Multiple approaches to type 1 diabetes

Type 1 diabetes, formerly called insulin-dependent diabetes, juvenile diabetes or childhood-onset diabetes, affects 1 to 2 million people in the U.S. and millions more worldwide.

In this country, it is second only to asthma as the most common chronic disease in children. However, it may begin at any age, when for yet-unknown reasons, a person's immune system mistakenly attacks beta cells that produce insulin. Patients with this type of diabetes are dependent for life on insulin injections or insulin medications.

The Children's Hospital of Philadelphia has set for itself the ambitious goal of advancing pediatric care worldwide. Its researchers are following multiple strategies to preventing, treating and possibly even curing type 1 diabetes.

Gene Discovery Helps Reveal Treatment Targets on Diabetes Pathways
Because all types of diabetes are complex diseases, affected by interactions among multiple genes, genomics researchers here focus on identifying all the genes involved, as a foundation for further investigating how genes function on biological pathways that lead to diabetes. At the Children's Hospital's Center for Applied Genomics, the world's largest pediatric genotyping project, a study team in July 2007 identified a previously unknown gene variant that raises a child's risk of type 1 diabetes. Using highly automated DNA scanners, the researchers have since discovered and confirmed other gene variants, and will augment the list with other findings in the coming months. Hakon Hakonarson, M.D., the center's director, says “better understanding of these gene pathways may shed light on ways to intervene early in life with targeted drugs or cell therapies that could prevent diabetes from developing.” (Center for Applied Genomics: http://www.chop.edu/consumer/jsp/division/generic.jsp?id=84930)

Findings on Beta Cells May Enable Body to Restore Insulin Production

Because the basic problem in type 1 diabetes is the body's lack of insulin, pediatric endocrinologist Jake Kushner, M.D., searched for adult stem cells thought to develop into the beta cells that secrete insulin in the pancreas. But those adult stem cells weren't there. Instead, in his animal studies, he found that beta cells themselves divided slowly to produce new beta cells after a prolonged delay never previously seen in mammals. Although most beta cells fall victim to the body's immune system in type 1 diabetes, Kushner says that learning how to manipulate the beta cells' development could make them replicate faster and outpace the disease. His approach dovetails with beta cell regeneration, a controversial area of diabetes research. In 2001, Boston researchers discovered that residual numbers of beta cells escape autoimmune destruction even in patients with longstanding type 1 diabetes. With deeper knowledge and better techniques, Kushner suggests that scientists might eventually stimulate patients' own residual beta cells to proliferate and produce therapeutic amounts of insulin. (More about Dr. Kushner's research: http://stokes.chop.edu/research/profiles/?ID=3013)

Screening and Insulin Pill May Prevent Type 1 Diabetes in Those at Risk

Children's Hospital is taking part in Type 1 Diabetes TrialNet, a worldwide consortium of research centers dedicated to delaying or preventing the onset of type 1 diabetes in children and adults. Under TrialNet, centers perform blood tests on children and adults who are at higher risk for type 1 diabetes because a close family member (first- or second-degree) has the disease. If the blood test detects autoantibodies to diabetes that may appear years before type 1 diabetes develops, the patient may enter a study of a new medical intervention that uses oral insulin. A preliminary study indicated that oral insulin may delay or prevent type 1 diabetes among some people found to be at risk of the disease. Children's Hospital is among 150 medical centers on three continents participating in Type 1 Diabetes TrialNet, sponsored by the National Institutes of Health. Lorraine Levitt Katz, M.D., a pediatric endocrinologist at the Hospital's Diabetes Center for Children, leads the study here. (Web page for the Diabetes Center for Children at http://www.chop.edu/consumer/jsp/division/generic.jsp?id=84041)

About The Children's Hospital of Philadelphia: The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking third in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 430-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu.

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