Several efforts examine the possibility of halting the development of type 1 diabetes. So far the results are mixed -- at best.
By Neil Osterweil
Reviewed By Charlotte Grayson
If you don't smoke cigarettes, you greatly reduce your risk for lung cancer and emphysema. If you maintain a healthy weight, eat a moderate diet, and get regular exercise, you greatly increase the chance that you'll have a healthy heart.
But if you're at risk for developing type 1 diabetes due to a family history of the disease or other factors, is there anything you can do to stop it? The answer is a definite "maybe."
Diabetes experts now recognize that type 1 diabetes is an autoimmune disease, in which the body's immune system for some reason turns on itself and begins to attack and destroy the beta- islet cells of the pancreas that produce and release insulin. When enough beta islets are destroyed, the body cannot produce enough insulin to properly regulate blood sugar, resulting in type 1 diabetes.
Because type 1 diabetes is caused by a normal immune system gone awry, researchers believe that it may be possible to step in and either prevent, interrupt, or at least slow down the disease-development process. Result thus far, however, have been mixed at best.
Diabetes Prevention Trial - type 1
The largest and most ambitious prevention trial conducted to date is the Diabetes Prevention Trial - type 1 (DPT-1), begun in 1994. The study was designed to determine if it is possible to prevent or delay the onset of type 1 diabetes in people who are at risk for developing the disease. The theory behind the trial was that by receiving low-doses of insulin over a sustained period, the immune system could learn to become "tolerant" to insulin and therefore leave the insulin-producing beta-islet cells alone.
After an initial screening, patients were assigned, depending upon their level of risk (based on family history and genetic profiles), to one of two trial arms:
- The insulin injection trial (completed). People who were determined to be at high risk of developing type 1 diabetes within five years were randomly assigned to either a treatment group or control (untreated) group. The treatment group received twice-daily injections of low-dose, long-acting insulin, plus a once-a-year, five-day treatment of intravenous insulin infusion. Unfortunately, this arm of the trial proved to be a bust, with 60% of patients in both the treated and untreated groups going on to develop type 1 diabetes.
- Oral antigen trial. This, the second arm of DPT-1, involved participants at intermediate risk (25-50%) of developing type 1 diabetes within five years who are randomly assigned to receive either oral insulin or a placebo (dummy pill). "This arm of the trial is based on a completely different hypothesis [than the injection arm]," says diabetes expert John Dupre, FRCP, MA, professor of medicine at the University of Western Ontario in London, Ontario. "There is a very plausible story about regulation of the immune system exerted by the intestine, and there is quite good animal data to suggest it." The trial is ongoing, with results expected to be announced in 2004.
The Trial to Reduce Diabetes in the Genetically At-Risk (TRIGR) is based on an intriguing but controversial idea. Both human and animal studies from Finland, which has among the highest rates of type 1 diabetes in the world, suggest that children who are breastfed exclusively from birth and are not exposed to proteins from cow's milk (in either infant formula or regular milk) may have a lower risk for developing type 1 diabetes.
"In studies done both in Toronto and Finland in mice, those mice that were fed the cow-milk protein were more likely to come down with diabetes than those fed a hydrolyzed formula [in which the proteins have been pre-digested and are not detected by the immune system]," says Peggy Franciscus, RN, coordinator for the U.S. arm of the TRIGR trial, based at Children's Hospital of Pittsburgh.
"Based on that and looking at some of the Finnish studies, those children who were weaned early from breastfeeding -- say before 4 months -- and then given a cow-milk protein formula had a higher incidence of type 1 diabetes than those who were either exclusively breastfed past that three-month period, or were put on a formula with pre-digested protein.'
The theory, Franciscus tells WebMD, is that the whole protein is seen by the child's still-developing immune system as foreign, causing it to produce antibodies that attack both the protein and the child's own store of insulin producing beta-islet cells of the pancreas. The theory is supported by data from a small Finnish study that shows children who received cow-milk protein formulas had evidence in the bloodstream of islet-cell autoantibodies, which are thought to be a possible cause of type 1 diabetes.
"The beginning of the story is that people noticed that in Western Samoa, there was no type 1 diabetes. But when those people move to societies that use milk products -- and in Western Samoa until recently they did not -- they begin to get diabetes, and they do get it in Western Samoa now and they do consume milk proteins," explains Dupre, who is a principal investigator for the Canadian branch of the TRIGR study.
Similar observations have been made in the island of Sardinia, where until recently goat's milk but not cow's milk was common in the diet, and in Puerto Rico, where government-sponsored nutrition programs have increased the use of infant formulas based on cow's milk, Dupre tells WebMD.
The final results from the TRIGR study are not expected until about 2007.
The DAISY trial (the Diabetes AutoImmune Study in the Young) was designed to answer the question whether certain types of stomach virus (enterovirus) could cause increased susceptibility to diabetes. The study looked at two alternate hypotheses: that enteroviruses are either transmitted from the mother at birth or acquired in early childhood, resulting in a chronic infection that leads to an autoimmune response, or that late infections acquired by children who already have abnormal beta-islet cell function can put the final nail in the coffin of the insulin-secreting cells.
But like the DPT-1 trial, this study yielded negative results. "There is no evidence from this study that enterovirus infection is a risk factor for development of beta-cell autoimmunity," researchers write in the January 2003 issue of the journal Diabetes Research and Clinical Practice.
The European Nicotinamide Diabetes Intervention Trial, or ENDIT, conducted in Europe, Canada, and the U.S., is looking at whether high doses of nicotinamide, a form of Vitamin B3 with antioxidant properties, can help to preserve beta-islet cell function in people at risk for type 1 diabetes due to their family history. Trial results, announced at a European diabetes meeting in early 2003, indicated that the supplement offered no additional protection against diabetes, Dupre tells WebMD.
Originally published March 17, 2003.
Medically updated June 18, 2004.
SOURCES: John Dupre, FRCP, MA, professor of medicine at University of Western Ontario. Peggy Franciscus, RN, U.S. Coordinator for the TRIGR trial, Children's Hospital of Pittsburgh. Medscape Medical News, Diabetes & Endocrinology April, 2002. Diabetes Research and Clinical Practice, January 2003.
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