Preserving Insulin Production In Newly Diagnosed Type 1 Diabetics

A drug used to treat lymphoma, rheumatoid arthritis and other immune disorders may enable newly-diagnosed type 1 diabetics to save some of their pancreas function and thereby reduce their susceptibility to long-term complications.

As the leaders of an international research trial, Indiana University School of Medicine scientists will begin testing the drug, rituximab, starting in April, said Mark Pescovitz, M.D., professor of surgery and of microbiology and immunology. Dr. Pescovitz and Henry Rodriguez, M.D., assistant professor of pediatric endocrinology, will lead the study.

If the drug is effective, it could help prevent some of the long-term complications that plague diabetics, said Dr. Pescovitz. Studies have shown that type 1 diabetics who retain some pancreas function have fewer complications of diabetes, which include heart disease, circulatory problems, loss of vision and kidney damage.

Dr. Pescovitz believes rituximab could be effective because it attacks a key component of the immune system, one that appears to play a role in the development of type 1 diabetes.

Type 1 diabetes develops in children when their pancreas stops making enough insulin, the body’s compound used to metabolize sugar. The disease is an immune system disorder in which white blood cells called T-cells turn their attention to their own body’s pancreas, attacking it as though it was an external invader. Nobody knows why this occurs.

Normally, T cells attack and ingest infected cells or tumor cells, but only after other immune cells present tiny pieces of the target cells, called antigens, to the T cells. Researchers designed this study based on the hypothesis that white blood cells called B cells serve as the "antigen presenting" cells, picking up antigens from the pancreas as though they were bits of infected cells, and presenting the pancreas antigens to the T cells.

As a result, said Dr. Pescovitz, "The T cells get excited and go back to where the antigens came from — in this case the pancreas — and start attacking the pancreas."

Rituximab attacks and destroys the body’s B cells, which researchers in the trial hope will stop the body’s attack on the pancreas by preventing the B cells from stimulating the T cells into action.

The study will test rituximab in recently diagnosed type 1 diabetes patients who are at least 8 years old and who still have some pancreas function. The patients will receive treatments once a week for four weeks. Two-thirds of the participating patients will receive rituximab, and the rest will receive a placebo.

It’s hoped that by wiping out a generation of B cells, the immune system’s attacks on the pancreas will be blocked permanently.

"Hopefully new B cells will grow up that won’t be interested in the pancreas," Dr. Pescovitz said.

It’s possible, he said, that rituximab treatment could completely reverse the diabetes so that insulin shots would not be needed. However, it’s more likely that patients would produce only some of their own insulin while still needing insulin injections, because the pancreas typically has been undergoing damage for several years before the patient visits a doctor and is diagnosed with diabetes. By then, damage to the affected portion of the pancreas may be permanent, said Dr. Pescovitz.

The study will enroll 66 patients over two years. In addition to Indianapolis, researchers at 14 other centers in the US and international sites including Australia and Italy will participate. "The participating patients will have follow-up exams for two years, and they will receive intensive diabetes care including insulin and dietary management," said Dr. Rodriguez.

The study is funded by TrialNet, a National Institute of Health, federally-funded research initiative focused on the development, prevention and early treatment of type 1 diabetes. https://www.indiana.edu

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FACT:
Coffee drinking and risk of type 2 diabetes: A recent report stated that a moderate consumption of both caffeinated and decaffeinated coffee may lower the risk of type 2 diabetes in younger and middle-aged women. This is not the first time that the association has been reported. Because the effect was seen using decaffeinated coffee, it may be possible to reduce the risk of type 2 diabetes while avoiding the potential detrimental effects of caffeine on blood pressure and sleep quality. Diabetes Care,29 (398-403): van Dam R, Willett W, Manson J, Hu F Coffee, caffeine, and risk of type 2 diabetes

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