Stem Cell Transplantation May Be Helpful in Type 1 Diabetes

Hematopoietic stem cell transplantation (HSCT) in patients with newly diagnosed type 1 diabetes mellitus (DM) helped patients achieve long-term insulin independence and improved beta-cell function, according to the results of a prospective phase 1/2 study reported in the April 15 issue of the Journal of the American Medical Association.

"In 2007, the effects of the autologous nonmyeloablative [HSCT] in 15 patients with type 1 [DM] were reported," write Carlos E.B. Couri, MD, PhD, from School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil, and colleagues. "Most patients became insulin free with normal levels of glycated hemoglobin A1c (HbA1c) during a mean 18.8-month follow-up. To investigate if this effect was due to preservation of beta-cell mass, continued monitoring was performed of C-peptide levels after stem cell transplantation in the 15 original and 8 additional patients."

The study sample consisted of 23 patients, aged 13 to 31 years, with type 1 DM diagnosed in the previous 6 weeks by clinical findings with hyperglycemia and confirmed by measurement of serum levels of anti–glutamic acid decarboxylase antibodies. Participants were enrolled from November 2003 to April 2008 and followed up until December 2008 at the Bone Marrow Transplantation Unit of the School of Medicine of Ribeirão Preto.

Hematopoietic stem cells were mobilized using the 2007 protocol. The main study endpoints were C-peptide levels measured during the mixed-meal tolerance test, both before and at different time points after HSCT. Secondary outcome measures included transplantation-related adverse events and death, temporal changes in requirements for exogenous insulin, and serum levels of HbA1c.

Mean follow-up was 29.8 months (median, 30 months; range, 7 – 58 months). During follow-up, 20 patients without previous ketoacidosis and who were not receiving corticosteroids during the preparative regimen became insulin-free. Of these 20 patients, 12 remained insulin-free for a mean duration of 31 months (range, 14 – 52 months), whereas 8 patients relapsed and again required insulin use at low doses of 0.1 to 0.3 U/kg.

In the group that continued to require insulin, HbA1c levels were less than 7.0%. Mean area under the curve (AUC) of C-peptide levels increased from 225.0 ± 75.2 ng/mL per 2 hours before transplantation to 785.4 ± 90.3 ng/mL per 2 hours at 24 months after transplantation (P < .001) and to 728.1 ± 144.4 ng/mL per 2 hours at 36 months after transplantation (P = .001).

In the group that was transiently insulin-free, mean AUC of C-peptide levels also increased from 148.9 ± 75.2 ng/mL per 2 hours before transplantation to 546.8 ± 96.9 ng/mL per 2 hours at 36 months after transplantation (P = .001), with this increase sustained at 48 months. Two patients in this group regained insulin independence after being treated with sitagliptin, and C-peptide levels concomitantly increased.

Adverse effects were bilateral nosocomial pneumonia in 2 patients, late endocrine dysfunction in 3 patients, and oligospermia in 9 patients. There were no deaths.

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

Limitations of this study include small sample size and lack of a control group.

"At the present time, autologous nonmyeloablative HSCT remains the only treatment capable of reversing type 1 DM in humans," the study authors write. "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."

The Brazilian Ministry of Health, FAEPA-HCRP, FUNDHERP, CAPES, FAPESP, CNPq, FINEP, Genzyme Corporation, and Johnson & Johnson-LifeScan–Brazil supported this study. The study authors have disclosed no relevant financial relationships.

JAMA. 2009;301:1573–1579.