OGTT ‐Derived β‐Cell Function–Based Stratification of 2‐Year Glycaemic Transitions in Chinese Adults With Prediabetes

Abstract

ABSTRACT Aims Prediabetes is heterogeneous, with variable progression to diabetes or reversion to normoglycemia. We evaluated whether the insulin secretion‐sensitivity index‐2 (ISSI‐2), an oral glucose tolerance test (OGTT)‐derived integrated surrogate of β‐cell function relative to insulin sensitivity and prevailing glycemia, was associated with baseline glycaemic profiles and 2‐year transitions in Chinese adults with prediabetes. We also examined whether these associations differed from those of the homeostasis model assessment of insulin resistance (HOMA‐IR) and whether cohort‐specific index‐based groups combining ISSI‐2 and HOMA‐IR stratified transition risk. Materials and Methods We analysed 645 Chinese adults with prediabetes and complete baseline OGTT glucose and insulin measurements from a multicentre lifestyle intervention cohort; 410 had 2‐year outcomes. ISSI‐2 and HOMA‐IR were examined in relation to baseline glycaemic measures and 2‐year progression or reversion using multivariable regression. Results Higher ISSI‐2 was associated with lower FPG, 1‐h PG, 2‐h PG and HbA1c, with the strongest association observed for 1‐h PG (β per 1‐SD increase −1.189 mmol/L; p < 0.001). During follow‐up, 136 participants progressed to diabetes and 61 reverted to normoglycemia. Each 1‐SD increase in ISSI‐2 was associated with lower progression risk (OR 0.505, 95% CI: 0.382–0.668) and higher likelihood of reversion (OR 1.447, 95% CI: 1.106–1.893), whereas HOMA‐IR showed less consistent associations. Compared with the Low IR + higher ISSI‐2 group, the dual‐defect group (higher HOMA‐IR and lower ISSI‐2) had higher progression risk (OR 2.764, 95% CI: 1.459–5.237). Conclusions ISSI‐2 was associated with baseline glycaemic profiles and bidirectional 2‐year transitions in Chinese adults with prediabetes. OGTT‐derived β‐cell function assessment may complement conventional glycaemic classification for short‐term risk stratification, pending validation in independent cohorts.