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

https://doi.org/10.14341/DM13319

Abstract

BACKGROUND. 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.

MATERIALS AND METHODS. 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.

RESULTS. 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]%.

CONCLUSION. 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.

About the Authors

N. V. Rusyaeva
Endocrinology Research Centre
Russian Federation

Nadezhda V. Rusyaeva, MD, PhD student

11 Dm. Ulyanova street, 117036 Moscow

Researcher ID: AAY-6365-2021;

Scopus Author ID: 57220024968



I. V. Kononenko
Endocrinology Research Centre
Russian Federation

Irina V. Kononenko, MD, PhD, Associate Professor

Moscow

Researcher ID: H-5947-2016;

Scopus Author ID: 35744972400



O. K. Vikulova
Endocrinology Research Centre
Russian Federation

Olga K. Vikulova, MD, PhD, Associate Professor

Moscow

Researcher ID: AAB-1682-2020;

Scopus Author ID: 8697054500



O. M. Smirnova
Endocrinology Research Centre
Russian Federation

Olga M. Smirnova, MD, PhD, Professor, chief research associate

Moscow



M. V. Shestakova
Endocrinology Research Centre
Russian Federation

Marina V. Shestakova, MD, PhD, Professor, Academician of the RAS

Moscow

Researcher ID: D-9123-2012;

Scopus Author ID: 7004195530



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Supplementary files

1. Рисунок 1. Дизайн исследования.
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2. Рисунок 2. Доля пациентов с положительными и отрицательными антителами с сохранным уровнем базального С-пептида на разных сроках заболевания.
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Type Исследовательские инструменты
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3. Рисунок 3. Структура сахароснижающей терапии на момент последнего визита в группах пациентов с отрицательными (n=276) и положительными (n=316) антителами.
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Type Исследовательские инструменты
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Indexing metadata ▾
4. Рисунок 4. Изменение диагноза у пациентов с положительными (а) и отрицательными (б) антителами к β-клеткам.
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Type Исследовательские инструменты
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5. ПРИЛОЖЕНИЕ 1. Рисунок 1. Количество пациентов с повышенными антителами и их комбинациями (n=370).
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Type Исследовательские инструменты
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Indexing metadata ▾

Review

For citations:


Rusyaeva N.V., Kononenko I.V., Vikulova O.K., Smirnova O.M., Shestakova M.V. Heterogeneity of autoimmune diabetes mellitus in adults: real-world clinical practice. Diabetes mellitus. 2025;28(2):136-150. (In Russ.) https://doi.org/10.14341/DM13319

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ISSN 2072-0351 (Print)
ISSN 2072-0378 (Online)