Anti-GIP Antibodies and Future Diabetes Risk: Eight-Year Prospective Cohort Study

Autoantibodies against incretin hormones have been implicated in metabolic dysregulation; however, their role in predicting future diabetes remains unclear. This prospective cohort study aimed to investigate whether baseline anti-glucose-dependent insulinotropic polypeptide (GIP) antibody levels are associated with incident diabetes. Serum samples from 218 adults without diabetes, collected during health checkups in 2013, were analyzed for anti-GIP and anti-GLP-1 antibodies using an AlphaLISA assay and followed up for 8.1 ± 2.9 years. During the follow-up, 21 participants (9.6%) developed diabetes, defined as fasting glucose ≥ 126 mg/dL or HbA1c ≥ 6.5%. Baseline anti-GIP antibody levels were significantly higher in participants who later developed diabetes than in those who did not (38,173 ± 13,465 vs. 30,417 ± 13,744 alpha counts; p  = 0.019). Receiver operating characteristic (ROC) analysis showed that anti-GIP antibody levels modestly predicted incident diabetes (AUC = 0.646), while HbA1c alone showed strong predictive ability (AUC = 0.865). Combining anti-GIP antibody levels with HbA1c slightly improved the predictive performance (AUC = 0.873; ΔAUC = 0.008, p  = 0.38), though not significantly. These findings suggest that elevated anti-GIP antibody levels may reflect subclinical immune-metabolic alterations preceding diabetes onset. While their independent predictive value is limited, anti-GIP antibodies may complement established biomarkers such as HbA1c. Larger multicenter studies are warranted to validate their clinical utility.