Pregnancy as an Immunometabolic Stress Test Revealing Latent Autoimmune Diabetes: A Systematic Review
Wiku Andonotopo, Muhammad Adrianes Bachnas, Wisnu Prabowo, Eric Edwin Yuliantara, Mochammad Besari Adi Pramono, Julian Dewantiningrum, Efendi Lukas, I Nyoman Hariyasa Sanjaya, Anak Agung Gede Putra Wiradnyana, Anak Agung Ngurah Jaya Kusuma, Khanisyah Erza Gumilar, Ernawati Darmawan, Muhammad Ilham Aldika Akbar, Dovy Djanas, Dudy Aldiansyah, Aloysius Suryawan, Ridwan Abdullah Putra, Theresia Monica Rahardjo, Rizna Tyrani Rumanti, Roland Frederik Lengkey, Anita Deborah Anwar, Cut Meurah Yeni, Nuswil Bernolian, Laksmana Adi Krista Nugraha, Waskita Ekamaheswara Kasumba Andanaputra, Wibisana Andika Krista DharmaBackground:
Pregnancy is accompanied by coordinated metabolic and immunological adaptations that support fetal tolerance while increasing insulin resistance. In some women, however, hyperglycemia during pregnancy appears to reflect underlying β-cell dysfunction rather than isolated metabolic stress. Conventional categories – gestational diabetes mellitus, type 1 diabetes, and latent autoimmune diabetes in adults – do not always capture this overlap. This systematic review aimed to examine clinical and immunological evidence linking pregnancy-associated hyperglycemia with islet autoimmunity and postpartum diabetes progression.
Methodology:
This review was conducted in accordance with PRISMA 2020 guidelines. A systematic search of PubMed and Scopus databases was performed from inception to December 2025 using predefined Boolean combinations of terms related to gestational diabetes, autoimmune diabetes, islet autoantibodies, and postpartum outcomes. Observational cohort studies, case–control studies, and well-described case reports or series were included. Data extraction focused on autoantibody profiles, β-cell reserve, and glycemic trajectories. Risk of bias was assessed according to the study design.
Results:
Nineteen primary studies met the inclusion criteria. Across diverse populations, islet autoantibody positivity – particularly glutamic acid decarboxylase, islet antigen-2, and zinc transporter 8 antibodies – identified a subgroup of women with distinct metabolic trajectories. These ranged from early postpartum insulin dependence to delayed progression following apparent remission. Several studies also reported coexisting autoimmune conditions emerging after delivery.
Conclusion:
Pregnancy may act as an immunometabolic stress test that reveals latent autoimmune diabetes. Incorporating autoantibody profiling into clinical evaluation may improve diagnostic accuracy and inform structured postpartum surveillance.