Dorothy B. Hausman

Background/Objectives: The folate Recommended Daily Allowance (RDA) for pregnant women is 600 μg/day dietary folate equivalents, which is equivalent to approximately 400 μg folic acid. Many prenatal supplements contain much higher doses of folic acid. The body’s ability to reduce synthetic folic acid to the metabolically active form may be exceeded with high levels of supplementation. The objective of this double-blinded randomized controlled intervention trial was to determine changes in unmetabolized folic acid and other biomarkers of folate and one-carbon metabolism in maternal and cord blood in response to a folic acid dose commonly found in prenatal supplements (800 μg/day) compared to the dose equivalent of the RDA (400 μg/day). Methods: Healthy pregnant women were randomized and provided supplements from their first prenatal visit (p = 0.0225) on serum unmetabolized folic acid concentration in mothers but no difference in cord blood unmetabolized folic acid concentrations between groups. Mixed effects analysis found a significant overall effect of pre-pregnancy BMI (p = 0.0360) and length of previous folic acid supplementation (p = 0.0281) on serum folate concentrations. No treatment effect was seen in RBC folate concentrations. Choline concentrations were higher in cord blood from the 800 μg/day group compared to the 400 μg/day group, but there was no group effect in maternal choline concentrations. Conclusions: The results indicate that folic acid dose during pregnancy affects certain folate and one-carbon biomarkers, and these effects are not consistent between maternal and cord blood. Potential long-term effects of these results on both mothers and offspring are unknown and merit further investigation.

This study aimed to investigate the relationships among osteocalcin, leptin and metabolic health outcomes in children ages 9–13 years. This was a cross-sectional analysis of baseline data from 161 boys and 157 girls (ages 9–13 years) who previously participated in a double-blinded randomized placebo controlled trial of vitamin D supplementation. Relationships among fasting serum total osteocalcin (tOC), undercarboxylated osteocalcin (ucOC), leptin, and metabolic health outcomes were analyzed. Approximately 52% of study participants were obese based on percent body fat cutoffs (>25% for boys and >32% for girls) and about 5% had fasting serum glucose within the prediabetic range (i.e. 100 to 125 mg/dL). Serum tOC was not correlated with leptin, glucose, insulin, HOMA-IR, or HOMA-β after adjusting for percent body fat. However, serum ucOC negatively correlated with leptin (partial r = −0.16; p = 0.04) and glucose (partial r = −0.16; p = 0.04) after adjustment for percent body fat. Leptin was a positive predictor of insulin, glucose, HOMA-IR, and HOMA-β after adjusting for age, sex and percent body fat (all p < 0.001). These data depict an inverse relationship between leptin and various metabolic health outcomes in children. However, the notion that tOC or ucOC link fat with energy metabolism in healthy children was not supported. NCT00931580 .

Adipose tissue is both an energy storage depot and an endocrine organ. The impaired regulation of the secreted proteins of adipose tissue, known as adipocytokines, observed during obesity contributes to the onset of whole-body insulin resistance and the pathobiology of type 2 diabetes mellitus (T2DM). In addition, the global elevation of the intracellular glycosylation of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) via either genetic or pharmacological methods is sufficient to induce insulin resistance in both cultured cells and animal models. The elevation of global O-GlcNAc levels is associated with the altered expression of many adipocytokines. We have previously characterized the rodent adipocyte secretome during insulin sensitive and insulin resistant conditions. Here, we characterize and quantify the secretome and glycome of primary human adipocytes during insulin responsive and insulin resistant conditions generated by the classical method of hyperglycemia and hyperinsulinemia or by the pharmacological manipulation of O-GlcNAc levels. Using a proteomic approach, we identify 190 secreted proteins and report a total of 20 up-regulated and 6 down-regulated proteins that are detected in both insulin resistant conditions. Moreover, we apply glycomic techniques to examine (1) the sites of N-glycosylation on secreted proteins, (2) the structures of complex N- and O-glycans, and (3) the relative abundance of complex N- and O-glycans structures in insulin responsive and insulin resistant conditions. We identify 91 N-glycosylation sites derived from 51 secreted proteins, as well as 155 and 29 released N- and O-glycans respectively. We go on to quantify many of the N- and O-glycan structures between insulin responsive and insulin resistance conditions demonstrating no significant changes in complex glycosylation in the time frame for the induction of insulin resistance. Thus, our data support that the O-GlcNAc modification is involved in the regulation of adipocytokine secretion upon the induction of insulin resistance in human adipocytes.

Anemia has been associated with increased physical and financial costs and occurs more frequently in older individuals. Therefore, the primary objectives of this study were to examine the prevalence and possible predictors of anemia in the very old. Hemoglobin was used to identify those with anemia in a group of centenarians and near centenarians (98+, n = 185) and octogenarians (n = 69), who were recruited as part of the population-based multidisciplinary Georgia Centenarian Study. Blood markers, including ferritin, vitamin B12, red blood cell folate, methylmalonic acid, creatinine, and C-reactive protein, demographic variables, and medication and/or supplement usage were used to determine possible predictors of anemia. The prevalence of anemia was 26.2% in octogenarians and 52.1% in centenarians. Low serum albumin (2) were predictors of anemia in centenarians. Anemia is a major health issue, particularly as people age. Because of the high prevalence of anemia in older individuals, awareness of the predictors associated with anemia becomes increasingly important so as to reduce the negative consequences associated with it and allow for the identification of steps that can be taken to correct anemia, including managing chronic disease.

A community-based intervention to reduce risk factors related to falls and fractures administered to Georgians participating in the Older Americans Act (OAA) congregate meal-site program (N = 691, mean age = 75, 84% female, 45% Black and 55% White, convenience sample) was evaluated. The intervention consisted of 16 weekly sessions, with 8 focused on prevention of falls and fractures, and all 16 including a physical activity component. Interviewer-administered pre- and posttests evaluated fall preventive home safety behavior, intakes of calcium- and vitamin D-rich foods, use of calcium- and vitamin D-containing supplements, and five modifiable fall- and fracture-related risk factors. Following the intervention, there were significant increases in the intake of calcium- and vitamin D-rich foods (p < 0.001), the use of calcium- or vitamin D-containing supplements (p < 0.05), days of week with physical activity (p < 0.001) and fall preventive home safety behaviors (p < 0.001), and decreases in overall modifiable fall- and fracture-related risk factors (≥4 to 5 risk factors: pre: 32% vs. post: 18%; p < .001). This evaluation provides evidence that a multi-factorial fall prevention intervention offered at senior centers and delivered by trained staff can be beneficial for improving behaviors that may contribute to decreasing the risk of falls and fractures in older adults.

Associations between body mass index (BMI) and dietary patterns and health conditions were explored in a population-based multiethnic sample of centenarians from northern Georgia. BMI ≤20 and ≥25 was prevalent in 30.9% and 25.3% of study participants, respectively. In a series of logistic regression analyses controlled for gender and place of residence, the probability of having BMI ≥25 was increased by being black versus white and having a low citrus fruit, noncitrus fruit, orange/yellow vegetable or total fruit and vegetable intake. The probability of having BMI ≤20 was not associated with dietary intake. When controlled for race, gender, residence, and total fruit and vegetable intake, BMI ≥25 was an independent risk factor for diabetes or having a systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, whereas BMI ≤20 was a risk factor for anemia. Given the many potential adverse consequences of under- and overweight, efforts are needed to maintain a healthy weight, even in the oldest old.