—by far the most common form—is usually caused by the development of insulin resistance, in which the cells of the body become less sensitive to insulin and stop responding adequately. Type 2 diabetes is associated with obesity and lack of physical exercise. Over time, high blood sugar levels cause serious health complications, including high blood pressure, kidney disease, heart disease, stroke, nerve damage (neuropathy), and blindness.
Most food is digested into a form of sugar called glucose, which provides energy to cells. The hormone insulin, which is produced in the pancreas and secreted into the bloodstream by beta cells of the islets of Langerhans, regulates the levels of glucose in the blood by various mechanisms. Insulin moves glucose out of the blood and into the cells of the body. It is also involved in converting sugars to glycogen, fatty acids, and triglycerides for stored energy, and in preventing the release of glucose from the liver into the bloodstream. Type 2 diabetes accounts for 90–95% of all diabetes cases. It is usually caused by insulin resistance or decreased insulin sensitivity, which results in glucose accumulating in the blood instead of entering cells. Type 2 diabetes used to be called adult-onset diabetes; however, it is increasingly diagnosed in children. Type 1, juvenile, or insulin-dependent diabetes, which usually strikes young people, is an autoimmune disease in which the pancreas produces little or no insulin. With type 2 diabetes, the pancreas usually produces adequate amounts of insulin.
Risk factors for type 2 diabetes include:
Far more Americans are developing type 2 diabetes today than in the past. In 2011, the Centers for Disease Control and Prevention (CDC) estimated that, in addition to the almost 26 million Americans with diabetes, 70–79 million adults (35% of those aged 20 and older) have prediabetes and will probably develop type 2 diabetes. This is a huge increase from the CDC's 2008 estimates of 23.6 million Americans with diabetes and 57 million with prediabetes. In part, this increase is due to improved screening and people living longer with diabetes due to improved disease management. As many as half of all those with type 2 diabetes are unaware of their disease.
More than half of adult Americans who are overweight or obese have diabetes or prediabetes. Among Americans aged 65 and older, almost 27% have diabetes and 50% have prediabetes. A 2010 study by the United Health Group's Center for Health Reform and Modernization estimated that if current trends continue, by 2020 more than 50% of all Americans could have prediabetes or diabetes. The largest increases are projected among Hispanic/Latino Americans, African Americans, and Native Americans.
Although the exact causes of diabetes are unknown, they appear to involve both a genetic predisposition and an environmental trigger. Specific genes that increase the risk for developing insulin resistance and type 2 diabetes have been identified. Excess body weight and lack of physical activity are the most common diabetes triggers in susceptible people. Diabetes also can develop as a result of pancreatic disease, alcoholism, malnutrition, or other severe illnesses that stress the body. A condition known as secondary diabetes can result from any of several common medications that interfere with the body's ability to utilize insulin.
Symptoms of type 2 diabetes develop slowly, sometimes over a period of several years, and patients are often unaware of them. Classic early symptoms include fatigue, lethargy, frequent urination, extreme thirst, excessive hunger, and weight loss. Other symptoms may include slow wound healing, urinary tract infections, gum disease, or blurred vision. Type 2 diabetes is often first diagnosed because it is causing some other medical condition.
Excessive urination is caused by water being drawn from cells to dilute the blood sugar and excrete it in the urine. People with undiagnosed diabetes may be constantly thirsty, despite drinking large quantities of water.
Although blood sugar levels are high, the cells of the body are starved for glucose and send hunger signals to the brain. Because the blood glucose is unavailable for energy needs, fats and proteins are converted to glucose, causing the formation of potentially toxic compounds called ketones in the blood and excretion of ketones in the urine.
Fasting plasma glucose (FPG) measures the glucose level in the blood following at least eight hours without eating. Normal blood sugar is 70–99 mg/dL (3.9–5.5 mmol/L). A glucose level of 100–125 mg/dL (5.6–6.9 mmol/L) indicates impaired fasting glucose (IFG) or prediabetes. Higher levels indicate diabetes.
An oral glucose tolerance test (OGTT) measures blood glucose after a fast of at least eight hours and again two hours after drinking glucose liquid supplied by a physician or laboratory. A two-hour glucose level of 140–199 mg/dL (7.8—11.1 mmol/L) indicates impaired glucose tolerance (IGT) or prediabetes. Higher levels indicate diabetes.
The hemoglobin A1c (Hg A1c) test measures glycated hemoglobin—the percentage of hemoglobin A in the blood that contains stably bound glucose. This indicates average blood glucose levels over the preceding two to three months. An A1c above 6.4% indicates diabetes. The A1c test is more convenient, since it does not require fasting, and is considered more accurate, since it measures average glucose levels over a period of 8–12 weeks.
Blood tests are usually repeated to confirm a diagnosis of diabetes. Tests for glucose in the urine are less accurate. Urine tests may be used to detect ketones and protein, both for diagnosis of diabetes and to monitor the effects of treatment.
Insulin levels in the blood may be measured. Unlike type 1 diabetes, in which little or no insulin is produced, people with type 2 diabetes usually have normal or high levels of insulin, as the body attempts to compensate for insulin resistance.
Type 2 diabetes is usually controlled with diet, physical activity, and possibly oral medications, although some patients require insulin injections. Diet, exercise, and careful monitoring of blood sugar levels with home tests are the most important factors for controlling blood sugar and preventing diabetes complications.
Weight loss, through diet and exercise, can be very important for overweight and obese patients with type 2 diabetes. A well-balanced, nutritious diet provides approximately 50%–60% of daily calories from carbohydrates, about 10%–20% from protein, less than 30% from total fat, and less than 10% of daily calories from saturated fat. Fruits, vegetables, beans, whole grains, fish, poultry, and lean meats, with only limited sugar, can reduce blood sugar levels. Caloric intake must be equalized over the course of the day, to prevent surges of glucose from entering the bloodstream.
Even small increases in physical activity can make a big difference in managing type 2 diabetes—30 minutes of moderate exercise, such as brisk walking or swimming, is recommended at least five times per week. Weight-loss support groups and exercise partners can help with initiating and maintaining these essential lifestyle changes.
In addition to diet and exercise, some patients with type 2 diabetes require medication to adequately control blood sugar levels. Some people require a drug combination or even oral medication combined with insulin injections.
Oral diabetes medications available in the United States:
There are two newer classes of diabetes medications. Dipeptidyl peptidase-4 (DPP-4) inhibitors (sitagliptin and saxagliptin) are a new class of medications that prevent the breakdown of the incretin hormone glucagon-like peptide-1 (GLP-1). GLP-1 reduces blood glucose by increasing insulin production, decreases glucagon (a hormone that controls the release of glucose from the liver after meals), promotes a feeling of fullness to prevent overeating, and slows the emptying of stomach contents into the intestines to prevent high blood glucose following a meal. However, GLP-1 is broken down very quickly. DPP-4 inhibitors enable GLP-1 to remain active longer and lower the blood glucose level only when it is elevated. GLP-1 receptor agonists or incretin mimetics (exenatide and liraglutide) are injected drugs that mimic the effects of GLP-1 but last much longer.
Diabetes is a chronic disorder that requires lifelong management to prevent complications from hyperglycemia. Mild type 2 diabetes can often be controlled with diet and exercise alone. Oral medications are most effective for people who have only recently developed type 2 diabetes. These medications usually lower blood glucose levels, but levels may not approach normal range.
Diabetes increases the risk of cardiovascular disease, including heart attack and stroke, by two- to fourfold, and 45% of all patients hospitalized for a heart attack have diabetes. Cardiovascular disease accounts for almost two-thirds of all deaths in diabetics.
Uncontrolled diabetes is a leading cause of blindness, end-stage kidney disease, and limb amputations. Diabetic peripheral neuropathy is a degenerative nerve condition, particularly in the legs and feet, that causes muscular weakness, pain, and numbness. Foot ulcers are a particular problem, since the patient may not feel the pain of a blister, callous, or other minor injury. Poor blood circulation in the legs and feet contribute to delayed wound healing. In cases of severe infection, the tissue breaks down and rots away, requiring amputation.
Maintaining a healthy weight, being physically active, and following a well-balanced nutritional diet are the best ways to prevent type 2 diabetes. The loss of just 10–15 lb (5–7 kg) can have a significant effect on blood sugar levels in prediabetics who are overweight. Adults who are overweight or obese and who have one or more additional risk factors should be tested for diabetes. People without risk factors should be tested for diabetes at least every three years, beginning at age 45.
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Ken R. Wells
Margaret Alic, PhD