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Vitamin B6 metabolism is implicated in chronic inflammation and insulin resistance, two important factors influencing stroke and type 2 diabetes, respectively. This study aimed to investigate the prospective associations of multiple plasma biomarkers of vitamin B6 homeostasis, i.e. 4-pyridoxic acid (PA), pyridoxal (PL), pyridoxal-5'-phosphate (PLP) and the ratio of PA:[PL+PLP] (PAr), with the risk of stroke in individuals with type 2 diabetes, and evaluate the predictive performance of these markers.

This nested case-control study involved individuals with type 2 diabetes, 967 cases of incident stroke and 967 matched controls without stroke from a prospective Chinese cohort. Plasma levels of PA, PL and PLP were measured using a targeted metabolomics approach. The net reclassification index (NRI) was calculated to assess the predictive performance of PA, PL, PLP and PAr.

Compared with individuals with the lowest quartile of plasma PAr, the odds ratio (OR) and 95% CI was 2.915 (2.072-4.101) for the highest quartile. By contrast, the ORs (95% CIs) of the highest quartile versus the lowest were 0.577 (0.432-0.771) for PL, 0.652 (0.488-0.871) for PLP, and 1.232 (0.897-1.692) for PA, respectively. In addition, adding plasma levels of PAr, PL and PLP offered incremental reclassification ability for incident stroke beyond the conventional risk factors. The greatest reclassification ability improvement was observed for the combination of PAr, PL and PLP (NRI: 0.482, 95% CI: 0.395-0.568).

Plasma levels of PAr, PL and PLP were significantly associated with the risk of incident stroke and provided incremental ability for the risk prediction of stroke in individuals with type 2 diabetes.