Sex-specific association of circulating Isthmin-1 with isolated post-challenge hyperglycemia

To explore the distribution of Isthmin-1 (ISM1) level and its association with isolated post-challenge hyperglycemia (IPH).

A total of 522 participants without a history of diabetes were invited to attend a standard 75g 2-h oral glucose tolerance test (OGTT), and 71 subjects were further invited for a 3-h oral minimal model test. Insulin sensitivity and β-cell function were evaluated using both HOMA and estimated from OGTT. Circulating ISM1 levels were determined by a commercially available ELISA kit.

A total of 76 (14.6%) participants were diagnosed as IPH, accounting for 61.3% of the newly diagnosed diabetes. ISM1 levels were significantly higher in men than in women (1.74 ng/mL versus 0.88 ng/mL). The inverse correlation between ISM1 and β-cell function and IPH was only significant in men. After multivariate adjustment, per unit increment in ISM1 was associated with 0.68-fold (95% CI: 0.49-0.90) reduced odds ratio (OR) of IPH in men. Compared to men with the lowest ISM1 levels, the adjusted OR of IPH with the highest ISM1 levels decreased by 73% (95% CI: 0.11-0.61). Moreover, incorporation of ISM1 into the New Chinese Diabetes Risk Score (NCDRS) model yielded a substantial improvement in net reclassification improvement of 58% (95% CI: 27%-89%) and integrated discrimination improvement of 6.4% (95% CI: 2.7%-10.2%) for IPH.

ISM1 was significantly and independently associated with IPH, and serves as a feasible biomarker for the early identification of men with high risk of IPH.