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Importance of GAD-Antibodies in Diabetes – Professor Åke Lernmark The more severe form of diabetes develops when the beta cells in the pancreatic islets are destroyed. Our body has only about 2 grams of beta cells. They make insulin that is delivered into the blood vessels of the pancreas to be transported all over the body. Insulin is necessary to allow cells in the liver, muscles and fat to use glucose as a fuel. Insulin keeps the blood glucose tightly regulated and although there is some overcapacity, loss of beta cells is bad news. If beta cells are killed, they are hard to replace. Eventually insulin production will lag behind demand and diabetes develops. Beta cells may be lost for several different reasons. The most dramatic killing occurs when our own immune system attacks the beta cells. Inflammatory cells usually defend us from invasion by infectious agents, virus, bacteria and the like. In autoimmune diabetes that is causing type 1 diabetes or insulin-dependent diabetes these inflammatory cells have turned themselves on the beta cells. Why and how this happens is not fully understood. The inflammatory cells use many weapons to kill the beta cells. The targets are molecules that are specific to the beta cells. One such target molecule is glutamic acid decarboxylase, abbreviated to GAD. GAD is an enzyme that makes GABA, a neurotransmitter substance that is also present in the brain. As a result of the beta cell attack, antibodies to GAD appear in the blood and can nowadays be measured with simple but very sensitive and realible tests. GAD antibodies are important since they can be used to predict diabetes. The antibodies signal or mark that an inflammation has or is taking place in the pancreatic islets. In combination with two other types of antibodies, insulin and IA-2 antibodies, it is now possible to predict type 1 diabetes in healthy children. In adults, GAD antibodies are the best markers for the inflammatory killing of beta cells and a more slowly developing diabetes. This mild type of diabetes in fact resembles type 2 diabetes. Type 2 diabetes patients with GAD antibodies (LADA) will after a few years require insulin to control their diabetes. The current ongoing phase II Diamyd trial in LADA patients treated with oral drugs is an important step in the effort to prevent LADA patients from developing insulin dependency.
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