American Diabetes Assoc Article

Research into Preventing Type 1 Diabetes

Type 1 diabetes occurs because of an autoimmune attack against the beta cells. If we could turn off the immune attack, then we could potentially prevent type 1 diabetes. That this might be possible was suggested by clinical research with drugs that are normally used to prevent rejection of transplanted organs such as kidneys and hearts. When these transplant drugs, which work by suppressing the immune system, were given to patients newly diagnosed with type 1 diabetes, they prolonged the honeymoon phase. The problem, however, was that these drugs had to be given continuously to be effective, and they also have serious side effects such as life-threatening infections and even cancer. For recipients of organ transplants, the benefi ts of these drugs clearly outweigh the risks, but this is not the case for diabetes. These studies did, however, provide support for this approach to diabetes prevention, and they opened the door for other therapies targeting the immune system.

Currently, a drug called humanized OKT3 is being investigated: in short-term clinical research studies with twelve days of drug, it has been shown to prolong the honeymoon phase in new onset type 1 patients. The drug has a number of advantages: fi rst, it does not have to be given continuously, and second, its side effects appear to be fairly modest. The problem is that the effect is not absolute and permanent�although it slows the beta cells loss, it does not stop it. Additional studies are in progress to see if giving more than one course will be more effective. A number of other immune modulating drugs are also being evaluated to see if they will prolong the honeymoon. Recently, a three-step procedure for eliminating the immune cells that are attacking the beta cells was shown to be successful in prolonging the honeymoon phase. In this procedure, stem cells that can remake some of the cells of the immune system are fi rst collected from the blood of the patient. Then the patient is given chemotherapy to kill off the immune cells that are attacking the beta cells. The third step is to inject the collected stem cells back into the patient to make new immune cells, which presumably will not attack the beta cells. Fifteen people with new onset type 1 diabetes received this treatment, and fourteen of them did not require insulin therapy during the follow-up period of the study, which lasted from 7 to 36 months (average of 18.8 months). It remains to be shown if this benefi cial effect is long lasting and whether the procedure is safe in the long term.

Even though the current research studies are being done in people with type 1 diabetes who are in the honeymoon phase, it is expected that if the studies are positive, the therapy will be used in people who are at high risk of developing type 1 diabetes in the future. The National Institutes of Health are funding a consortium called TrialNet to coordinate many of these studies. You can fi nd out more information about these studies at the TrialNet website.