Serum Folate Levels and Fatality among Diabetic Adults: A 15-Y Follow-Up of a National Cohort

Objective: Folate 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. 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-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. Results: The 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. Conclusion: Results 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.