Diabetes Caused by Genetic Defects in Insulin Action

A number of types of diabetes result from genetic defects in insulin action. Changes to the insulin receptor may cause mild hyperglycemia—high blood glucose—or severe diabetes. Symptoms may include acanthosis nigricans, a skin condition characterized by darkened skin patches, and, in women, enlarged and cystic ovaries plus virilization and the development of masculine characteristics such as excess facial hair. Two syndromes in children, leprechaunism and the Rabson-Mendenhall syndrome, cause extreme insulin resistance.

Diabetes Caused by Diseases of the Pancreas

Injuries to the pancreas from trauma or disease can cause diabetes. This category includes pancreatitis, infection, and cancer of the pancreas. Cystic fibrosis and hemochromatosis can also damage the pancreas enough to cause diabetes.

Diabetes Caused by Endocrinopathies

Excess amounts of certain hormones that work against the action of insulin can cause diabetes. These hormones and their related conditions include growth hormone in acromegaly, cortisol in Cushing’s syndrome, glucagon in glucagonoma, and epinephrine in pheochromocytoma.

Diabetes Caused by Medications or Chemicals

A number of medications and chemicals can interfere with insulin secretion, leading to diabetes in people with insulin resistance. These medications and chemicals include pentamidine, nicotinic acid, glucocorticoids, thyroid hormone, phenytoin (Dilantin), and Vacor, a rat poison.

Diabetes Caused by Infections

Several infections are associated with the occurrence of diabetes, including congenital rubella, coxsackievirus B, cytomegalovirus, adenovirus, and mumps.

Rare Immune-mediated Types of Diabetes

Some immune-mediated disorders are associated with diabetes. About one-third of people with stiff-man syndrome develop diabetes. In other autoimmune diseases, such as systemic lupus erythematosus, patients may have anti-insulin receptor antibodies that cause diabetes by interfering with the binding of insulin to body tissues.

Other Genetic Syndromes Sometimes Associated with Diabetes

Many genetic syndromes are associated with diabetes. These conditions include Down syndrome, Klinefelter’s syndrome, Huntington’s chorea, porphyria, Prader-Willi syndrome, and diabetes insipidus.

How is diabetes diagnosed?

The fasting blood glucose test is the preferred test for diagnosing diabetes in children and nonpregnant adults. The test is most reliable when done in the morning. However, a diagnosis of diabetes can be made based on any of the following test results, confirmed by retesting on a different day:

• A blood glucose level of 126 milli grams per deciliter (mg/dL) or higher after an 8-hour fast. This test is called the fasting blood glucose test.
• A blood glucose level of 200 mg/dL or higher 2 hours after drinking a beverage containing 75 grams of glucose dissolved in water. This test is called the oral glucose tolerance test (OGTT).
• A random—taken at any time of day—blood glucose level of 200 mg/dL or higher, along with the presence of diabetes symptoms.

Gestational diabetes is diagnosed based on blood glucose levels measured during the OGTT. Glucose levels are normally lower during pregnancy, so the cutoff levels for diagnosis of diabetes in pregnancy are lower. Blood glucose levels are measured before a woman drinks a beverage containing glucose. Then levels are checked 1, 2, and 3 hours afterward. If a woman has two blood glucose levels meeting or exceeding any of the following numbers, she has gestational diabetes: a fasting blood glucose level of 95 mg/dL, a 1-hour level of 180 mg/dL, a 2-hour level of 155 mg/dL, or a 3-hour level of 140 mg/dL.

What is pre-diabetes?

People with pre-diabetes have blood glucose levels that are higher than normal but not high enough for a diagnosis of diabetes. This condition raises the risk of developing type 2 diabetes, heart disease, and stroke.

Pre-diabetes is also called impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), depending on the test used to diagnose it. Some people have both IFG and IGT.

• IFG is a condition in which the blood glucose level is high—100 to 125 mg/dL—after an overnight fast, but is not high enough to be classified as diabetes. The former definition of IFG was 110 mg/dL to 125 mg/dL.
• IGT is a condition in which the blood glucose level is high—140 to 199 mg/dL—after a 2-hour OGTT, but is not high enough to be classified as diabetes

Pre-diabetes is becoming more common in the United States. The U.S. Department of Health and Human Services estimates that at least 57 million U.S. adults ages 20 or older had pre-diabetes in 2007. Those with pre-diabetes are likely to develop type 2 diabetes within 10 years, unless they take steps to prevent or delay diabetes.

The good news is that people with pre-diabetes can do a lot to prevent or delay diabetes. Studies have clearly shown that people can lower their risk of developing diabetes by losing 5 to 7 percent of their body weight through diet and increased physical activity. A major study of more than 3,000 people with IGT found that diet and exercise resulting in a 5 to 7 percent weight loss—about 10 to 14 pounds in a person who weighs 200 pounds—lowered the incidence of type 2 diabetes by nearly 60 percent. Study participants lost weight by cutting fat and calories in their diet and by exercising—most chose walking—at least 30 minutes a day, 5 days a week.

What are the scope and impact of diabetes?

Diabetes is widely recognized as one of the leading causes of death and disability in the United States. In 2006, it was the seventh leading cause of death. However, diabetes is likely to be underreported as the underlying cause of death on death certificates. In 2004, among people ages 65 years or older, heart disease was noted on 68 percent of diabetes-related death certificates; stroke was noted on 16 percent of diabetes-related death certificates for the same age group.

Diabetes is associated with long-term complications that affect almost every part of the body. The disease often leads to blindness, heart and blood vessel disease, stroke, kidney failure, amputations, and nerve damage. Uncontrolled diabetes can complicate pregnancy, and birth defects are more common in babies born to women with diabetes.

In 2007, diabetes cost the United States $174 billion. Indirect costs, including disability payments, time lost from work, and reduced productivity, totaled $58 billion. Direct medical costs for diabetes care, including hospitalizations, medical care, and treatment supplies, totaled $116 billion.