Over the course of the nineteenth and twentieth centuries, progress in medical technology has unfolded at a staggering pace. From the discovery of penicillin to the advent of sterile surgical care, scientific understandings of the human body have led to paradigm shifts in medicine and human longevity.
This trend of progress is illustrated perfectly in the treatment of diabetes. The discovery of insulin, barely more than a century ago, revolutionized prognoses for the condition by offering patients some measure of control over their deficient endocrine systems.
More recently, novel techniques have sought to achieve something like a cure to the underlying condition itself, with islet cell transplantation representing the cutting edge of progress on this front. This article explores the fascinating reality and potential of what could one day be a cure for type 1 diabetes.
Diabetes: Background Information
Diabetes mellitus is a condition characterized by an inability to appropriately metabolize sugar, which can stem from one of two main causes. Cases of diabetes are categorized by their underlying cause into two main sub-types: type 1 and type 2. Type 1 diabetes results from an immunological condition where the body destroys its own ability to produce insulin, whereas type 2 diabetes involves an inability to respond to the insulin naturally produced in the body.
Symptoms and causes
Insulin is normally produced in the pancreas, where clusters of special cells (beta cells) detect glucose levels in the bloodstream and cause an appropriate amount of insulin to be produced in response. These clusters are referred to as islets of Langerhans, or just “islets”. In type 1 diabetics, the body’s immune system incorrectly views these islets as foreign entities and mobilizes an immune response to destroy them, impairing the body’s ability to properly metabolize and make use of sugar as fuel.
This metabolic deficiency can have disastrous results for sufferers of the condition. Left unchecked, blood sugar levels can spiral out of control, causing a host of nasty complications which have the potential to leave patients debilitated and reduce their life expectancy.
Current treatment options
Thankfully, many complications of type 1 diabetes can be mitigated with proper treatment. Current approaches typically involve supplementing the body with an external source of insulin, typically via regular injections. This approach certainly represents an improvement over the absence of care, but it also leaves much to be desired. Taking insulin is a fussy business, and requires careful planning and monitoring to strike just the right balance to keep blood sugar levels within a healthy range at all times. Insulin products are also notoriously expensive and must be carried around and stored properly.
Islet Transplantation as a Treatment
Though less common than insulin therapy, islet transplantations seek to improve type 1 diabetes treatment by resolving the underlying issue. Perfecting such a technique would pose clear benefits over the existing alternatives.
How it works
Though islet transplantation is a technically complex procedure, the idea behind it is actually quite straightforward. In essence, surgeons extract and isolate many thousands of functional islets from the pancreas of a non-diabetic organ donor. These islets are then delivered intravenously into the liver of the recipient, where some of them will implant into the liver tissue. Successfully implanted islets will resume their normal function of producing insulin in response to detecting fluctuations in the recipient’s blood sugar levels as they would in a healthy pancreas.
Pros and Cons
When successful, this procedure offers type 1 diabetics the potential to experience something close to life without diabetes. Because the implanted islets assume responsibility for monitoring blood sugar and administering insulin, the two primary aspects of diabetes treatment, some recipients can cease most or all of their daily treatment regimen. They are also likely to experience far fewer episodes of severe hypo- or hyper-glycemia, improving their long-term prognoses.
The boost in convenience and cost that successful islet transplants can entail offers a clear and enticing advantage over traditional diabetes treatments. However, these procedures also carry their fair share of risks.
The procedure itself is fairly benign, carrying relatively minor risks of bleeding or clotting during or after the surgery. Some pain may also be experienced, for which a mild anesthetic may be administered. And of course, there is always a risk that the transplants will not “take”, or fail to integrate successfully into the recipient’s tissue.
The more severe potential complications of the procedure are associated with the chronic regimen of immunosuppressant medications that recipients will need to prevent their bodies from rejecting the foreign cells, as well as preventing a recurrence of the immune response that destroyed their native beta cells in the first place. These immunosuppressants can entail a range of severe complications, including serious infections, cancers, kidney disease, high blood pressure, and digestive disturbances.
Though some of these risks will desist upon ceasing the immunosuppressant regimen, doing so will cause the transplanted cells to be rejected and destroyed, negating the positive effects of the procedure.
The Procedure in Detail
Screening and preparation
Because not every individual is a suitable match for islet transplantation, the procedure must begin by screening for suitability. This involves a series of tests and examinations to assess relevant factors about a person’s health and medical history. This can include an inquiry into the history of your diabetes treatment and control, as well as into any unrelated surgeries, hospitalizations, or diagnoses.
Your doctor may also request that you undergo various medical tests, ranging from a basic physical examination to more advanced laboratory tests or imaging studies. These are primarily intended to assess your renal (kidney), hepatic (liver), and pancreatic function, as problems with these organs may indicate an increased risk of complications.
The general goal of this screening process is to predict, based on known risk factors for complications or implantation failure, your individual suitability for the procedure. Examples of risk factors your doctor may assess include ongoing infections or diseases, compromised organ function, an active diagnosis of cancer, or generally poor health.
As important as ensuring recipient suitability is ensuring compatibility of the donor pancreas. Not every pancreas comes from a healthy donor, and islet extracts from an unhealthy pancreas may carry pathogens like hepatitis B or C, or may simply not be viable for other reasons.
A team of experts will typically evaluate donors and tissue samples for various pathogens and other criteria in order to ensure that the donated samples are likely to yield a successful transplant with minimal complications.
Islet isolation and transplantation
Once a suitable donor has been identified, their pancreas is surgically removed and treated with special enzymes. These enzymes target the islets and cleave them from their surrounding pancreatic tissue. This enzymatic slurry is then drained and purified, leaving behind the isolated islets, which are subsequently brought to a laboratory for counting and further analysis.
The refined islets are then injected into a catheter, or tube, which is surgically connected to the vein supplying the liver with blood. The liver is chosen as the optimal site of injection because the conditions there are optimal for providing the cells with oxygen and nutrients pending implantation within the recipient tissue. This part of the procedure is generally performed while patients are conscious, though local anesthesia may be used.
Islet transplantations are not always successful. The donor cells may fail to implant in the recipient tissue, often for reasons that are hard to predict, or they may only survive for a short while. However, recent research data shows that many recipients can expect to experience a wide range of positive effects several years post-procedure, even if their diabetes still requires some level of active management.
For example, a recent phase 3 clinical trial periodically assessed the long-term success rates of transplants in recipients whose pre-procedure diabetes was particularly problematic. The researchers observed various outcomes, including A1C levels and insulin usage, and found that 40% of subjects still had no need for insulin injections two years after the procedure. They also found that 70% of subjects had A1C levels below 7% (a common target for type 1 diabetics), and follow-up research has confirmed ongoing improvements in quality of life and health status. Even after eight years, more than half of subjects were found to still have some surviving islet implants at the transplant site.
Though some uncertainty still surrounds the effective duration for these procedures, research indicates that it is likely to impart some benefit to many recipients Doctors will still need to weigh the potential benefits against the risks in each individual case, though the authors of the aforementioned study highlighted that this procedure may be ideal and potentially lifesaving for patients whose diabetes is particularly severe, and who may experience uncontrollable or unpredictably severe irregularities in their blood sugar levels.
Future of the Procedure
Though it represents the remarkable potential for curing type 1 diabetes, islet transplantation is still a relatively uncommon procedure in the US. This is due to several challenges which make it less than ideal, including the mandatory lifelong immunosuppressant regimes recipients must follow, a chronic shortage of donor islets, and the experimental designation of the procedure by the FDA.
Though still experimental, this procedure’s awe-inspiring potential is driving researchers around the globe to find ways of overcoming its existing technical barriers. Advances in the field may soon address some or all these challenges, making the procedure far more effective and accessible.
As described above, current protocols for transplantation call for continuous treatment with immunosuppressant medications. These are necessary to avoid immune rejection of the transplanted tissues but come with the risk of serious side effects. Researchers have devised a conceptual alternative to this approach which involves physically protecting the transplanted islets from immune response with a physical barrier, or capsule.
Known as encapsulation, this technology is still in its infancy. Many researchers are actively testing high-tech semi-permeable materials, including porous polymeric hydrogels, which would allow adequate blo