# Autoimmune pathogenesis of gestational diabetes mellitus: the risk of progression to type 1 diabetes mellitus

**Authors:** Milena Skibińska, Marian Kacerovsky, Mariusz Grzesiak, Wioletta Izabela Wujcicka

PMC · DOI: 10.3389/fendo.2025.1663643 · Frontiers in Endocrinology · 2025-10-07

## TL;DR

This paper explores how gestational diabetes can involve autoimmune processes that may lead to type 1 diabetes after pregnancy.

## Contribution

The paper highlights the role of autoimmune mechanisms in gestational diabetes and their potential to progress to type 1 diabetes.

## Key findings

- Autoantibodies targeting pancreatic beta cells are detected in some gestational diabetes patients.
- Genetic factors like HLA, CTLA-4, PTPN22, and IL2RA increase the risk of progressing to type 1 diabetes.
- Immune mechanisms may be key in identifying patients at risk of developing permanent diabetes.

## Abstract

Gestational diabetes mellitus (GDM) is one of the most commonly diagnosed metabolic disorders in pregnancy, affecting between 5% and 20% of patients worldwide, depending on the diagnostic criteria and population. Although GDM pathogenesis is predominantly based on insulin resistance mechanisms resulting from the influence of pregnancy hormones, an increasing number of studies point to a significant role of immunological factors in the process of GDM development. In some GDM patients, autoantibodies targeting pancreatic beta cells are detected. Consequently, autoimmune processes may constitute an important element of GDM etiology, particularly in cases where GDM is a transitive condition leading to type 1 diabetes mellitus (T1DM) after the pregnancy. Disorders causing the destruction of beta cells within the pancreas precipitate permanent hyperglycemia in patients with autoimmune GDM (gestational diabetes mellitus with autoantibodies). characteristics. Genetic factors also play a significant role in this process, including single-nucleotide polymorphisms associated with the tissue compatibility system, such as HLA, CTLA-4, PTPN22 and IL2RA, which cause predisposition to T1DM. The following article discusses the current state of knowledge and presents GDM pathogenesis from the standpoint of immune mechanisms capable of affecting the development of this condition. It discusses potential markers that may help identify GDM patients at risk of progressing to permanent diabetes mellitus as well as possible diagnostic and therapeutic strategies based on the latest findings.

## Linked entities

- **Genes:** CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493], PTPN22 (protein tyrosine phosphatase non-receptor type 22) [NCBI Gene 26191], IL2RA (interleukin 2 receptor subunit alpha) [NCBI Gene 3559]
- **Diseases:** gestational diabetes mellitus (MONDO:0005406), type 1 diabetes mellitus (MONDO:0005147)

## Full-text entities

- **Genes:** IL2RA (interleukin 2 receptor subunit alpha) [NCBI Gene 3559] {aka CD25, IDDM10, IL2R, IMD41, TCGFR, p55}, HLA-A (major histocompatibility complex, class I, A) [NCBI Gene 3105] {aka HLAA}, PTPN22 (protein tyrosine phosphatase non-receptor type 22) [NCBI Gene 26191] {aka LYP, LYP1, LYP2, PEP, PTPN22.5, PTPN22.6}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}
- **Diseases:** hyperglycemia (MESH:D006943), diabetes mellitus (MESH:D003920), metabolic disorders (MESH:D008659), insulin resistance (MESH:D007333), GDM (MESH:D016640), T1DM (MESH:D003922)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12537413/full.md

## References

94 references — full list in the complete paper: https://tomesphere.com/paper/PMC12537413/full.md

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Source: https://tomesphere.com/paper/PMC12537413