"Stem cell transplants 'have freed patients with type 1 diabetes of daily insulin injections'" The Daily Telegraph has said. The news comes after research which allowed volunteers to go, on average, for two and a half years without using the multiple daily injections normally needed to manage their condition.
The small study involved 23 patients with newly-diagnosed type 1 diabetes, a condition in which the immune system can rapidly destroy the insulin-producing cells in the pancreas. These stem cell transplants apparently work by ‘resetting’ the immune system so that the body stops attacking the pancreas. The researchers themselves say that this treatment can only be used when the condition is caught early enough (within six weeks of diagnosis), before the pancreas has been irreversibly damaged and before any complications from very high blood sugar have developed.
The study provides another avenue for research, but this treatment is still at a early stage of development and does come with some side effects and risks. Dr Iain Frame, research director of Diabetes UK, has emphasised that "this is not a cure for type 1 diabetes”.
Where did the story come from?
This research was conducted by Dr Carlos EB Couri and colleagues from the University of Sao Paulo, Brazil along with Dr Richard K Burt from the Division of Immunotherapy, Northwestern University Feinberg School of Medicine in Chicago.
The study was supported by a range of public and private organisations including the Brazilian Ministry of Health, Genzyme Corporation and Johnson & Johnson. The study was published in the peer-reviewed Journal of the American Medical Association.
What kind of scientific study was this?
This was a prospective case series of 23 individuals who had received stem cell treatment to treat new onset cases of type 1 diabetes. This used follow-up data on 15 patients who were first transplanted with stem cells in a study that was previously published in 2007, and combined it with eight additional recruits who joined the study up to April 2008.
The researchers were interested in the effects of the ‘autologous nonmyeloablative hematopoietic stem cell transplantation’ (HSCT), a form of stem cell transplant where stem cells derived from the patient’s own bone marrow are collected from the blood. Around the same time, chemotherapy is used to partly destroy the patient’s own bone marrow cells. This type of stem cell transplantation is a medical procedure most often performed for people with diseases of the blood, bone marrow or blood cancers such as leukaemia.
The researchers recruited 23 patients aged 13 to 31 years (average age 18.4 years) into the study between November 2003 and April 2008. The recruits were mainly men with a short duration of disease (average 37 days) and mostly without previous diabetic ketoacidosis, a dangerous complication of type 1 diabetes.
Participants had a diagnosis of type 1 diabetes confirmed by using tests for high blood sugars and a specific antibody that indicates autoimmune diseases such as diabetes. The average level of this antibody was 24.9 U/mL suggesting the presence of antibodies to the islet cells that produce insulin in the pancreas. Average body mass index at diagnosis was 19.7.
In this study, the researchers released stem cells from the marrow using the drugs, cyclophosphamide and granulocyte colony-stimulating factor. A process known as leukapheresis was used to collect blood and then extract the white blood cells it contained. White blood cells were harvested until progenitor stem cells reached at least 3 million CD34 type cells per kilogram of body weight. To partly suppress the response of the patient’s immune system to stop is attacking the pancreas, they were also given a course of ‘cytotoxic’ conditioning drugs.
The average time from diagnosis to mobilisation of the stem cells from the blood was 37.7 days, and the patients’ stays in hospital for their transplantation lasted around 19 days on average.
The researchers measured C-peptide levels, which are related to the number (mass) of insulin producing cells that remain in the pancreas, with higher levels suggesting that the pancreas is still producing its own insulin. Levels were measured before and during a meal test at different times following transplantation.
The researchers also aimed to record any complications (including death) from transplantation, and any changes in insulin injections required by the participants to maintain their control of blood sugar.
What were the results of the study?
The researchers had follow-up data for between seven and 58 months on each of the 23 patients who received a transplant. They found that 20 patients with no previous ketoacidosis and no use of corticosteroids during the preparative regimen became free of insulin and injections. Twelve patients remained insulin-free for an average of 31 months, and eight patients relapsed and then restarted insulin use at a low dose.
Among the 12 patients who remained free of insulin injections, C-peptide levels had increased significantly at 24 and 36 months after transplantation compared to levels pre-transplantation. C-peptide levels also increased in eight patients who were only temporarily free of insulin injections and this increase was sustained at 48 months after the transplant.
During treatment and follow-up, two patients developed bilateral pneumonia (on both sides of the lungs) and three patients developed problems with endocrine function after more than a year (mostly thyroid problems). Nine patients became “sub-fertile” with extremely low-sperm counts. There were no deaths.
What interpretations did the researchers draw from these results?
The researchers say that at about 30 months following treatment, C-peptide levels increased significantly and the majority of patients achieved insulin independence with ‘good glycemic control’.
The researchers say that at this point in time, their autologous nonmyeloablative HSCT treatment “remains the only treatment capable of reversing type 1 [diabetes mellitus] in humans."
What does the NHS Knowledge Service make of this study?
This was a non-randomised study that did not feature a control group for comparison. As the researchers have stated, randomised trials are necessary to confirm the role of this new treatment in changing the natural history of type 1 diabetes.
There are other points to note:
- Of the 160 patients that volunteered for this trial only 71 were suitable, and of these suitable candidates only 23 opted to participate: the researchers say that although some did not fulfil the strict requirements of the study, such as recent onset of the disease, others declined to participate once they were made aware of the potential adverse effects.
- White male participants were the main recruits so the applicability of this treatment to women and other ethnicities will need further study.
- One of the criticisms of the researcher’s previous study was that the short period of follow-up and the lack of convincing C-peptide data, meaning that there were alternative explanations for the effect seen. For example, the selected patients could have entered a phase of improved diabetic control due to close medical monitoring and physician-directed changes in lifestyle. The researchers claim that this recent study with longer follow-up confirms the treatment effect of HSCT and that the long insulin-free period (over four years one person in this study) is unlikely to have occurred without a true effect of the transplant.
Overall, despite the small number of patients and lack of a control group, this study illustrates a promising approach to treating type 1diabetes in cases where it is caught early enough and patients are willing to accept the adverse effects of treatment. Randomised trials to test the new treatment against current care in a larger group of patients will help establish whether this is truly a ‘cure for diabetes’ or simply a way of prolonging insulin production by a few years.
Analysis by Bazian
Edited by NHS Website
Links to the science
JAMA. 2009; 301(15):1573-1579