Prediabetes, diabetes, and folate status among United States women of reproductive age: NHANES 2011–March 2020

BACKGROUND: Pregestational diabetes increases the risk of adverse outcomes including congenital malformations, stillbirth, developmental disabilities, and maternal morbidity. Periconceptional glycemic control and folic acid (FA) supplementation are 2 of the most effective birth defects prevention strategies. OBJECTIVES: The objectives are to describe the proportion of and risk factors for diabetes and prediabetes and assess the association of folate status and diabetes among a nationally representative sample of nonpregnant women of reproductive age (WRA). METHODS: WRA (12‒49 y) from the NHANES 2011‒March 2020 (n = 3731) were included. Diabetes status was defined by glycated hemoglobin (HbA1c) ≥6.5%, fasting plasma glucose (FPG) ≥126 mg/dL, or self-report. Prediabetes was defined as HbA1c ≥5.7 <6.5% or FPG ≥100 <126 mg/dL. The associations were assessed by multivariate regression models. RESULTS: Among all WRA, 32.3% [95% confidence interval (CI): 30.0%, 34.7%] had prediabetes and 5.3% (95% CI: 4.4%, 6.3%) had diabetes [1.8% undiagnosed, 95% CI: 1.4%, 2.3%; 3.1% diagnosed but uncontrolled (HbA1c ≥5.7), 95% CI: 2.5, 4.0; 0.4% diagnosed but controlled (HbA1c<5.7), 95% CI: 0.2, 0.6]. The prevalence of diabetes was associated with increased age, BMI, serum pyrazino-s-triazine, an oxidation form of 5'-methyltetrahydrofolate (MeFox), and red blood cell (RBC) folate concentrations (all P < 0.0001) but not unmetabolized FA. Among WRA ≥35 y, 10.5% (95% CI: 8.5%, 12.8%) had diabetes and 40.3% (95% CI: 37.1%, 43.5%) had prediabetes. In adjusted regression models, diabetes was associated with altered folate metabolism [i.e., high (>90th %) RBC folate concentrations with lower (<400 μg/d) FA intake; adjusted odds ratio 2.28 (95% CI: 1.23, 4.24)]. Among those with diabetes, high serum MeFox and RBC folate concentrations were lower with euglycemia. CONCLUSIONS: Diabetes and prediabetes were common among WRA. Diabetes was associated with high RBC folate concentration and high MeFox despite low FA intake; however, these associations were reduced among those with good glycemic control. Screening for and preventing the progression of prediabetes, diagnosis, and glycemic control among those with diabetes has the potential to prevent adverse outcomes.