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

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.