Islet Transplantation for Type 1 Diabetes Studied

New research is underway to study islet transplantation in patients with type 1 diabetes, according to the National Institutes of Health (NIH).

Type 1 diabetes accounts for up to 10 percent of diagnosed cases of diabetes in the US (up to 1 million people).

This form of diabetes usually strikes children and young adults, who need several insulin injections a day or an insulin pump to survive. Insulin, though critical for controlling blood glucose, is no cure.

Most people with type 1 diabetes eventually develop one or more complications, including damage to the heart and blood vessels, eyes, nerves, and kidneys.

Therapeutic Approach Still Investigational

In islet transplantation, islets are extracted from the pancreas of a deceased donor and infused into a person with difficult-to-control type 1 diabetes though the portal vein of the liver. In successful transplants, the cells lodge in the liver’s small blood vessels and begin producing insulin.

The studies will focus on improving the long-term success of methods for transplanting islets, the insulin-producing cells of the pancreas, in people whose own islets have been destroyed by the autoimmune process that characterizes type 1 diabetes.

Some studies will focus on improving combined islet and kidney transplants in patients with type 1 diabetes and kidney failure, a common complication of diabetes.

“This award accelerates studies of an experimental approach that could be very promising for some people with severe type 1 diabetes if specific barriers can be overcome,” said Dr. Thomas Eggerman, who oversees the consortium for the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Two institutes of the NIH - the NIDDK and the National Institute of Allergy and Infectious Diseases (NIAID) - sponsor the consortium.

In the 1990’s, islet transplantation rarely succeeded in freeing patients from insulin injections for more than a year.

In June 2000, however, a research team led by Dr. James Shapiro at the University of Alberta in Edmonton, Canada, reported sustained insulin independence in seven patients transplanted with islets from two to four donor pancreases.

The patients received an immunosuppressive regimen that omitted glucocorticoids, also known as steroids, which were often used to prevent rejection but are now thought to be toxic to islets.

In the next few years, researchers participating in the Immune Tolerance Network (ITN), a collaboration of clinical and basic researchers sponsored by the NIAID, NIDDK, and the Juvenile Diabetes Research Foundation International, replicated what became known as the “Edmonton protocol.”

Despite these gains, scientists continue to grapple with several impediments to the wider testing of islet transplantation.

One is the scarcity of islets. Only about 6,000 donor pancreases become available each year, and many are used for whole organ transplantation.

Posing another obstacle are the potentially serious side effects, such as anemia, nerve damage, meningitis, and vulnerability to infection, of the medications that stop the immune system from rejecting donor islets.

Finally, in some transplanted patients, donor islets function well initially, but in time diabetes recurs. Why the islets die is not well understood.

Promising Research Holds Hope

Recent NIH-funded advances may lead to some answers.

“Newly developed immune assays are helping us flesh out a more complete picture of the immune events that trigger rejection,” says Dr. Nancy Bridges, who oversees the consortium for NIAID. “Studies are also laying the groundwork for less toxic immunosuppressive agents, which will be tested in upcoming trials.

"Our ultimate goal is to develop ways to induce tolerance, a state of immune acceptance of the donor tissue or organ,” she says.

Always consult your physician for more information.

Online Resources

American Diabetes Association

Centers for Disease Control and Prevention (CDC)

Everyday Choices, ADA, AHA, and ACS

HealthierUS.Gov

National Diabetes Education Program

National Diabetes Information Clearinghouse

National Institute of Diabetes & Digestive & Kidney Diseases

National Institutes of Health (NIH)

National Library of Medicine

Prevengamos la diabetes tipo 2. Paso a Paso

December 2004

Islet Transplantation for Type 1 Diabetes Studied

Therapeutic Approach Still Investigational

Promising Research Holds Hope

Lab Studies Look at Insulin Resistance in Type 2 Diabetes

Online Resources

Other Resources:

Find a St. John's Mercy Physician

Diabetes Services at St. John's Mercy

Diabetes Health Information

St. John's Mercy Classes and Programs

Lab Studies Look at Insulin Resistance in Type 2 Diabetes

Scientists know that obesity is a key player in the development of type 2 diabetes, but exactly how excess weight causes the disease is not clear.

While trying to answer that question, Harvard University researchers discovered a new pathway in a study with mice that sets in motion a series of reactions that leads to the development of insulin resistance, a precursor of type 2 diabetes, a new study reports in the journal Science.

The researchers found that obesity causes stress in a system of cellular membranes called endoplasmic reticulum (ER), which in turn causes the endoplasmic reticulum to suppress the signals of insulin receptors, which then leads to insulin resistance.

Endoplasmic reticulum is a network of membranes found inside cells.

Study author Dr. Gokhan Hotamisligil, a professor of genetics and metabolism at Harvard School of Public Health, says endoplasmic reticulum is "really the synthetic machine of the cell." It is responsible for processing proteins and fats.

In an editorial in the journal accompanying the study, Dr. Christopher Newgard, a scientist at Duke University Medical Center, suggested thinking of endoplasmic reticulum "as a factory for producing protein and the site at which excess lipids - blood fats - are processed."

"As you enter a state of overnutrition, as we often do living in our supersized society, all of those nutrients that come in need to be processed, stored, and utilized and the ER factory is overworked and starts sending out SOS signals," Dr. Newgard explains.

These SOS signals, he says, tell cells to dampen their insulin receptors. Insulin is the hormone that converts blood sugar to energy for the body's cells.

"In the case of obesity, what is designed as a short-term adaptive response triggers long-term chronic illness," says Dr. Hotamisligil.

"It's the ER's way of saying, 'Enough, already; you're bombing us with nutrients,'" Dr. Newgard says.

"When there's too much going on, the cell knows that insulin is out there, but doesn't want insulin receptors signaling for more insulin because there's already enough on board," Dr. Newgard notes. "This has a downside, because insulin soon loses its ability to help clear sugar from the body."

"In the future, if one can develop ways to reduce ER stress or generate less ER stress or to find a way to boost the system's ability to handle stress, all of these maneuvers could help cope with [type 2 diabetes]," Dr. Newgard says.

Always consult your physician for more information.