Disease Duration and Chronic Complications Associate With Immune Activation in Individuals With Longstanding Type 1 Diabetes

Abstract

Abstract Context Type 1 diabetes (T1D) is associated with alterations of the immune response which persist even after the autoimmunity aspect is resolved. Clinical factors that cause dysregulation, however, are not fully understood. Objective To identify clinical factors that affect immune dysregulation in people with longstanding T1D. Design In this cross-sectional study, 243 participants with longstanding T1D were recruited between February 2016 and June 2017 at the Radboudumc, the Netherlands. Blood was drawn to determine immune cell phenotype and functionality, as well as circulating inflammatory proteome. Multivariate linear regression was used to determine the association between glycated hemoglobin (HbA1c) levels, duration of diabetes, insulin need, and diabetes complications with inflammation. Results HbA1c level is positively associated with circulating inflammatory markers (P < .05), but not with immune cell number and phenotype. Diabetes duration is associated with increased number of circulating immune cells (P < .05), inflammatory proteome (P < .05), and negatively associated with adaptive immune response against Mycobacterium tuberculosis and Rhizopus oryzae (P < .05). Diabetes nephropathy is associated with increased circulating immune cells (P < .05) and inflammatory markers (P < .05) Conclusion Disease duration and chronic complications associate with persistent alterations in the immune response of individuals with long standing T1D.