Diabetes Mellitus

Definition

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.

Description

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

Risk factors for type 2 diabetes include:

Demographics

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.

Causes and symptoms

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.

Diagnosis

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.

Treatment

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.

Lifestyle

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.

KEY TERMS
Dipeptidyl peptidase-4 (DPP-4) inhibitors—
A class of type 2 diabetes medications that prevents the breakdown of glucagon-like peptide-1 (GLP-1), thereby lowering blood sugar levels.
Fasting plasma glucose (FPG)—
A measure of blood glucose after fasting for at least eight hours; usually tested in the morning.
Glucagon—
A protein hormone produced by the pancreas that increases the rate of glycogen breakdown in the liver to increase blood sugar.
Glucagon-like peptide-1 (GLP-1)—
A hormone that controls blood glucose levels by increasing insulin, decreasing glucagon, promoting a feeling of fullness, and slowing the emptying of the stomach contents.
Glucose—
The form of sugar that the body assimilates and utilizes.
Hemoglobin A1c (Hg A1c)—
Glycated hemoglobin; a stable binding of glucose to hemoglobin A in the blood, which can be used to determine the average blood glucose level for the previous two to three months.
High-density lipoprotein (HDL) cholesterol—
“Good” cholesterol. Protein in the blood that includes small amounts of triglycerides and cholesterol and that helps protect against heart disease.
Hormone—
A substance, such as a protein, that is produced in one part of the body and then travels through the bloodstream to affect another part of the body.
Hyperglycemia—
An abnormally high blood glucose level.
Hypoglycemia—
An abnormally low blood glucose level.
Impaired fasting glucose (IFG)—
An abnormally high level of blood glucose after an eight-hour fast.
Impaired glucose tolerance (IGT)—
An abnormally high blood glucose level with an oral glucose tolerance test.
Incretin mimetics—
GLP-1 receptor agonists; a class of type 2 diabetes medications that mimics the effects of the incretin hormone GLP-1 by binding to GLP-1 receptors, thereby lowering blood sugar levels.
Insulin—
A protein hormone synthesized in the pancreas and secreted by beta cells of the islets of Langerhans. Insulin is required for the metabolism of carbohydrates, lipids, and proteins and regulates blood sugar levels by facilitating the uptake of glucose into tissues; converting sugars to glycogen, fatty acids, and triglycerides; and preventing the release of glucose from the liver.
Insulin resistance—
Reduced sensitivity to insulin by insulin-dependent processes such as glucose uptake, resulting in the lower activity of these processes and/ or increased insulin production. Typically occurs with type 2 diabetes.
Ketones—
Breakdown products of fat that are toxic at high levels.
Low-density lipoprotein (LDL) cholesterol—
“Bad” cholesterol. A lipoprotein in the blood with a high proportion of cholesterol, which increases the risk of heart disease.
Neuropathy—
A degenerative disorder of the nerves or nervous system.
Oral glucose tolerance test (OGTT)—
A measure of the blood glucose level after a fast of at least eight hours and two hours after drinking a specific glucose solution.
Prediabetes—
A condition characterized by blood glucose levels above normal but lower than diabetic levels; usually progresses to type 2 diabetes.
Triglycerides—
Neutral fats; lipids formed from glycerol and fatty acids that circulate in the blood as lipoprotein. Elevated triglycerides are a risk factor for diabetes.

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.

Oral medications

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.

Prognosis

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.

QUESTIONS TO ASK YOUR DOCTOR

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.

Prevention

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.

Resources

BOOKS

American Diabetes Association. Diabetes A to Z: What You Need to Know About Diabetes, Simply Put, 7th ed. Alexandria, VA: American Diabetes Association, 2016.

Codario, Ronald A. Type 2 Diabetes, Pre-Diabetes, and the Metabolic Syndrome, 2nd ed. Totowa, NJ: Humana, 2011.

Collazo-Clavell, Maria. Mayo Clinic: The Essential Diabetes Book. New York: Time, 2014.

Ezrin, Calvin, and Robert E. Kowalski. The Type 2 Diabetes Diet Book, rev. 4th ed. New York: McGraw-Hill, 2011.

Hurley, Dan. Diabetes Rising: How a Rare Disease Became a Modern Pandemic, and What to do About It. New York: Kaplan, 2010.

Napora, Joseph P. Stress-Free Diabetes: Your Guide to Health and Happiness. Alexandria, VA: American Diabetes Association, 2010.

O'Connell, Jeff. Sugar Nation: The Hidden Truth Behind America's Deadliest Habit and the Simple Way to Beat It. New York: Hyperion, 2011.

Tsatsoulis, Agathocles, Jennifer Ann Wyckoff, and Florence M. Brown. Diabetes in Women. Totowa, NJ: Humana, 2010.

PERIODICALS

Gilmer, Todd P., and Patrick J. O'Connor. “The Growing Importance of Diabetes Screening.” Diabetes Care 33, no. 7 (July 2010): 1695–97.

Parikh, Punam, et al. “Results of a Pilot Diabetes Prevention Intervention in East Harlem, New York City: Project HEED.” American Journal of Public Health 100, no. S1 (2010): S232–39.

WEBSITES

“AHA/ACC Issue Advisory on Diabetes Drugs and Heart Risk.” American Heart Association. February 22, 2010. http://www.pharmpro.com/news/2010/02/ahaacc-issueadvisory-diabetes-drugs-and-heart-risk (accessed January 15, 2017).

“Diabetes Programme.” World Health Organization. http://www.who.int/diabetes/en (accessed January 15, 2017).

Eckman, Ari S. “Type 2 Diabetes.” MedlinePlus. July 24, 2015. https://medlineplus.gov/ency/article/000313.htm (accessed January 15, 2017).

“Living with Diabetes.” American Diabetes Association. http://www.diabetes.org/living-with-diabetes (accessed January 15, 2017).

Maruthur, N. M., et al. “Diabetes Medications for Adults with Type 2 Diabetes: An Update.” Agency for Healthcare Research and Quality. April 19, 2016. https://effectivehealthcare.ahrq.gov/search-for-guidesreviews-and-reports/?pageaction=displayproductproductid=2207 (accessed January 15, 2017).

ORGANIZATIONS

American Diabetes Association, 2451 Crystal Dr., Ste. 900, Arlington, VA, 22202, (800) DIABETES (342-2383), http://www.diabetes.org .

American Dietetic Association, 120 S Riverside Plaza, Ste. 2190, Chicago, IL, 60606, (312) 899-0040, (800) 877-1600, http://www.eatright.org .

Centers for Disease Control and Prevention, 1600 Clifton Rd., Atlanta, GA, 30333, (800) 232-4636, cdcinfo@cdc. gov, http://www.cdc.gov .

National Diabetes Education Program, 1 Diabetes Way, Bethesda, MD, 20814-9692, (800) 860-8747, healthinfo@ niddk.nih.gov, http://www.ndep.nih.gov .

Ken R. Wells
Margaret Alic, PhD

  This information is not a tool for self-diagnosis or a substitute for professional care.