Stem Cells Freed Type 1 Diabetes Patients From Daily Insulin

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Main Category: Diabetes
Also Included In: Stem Cell Research
Article Date: 15 Apr 2009 - 10:00 PDT

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A research team comprising scientists in the US and Brazil implanted recently diagnosed diabetes type 1 patients with their own stem cells so that they became insulin free and then showed that this was due to preserved beta cell function because their C-peptide levels went up significantly after transplant.

The study was the work of researchers from the Departments of Clinical Medicine and Social Medicine at the School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil, and the Division of Immunotherapy, Northwestern University Feinberg School of Medicine, Chicago, Illinois. It is published in the 15 April online issue of the Journal of the American Medical Association. The first author is Carlos E. B. Couri, a member of the Brazilian team.

The researchers had already reported having successfully freed diabetes type 1 patients from having to inject themselves with daily insulin for about 19 months back in 2007.

They used a method called autologous nonmyeloablative HSTC (hematopoietic stem cell transplantation) to implant 15 patients with their own stem cells. Most of them became insulin independent for a mean period of 18.8 months.

Insulin independence was established when the patients attained normal levels of available glucose in their blood (they measured the patients' glycated hemoglobin A1c count, called HbA1c for short).

They suggested but could not prove that the patients were making their own insulin because the stem cells preserved functioning beta cells in the pancreas.

But critics suggested that the success could have been the result of a "prolonged honeymoon period" caused by the changes in diet and exercise that occur when patients are closely monitored after a transplant operation.

So the researchers went back to do more tests to find out if the success was actually due to the stem cells preserving the insulin-producing beta cells.

There is evidence from clinical studies that the more C-peptide a person with type 1 diabetes has, the less severe their condition, and that fewer working beta cells makes the condition worse, so all they had to prove was that the C-peptide levels in the patients that didn't need insulin any more had gone up.

For this study, Couri and colleagues continuously monitored the post-transplant C-peptide levels of all 15 of the original patients and another 8 who also received stem cell transplants.

This came to a total of 23 patients aged 13 to 31 years who had been newly diagnosed with diabetes mellitus (type 1) in the preceding 6 weeks. All the patients were treated at the Bone Marrow Transplantation Unit of the School of Medicine of Ribeirão Preto, Ribeirão Preto, Brazil. Enrollment was from November 2003 to April 2008 and follow up finished in December 2008.

The results showed that:

• Over a 7 to 58 month follow up (mean was 29.8 months, median was 30 months), 20 patients became insulin free. None of them had a history of ketoacidosis, nor were they receiving corticosteroids during the preparation phase.


• 12 patients stayed insulin free for between 14 and 52 months (mean was 31 months).


• 8 patients relapsed and resumed insulin at a low dose.


• In the group that stayed insulin free continously, HbA1c levels remained low (under 7 per cent) and the C-peptide levels went up significantly.


• The C-peptide levels went up from 225.0 (SE 75.2) ng/mL per 2 hours before the transplantation to 785.4 (SE 90.3) ng/mL per 2 hours at 24 months after the transplantation (P < .001). The C-peptide levels are measured as AUC (area under the curve).


• At 36 months, the AUC levels of C-peptide per 2 hours was 728.1 (SE 144.4) ng/mL (P = .001).


• In the transient insulin-independent group, average AUC of C-peptide levels also went up from 148.9 ng/mL per 2 hours before transplantation to 546.8 ng/mL per 2 hours at 36 months, and was sustained at 48 months.


• In this group, 2 patients regained insulin independence after taking the antihyperglycemic drug sitagliptin, and their C-peptide levels also went up.

2 patients developed pneumonia, 3 developed late endocrine dysfunction, and 9 developed oligospermia (sperm deficiency). None of the patients died.

The researchers concluded that:

"After a mean follow-up of 29.8 months following autologous nonmyeloablative HSCT in patients with newly diagnosed type 1 DM [diabetes mellitus], C-peptide levels increased significantly and the majority of patients achieved insulin independence with good glycemic control."

They added that:

"At the present time, autologous nonmyeloablative HSCT remains the only treatment capable of reversing type 1 DM in humans. Randomized controlled trials and further biological studies are necessary to confirm the role of this treatment in changing the natural history of type 1 DM."

"C-Peptide Levels and Insulin Independence Following Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation in Newly Diagnosed Type 1 Diabetes Mellitus."
Carlos E. B. Couri; Maria C. B. Oliveira; Ana B. P. L. Stracieri; Daniela A. Moraes; Fabiano Pieroni; George M. N. Barros; Maria Isabel A. Madeira; Kelen C. R. Malmegrim; Maria C. Foss-Freitas; Belinda P. Simoes; Edson Z. Martinez; Milton C. Foss; Richard K. Burt; Julio C. Voltarelli.
JAMA. 2009;301(15):1573-1579.
Vol. 301 No. 15, April 15, 2009

Sources: Journal Abstract, Kaiser Permanente via PR Newswire.

Written by: Catharine Paddock, PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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