Halting the autoimmune destruction of beta cells, ensuring their future survival and replacing cells already lost represent key future goals in type 1 diabetes research. Since much of the beta cell mass has already been lost at diagnosis, therapies must aim to salvage and replace beta cells. Currently, beta cells may be replaced by whole pancreas or islet cell transplantation, but the limited availability of human pancreas and the need for immunosuppression represent major drawbacks. Restoration of beta cells might be achieved by stem cell replacement therapy (embryonic or adult, including induced pluripotent stem cells) or by generation of new beta cells (e.g. by reprogramming alpha cells, or replication of existing beta cells). Encapsulation or other forms of sequestration from the immune system could also offer protection against rejection or recurrence of anti-islet autoimmunity without the complications of immunosuppressive therapy. Finally, many attempts have been made to grow beta cells in culture, and to devise means by which these might be introduced into the body without provoking their immune destruction. These efforts all represent biological approaches to cure, but improved improved technology (insulin pumps, continuous glucose monitors and when combined an artificial pancreas) offers the prospect of control in type 1 diabetes.
What does the future hold for type 1 diabetes?
Yogi Berra, the famous baseball player, once said that 'it's tough to make predictions, especially about the future'. This applies to any attempt to predict the future for research in type 1 diabetes. Six approaches that currently appear to offer the greatest promise of practical progress are described here.
At the current time, type 1 diabetes is predictable with the measurement of antibodies directed against insulin and proteins in beta cells but not yet preventable. It naturally follows that diabetes should be a preventable disease and ultimately cured and this aspect is highlighted in the section on population-based measures. In short, type 1 diabetes is most likely to develop in first degree relatives of those with the disease. Notwithstanding, some 85–90% of new cases develop within the general population (those not having such a history), and effective screening and prevention measures must target this group. In addition, since the increasing incidence of childhood type 1 diabetes cannot be explained solely on genetic grounds, some form of environmental explanation seems likely, and the environment can be manipulated. The challenges, ranging from the practical to the financial, are considerable, yet population-based measures offer the best long-term prospects for putting the rise of type 1 diabetes into reverse.
Steady improvements of existing therapies have driven many of the advances leading up to our current therapy for diabetes, and this pattern is likely to hold true for the future. These range from tweaking standard therapies, such as insulin, to more radical concepts, including the therapeutic manipulation of other hormones in the attempt to imitate normal physiology more closely in type 1 diabetes patients.
New technologies for type 1 diabetes have been introduced at an accelerating rate over recent years. From the patient’s perspective, this is not only exciting, but has also led to growing optimism amongst healthcare providers. Technologies that are now commonplace, such as rapid glucose estimation from a drop of blood, insulin pumps and point of care HbA1c results were 'new technologies' not that long ago. Indeed, it could be argued that the major advances in type 1 diabetes care made within the last quarter of a century have come from technology rather than biology. At the same time, not all new technologies succeed, regardless of their purported promise, and escalating costs represent a further concern. While, therapies aiming at beta cell replacement could ultimately represent a biological cure for diabetes; in the interim, technical solutions strive for the reversal of hyperglycaemia. The optimal solution would be a closed-loop system or ‘artificial pancreas’ capable of continuous glucose monitoring linked to an implanted or external insulin delivery device and controlled by a simple computer algorithm. Mathematicians, engineers, physicians, computer scientists, patients and clinicians have combined their efforts to develop an 'artificial pancreas', and the section on new technologies describes the progress that has been made.
Stem cell therapies
Over the last decade, few topics in type 1 diabetes research have attracted more attention, conveyed a larger sense of promise, or – as some might argue – provided more 'hype' than the notion of stem cell therapies. Indeed, stem cell therapies have not only stimulated major scientific effort, but also political debate, extensive financial investment, controversy over intellectual property rights, battles over ethics, morality and religion, and more. Although the road that has brought us to the present state of affairs has been long and hard, type 1 diabetes we may soon see a variety of stem cell therapies entering clinical trials. These might finally resolve the debate over 'embryonic versus adult' stem cells, at least in terms of which has the most therapeutic potential. A series of major hurdles still remain before the promise of stem cell therapies becomes reality. The section on stem cell therapies discusses the promise, the hype, the remaining hurdles, and the hope that this form of therapy offers for those with the disease.
Genetic engineering is the process by which a functional gene is introduced into a new tissue or organ in order for it to express a new characteristic or feature. Genetic engineering, in the form of 'gene therapy', reached the public media through attempts in the early 1990s to cure severe combined immunodeficiency disorder (SCID; aka, 'bubble boy disease'). Investigators in type 1 diabetes, as in many other fields of medicine, rushed into this promising area; leading objectives were modification of islet cells to render them resistant to immune destruction prior to transplantation, altering various cell types to convert them into insulin-producing cells for later transplantation into the same individual, or altering bone marrow cells in such a way that they would improve therapeutic outcomes (such as prevention of late complications) following transplantation. Sadly, the reality of genetic engineering did not match its promise, and scientific research in this area declined dramatically in recent years relative to a decade ago. However, progress in other medical disciplines over the same time period has recently rekindled interest in this otherwise promising notion.
One word with many letters, 'xenotransplantation', is a process whereby an individual receives a transplant of tissues or cells obtained from another species. Indeed the word 'xeno' derives from the Greek word meaning stranger. The notion is not new (ancient civilizations attempted it) nor is it without modern success stories (e.g. pig heart values rendered non-living by chemicals are commonly used). While the organ transplantation field would, in theory, see a revolution were all forms of cell and tissues subject to such a method, significant hurdles – from those real in nature (xenorejection) to those more theoretical (genetic transfer of harmful viruses from the donor animal species to the recipient human) – have thus far severely limited this procedure. However, the promise for this approach is so great, and recent advances so transforming, that much hope resides for the future of this field, including what it would bring to those with type 1 diabetes.
^ Gregory JM et al. Incorporating type 1 diabetes prevention into clinical practice. Clin Diabetes 2010;28(2):61–70
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^ Wong MS et al. Gene therapy in diabetes. Self Nonself 2010;1(3):165–75
^ Ekser B et al. Clinical the next medical revolution? Lancet 2012;379(9816):672–83