Aberrant levels of B12 and folate may be associated with increased risk of cardiovascular death in patients with diabetes

1. In this study, both low and high levels of B12 in serum was associated with higher risk of cardiovascular disease death amongst patients with type 2 diabetes.

2. Low level of serum folate were also associated with higher risk of cardiovascular disease death in patients with type 2 diabetes.

Evidence Rating Level: 2 (Good)

Folate (vitamin B9) and cobalamin (vitamin B12) are essential vitamins that play important roles in nucleotide and amino acid biosynthesis. Deficiency in folate and B12 are associated with many hematologic and neurologic abnormalities. Furthermore, folate deficiency has been observed in patient with diabetes and was shown to be associated with increased risk of cardiovascular disease (CVD). However, studies assessing the association between serum folate levels and CVD-related mortality in patients with diabetes have reported conflicting results.

This prospective cohort study looked at 8067 adults with type 2 diabetes in the United States. 7700 of these patients (50.5% male) had available serum folate levels and 4860 of these participants (50.7% men) had available serum B12 levels. Patients who were pregnant or had cancer were excluded from analysis. The primary outcome measured was number of CVD-related deaths among patients with different levels of serum folate and B12, with concentrations in the 25^th percentile use as reference.

Results showed that for folate, hazard ratio for CVD mortality was significantly higher for patients in the lower quartile (1.43) even after adjusting for potential confounders such as age, sex, race, education, income, alcohol, and physical activity. For vitamin B12, the hazard ratio for CVD mortality was increased in participants in both the lowest quartile (1.74) and highest quartile (2.32). Similar patterns were identified in terms of all-cause mortality. Unfortunately, this study was limited as the chronic state of B12 and folate level in these patients were unclear as the serum levels were only measured once. Nevertheless, this study provided robust data that suggest aberrant levels of B12 and folate may be associated with higher risk of CVD-related mortality in patients with diabetes. Therefore, prospective studies that test whether careful therapeutic control of folate and vitamin B12 levels can modulate rates of CVD mortality in patients with diabetes would be of interest.

Click to read the study in JAMA Network Open 

Image: PD

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