Type 1 diabetes onset is sudden and unexpected. The disease is typically diagnosed during a trip to the emergency room for treatment of dangerously high blood sugars. By then, beta cells have been almost completely destroyed by the immune system. The American Diabetes Association (ADA) and the JDRF want to be able to detect type 1 diabetes earlier in its progression, before the immune system can damage the insulin-secreting cells, and hopefully intervene to prevent the development of the damaging symptoms of type 1 diabetes.
“The overall goal is to try to develop approaches that can preserve residual beta cell function, but that means we have to identify risk for type 1 diabetes before substantial amounts of beta cells have been irreversibly destroyed by the immune system. If this earlier stage can be identified with certainty, there can be interventions earlier in the process when there are greater amounts of functioning beta cells to preserve, rather than at the current stage of diagnosis when the overwhelming majority have been destroyed or damaged”, says Lori Laffel, M.D., M.P.H., Chief, Pediatric, Adolescent, and Young Adult Section at Joslin Diabetes Center.
The ADA and the JDRF recently released a suggested three-stage classification system for diagnosing type 1 diabetes and clarifying risk. Stage 1 indicates the presence of some autoimmunity. Stage 2 happens when the autoimmunity starts to affect blood sugar levels. Stage 3 is the state at which most people are currently diagnosed, involving symptoms such as excessive thirst, hunger and urination. Investigators hope to use this staging system as a research roadmap, to help investigators better plan intervention strategies.
Catching the disease at an early stage requires screening, before individuals start showing symptoms. This could get complicated; while there is a degree of genetic susceptibility, the disease is mostly unpredictable, affecting many persons without any family history of type 1 diabetes.
“The risk is increased when you have a first degree relative with type 1 diabetes,” says Dr. Laffel. “But just because you have genetic susceptibility doesn’t mean you’ll develop type 1 diabetes. It’s a multifactorial disease, which means that genetic susceptibility is just one factor that combines with yet unknown environmental influences to promote the autoimmune destruction of the insulin producing beta cells. In addition, these different factors may play a role in the development of type 1 diabetes at different points in time, or at different life stages. This multi-factorial, multi-stage nature of type 1 diabetes makes it so hard to figure out the processes that lead to type 1 diabetes.”
The staging system has been developed using data gathered from clinical trials that screened first and second degree relatives of people already diagnosed with type 1 diabetes. The trial participants were shown to have auto-antibodies prior to being diagnosed with the disease, indicating that there are detectable changes happening in the body before beta cells are destroyed and blood sugar rises.
Researchers are working on interventions that could be applied to people diagnosed in either Stage 1 or Stage 2, when these auto-antibodies are present but before beta cells are destroyed. These interventions could prevent the progression to the symptomatic Stage 3 by preserving the beta cells or halting the autoimmunity before it can do too much damage.
“Or even if you do progress to type 1 diabetes, you may progress with ongoing residual beta cell function which makes management of type 1 diabetes easier for the future,” says Dr. Laffel.
TrialNet, a network of family screenings and clinical trials that Joslin is involved in, offers participants the option of joining an intervention trial if they test positive for a certain number of autoimmunity markers. Joslin’s participation in TrialNet is headed by Jason Gaglia, M.D., M.M.Sc.
Knowing about the presence of auto-antibodies has also helped keep children safer at the diagnosis of the disease. In the DAISY study, according to the statement paper, “only 3 percent of study participants were hospitalized at diagnosis compared with 44 percent of age- and sex-matched children diagnosed in the community.” The paper also discussed the TEDDY study, in which “30 percent of children aged 5 years were presymptomatic at the time of diagnosis of type 1 diabetes based on ADA diagnostic criteria and, if symptomatic, were signiﬁcantly less likely to experience DKA at onset than comparable populations.”
This means that the children who were identified as at risk were able to better avoid dangerous diabetic ketoacidosis at diagnosis. The ADA and JDRF hope that by encouraging people who have genetically close relatives with type 1 diabetes to get screened before they notice symptoms, the numbers of hospitalizations due to dangerously high blood sugar levels are diagnosed will be reduced.
Currently this concept is still in clinical trial phase, but the hope is that it will lead to better preventive treatments in the future.
“Right now, this is a research agenda,” says Dr. Laffel. “Scientists and physicians are trying to understand which patient populations should be targeted for these early intervention studies aimed at preserving beta cell function and preventing progression to type 1 diabetes.”
For more information about Joslin Pediatrics or to make an appointment, click here.