A-039 Preclinical stages of type 1 diabetes: epidemiological data

Abstract Background Type 1 diabetes is a challenging disease associated with serious and life threatening complications. The diagnosis is usually made late in the course of the disease, with beta cell secretory capacity almost completely compromised. In view of new treatments like teplizumab, an anti-CD3 monoclonal antibody, the first approved to delay the onset of clinical stage of type 1 diabetes, we do not have strategies to identified patients in these early stages when hyperglycemia is not stablished yet, making precocious treatment possible. Many countries including Brazil lack epidemiological studies on the prevalence of preclinical stages of Type 1 diabetes, thus justifying this study. The aim of this study was to describe the prevalence of subjects with positive type 1 diabetes autoantibodies (T1DM) with normal glucose or HbA1c levels (stage 1 T1DM), of those with positive T1DM autoantibodies and levels of glucose or HbA1c compatible with prediabetes (stage 2 T1DM) and of those with is the onset of symptomatic disease and dysglycemia, without the use of insulin therapy (stage 3 T1DM). Methods Cross-sectional study with consultation of the anonymized database of a Brazilian company in the clinical analysis sector. Data were obtained from January 2018 to January 2025 and filtered in 5 refinement stages. The tests of interest were evaluated according to the alteration criteria described in the literature: Stage 1 characterized by persistent autoimmunity against ß cells without dysglycemia (blood glucose below 100mg/dL and glycated hemoglobin less than 5.7%) with at least one autoantibody (Anti-GAD, Anti-insulin, Anti-islet, Anti-IA2, against islet and Anti-zinc transporter) associated with normoglycemia; Stage 2 where autoimmunity against ß cells is associated with two values of asymptomatic glucose intolerance (blood glucose between 100 mg/dL and 125 mg/dL and/or glycated hemoglobin between 5.7 and 6.4%) and Stage 3 which is the onset of symptomatic disease (which may include fatigue, weight loss, polyuria, polydipsia, diabetic ketoacidosis) and dysglycemia (blood glucose greater than or equal to 125mg/dL and/or glycated hemoglobin greater than or equal to 6.4%). Results A total of 88,507,230 tests were performed, from 31,328,007 different patients. Of these, 36,392 patients had at least one positive antibody. Among them, 17,343 patients underwent, in addition to the antibody test, at least one glycated hemoglobin test and one fasting glucose test. 19,049 tested only autoantibodies, without any glycated hemoglobin or any fasting glucose. Of these patients, 10,935 were in stage 3 (63%), 3,850 in stage 2 (22.2%) and 2,558 in stage 1 (14.7%). Conclusion Most patients are in stage 3, followed by stage 2 and stage 1. These findings highlight the importance of monitoring the early stages of type 1 diabetes, providing new opportunities for early detection and intervention and better control of disease progression, as actions that delay the onset of insulinization are discussed.