My daughter Bisi was diagnosed with type 1 diabetes three years ago at the age of six. The first night after she was diagnosed, once she finally fell asleep in her hospital bed, tossing and turning despite the IV in her arm, I remember standing outside in the hall with my husband and a couple of medical residents, talking with them about her diagnosis. “Could this have been coming on for a while?” we asked them. I described how for a couple of years, Bisi had been almost unbearably cranky when she was hungry—to the point where I’d asked her pediatrician more than once if something might be wrong. No, the residents told us. Type 1 diabetes comes on very suddenly, in a matter of weeks, as the body’s beta cells suddenly die out under attack from the immune system. Every doctor or nurse we spoke with during the three days in the hospital (except for one, who said that our instincts were probably right), echoed what the two residents, fresh from medical school, told us.
But it turns out they were wrong.
JDRF and the American Diabetes Association, supported by other organizations in the field, recently put forth a new staging system for type 1 diabetes, where full-blown disease, like what landed Bisi in the hospital, is characterized as stage 3, part of an extended auto-immune process that often starts in infancy. This fall, Dr. Richard Insel, JDRF’s Chief Scientific Officer, explained the classification system to a group of reporters, talking through the importance of early diagnosis, and the hope that diagnosing the disease at an earlier stage could lead to breakthroughs in stopping the beta-cell destruction process—essentially, stopping the disease before it starts.
Insel explained that stage 1 is when people test positive for multiple pancreatic islet auto-antibodies—meaning that the immune system has begun to attack the pancreas. (My husband and I tested negative for these auto-antibodies, through TrialNet; our son, who does not have diabetes, is tested every year, since his status is more likely to change than ours. So far, knock on wood, he’s tested negative too.) In stage 2, people start processing glucose differently. While people in stage 2 are not yet experiencing the classic signs of type 1 diabetes (weight loss, tiredness, excessive thirst and polyuria), if given a glucose-tolerance test, their blood sugar would rise more than normal. Their A1C (a measure of average blood glucose level over a three-month period) might also start rising above normal. (The paper explaining all this in scientific terms is:
“Staging Presymptomatic Type 1 Diabetes: A Scientific Statement of JDRF, the Endocrine Society, and the American Diabetes Association.” Being able to diagnose diabetes early—before precipitous loss of beta cells catapults someone into full-blown disease—is important for a few reasons. Right now, many children (46%, according to one study, of children in Colorado) are not diagnosed until they’re in DKA (diabetic ketoacidosis), a condition that is fatal if not caught in time. (Bisi was not in DKA when she was diagnosed; but they put the IV line in her arm to be prepared in case her status changed and they needed to give her insulin and fluid through her veins.) The later in the disease process someone is diagnosed, the more beta cells have already been destroyed. One of the things researchers are looking into is whether having more beta cells at diagnosis leads to better outcomes in terms of glucose control and long-term complications from the disease. The hope is that researchers will figure out a way to stop the progression to full-scale disease while patients are still in stage 1 or 2; right now, this idea is being tested through clinical trials, including a couple run by TrialNet.
Researchers have gained an understanding of these presymptomatic stages of type 1 diabetes through the TrialNet data, and through studies including TEDDY (The Environmental Determinants of Diabetes in the Young), which for the past decade has been collecting data from 400,000 children genetically at risk of developing T1D. Insel described how these studies have helped change our idea of when the disease begins—and when you’d have to intervene to keep it from developing. “One of the things we know from TEDDY, which I don’t think we appreciated ten years ago, is that with childhood onset of type 1 diabetes, the autoimmune process begins very early in life,” Insel said. People who develop T1D as children have already developed their autoantibodies during the first 2-3 years of life, with peak incidence at nine months of age. This is why any efforts to head off the disease need to happen early, perhaps as a vaccine in infancy.
While someone who tests positive for one autoantibody may never develop the disease, someone with multiple autoantibodies has a lifetime risk of 100%. As Insel explained it: “The more autoantibodies you have, the more aggressive the autoimmune destruction is… the faster your rate of progression.” Another factor in speed of progression is the age you are at the onset of autoantibodies, or stage 1. In other words, while a very young child might progress from stage 1 to stage 3 in a matter of months, an adult might progress over a period of years or decades.
What would we have done differently if we had known beforehand that Bisi was going to get diabetes? If she had been tested months or years before her diagnosis, and we had seen that she was positive for multiple autoantibodies? Or if the dysglycemia (difficulty regulating blood sugar levels) we had anecdotally observed had been confirmed by a blood glucose or A1C test? We would have seen if she was eligible for any clinical trials, where oral insulin is given to try to spur an immunoregulatory response. I like to think we would have cut down on her sugar and overall carbohydrate intake, to preserve as many of her beta cells as possible (every time Bisi ate something with carbs before her diagnosis, she was tiring out her failing insulin-producing beta cells), and I know that we would have started her on insulin earlier, before so many of her beta cells had been destroyed.
So the news that JDRF was putting forth this staging system was bittersweet. The fact that diabetes starts way before the most obvious symptoms present themselves matches what my instinct told me was true, even if Bisi’s pediatrician and doctors at the hospital where she was diagnosed didn’t know it yet. Here’s hoping that someday kids will be diagnosed by their pediatricians at stage 1, and that they won’t progress to type 1 diabetes as we know it today.