A Brazilian study has shown that stem cell transplants in patients with diabetes type 1 may kick start the pancreas into producing insulin again. It is still too early to tell if the effect is permanent, but some patients have remained insulin free for over 20 months.
The study is published in the Journal of the American Medical Association (JAMA).
Type 1 diabetes mellitus, formerly known as childhood or insulin dependent diabetes, occurs in about 1 in 10 cases of diabetes, the rest being of type 2. It is not primarily a childhood illness, the adult incidence is similar but is often misdiagnosed as type 2 to begin with.
Type 1 diabetes develops because the immune system attacks insulin producing beta cells in the pancreas. This can go undetected until 60 to 80 per cent of the cells have been destroyed, when the body can no longer keep glucose levels in balance and the condition comes to the patient’s awareness.
Treatment for type 1 diabetes consists of insulin replacement therapy, usually by injection or insulin pump, careful monitoring of blood sugar and watching carbohydrate intake.
The cause is unknown, there could be a genetic predisposition that is triggered by an infection, for instance German measles is thought to trigger type 1 diabetes in some people. Some scientists say that infants that were never breast fed are more likely to develop type 1 diabetes because their immune systems were exposed too early to cow’s milk.
Since 1996, other autoimmune diseases have been treated successfully by suppressing the immune system and then transplanting blood stem cells to kick start fresh cell production of damaged tissue. This transplant of blood stem cells is called “autologous nonmyeloablative hematopoietic stem cell transplantation”, or AHST.
Also, previous trials have shown that newly diagnosed type 1 diabetes responds to moderate suppression of the immune system and can stop further loss of the cells that produce insulin and reduce the need for external insulin.
However, this study is the first to combine both the immunosuppression and the stem cell transplant in newly diagnosed type 1 diabetes patients.
Julio Voltarelli and colleagues from the Regional Blood Center (Hemocentro), University of Sao Paulo in Brazil, recruited 15 recently diagnosed type 1 diabetes patients aged 14 to 31 years. They were all dependent on supplemental insulin.
After receiving drugs to stimulate stem cell production, the patients had some bone marrow removed to harvest a supply of blood stem cells, and then their immune systems were suppressed with drugs and they also took antibiotics and stayed in isolation to protect them from infection.
After two weeks their extracted and conditioned stem cells were infused into their bloodstream, via the jugular vein.
The treatment took place between November 2003 and July 2006 with further observation until February 2007 at the Bone Marrow Transplantation Unit of the School of Medicine of Ribeirão Preto, Brazil.
During this time the patients were monitored and blood samples taken to test for insulin and other markers.
As the treatment took effect, the patients gradually, at different rates, reduced their need for external insulin.
14 of the 15 patients were insulin-independent over the 7 to 36 month follow up period. The average insulin free period was nearly 19 months.
One patient was still insulin-free at 35 months, another 4 for 21 months, 7 for 6 months and 2 with late response were insulin-free for 1 and 5 months respectively.
The treatment failed in the first patient, probably because their beta cell count was too low when they started the treatment. The remaining patients were more carefully selected after this.
No patients died; one got pneumonia and two others developed late endocrine dysfunction (hypothyroidism or hypogonadism). It is not clear if this was as a result of the treatment.
At 6 months after AHST treatment, the level of C-peptide, a marker that shows the presence of the body’s own produced insulin, was significantly greater than the pre-treatment values, and did not change at 12 and 24 months.
The study concluded that:
“High-dose immunosuppression and AHST were performed with acceptable toxicity in a small number of patients with newly diagnosed type 1 DM. With AHST, beta cell function was increased in all but 1 patient and induced prolonged insulin independence in the majority of the patients”.
In an accompanying editorial, Jay Skyler who directs the Diabetes Research Institute at the University of Miami in Florida, USA, said that while these results are promising, they should be treated with some caution.
It is not unusual for recently diagnosed type 1 patients to go through what is called a “honeymoon” period where for some reason they experience a rise in their own bodily insulin production.
This trial was really an observational study – it did not include a control group, which would have controlled for effects such as the honeymoon period, noted Skyler.
Also, it is not clear what exactly is going on. Is the insulin level going up because the stem cells generated extra beta cells, or because the immune system stopped attacking the beta cells and the 20 or so per cent that were still left in the patients was enough to keep insulin production at the right level, or a mixture of the two?
Voltarelli and his team recognized that it is early days, and expressed their hope that this study opens the door to helping type 1 diabetes patients to overcome some of the side effects of having too much glucose in the blood, such as damage to the kidneys, eyes and nervous system.
“Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation in Newly Diagnosed Type 1 Diabetes Mellitus.”
Júlio C. Voltarelli, Carlos E. B. Couri, Ana B. P. L. Stracieri, Maria C. Oliveira, Daniela A. Moraes, Fabiano Pieroni, Marina Coutinho,Kelen C. R. Malmegrim, Maria C. Foss-Freitas, Belinda P. Simões, Milton C. Foss, Elizabeth Squiers, Richard K. Burt.
JAMA. 2007;297:1568-1576.
Vol. 297 No. 14, April 11, 2007.
Click here for more information on Type 1 Diabetes (American Diabetes Association).
Written by: Catharine Paddock
Writer: Medical News Today