A RECENT study has found that elevated incretin autoantibodies in patients with diabetes may serve as markers of poor clinical outcomes. The research examined autoantibodies against key incretin hormones, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1), which play central roles in regulating blood glucose and insulin secretion.
Study Overview and Methods
The retrospective cohort study included 274 patients with diabetes (mean age: 63.1 years; 77.8% with type 2 diabetes) and 109 healthy controls (mean age: 58.0 years). Researchers measured antibody titres using a highly sensitive amplified luminescent proximity homogeneous assay-linked immunosorbent assay. Both GIP and GLP-1 autoantibody levels were significantly higher in patients with diabetes compared with controls (P < 0.01).
Participants were followed for a mean of 4.9 years, with a maximum follow-up of 10 years, to determine associations between autoantibody status and clinical outcomes.
Prognostic Implications of Incretin Autoantibodies
Results demonstrated that patients testing positive for GIP autoantibodies had significantly worse prognoses than those who tested negative (P = 0.0072). GLP-1 autoantibody positivity also correlated with a trend toward poorer outcomes, although this result approached but did not reach statistical significance (P = 0.06).
The findings suggest that autoantibodies targeting incretin hormones may interfere with their physiological effects, potentially reducing the efficacy of glucose regulation and incretin-based therapies. This represents a novel mechanism that could contribute to the heterogeneity of disease progression in patients with diabetes.
Clinical and Research Significance
This study is the first to investigate the prognostic value of incretin autoantibodies in diabetes, highlighting their potential as biomarkers for identifying high-risk patients. These results could inform future personalised medicine approaches, guiding clinicians in tailoring treatment strategies, particularly regarding incretin-based therapies such as GLP-1 receptor agonists.
Further research is needed to confirm these findings in larger and more diverse populations, and to explore how incretin autoantibody presence influences responses to current and emerging therapies.
Reference
Takemoto M et al. Increased autoantibodies against incretin indicate poor prognosis in patients with diabetes. Sci Rep. 2025;15(1):38313.
