Treatment for rare form of diabetes discovered by NIH researchers
Thursday, October 14, 2010
Finding on extreme insulin resistance may hold promise for other autoimmune diseases
An intensive combination of three immune-modulating drugs has driven a rare form of extreme insulin resistance into long-term remission in all seven patients who received the treatment, according to researchers with the National Institutes of Health and Cambridge University, England. Results of the trial, conducted at the NIH Clinical Center in Bethesda, Md., are published in the Journal of Clinical Endocrinology and Metabolism.
“We were happy to see that this unique combination of drugs was so effective in treating type B insulin resistance, which leads to a severe form of diabetes,” said Phillip Gorden, M.D., an endocrinologist and senior investigator at the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK), and co-author of the paper. “It’s the hallmark of medicine: We combine medications in relatively low dosages to reduce toxicity and get the maximum beneficial effects from individual drugs. We were simply using a cocktail of these three drugs in the right ratio to achieve the most favorable outcome.”
In type B insulin resistance, the body’s immune cells make antibodies that block insulin receptors on cells, preventing the cells’ response to insulin, a critical hormone that converts glucose to energy. Patients develop a severe form of diabetes that does not respond to insulin injections, even at high doses. The disease includes extreme weight loss and a skin condition known as acanthosis nigricans, with which a person has darkened, velvety-like skin on the face, under the arms and in the groin area. With conventional treatment, more than half of patients die within 10 years of diagnosis.
Type B insulin resistance tends to occur in African-American women.
The study marks the first time the three drugs -- rituximab, cyclophosphamide and pulse corticosteroids -- have been combined to treat type B insulin resistance and may point the way to treating other diseases that occur when the body is attacked by its own immune system.
“For the first time, we have targeted each step along the disease’s pathway,” said Rana Malek, M.D., an endocrinologist and staff clinician at NIDDK, and study co-author. “This advance is a great example of what medicine can achieve when we broaden our perspective instead of thinking strictly as endocrinologists, in our case simply treating high blood glucose levels with insulin. As a result, we ended up using drugs to treat endocrine symptoms that endocrinologists typically do not use.”
The NIDDK, a component of the National Institutes of Health (NIH), conducts and supports research on diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition and obesity; and kidney, urologic and hematologic diseases. Spanning the full spectrum of medicine and afflicting people of all ages and ethnic groups, these diseases encompass some of the most common, severe and disabling conditions affecting Americans. For more information about the NIDDK and its programs, see www.niddk.nih.gov.
The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
Editor’s Note: Dr. R.K. Semple at Cambridge University, United Kingdom collaborated on the study, performing antibody testing procedures.
Contact: Bill Polglase
Page last updated: December 21, 2010