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Irvine scientist works on transplant to help diabetes patients
October 14th, 2010
Related Documents
Irvine scientist works on transplant to help diabetes patients, October 13, 2010
Dr. Jonathan Lakey has been interviewed about the Solving Diabetes Research on KPCC / Southern California Public Radio.
Click here to read the full transcript.
Click here for audio clip of the interview
Unfotunately, the published article further contributes to the confusion between type 1 and type 2 diabetes by saying, quite inaccurately, that type 2 diabetes ‘converts’ into type 1 diabetes when insulin becomes required to keep it under control. The patient does not develop the autoimmune beta cell destruction of type 1 diabetes because the insulin resistance of type 2 diabetes worsens so that the patient must inject insulin to control the blood sugar levels. Also, the comment about excess food consumption and lack of exercise as a cause of the rise of diabetes has no relevance to type 1 diabetes, which is the actual subject of this article.
It is puzzling that the experimenter is prepared to risk using potentially carcinogenic stem cells to generate a sufficient supply of islet cells even when it is now known to all informed researchers that pathogen-protected pigs are available to provide an equally unlimited and relatively harmless supply of islets for transplant. SInce the implants are protected from the immune system by a differentially permeable membrane, the hyperacute rejection normally expected with animal tissue grafts in humans would not be a problem, so the advantage of using human tissue is lost. The author suggests that everything is just fine because the implants can be removed if the stem cells develop into carcinomic forms, but how can he know what is happening inside the capsule without constantly surgically accessing the pancreas — an extremely difficult procedure — to check? Since beta cells spontaneously adjust their output to compensate for shortfalls in other beta cells, if even a large percentage of the graft had turned cancerous, there might still be no change in blood sugar control to suggest a problem. If a rapidly-developing cancer bursts the capsule prior to extraction the metastasis may be well underway before it can be extracted.
The only intelligent development reported here is the use of the pancreas as the site of implantation, since previous research has shown that engrafting islets in the pancreas seems to be important to their function. However, because of the extreme difficulty of accessing the pancreas, this would be a much more difficult procedure to perform than abdominal implantation, and the demand on medical resources as well as the cost would limit this intervention’s public health significance for the large population of type 1 diabetics.
Insulinoma, the cancer of beta cells of the islets, cause hypoglycemia because of unrestrained insulin secretion. This cancer can be treated with beta-cell killing streptozotocin (http://en.wikipedia.org/wiki/Insulinoma#Treatment). It surely would be practical to remove the sheet if the stem-cell islets became insulinoma’s.
You are right about type 2-type 1 conversion. But as clinical reality type 1′s diagnosed late in life are often misdiagnosed as type 2, and over time the reality of type 1 becomes obvious. Doctors call this (inaccurately) conversion.
Insulinomas can be hard to diagnose since the characteristic marker of ‘Whipple’s Triad’ is present only in about three quarters of cases. If we suppose, for example, that only 10% of the islets in a cluster are affected, and the remaining 90% respond to the hyperinsulinemia produced by the overactive 10% by reducing their own insulin output, the hypoglycemic effect of the cancerous 10% may be buffered by the normal beta cells. I suppose the patients receiving the Irvine implant would have to be monitored closely for the rest of their lives for insulinomas, but for my money I’d rather be treated with normal porcine cells.
Accessing the engrafted cell capsule in the Irvine experiment would be difficult if it is placed, as they suggest, at the site of the pancreas, which is infamously hard to access surgically. It seems that the Irvine researchers are introducing two unnecessary problems — potentially carcinogenic islets and difficult-to-access pancreatic placement of those islets — without much to show for this.
The pancreas is only one intraperitoneal site under consideration. The abdominal wall is likely to work as well, and there is at lot of abdominal wall that is surgically accessible.
It is possible that the pancreatic site will have advantages (perhaps metabolic) compared with other sites. It should be possible to demonstrate advantages by comparative studies in animals.
I agree that from what we know now pig islets are likely to be safer. We certainly intend to study pig islets and we are in conversations with pig islet producers. However, over time, it may be possible to establish that islets-from-stem-cells are safe. No one has done that yet, and I don’t think there is yet consensus on how one might prove it.