Type 1 Diabetes Autoantibodies in Acute, Recurrent Acute, and Chronic Pancreatitis

Pancreatogenic or type 3c diabetes, which occurs as a consequence of pancreatitis, may have several mechanisms. Mechanisms overlapping with those of type 2 diabetes have been explored, including insulin resistance and insulin deficiency. However, autoimmune mechanisms in response to unmasking β-cell antigens, similar to those of type 1 diabetes (T1D), have not been thoroughly examined. We performed cross-sectional T1D autoantibody profiling in a large prospective cohort (N = 927) of adults with acute, recurrent acute, or chronic pancreatitis. We examined correlations of prevalence of autoantibodies against GAD (GAD antibody), IA-2 (IA-2 antibody), zinc transporter 8 (ZnT8; ZnT8 antibody), and insulin (insulin autoantibody [IAA]) with clinical and demographic features, including presence of diabetes, diabetes treatment, and family history of diabetes. Diabetes was present in 11 (12%) of 94 participants with acute pancreatitis, 69 (27%) of 273 with recurrent acute pancreatitis, and 235 (43%) of 560 with chronic pancreatitis. Among these groups, islet autoantibodies were respectively found in five (5.3%) of 94, 48 (17.6%) of 273, and 127 (22.6%) of 560. The proportions of individuals with diabetes who were autoantibody positive were 45%, 70%, and 54%, respectively (most commonly IAA, which may reflect exogenous insulin use). However, across the entire cohort, 27 participants (2.9%) had two, two (0.2%) had three, and one (0.1%) had four T1D-associated autoantibodies, respectively, suggesting a potential pathogenic link that should be further explored. ARTICLE HIGHLIGHTS Type 1 diabetes–associated autoimmune mechanisms have not been thoroughly examined in pancreatitis-associated diabetes. We assessed the prevalence of four islet autoantibodies in serum from a large prospective cohort of patients with acute, recurrent acute, or chronic pancreatitis. Diabetes was present in 11 (12%) of 94 participants with acute pancreatitis, 69 (27%) of 273 with recurrent acute pancreatitis, and 235 (43%) of 560 with chronic pancreatitis. Excluding those with only insulin autoantibody positivity, which is confounded by insulin treatment, islet autoantibodies were identified in 51 (5.5%) of 927 participants, and 30 (3.2%) of 297 were positive for two or more autoantibodies. Our findings suggest pancreatitis may elicit islet autoimmunity in a subset of patients, necessitating prospective longitudinal follow-up.