What is diabetes?

Diabetes is a complex group of diseases with a variety of causes. People with diabetes have high blood glucose, also called high blood sugar or hyperglycemia.

Diabetes is a disorder of metabolism—the way the body uses digested food for energy. The digestive tract breaks down carbohydrates—sugars and starches found in many foods—into glucose, a form of sugar that enters the bloodstream. With the help of the hormone insulin, cells throughout the body absorb glucose and use it for energy. Diabetes develops when the body doesn’t make enough insulin or is not able to use insulin effectively, or both. Insulin is made in the pancreas, an organ located behind the stomach. The pancreas contains clusters of cells called islets. Beta cells within the islets make insulin and release it into the blood.

If beta cells don’t produce enough insulin, or the body doesn’t respond to the insulin that is present, glucose builds up in the blood instead of being absorbed by cells in the body, leading to prediabetes or diabetes. Prediabetes is a condition in which blood glucose levels or A1C levels—which reflect average blood glucose levels—are higher than normal but not high enough to be diagnosed as diabetes. In diabetes, the body’s cells are starved of energy despite high blood glucose levels.

Over time, high blood glucose damages nerves and blood vessels, leading to complications such as heart disease, stroke, kidney disease, blindness, dental disease, and amputations. Other complications of diabetes may include increased susceptibility to other diseases, loss of mobility with aging, depression, and pregnancy problems. No one is certain what starts the processes that cause diabetes, but scientists believe genes and environmental factors interact to cause diabetes in most cases.The two main types of diabetes are type 1 diabetes and type 2 diabetes. A third type, gestational diabetes, develops only during pregnancy. Other types of diabetes are caused by defects in specific genes, diseases of the pancreas, certain drugs or chemicals, infections, and other conditions. Some people show signs of both type 1 and type 2 diabetes.

What causes type 1 diabetes?

Type 1 diabetes is caused by a lack of insulin due to the destruction of insulin-producing beta cells in the pancreas. In type 1 diabetes—an autoimmune disease—the body’s immune system attacks and destroys the beta cells. Normally, the immune system protects the body from infection by identifying and destroying bacteria, viruses, and other potentially harmful foreign substances. But in autoimmune diseases, the immune system attacks the body’s own cells. In type 1 diabetes, beta cell destruction may take place over several years, but symptoms of the disease usually develop over a short period of time.

Type 1 diabetes typically occurs in children and young adults, though it can appear at any age. In thepast, type 1 diabetes was called juvenile diabetes or insulin-dependent diabetes mellitus.Latent autoimmune diabetes in adults (LADA) may be a slowly developing kind of type 1 diabetes. Diagnosis usually occurs after age 30. In LADA, as in type 1 diabetes, the body’s immune system destroys the beta cells. At the time of diagnosis, people with LADA may still produce their own insulin, but eventually most will need insulin shots or an insulin pump to control blood glucose levels.

Genetic Susceptibility

Heredity plays an important part in determining who is likely to develop type 1 diabetes. Genes arepassed down from biological parent to child. Genes carry instructions for making proteins that are needed for the body’s cells to function. Many genes, as well as interactions among genes, are thoughtto influence susceptibility to and protection from type 1 diabetes. The key genes may vary in different population groups. Variations in genes that affect more than 1 percent of a population group are called gene variants.

Certain gene variants that carry instructions for making proteins called human leukocyte antigens(HLAs) on white blood cells are linked to the risk of developing type 1 diabetes. The proteins produced by HLA genes help determine whether the immune system recognizes a cell as part of the body or as foreign material. Some combinations of HLA gene variants predict that a person will be at higher risk for type 1 diabetes, while other combinations are protective or have no effect on risk.

While HLA genes are the major risk genes for type 1 diabetes, many additional risk genes or generegions have been found. Not only can these genes help identify people at risk for type 1 diabetes, but they also provide important clues to help scientists better understand how the disease develops and identify potential targets for therapy and prevention.

Genetic testing can show what types of HLA genes a person carries and can reveal other genes linked to diabetes. However, most genetic testing is done in a research setting and is not yet available to individuals. Scientists are studying how the results of genetic testing can be used to improve type 1 diabetes prevention or treatment.

Autoimmune Destruction of Beta Cells

In type 1 diabetes, white blood cells called T cells attack and destroy beta cells. The process begins well before diabetes symptoms appear and continues after diagnosis. Often, type 1 diabetes is not diagnosed until most beta cells have already been destroyed. At this point, a person needs daily insulin treatment to survive. Finding ways to modify or stop this autoimmune process and preserve beta cell function is a major focus of current scientific research.

Recent research suggests insulin itself may be a key trigger of the immune attack on beta cells. The immune systems of people who are susceptible to developing type 1 diabetes respond to insulin as if it were a foreign substance, or antigen. To combat antigens, the body makes proteins called antibodies. Antibodies to insulin and other proteins produced by beta cells are found in people with type 1 diabetes. Researchers test for these antibodies to help identify people at increased risk of developing the disease. Testing the types and levels of antibodies in the blood can help determine whether a person has type 1 diabetes, LADA, or another type of diabetes.

What causes type 2 diabetes?

Type 2 diabetes—the most common form of diabetes—is caused by a combination of factors, including insulin resistance, a condition in which the body’s muscle, fat, and liver cells do not use insulin effectively. Type 2 diabetes develops when the body can no longer produce enough insulin to compensate for the impaired ability to use insulin. Symptoms of type 2 diabetes may develop gradually and can be subtle; some people with type 2 diabetes remain undiagnosed for years.

Type 2 diabetes develops most often in middle-aged and older people who are also overweight orobese. The disease, once rare in youth, is becoming more common in overweight and obese children and adolescents. Scientists think genetic susceptibility and environmental factors are the most likely triggers of type 2 diabetes.

Genetic Susceptibility

Genes play a significant part in susceptibility to type 2 diabetes. Having certain genes or combinations of genes may increase or decrease a person’s risk for developing the disease. The role of genes is suggested by the high rate of type 2 diabetes in families and identical twins and wide variations in diabetes prevalence by ethnicity. Type 2 diabetes occurs more frequently in African Americans, Alaska Natives, American Indians, Hispanics/Latinos, and some Asian Americans, Native Hawaiians, and Pacific Islander Americans than it does in non-Hispanic whites.

Recent studies have combined genetic data from large numbers of people, accelerating the pace of gene discovery. Though scientists have now identified many gene variants that increase susceptibility to type 2 diabetes, the majority have yet to be discovered. The known genes appear to affect insulin production rather than insulin resistance. Researchers are working to identify additional gene variants and to learn how they interact with one another and with environmental factors to cause diabetes.Studies have shown that variants of the TCF7L2 gene increase susceptibility to type 2 diabetes. For people who inherit two copies of the variants, the risk of developing type 2 diabetes is about 80 percent higher than for those who do not carry the gene variant.1 However, even in those with the variant, diet and physical activity leading to weight loss help delay diabetes, according to the Diabetes Prevention Program (DPP), a major clinical trial involving people at high risk.