Background: Polyclonal autoantibodies against various proteins that do not cause autoimmune diseases have been reportedly observed in the serum. The presence of polyclonal antibodies against glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have been observed in the blood of patients who have not previously used the GLP-1 receptor agonist. Therefore, this study aimed to investigate the clinical significance of measuring anti-GIP and GLP-1 autoantibodies (Abs) in the plasma. Two groups consisted of 1healthy donors (HD) and 274 patients with diabetes mellitus (DM) were investigated. AlphaLISA was used to measure both GIP and GLP-1 Abs. This study was approved by the ethical review board of our university (approval number 21-Im-03) .

Results: The serum concentration of anti-GIP Abs was significantly greater in the DM group than in the HD group (2697.6 ± 1998 vs. 2277.6 ± 821, p = 0.0001) , while the levels of anti-GLP-1 Abs were not different between the two groups. Since the concentration of anti-GIP Abs was significantly related to age, binary logistic regression analysis was perfomed for adjusting the age factor to reveal that anti-GIP Abs were greater with DM than without (OR: 1.0004; 95% CI 1.0001-1.001, p = 0.049) . Discussion: Several autoantibodies have been reportedly used as markers for various diseases, such as atherosclerosis, diabetes, and cancers. We found that the patients with DM had greater serum levels of anti-GIP Abs than those without it, indicating that the functions of GIP are inhibited in the presence of anti-GIP Abs in patients with DM. Since GIP is an insulinotropic intestinal hormone and the GLP-1/GIP dual agonist have been demonstrated to reduce both HbA1c and body weight, the functions of GIP inhibited by anti-GIP Abs may worse glucose metabolism.

Conclusions: The patients with DM showed higher levels of anti-GIP autoantibodies.


H.Yamagata: None. S.Onishi: None. T.Yoshida: None. T.Hiwasa: None. M.Takemoto: None.

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