Serum folate levels and fatality among diabetic adults: A 15-y follow-up study of a national cohort

• Contrary to popular belief, high levels of serum folate were found to be significantly associated with a high risk for all-cause death.
• There was a significant association between high serum folate levels and death from diabetes.
• A more rigorous toxicologic assessment is warranted to clearly define the relationship between folate and conditions other than neural tube defects.

ObjectiveFolate is involved in carbohydrate metabolism, a process that can have clinical implications regarding diabetes management. The aim of this study was to assess the relationship between serum folate and fatality among adults with diabetes.MethodsA retrospective cohort study was conducted with 532 adults with diabetes who participated in Phase II of NHANES III (National Health and Nutrition Examination Survey III; 1991–1994). This study served as baseline and was linked to the National Death Index database for a 15-y (1991–2006) follow-up study. Estimates of hazard ratios (HRs) for all-cause and cancer-related deaths, cardiovascular disease (CVD), and diabetes for individuals with different serum folate levels were obtained from Cox proportional hazards regression.ResultsThe mean age of adults with diabetes and detected serum folate at baseline was 63.2 y (SD 13.8 y). During follow-up, diabetes was listed as a contributor for 138 of 299 deaths. For all-cause deaths, the fatality rate of the upper quartile (74.30/1000 person-years [PY]) was almost twofold higher than the lower quartile (41.75/1000 PY) of serum folate levels. After adjusting for several covariates, including serum vitamin B12, cotinine, homocysteine and CVD history at baseline; the HRs for all-cause fatalities were 1.00 (reference), 1.62 (95% confidence interval [CI], 1.06–2.47) and 1.76 (95% CI, 1.09–2.83) among adults with diabetes in the lower, intermediate, and upper quartiles of serum folate levels, respectively.ConclusionResults indicate that high serum folate concentrations are associated with an increased fatality risk among adults with diabetes. Further studies are warranted to determine the mechanism(s) of this phenomenon.