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July 31st, 2011
“Targeting a Cure for Type 1 Diabetes” has been published on diaTribe by Kelly Close’s Close Concerns diabetes research organization. It is detailed, well considered, and makes room for personal opinions, observations and predictions. I recommend you download and read it, here. Our work on the Islet Sheet is described in page 67 in the islet transplantation chapter.
A friend who has studied the report and writes about diabetes sent me a note:
Reading the book gave me a good overview of the pros and cons of each major type of research. BTW, would you agree with their breakdown?
Anyway, what I’d really like to know is why you have chosen to dedicate yourself to option 2 (both as someone with diabetes and as a solution seeker) — and by extension, why Hanuman Medical Foundation has chosen to support this work rather than some other kind of diabetes research. Could you write a few paragraphs making that case in your own way?
I think their breakdown is useful, my only complaint being that “Drugs that aim to regenerate or sustain beta cells” will probably require “Drugs that aim to control the immune malfunction that attacks islets/beta cells” to work. That is, we know all people with autoimmune (type 1) diabetes have permanent auto-immunity that quickly kills native, transplanted and regenerated islets alike; therefore some form of immune suppression will be required for regeneration to be useful.
The ultimate cure for autoimmune diabetes will be immune suppression that is safe enough for me to use in conjunction with islet regeneration drugs. (These are my personal opinions, therefore what I am willing to do to myself.) This would restore normal islet function and cure the metabolic disease, and would have a much smaller side effect profile than current immune suppression. Regeneration will require technology to simultaneously do two very difficult things, regenerate islets and selectively suppress the immune system without side effects. It’s a great idea but it is something like 50 years away.
Which brings me to my personal answer to the question you pose: I believe implantation of Islet Sheets is as close as we will get to a cure in my lifetime. I reached this conclusion thirty years ago, published here.
Why don’t I have more hope for the artificial pancreas? Because I am the artificial pancreas, I am the cyborg envisioned. I just checked my Dexcom CGM and my blood glucose is 118. So far today my OmniPod pump as administered 25.2U, 60% bolus, at my direction. Nine-tenths of my blood sugars are between 80 and 220. I have had no hypoglycemia in weeks. The artificial pancreas works for me.
So you ask, why can’t it work for everyone? The answer is my mind which I have trained for decades to use these devices. Every decision on insulin administration uses knowledge of the previous 24 hours and plans for the next 12 added to the experience of thirty years. Patience is essential; a serious high needs to be brought down slowly so it stays down. You must be constantly suspicious of both your devices. If BG goes up unexpectedly I immediately question insulin delivery has failed (both times it happened because the cannula came out). The BG readings from the Dexcom are 85% reliable, which means some days I don’t trust it, and finger-stick BG’s confirm it is wrong, so I might do a manual BG every two hours (reverting to to pre-CGM management!)
And I know my body. Last night I stayed home and watched a movie. I ordered pizza and ate too much. So by 2AM I was up to 240; I took some extra insulin, but my BG did not come down much. So at breakfast when the OmniPod controller calcuated my breakfast insulin, I knew (because I had taken insulin without BG response) that I would need less insulin than the calculation. I subtracted 1 U, and I was right, because I stabilized mid-morning at 120. I have scores of such rules. A moderate swim means I drop basal in half for 1 hour. My basal is optimized for 1-2 glasses of wine with dinner; if I don’t drink the basal should be lowered by a a third for 4 hours at bedtime.
My point is these two devices give me the power to experiment on myself and know in detail the effect of differing insulin regimes on my body. I keep getting better. I backslide, forgive myself, and get better again. I am an ongoing experiment, and there can never be an algorithm that does what my mind does. I can never finally figure out everything there is to know in self management. It is endless work with no time off. So thank God for CGM and programmable pumps. They make management better, but not easier. And the artificial pancreas will never be a cure because no computer program can know what I know and think as I think.
When I considered the same possibilities/hopes for curing diabetes as the diaTribe report thirty years ago, the closest to a cure was autologous islet transplantation. Immunology does not figure into this procedure because the patient does not have autoimmune diabetes and the implants are their own islets isolated from their own pancreas. Remarkably, even in 1980, long before the Edmonton protocol, when enough islets were recovered from the pancreas the diabetes is cured through autologous islet transplantation. How hard would it be to solve the immune barrier in human-to-human transplants?
Predicting when islet transplantation would be available to everyone with autoimmune diabetes was the question of how difficult it would be to prevent rejection of allograft islets, that is islets from a human donor. It seemed possible thirty years ago that pharmaceutical immune suppression would become safe and effective. It has not; it is improved, but is not yet safe enough to routine use. The other approach, encapsulation, appeared to be the technology that I myself could foster and promote. So I have. The reasons the journey to the clinic will have taken over thirty years rather than ten (as I predicted) is another story for another day.
So to answer your question, Diana, when I considered the matter thirty years ago the Islet Sheet looked to be the most promising new therapeutic technology that would work in my lifetime. Thirty years later much has happened, clinical and scientific knoledge have expanded greatly, but — nothing has happened to change my mind. I believe implantation of Islet Sheets is as close as we will get to a cure in my lifetime. I shall continue to foster and promote the Islet Sheet until the end.