LAUSR

Introduction and Objective: A lower ODI (secretion x sensitivity) has been shown to be predictive of T1D. In a longitudinal analysis, we assessed whether there is differential change during the progression to T1D between the two components of ODI, secretion and sensitivity. Methods: TrialNet Pathway to Prevention progressors to T1D (n=336) were studied. All had OGTTs at baseline, 0.5 years before diagnosis, and at diagnosis. The mean (±SD) interval from baseline to 0.5 years before diagnosis was 3.6 (2.4) years. AUC C-peptide/AUC glucose (AUC Ratio) and 1/fasting insulin (1/FI) were used as proxies for secretion and sensitivity, respectively. Change/yr was calculated. Results: Mean (±SD) baseline age and BMI were 13.3 (10.7) years and 23.0 (41.8) kg/m2, respectively. The majority were male (53.3%) and White (91.7%). The change/yr of both ODI and AUC Ratio was not significant from baseline to 0.5 years before diagnosis (table). However, from 0.5 years before to diagnosis, ODI and AUC Ratio declined appreciably (both p<0.001). In contrast, 1/FI did not change significantly in either interval. Conclusion: In progressors to T1D, insulin secretion (measured by AUC Ratio) has an accelerated decline proximal to diagnosis of T1D, whereas insulin sensitivity (measured by 1/FI) changes minimally. These findings are relevant to the interpretation of the ODI in Ab+ individuals. H.M. Ismail: Consultant; Sanofi, Rise Therapeutics. D.D. Cuthbertson: None. L.M. Jacobsen: Advisory Panel; Insulet Corporation. M.A. Atkinson: None. I. Libman: None. M.J. Redondo: None. J. Sosenko: None. National Institute of Diabetes and Digestive and Kidney Diseases