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Diabetes & cure
Dr Asheesh Mehta Internal Medicine Specialist July 12, 2018
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Diabetes has erupted in the recent past as one of the most pressing health problems. It has reached pandemic proportions with no signs of it coming under control any time soon. About 450 million adults are affected by diabetes worldwide with about half of them remaining undiagnosed. This means that 1 in 11 adults has diabetes. About one million children and teenagers also suffer from diabetes. Uncontrolled, diabetes undermines one’s health and leads to complications that contribute significantly to morbidity and mortality. Diabetes is one of the most important risk factors for ischaemic heart disease which is the commonest cause of death in diabetics also. Global expenditure on diabetes for the year 2017 has been estimated at 850 billion dollars. The number of diabetics is projected to rise substantially over the coming decades and by 2045 it is estimated that it will affect about 693 million people. Much of the increased prevalence is going to be in developing countries which are least able to afford the massive social and healthcare costs of this chronic disease. Considering the magnitude of the global problem, it is apparent that all aspects of diabetes including causation, prevention and treatment are the subject of extensive research and some of this research gets translated to practical applications helping to improve life for the diabetic.

As is well known the two main types of diabetes are type 1 and type 2. In type 1 diabetes there is a failure of the beta cells to produce insulin while in type 2 diabetes there is resistance to the action of insulin at the cellular level coupled with deficit in production of insulin. About 10% of diabetics have type 1 disease. The lack of insulin in this type of diabetes is due to immune damage by one’s own immune system, in other words it is an autoimmune disease. Genetic susceptibility increases the risk for development of this type of diabetes with some environmental factors believed to trigger its development. Type 1 diabetes can only be controlled by insulin administration which usually means the inconvenience and discomfort of multiple daily injections or use of an insulin pump. The alternative delivery method of inhaling insulin through a nasal spray has somehow not been able to achieve satisfactory commercial acceptance.

As is well known the two main types of diabetes are type 1 and type 2. In type 1 diabetes there is a failure of the beta cells to produce insulin while in type 2 diabetes there is resistance to the action of insulin at the cellular level coupled with deficit in production of insulin
Although control is possible to achieve in the vast majority of diabetics this is a continuing process on the part of both patient and healthcare staff. About half of diabetics are not even aware that they have diabetes and even among those taking treatment the percentage of those well controlled is far from satisfactory. Rather than control, the aim in treatment of any disease is to achieve a cure. Unfortunately, this still is not the case for diabetes although there are a number of possible approaches that look promising. Currently, the closest to a cure is the use of stem cells or pancreatic beta cells that can again produce insulin on their own. Stem cells are progenitor cells that have the capability of evolving into other cell types. In diabetics stem cells are implanted with the aim of them forming beta cells which are normally present in the islets of Langerhans located mainly in the tail of the pancreas and which produce insulin in response to metabolic needs of our body. An alternative approach is transplanting islet tissue containing beta cells directly with the aim that they will produce insulin as in a nondiabetic individual. Theoretically, this would cure diabetes. A major drawback of both these procedures is that the cells being implanted are foreign to the patient. To prevent the patient’s immune system rejecting them, immune suppressive therapy needs to be administered and this has significant side-effects and toxicity and is also fairly expensive.

Use of stem cells to replace insulin producing cells lost by disease has been proposed and studied since quite some time. An implantable device that grows insulin producing cells from stem cells has been developed by a company called ViaCyte. Trials are underway with this product on patients under approval from FDA USA and Health Canada. The insulin producing cells in the implant interact with the patient’s blood and these cells produce insulin only when required thus mimicking the position in a normal individual without diabetes. If successful this does away with need for exogenous insulin. The major drawback is the need for immune suppressive drugs since these stem cells are not derived from the patient in whom the device is implanted. Currently, it is proposed for use in people at high risk for death from complications of diabetes such as episodes of severe hypoglycaemia, unawareness of hypoglycaemia and particularly labile diabetes. Hypoglycaemia refers to a drop in blood glucose level and is the most important potential complication of insulin treatment. This is all the more dangerous when a person is unaware that blood glucose has become low. Hypoglycaemia unawareness may occur because of diabetic autonomic neuropathy and is also commoner in older individuals. Diabetics who are already on immune suppressive drugs for other indications such as kidney transplant may also benefit from this type of therapy. Ideal would obviously be to implant stem cells derived from the patient so that there would be no need for immune suppression and if this becomes possible it really would be a cure.

A procedure using the same logic of providing insulin producing cells so that the patient does not need externally administered insulin is that of pancreatic islet transplant. This is an option in people undergoing removal of their pancreas for severe pancreatic disorders such as chronic pancreatitis with intractable pain. Islet tissue is separated from the rest of the pancreas, processed and purified and transplanted back into the patient to try and prevent development of diabetes which would otherwise occur due to removal of the pancreas. The transplantation is usually done by injecting islet cell tissue into the portal vein so that it lodges in the liver. This is called auto-transplant because the patient receives own tissue in the transplant and so does not need immune suppression. In a person already having diabetes transplant of insulin producing cells can only be from other persons as the disease is due to the lack of these very cells. This is known as allo-transplant and is carried out from donors, usually otherwise healthy people involved in fatal accidents. Since the transplant involves implantation of tissue from another person immune suppressive medication needs to be continued indefinitely. The significant potential for side-effects and toxicity needs to be considered fully before the transplant by both patient and doctor. Patients already on immune suppressive medication for other conditions like kidney transplant may be more suited for this procedure as there is no need for additional medication. In some patients receiving the transplant, the pancreatic beta cells are not able to implant successfully and do not produce adequate amounts of insulin. Very often two transplants are given to circumvent this problem but this too may fail. There are also problems related to the procedure itself with possibility of bleeding and clot formation. Alternative sites to the liver, such as the omentum in the abdomen may give better success rates for transplant and are being studied. There is also a substantial shortfall in availability of pancreatic tissue for transplant and the costs of the transplant as well as follow up care and medication are also quite steep. Allo-transplant of pancreatic islet to treat diabetes is still considered an experimental procedure having limited indications similar to those for the stem cell implant discussed above. Patients with very difficult to control diabetes especially on account of potentially fatal severe hypoglycaemia episodes and hypoglycaemia unawareness are the usual candidates.

The need for immune suppressive treatment with stem cells can be avoided if these cells are specially encapsulated so that blood but not the immunologically active white blood cells has contact with the insulin producing cells. In this case changes in level of glucose in blood will activate the cells to produce insulin as appropriate. This approach appears promising but technical issues need to be resolved. Another possibility is a vaccine to prevent the autoimmune attack against pancreatic beta cells which causes type 1 diabetes. This is really prevention of diabetes but prevention is really the best form of cure. Such vaccines are under development and testing although the outlook for a breakthrough in the near future is not too bright.

Regarding the much commoner type 2 diabetes, a cure of sorts is achievable in obese individuals by weight reduction surgery. This is more a deferral of diabetes rather than a cure since most of the people responding initially with disappearance of diabetes again develop it after a few years. However, the surgery does retard the development of diabetes significantly. The other types of potentially curative treatments such as stem cell or islet cell transplant may also be effective in type 2 diabetics who have reached end stage disease when the pancreas is no longer producing any insulin and they are completely dependent on externally administered insulin.

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