Folic Acid Therapy is Associated with a Lower Risk of Incident Diabetes and Better Glycemic Status in Patients with...

Although elevated homocysteine has been consistently linked to cardiovascular disease development and progression, whether homocysteine-lowering therapy reduces diabetes risk and improves glycemic status in patients with coronary heart disease (CHD) remains unclear. This study investigated whether folic acid (FA) therapy and different treatment doses were associated with reduced new-onset diabetes risk and improved long-term glycemic control in CHD patients.

The multicenter study used a propensity score-matched design. Patients with CHD were categorized as FA users or non-users, followed by 1:4 propensity score matching to minimize baseline imbalance, ultimately yielding 2440 patients for analysis. During a median follow‑up of 3.35 years, 510 incident cases of diabetes were recorded. Multivariable Cox regression models evaluated the associations of FA use and daily dose with diabetes risk. Kaplan-Meier curves compared cumulative diabetes risk between groups. Repeated glycated hemoglobin (HbA1c) measurements were used to assess long-term glycemic trajectories, and restricted cubic spline analysis examined the dose-response relationship between cumulative FA dose and diabetes risk.

Multivariable Cox regression analyses showed that FA use was significantly associated with lower new-onset diabetes risk in CHD patients before and after matching (HR: 0.749; 95% CI:0.586-0.957; P=0.021). Dose-stratified analyses indicated that the 0.8 mg/day group had the greatest risk reduction and a more favorable long-term HbA1c trajectory (HR: 0.637; 95% CI:0.453-0.897; P=0.010). FA also showed a cumulative dosage effect, with risk-lowering benefits becoming more evident when cumulative dose exceeded 140 mg (HR: 0.478; 95% CI:0.351-0.650; P<0.001).

FA use was significantly associated with reduced new-onset diabetes risk and improved long-term glycemic status in CHD patients, particularly at 0.8 mg/day and cumulative dose >140 mg. These findings suggest that FA may have a potential role in diabetes prevention among CHD patients, although this should be interpreted cautiously given the observational study design.