Increased autoantibodies against incretin indicate poor prognosis in patients with diabetes

This retrospective cohort study aimed to elucidate the clinical significance of measuring autoantibodies against incretins in diabetes. We enrolled 274 patients with diabetes (mean age ± standard deviation [SD]: 63.1 ± 12.1 years) and 109 healthy controls (mean age: 58.0 ± 5.8 years). Titers of autoantibodies against incretins (glucose-dependent insulinotropic peptide and glucagon-like peptide-1) were measured using an amplified luminescent proximity homogeneous assay-linked immunosorbent assay. Both incretin antibody titers were significantly higher in patients with diabetes than in healthy controls (both P < 0.01). A mean 4.9-year (maximum 10-year) follow-up study revealed that patients who tested positive for glucose-dependent insulinotropic peptide antibodies had significantly worse prognoses than those who tested negative (P = 0.0072). Patients who tested positive for glucagon-like peptide-1 antibodies also tended to have worse prognoses (P = 0.06). To the best of our knowledge, this is the first study to investigate autoantibodies against incretin hormones in patients with diabetes. These autoantibodies may serve as novel prognostic biomarkers and provide a rationale for further studies on incretin-based therapies.