Elevated homocysteine levels are associated with increased diabetes risk in patients with hypertension: a multicenter longitudinal study

Background: Previous studies have consistently confirmed an association between homocysteine (Hcy) and hypertension. However, whether homocysteine is also associated with diabetes remains controversial. The aim of this study was to investigate the potential relationship between Hcy and the risk of diabetes in patients with hypertension. Methods: This study enrolled 5,981 hypertensive patients from three centers. Multivariable Cox regression was used to assess the association between Hcy and diabetes risk. Kaplan-Meier (KM) curves compared diabetes risk across groups, while restricted cubic spline (RCS) analysis with sex stratification explored threshold effects, followed by two-stage comparisons. Subgroup analyses based on Hcy status, baseline characteristics, disease status, and medication use evaluated result robustness. Results: Elevated Hcy was significantly associated with increased diabetes risk. Each 1 μmol/L and 1-standard deviation increase in Hcy corresponded to 3.3% and 27.7% higher risk, respectively. The highest diabetes risk during follow-up was observed in the group with elevated Hcy. RCS analysis revealed thresholds of 15.2 μmol/L in females and 15.9 μmol/L in males, beyond which diabetes risk increased markedly. Consistent findings across subgroup analyses further confirmed the robustness of the results. Conclusion: Elevated Hcy levels in patients with hypertension are significantly associated with an increased future risk of diabetes, with this association becoming particularly pronounced when Hcy levels exceed 15.2 μmol/L in females and 15.9 μmol/L in males. This finding further suggests that lowering Hcy levels may not only contribute to blood pressure control but also reduce the risk of diabetes, exerting a dual protective effect.