5041 Lifecourse Changes in Insulin Demand-adequacy Association and Utility of a Novel Index for Predicting Abnormal Glucose Tolerance

Abstract Disclosure: Y. Zhang: Other; Self; YCZ acknowledges receiving travel support from ENDO T1D Fellow Program and Vice-Chancellor’s PhD scholarship from the Chinese University of Hong Kong. N.Y. Ng: None. A. Yang: None. E.Y. Chow: None. A.O. Luk: None. A.P. Kong: None. W. Tam: None. J.C. Chan: None. R.C. Ma: Grant Recipient; Self; RCWM acknowledges support from the Research Grants Council Research Impact Fund (R4012-18) and University Grants Committee Research Grants Matching Scheme. Aims: Insulin requirements in the human body undergo continuous changes in response to growth and development. We assessed insulin demand and adequacy at different stages of life course, and derived a novel index of insulin demand and adequacy for predicting the risk of abnormal glucose tolerance (AGT). Methods: We conducted 75g oral glucose tolerance tests (OGTT) at 5-time points (0, 15, 30, 60, and 120 min) at baseline in 3 independent cohorts - children (n = 204), adolescents (n = 214), and adults (n = 605) - in Hong Kong in 1998-2006, targeting various age stages throughout the life course (aged 5.5 - 73.0 years). We calculated insulin sensitivity and secretion indices during 3 phases of OGTT (fasting phase, phase 1, and phase 2) using published formulae and assessed insulin demand and adequacy using the standardized major axis regression method. We developed a novel index, the natural logarithm ratio of the exponential function of insulin adequacy and the exponential function of insulin demand (RAD), to assess the balance of insulin demand and adequacy (RAD <0 vs ≥ 0: imbalanced vs balanced). We used logistic regression, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) to assess the predictive performance of RAD for AGT during follow-up. Results: Mean age ± SD (years) at recruitment were 7.00 ± 0.46 for children, 15.01 ± 1.79 for adolescents, and 41.48 ± 9.33 for adults. Insulin sensitivity was highest in children, lowest in adolescents, and intermediate in adults across all phases. Adolescents had the highest insulin secretion, followed by adults and children. Insulin demand was highest among adolescents, followed by adults, and lowest for children, and consistent for all phases. Children and adults with normal glucose tolerance (NGT) exhibited positive RAD values throughout the phases, while adolescents had negative RAD values, even among those with NGT and non-obese. Models incorporating RADs accurately predicted the risk of AGT and phase 2 demonstrated the best performance among all phases, compared with a base model adjusting for age and sex [NRI (95% CI): 0.350 (0.190, 0.510); IDI (95% CI): 0.033 (0.015, 0.050)]. Conclusions: The association between insulin demand and adequacy changes throughout the lifecourse. Optimal balances were observed in children and adults, whereas NGT adolescents showed an imbalance even in the absence of obesity. The RAD index is a novel tool that enhances the prediction of AGT in the lifecourse. Presentation: 6/2/2024