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In some cases, diabetes may be triggered suddenly when those who might have a genetic predisposition encounter a factor in the environment. Joey Knoop, a 47-year-old woman from Valparaiso, Indiana, may be one such case. She was diagnosed with Type 1 diabetes at age 17 after coming down with a virus.
"I was trying to lose a little bit of weight," remembered Knoop, now a married mother and schoolteacher. "A girlfriend and I were eating apples at lunch and drinking Tab, which was common in 1980. Then I caught a strange virus. I thought it was a cold."
A week later, Knoop started losing weight. At first, she was thrilled. Then she became thirsty and started craving sugar. She eventually was diagnosed with type 1 diabetes.
"Viruses may precipitate autoimmune diabetes in those who are highly predisposed," said Siri Atma Greeley, MD, PhD, instructor in pediatric endocrinology at the University of Chicago. "It’s probably something ongoing where the virus tipped them over the edge."
Type 1 diabetes is a polygenic disorder, involving multiple genes that cause the body to attack its own beta cells. "There are over 40 different gene loci that researchers are looking at, and it’s not entirely clear which genes are playing which roles," Greeley said.
However, in Type 1 diabetes, the human leukocyte antigen (HLA) complex is involved. The HLA complex contains a number of genes that control immune responses in the body. In cases like Knoop’s, where a virus seems to trigger diabetes, the virus may contain substances similar to pancreatic beta cells, which produce insulin. In some people, this could cause the immune system to turn against both the virus and the beta cells.
More recent studies suggest that autoimmune destruction of beta cells in human Type 1 diabetes involves a very slow inflammatory process that may take years to progress to overt disease. During this long process, even a small percentage of functioning cells can produce enough insulin to control blood sugar levels. Anything that suddenly heightens this level of inflammation, such as a nasty virus, may be enough to kill off the last remaining cells producing insulin.
After the first transplant, my insulin need was cut in half. After the second, it was cut in half again. After the third, it was gone. I was making my own insulin.
Knoop spent the 25 years after her diagnosis experiencing severe blood sugar spikes and crashes, in spite of strict exercise and nutritional control. "My doctors kept thinking I was cheating. I could not convince anybody how hard I was trying," she said. "Even on an insulin pump, I was having a terrible time."
Knoop’s problem was that she was extremely sensitive to the insulin shots she took. Even one extra unit of insulin could cause fainting or seizures, and, as she says, "One unit can fit on the head of a pin." Knoop was blacking out several times a month and feared she might not keep her job as an elementary school teacher. "I would just go into my room and want to cry, I felt so hopeless," she said.
Then her physician in Valparaiso referred her to the University of Chicago Medicine.Her endocrinologist, Louis Philipson, MD, PhD, medical director of the University of Chicago Medicine Kovler Diabetes Center, recommended Knoop for an islet cell transplant. The experimental clinical treatment involves transplanting islet cells from a deceased donor into a living recipient. Islets are clusters of cells scattered throughout the pancreas that contain beta cells.
Knoop underwent the transplant in three stages. "After the first transplant, my insulin need was cut in half," she said. "After the second, it was cut in half again. After the third, it was gone. I was making my own insulin."
Knoop now lives a normal life while taking immunosuppressive medications, and in October 2017 she celebrated 12 years completely off insulin. She has no regrets about undergoing an experimental treatment. "It was absolutely the most wonderful experience," she said. "It was really reassuring. I knew that I was getting the best care."
In an islet cell transplant, islet cells are isolated from the pancreases of deceased donors and then infused through the veins into the liver of the recipient. Eventually recipients produce insulin on their own. Piotr Witkowski, MD, PhD, director of pancreas and islet cell transplant, performs the transplants as part of clinical studies. He hopes to obtain approval for the procedure from the Food and Drug Administration so that it will be covered by insurance companies.
"Our hope is to get even better results by increasing the effectiveness of immunosuppressive medicines used in the transplants," said Witkowski, associate professor of surgery and director of the Pancreatic Islet Transplant Program.
UChicago Medicine is one of only a handful of medical centers in the United States that offer experimental islet cell transplants to Type 1 diabetes patients meeting certain clinical criteria.
Patients typically qualify for the transplants because they suffer from hypoglycemic unawareness — dangerous episodes when their blood sugar drops too low without any warning symptoms, causing sudden loss of consciousness, seizures or brain damage.