I’ve just gotten back from the 12th Network for Pancreatic Organ Donors with Diabetes (nPOD) Annual Meeting, which was held February 23-26, 2020, and featured some of the most world-renowned diabetes investigators. nPOD is now the world’s largest tissue bank dedicated to the study of the human pancreas in type 1 diabetes (T1D), and the latest advances—using nPOD samples—were discussed, including:
- Martha Campbell-Thompson, DVM, Ph.D., of the University of Florida, found that in first-degree relatives, individuals have a smaller pancreas before they even test positive for autoantibodies. She posited, therefore, that T1D might be a pancreas disease rather than an autoimmune disease. (Mark Atkinson, Ph.D., executive director of nPOD and a professor at the University of Florida, stressed that we must be careful when considering a reclassification of T1D from what has been, for decades, thought of as an autoimmune disease. “This would be a monumental shift in thought,” he says.)
- Mark Mamula, Ph.D., of Yale University, asked, “Why should we care about proteins that are modified in the human body?” Because they are really important in autoimmune diseases! The good thing is that many of these modified proteins are reversible with therapy, but we have to know which proteins to target in T1D. Dr. Mamula has a new favorite modified protein that does not respond to glucose as efficiently as the non-modified version. (“It’s my favorite modified protein!” he said.) Next steps: Linking it to autoimmune pathways.
- Jeffrey Krischer, Ph.D., of the University of South Florida, and Rick Lloyd, Ph.D., from Baylor College of Medicine, gave an update on the TEDDY (The Environmental Determinants of Diabetes in the Young) study. They screened 435,000 infants, and then enrolled more than 8,500 of those people based on genetic risk for T1D. They followed the enrolled participants until age 15. A gene called HLA determined the first autoantibody to appear: If it’s the HLA gene DR4-DQ8, they had the insulin autoantibody first; if it’s the HLA gene DR3, they develop the GAD autoantibody first. Dr. Lloyd briefed us on the association of enteroviruses in T1D risk, which triples the odds of insulin autoantibody conversion. Interestingly, adenovirus C—which can cause respiratory infection—had an inverse association with islet autoimmunity early in life.
- Jessica Dunne, Ph.D., senior director and head of the Prevention Program at JDRF, gave an update on the partnership that JDRF has with IBM, to apply world-class computing power to analyze years of global T1D data and identify factors leading to the onset in children. IBM harmonized more than 24,000 participants* and their 280,000 visits from geographically disparate and racially diverse populations. (“This was not an easy task,” Dr. Dunne said.) The one thing (that was iterated by almost all of the presentation speakers) was heterogeneity. T1D may have various processes driving the onset or progression of the disease, as well as responses to therapies. A preliminary analysis showed that age impacts progression to T1D, with younger children progressing much faster to this disease, and that HLA risk to T1D was important in single autoantibody positive individuals, but not in children with 2 or more autoantibodies. There will be much more on heterogeneity, and how this emerging concept can help create more personalized therapies, in the future.
Since being established in 2007 with a $7 million grant from JDRF, nPOD has collected and processed more than 50,000 tissue samples from organ donors who had or were at increased risk for T1D. nPOD is conducting more than 250 studies to unlock the mysteries of the human pancreas. For more information on nPOD, you can visit their website here.
You are helping us find ways to prevent, treat, and—one day—find cures for T1D. Find out more about JDRF here.
*They took data from the following studies:
BABYDIAB (1989-), Germany
DAISY (Diabetes Autoimmunity Study in the Young) (1993-), Colorado, United States
DIPP (Type 1 Diabetes Prediction and Prevention) (1994-), Finland
DiPiS (Diabetes Prediction in Skåne) (2000-), Sweden
DEW-IT (Diabetes Evaluation in Washington) (2002-), Washington, United States