Four implanted Islet Sheets should be enough for most people to achieve normal blood sugars without injections, after a transition period.

What Happens in Islet Sheet Therapy? A Future Scenario

We get lots of questions about the Islet Sheet from people both in and outside the diabetes community. If you’re interested in how our research is progressing, you can find current information at The Islet Sheet Project. Research professionals may want details found in For Scientists.

But most of the questions come from people with type 1. Typically these are folks who have lived with the disease for many years. Even if they have good control of their blood sugars, they are heartily sick of how type 1 tends to dominate their lives. On learning about the Islet Sheet and other ways of encapsulating islets, they recognize that success for this technology could mean a giant leap toward freedom for them.

But how would it actually work? What would it be like to undergo laparoscopic surgery to receive Islet Sheet therapy? How long would it take for the Islet Sheets to take over from their current therapy of injections or the pump?

Here’s a story of one person’s experience with the Islet Sheet.

Theresa’s Story

When she heard from her endocrinologist that her Islet Sheet implant was scheduled for the 10th of October, Theresa was thrilled. She had been looking forward to this day since she first found out about the Islet Sheet technology. After talking it over with her medical team, and reading published reports of success with the first patients, she knew that this was for her. She looked forward eagerly to the end of years of 24/7 drudgery, anticipating that the quality of her life would  improve and her risk of diabetic vascular disease would plummet.

Theresa had been diagnosed with type 1 diabetes thirty years earlier, when she was eleven. She remembered how worried her mom and dad were when they all found out. They’d told her that it would be hard work for her to learn to take care of her diabetes, but promised there would be a cure in a few years. Little did she know that “a few years” would turn out to be thirty!

Theresa had worked hard to have good control of her diabetes. She used a continuous glucose monitor most of the time, and a pump, and she relied on her medical team for help with making the endless small adjustments needed for good control. She rarely had low blood sugar, and her A1c was generally 7.1 to 7.4.  She was a little resentful that her good control kept her from being one of the first to get an Islet Sheet implant—the government insisted that the sickest be treated first. It didn’t seem fair that she had to wait several more years. But the time seemed to go more quickly because she had an exciting goal.

Theresa emailed her latest data to her endocrinologist on the 9th. Initial clinical studies had shown that Islet Sheets worked best when the recipient had good control in the period leading up to the implant. So she was delighted to learn that her early October control made the grade—she could show up at City Hospital as scheduled the next morning.

The surgery itself was pretty simple—Theresa was awake the whole time because the Islet Sheet is implanted using minimally invasive (aka “keyhole”) surgery. Essential to the surgery is the use of a laparoscope, a camera that allows the surgeon to see the surgical field without cutting open the abdomen to see what’s inside. They numbed her right side, and the surgeon made three small incisions in her abdomen.

They blew up her belly with CO2 gas—she looked fat! This enabled the surgeon to introduce several small instruments (graspers, scissors, suture applier) into the abdomen, inside sealed tubes. She could see and hear the surgeon grasping levers and knobs on the instruments and feel numb little sensations inside her belly. He watched what was doing on a monitor and said she could watch too, but she didn’t want to.

One of the nurses showed Theresa a small plastic cylinder filled with clear fluid. “See that cloudy square? That’s one of your Islet Sheets!” The cylinder with the sheet went in, and as he worked, the surgeon explained he was “decanting” the sheet, placing it on her abdominal wall, then suturing the corners down. He repeated the process, and confirmed that the first two sheets were in  place. Then they removed the instruments from her abdomen and made a pocket under her skin near one of the incisions. Two more sheets were attached in the pocket. As they’d explained to her, studies had shown that metabolic control would be best with some sheets delivering insulin directly to her liver and some to the whole body—via abdominal and subcutaneous sheets, respectively.

And they were done—four sheets in all. It seemed quick to Theresa, but maybe it was the anaesthetic.

Her endocrinologist was waiting in the recovery room. Handing Theresa’s pump controller back to her, she said, “You see, we left the pump on. I’ve made a new program so you’re now getting about half your usual basal profile.” She went on to explain that Theresa would also be taking about half of her usual mealtime boluses. “We’ll monitor your BGs with the CGM for a while, and gradually lower the total insulin.”  Islet Sheets need some time to engraft into the body and become fully functioning. The insulin step-down usually took 7 to 21 days.

Theresa followed instructions to the letter and felt fine all during the step-down period. On Halloween Day, October 31—after another consult with the endocrinologist—Theresa took off her pump and monitor, and left them off for the first time in many years. Even though it was such a small act, it felt big. Theresa spent part of that day imagining some of the ways her life would be simpler and more spontaneous without the endless routine of monitoring, recording, and getting insulin from outside. She knew she’d be discovering a new way of living day by day.

In a few more days (a month after the surgery), free of injected insulin, Theresa had a Glucose Tolerance Test. Brad at the medical office had her eat sugar and took blood samples for about two hours. Based on the glucose in her blood, they know the Islet Sheets were functioning to specifications. So far, so good!

And it stayed good. Once a week—even once a month, when she got lazy—she would measure her BG two hours after a meal and e-mailed the result to her endocrinologist. No problems arose. Theresa knew a day would come when her Islet Sheets would start to wear out, but she also knew there would be more to replace them. Studies had shown that the Islet Sheets’ function decays slowly, so this could be detected long before replacement sheets would be needed to maintain euglycemia.

 

For now, Theresa’s story is science fiction. But not for long, we project. Islet Sheets essentially identical to the ones Theresa might receive will soon be implanted into large mammals at major medical research centers such as Cedars-Sinai in Los Angeles and UC Irvine in Orange, California. If those diabetic animals are cured, the Islet Sheet Project will press forward as soon as possible to clinical trials in Los Angeles and overseas.