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TRANSPLANTS FOR DIABETICS ARE A SUCCESS IN EARLY RESULTS

DATE: JUNE 20, 2003

When diabetic Anthony Pecora took his last insulin dose on July 7, 2002, he didn't regret his many trips from Ashland, Va., to the University of Minnesota to take part in an international diabetes treatment experiment.

Pecora, 46, who has had diabetes for 29 years, was on hand Monday as researchers in Washington unveiled preliminary results of a study of a pancreas transplant procedure that has helped Pecora and others with type 1 diabetes reduce or end their insulin use. The university has taken a leading role.

Although investigators did not disclose which sites had the most success, they noted in a news releases that more than 90 percent of patients were insulin-free at "the three most experienced clinical centers."

The University of Minnesota has for years been considered a diabetes treatment leader. "We are the only group that can consistently reverse diabetes with the pancreas from [only] one donor," said Dr. Bernhard Hering, director of the university's Islet Transplant Program and co-principal investigator for the study.

Pecora chose the university partly because he had confidence in the medical staff. "Minnesota's much farther away than the others, but it turned out to be one of the best decisions I've ever made,"he said.

Nine medical institutions worldwide are taking part in the study. Preliminary numbers show that 12 of the 15 patients who completed their transplants are insulin-free. The rest are decreasing their insulin dependence.

"I think we are beyond the experiment stage," Hering said. "I think it works already."

But the procedure, which involves the pancreas' islet cells, is currently done only on selected patients, he said.

"It may take a number of years," he said. "The science has delivered. The question is how much do we as a society want to make this transition."

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JOSLIN STUDY SHOWS KIDNEY DISEASE IN PEOPLE WITH TYPE 1 DIABETES IS FREQUENTLY REVERSIBLE IN EARLIEST STAGE; FINDINGS MAY LEAD TO IMPROVED TREATMENT

DATE: JUNE 13, 2003

A new study by Joslin Diabetes Center researchers published in last week's New England Journal of Medicine (NEJM) is good news for the thousands of Americans with type 1 diabetes who have microalbuminuria, the earliest sign of kidney disease.

One in three patients with type 1 diabetes develop end-stage kidney disease, which eventually requires either a kidney transplant or every-other-day dialysis treatment for life. The earliest sign of kidney disease is the leakage of small amounts of proteins from the blood into the urine, called microalbuminuria. When it appears in the urine, it was once believed that one could only hope to postpone - but not prevent - kidney disease by intensified efforts to control blood sugar, treatment with certain blood pressure drugs, and a low protein diet.

However, the prognosis for patients with microalbuminuria turns out to be not so dire, according to the results from the Joslin Kidney Study being reported in the NEJM. Andrzej Krolewski, M.D., Ph.D., head of the Section on Genetics and Epidemiology at Joslin, and his colleagues found in this study of people with type 1 diabetes that early signs of microalbuminuria can be reversed with proper medical screening and diabetes control. Dr. Krolewski is Associate Professor of Medicine at Harvard Medical School (HMS) and Associate Professor of Epidemiology at Harvard School of Public Health.

"In this early stage, we found kidney injury is still a dynamic process that can either get worse or get better -- even revert back to normal," said Bruce Perkins, M.D., M.P.H., F.R.C.P., and a lead author of the paper. Dr. Perkins is a Clinical Fellow in Endocrinology at HMS.

In this study, 400 patients with microalbuminuria persisting over a two-year period were followed for six additional years. "Surprisingly, the leakage of protein subsided in 58 percent of them, even among those who were not taking ACE inhibitors, a type of drug known to be helpful in people with microalbuminuria," Dr. Perkins said.

"It stands to reason that these landmark studies will heighten physicians' awareness of the importance of screening for microalbuminuria to permit aggressive early intervention, particularly intervention that leads to tight glycemic control," Eberhard Ritz, M.D., of the University of Heidelberg in Germany, writes in an accompanying editorial in the NEJM on the Joslin study and another study appearing in the journal.

Among the factors associated with a return to normal kidney function were an early diagnosis of microalbuminuria by frequent screening and very good levels of blood sugar, blood pressure and cholesterol. Although high cholesterol was known to be bad for patients with advanced kidney disease, it was not known just how important it is to keep cholesterol levels low in the earliest stages of the disease. "In view of this finding, perhaps cholesterol-lowering drugs should be given a trial," Dr. Perkins said.

"Since microalbuminuria can go away and certain factors are associated with its remission, we infer that specific mechanisms of repair exist in the kidney that enable the kidney to repair itself in the early stages. When we understand these mechanisms better, we can develop more effective treatments for preventing serious kidney disease," Dr. Perkins said. "In the meantime, the study highlights the need for frequent screening and early intervention for microalbuminuria in patients with type 1 diabetes. Once it is identified, the treatment plan should be directed toward improving multiple factors -- blood sugar control, blood pressure control, and cholesterol lowering -- rather than relying on ACE-inhibitor treatment alone."

About Joslin Diabetes Center

Joslin Diabetes Center, established in Boston in 1898, is the foremost diabetes research, care and education center in the world. Devoted to the prevention and cure of the disease and improving the lives of people with diabetes and its many complications, Joslin is unique in its integration from research bench, to patient bedside, to the entire diabetes community. Joslin conducts the world's largest academic diabetes research effort, with a research team of over 300 people supported by $40 million in research funds. Joslin Clinic is dedicated to providing the best in treatment and education for individuals with type 1 (insulin dependent), type 2 (adult onset) diabetes and related complications. Joslin Clinic offers a Renal Service, which is staffed by physicians and others who are experts in treating kidney disease in people with diabetes. For more information about Joslin's Renal Services, call 617-732-2477.

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MORE PROOF PUBLISHED THAT COMMON CHILDHOOD VACCINES MAY CAUSE DIABETES

DATE: JUNE 06, 2003

The prestigious peer reviewed journal, Journal of Pediatric Endocrinology and Metabolism, published a study during the last week of May 2003 by Dr J Bart Classen, an immunologist at Classen Immunotherapies, and David Carey Classen, an infectious disease specialist at the University of Utah, providing support for a causal relationship between several common paediatric vaccines and the development of insulin dependent diabetes. Their previously published work proved the hemophilus vaccine, a common paediatric vaccine, caused a 25% rise in insulin dependent diabetes in children under the age of 7. Classen's research indicates most cases of diabetes caused by vaccines occur between 24 to 48 months after immunization of young children but the delay can be shorter in older children with prior damage to their pancreas. The time delay between vaccination and diabetes corresponds exactly to work from several independent groups, which showed a similar delay between the initiation of autoimmunity to the insulin secreting islet cells and the development of diabetes.

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ISRAELI-US TEAM CREATE INSULIN-PRODUCING CELLS FROM STEM CELLS

DATE: MAY 30, 2003

Tel Aviv University and American researchers have managed to cure diabetes in mice by creating insulin- producing cells from stem cells taken from the liver of a four-month-old miscarried human embryo and implanting them into Type I (insulin-dependent) diabetic mice.

Prof. Shimon Efrat of the department of Human Genetics and Molecular Medicine at TAU's Sackler School of Medicine and colleagues in Israel and the US hope that eventually such cells could be transplanted into human diabetics - if a way is found to protect them from rejection through an autoimmune attack.

The genetically engineered human cells will theoretically be ready for clinical trails in two or three years, but in order it to become practical, some capsules or other "vehicle" that holds and protects the cells from being attacked by the body's immune system must be developed. The team is working on such a vehicle, as are many other teams abroad, but so far no one has succeeded.

The important development - the first time that an unlimited supply of insulin-producing human cells has been developed - was reported in the latest issue of the Proceedings of the [US] Academy of Sciences (PNAS).

Efrat, who returned from Israel a few years ago after working at Yeshiva University's Einstein College of Medicine, worked for 12 years on mice cells. Three years ago, the team advanced to human cells.

"There have been suggestions of a synthetic structure to hold the insulin-producing cells while protecting them from an autoimmune attack, but it hasn't yet proved itself. It's likely that a combined technique will be developed," Efrat said. "If the cells become part of body tissue, with blood supply, it could be a one-time implantation, but if in a capsule, they would have to be implanted from time to time."

The embryonic cells were grown in a tissue culture. The team, which included scientists from Einstein and the University of California at Sacramento, showed that these cells can produce a third of the amount of insulin normally secreted in the body by beta cells in a normal pancreas. That would be enough to cure Type I diabetes, which occurs when the body's immune system mistaken recognizes beta cells as "strangers," attacks them and destroys them. The body suddenly has no insulin to metabolize sugar in the blood, which can cause death without insulin injections.

Another treatment is a pancreas transplant, but the supply of organs is short and the recipient has to take anti-rejection drugs for the rest of his life.

The development is also expected to help patients with Type II diabetes, who produce some insulin but whose body suffers from insulin resistance, making its use inefficient. About a third of these patients have to inject themselves with synthetic insulin. If blood sugar levels are not kept in balance with insulin levels, the patient is at higher risk for a stroke, heart disease, blindness, and limb amputation.