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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 p0.001). 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. Disclosure 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. Funding National Institute of Diabetes and Digestive and Kidney Diseases
Ismail et al. (Fri,) studied this question.