18-OR: Lower Incretin Effect and Reduced GIP Characterize the Metabolic Phenotype of People with Multiple Islet Autoantibodies and Normal Glucose Tolerance

Le résumé fourni par la source

Introduction and Objective: The incretin effect measures the contribution of gut-derived hormones GLP-1 and GIP to insulin secretion. There is limited evidence of the role of incretins in preclinical type 1 diabetes (T1D). We compared the incretin effect in individuals with normal glucose tolerance and a single autoantibody (Ab+) (Stage 0) to those with multiple Ab+ (Stage 1) Methods: Participants had a 3-hour, 7-point oral glucose tolerance test (OGTT) and an iso-glycemic IV glucose tolerance test (iso-IVGTT), with measurements of glucose, C-peptide, insulin, GIP, and GLP-1. Glucose profiles during the OGTT and iso-IVGTT were matched. Insulin secretion rate (ISR) was estimated using the oral minimal model. Incretin effect was quantified as the percentage difference between the OGTT and iso-IVGTT ISRs. Results: We enrolled 10 participants (age 21.6±8.8 years; BMI 24.9±7.0kg/m²), 5 with Stage 0 and 5 with Stage 1 T1D. The groups had similar age and BMI. Participants with Stage 1 had a 45% reduction in the incretin effect compared to those with Stage 0 (36.4±15.6% vs.19.7±4.9%, p=0.046). Those with Stage 1 had a lower area under the curve (AUC) of GIP during the OGTT compared to those with Stage 0 (p=0.038). GLP-1 tended to be lower in Stage 1 (p=0.113). Conclusion: Multiple vs single islet autoantibodies is associated with a reduced incretin effect and lower GIP. Disclosure A. Galderisi: None. H. Marchiori: None. M.D. Alguard: None. M. DeSousa: None. E.M. Tichy: None. A. Flynn: None. J.L. Gaglia: Consultant; Vertex Pharmaceuticals Incorporated. Stock/Shareholder; Vertex Pharmaceuticals Incorporated. Consultant; Avotres Inc. Research Support; Avotres Inc. Consultant; Kriya Therapeutics, Imcyse, Diamyd Medical AB. Research Support; Diamyd Medical AB, Sanofi, Biomea Fusion. C. Dalla Man: None. J.L. Sherr: Consultant; Abbott. Advisory Panel; StartUp Health T1D Moonshot. Research Support; Dexcom, Inc. Advisory Panel; Cecelia Health, MannKind Corporation. Consultant; Insulet Corporation, Vertex Pharmaceuticals Incorporated, Ypsomed AG. Advisory Panel; Medtronic, Vertex Pharmaceuticals Incorporated. Funding Breakthrough T1D (3-SRA-2022-1186-S-B and 3-SRA- 2023-1422-S-B to AG)

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.