Influence of Serum Folate Levels on Fatality Among Diabetic Adults in the U.S. Using a 15-Year Follow-Up Cohort Study

Background: Folate is involved in carbohydrate metabolism, a process that can have clinical implications regarding diabetes management. Purpose: To assess the relationship between serum folate and fatality among diabetic adults.

Data and Methods: A 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-year (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.

Results: The mean age of adults with diabetes and detected serum folate at baseline was 63.2 years (SD=13.8 years). During the follow-up, diabetes was listed as a contributor for 138 of 299 deaths. For all-cause deaths, fatality rate of upper quartile (74.30/1000 person-years [PY]) was almost two-fold 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% 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.

Conclusion: Results indicate that high serum folate concentrations are associated with increased risks of fatality among adults with diabetes. Further studies are warranted to determine the mechanism(s) of this phenomenon.