Vaccine shows promise in reversing Type 1 diabetes

The new findings hint that even in patients with long-standing diabetes, the body retains the potential to restore pancreas function if clinicians can only block the parts of the immune system that are killing the beta cells.

By Thomas H. Maugh II
Los Angeles Times

LOS ANGELES — Preliminary experiments in a handful of people suggest that it might be possible to reverse Type 1 diabetes using an inexpensive vaccine to stop the immune system from attacking cells in the pancreas.

Research in mice had already shown that the tuberculosis vaccine called BCG prevents T cells from destroying insulin-secreting cells, allowing the pancreas to regenerate and begin producing insulin again, curing the disease.

Now tests with very low doses of the vaccine in humans show transient increases in insulin production, researchers report Sunday at a San Diego meeting of the American Diabetes Association.
The Massachusetts General Hospital team is now gearing up to use higher doses of the vaccine in larger numbers of people in an effort to increase and prolong the response.

The findings contradict an essential paradigm of diabetes therapy — that once the insulin-secreting beta cells of the pancreas have been destroyed, they are gone forever. Because of that belief, most research today focuses on using vaccines to prevent the cells’ destruction in the first place, or on using beta-cell transplants to replace the destroyed cells.

The new findings, however, hint that even in patients with long-standing diabetes, the body retains the potential to restore pancreas function if clinicians can only block the parts of the immune system that are killing the beta cells.

The results are “fascinating and very promising,” said immunology expert Dr. Eva Mezey, director of the adult stem-cell unit at the National Institute of Dental and Craniofacial Research. But Mezey noted that the results have been achieved in only a small number of patients and that they suggest that the vaccinations will have to be repeated regularly.

The key player in the diabetes study is a protein of the immune system called tumor necrosis factor, or TNF. Studies by others have shown that if you increase levels of TNF in the blood, it will block other parts of the immune system that attack the body, especially the pancreas.

To raise TNF levels, Dr. Denise Faustman of Massachusetts General Hospital and her colleagues have been working with the BCG vaccine, known formally as bacillus Calmette-Guérin. BCG has been used for more than 80 years in relatively low doses to stimulate immunity against tuberculosis. More recently, it has been used in much higher doses to treat bladder cancer.

Faustman first reported her findings in mice in 2001 in a paper in the Journal of Clinical Investigation, but scientists reviewing her findings for that journal were so skeptical that she was not allowed to say “regeneration” of the pancreas in the paper. Instead, she was told to say “restoration of insulin secretion by return of blood sugar to normal.”

In 2003, she published a report in the journal Science in which she was able to use the word “regeneration,” but that finding was met by an “explosion of skepticism,” she said. Nonetheless, by 2007, “six international labs had duplicated the mouse experiments,” she said. “We needed to move forward into humans.”

In the human trial, Faustman and her colleagues studied six patients who had been diagnosed with Type 1 diabetes for an average of 15 years. They were randomly selected to receive either two doses of BCG spaced four weeks apart or a placebo.

Careful examination of those receiving the vaccine showed a decline of T cells that normally attack the pancreas. It also revealed a temporary but statistically significant elevation of an insulin precursor called C-peptide, an indication that new insulin production was occurring.

“If this is reproducible and correct, it could be a phenomenal finding,” said Dr. Robert R. Henry of the University of California, San Diego, who chaired the scientific program at the meeting. It suggests that once the destructive immune response is controlled, the body has the capability to produce more insulin, he said.

Number of adults with diabetes rises

LONDON — The number of adults worldwide with diabetes has more than doubled in three decades, jumping to an estimated 347 million, a new study says.
Much of that increase is because of aging populations — since diabetes typically hits in middle age — and population growth, but part of it has also been fueled by rising obesity rates.

With numbers climbing almost everywhere, experts said the disease is no longer limited to rich countries and is now a global problem. Countries in which the numbers rose fastest include Cape Verde, Samoa, Saudi Arabia, Papua New Guinea and the United States.

“Diabetes may well become the defining issue of global health for the next decade,” said Majid Ezzati, chair of global environmental health at Imperial College London, one of the study authors.

He noted the figures don’t reflect the generations of overweight children and young adults who have yet to reach middle age. That could create a massive burden on health systems.

Still, in Britain and elsewhere in Western Europe, despite growing waistlines, there was only a slight rise in diabetes.

Women in Singapore, France, Italy and Switzerland remained relatively slim and had virtually no change in their diabetes rates. Numbers also stayed flat in sub-Saharan Africa, central Latin America and rich Asian countries.

Type 2 is the most common type of diabetes and is often tied to obesity.

For their estimate, Ezzati and colleagues examined more than 150 national health surveys and studies that tracked type 2 diabetes in adults older than 25 in 199 countries and territories. They used modeling to estimate cases for another 92 countries.

They calculated there were 347 million people worldwide with diabetes. In 1980, there were 153 million. Their figures come with a big margin of error, ranging from 314 million to 382 million. A previous study using different methods estimated there were 285 million people with diabetes in 2010.

— The Associated Press

Source: The Seattle Times