Heterogeneity of autoimmune diabetes mellitus in adults: real-world clinical practice

To investigate the heterogeneity of autoimmune diabetes mellitus (DM) in adults and identify factors associated with delayed initiation of insulin therapy in real-world clinical practice. A retrospective analysis was conducted on clinical and laboratory data from 717 patients with DM onset after the age of 18 who were tested for antibodies against β-cell antigens (GAD, IA-2, ICA, ZnT8, insulin) at the National Medical Research Center for Endocrinology (NMRCE) between 2017 and 2022. Data were obtained from the electronic medical records of the NMRCE database and questionnaires from the nationwide clinical and epidemiological diabetes monitoring system in the Russian Federation. Patients with elevated vs normal antibody titers were compared, as well as patients with autoimmune DM based on the timing of insulin therapy initiation. Elevated antibodies to β-cell antigens were identified in 370 patients (51.6%). A combination of two or more antibodies at DM onset was found in 63.7% of cases. The most frequently elevated antibodies were ZnT8, GAD, and IA-2. There was no significant difference in age at onset between patients with positive and negative antibodies; however, those with positive antibodies had lower body mass index (BMI), a higher incidence of ketoacidosis, and lower levels of C-peptide, uric acid, and triglycerides at disease onset. Among antibody-positive patients, 36.8% did not require insulin therapy until at least 6 months after disease onset (median: 2 [1; 3] years). During onset and the first 5 years, these patients demonstrated higher BMI, triglycerides, and C-peptide levels. Notably, 8.9% of patients with elevated antibodies were managed exclusively with oral glucose-lowering agents and/or glucagon like peptide 1 (GLP-1) receptor agonists for a median of 3 [2; 7.5] years after disease onset, maintaining an HbA1c level of 6.7 [6.2; 7.75]%. Autoimmune DM in adults demonstrates heterogeneity in the rate of β-cell function decline and the development of insulin dependence. Later initiation of insulin therapy in autoimmune DM is associated with older age at onset, higher BMI, triglycerides, and C-peptide levels at diagnosis and during follow-up. The use of oral antidiabetic drugs and/or GLP-1 receptor agonists may be considered for patients with preserved C-peptide levels, provided that carbohydrate metabolism and C-peptide levels are regularly monitored. Nonetheless, insulin replacement therapy remains the primary pathogenetic treatment for autoimmune DM.