OBJECTIVES:Our study goal was to evaluate a set of nutritional indicators among adults with confirmed or suspected active tuberculosis disease in southern India, given the limited literature on this topic. Study objectives were to assess the: I) double burden of malnutrition at individual and population levels; II) relative performance of anthropometric indicators (body mass index, waist circumference) in diabetes screening; and III) associations between vitamin D and metabolic abnormalities.DESIGN:Cross-sectional study.SETTING:Hospital in rural southern India.PARTICIPANTS:Among adult patients (n = 834), we measured anthropometry, body composition, and biomarkers (vitamin D, glycated hemoglobin, hemoglobin) of nutritional status. Subsets of participants provided blood and sputum samples.RESULTS:Among participants, 91.7% had ≥ 1 malnutrition indicator; 34.6% had both undernutrition and overnutrition indicators. Despite the fact that >80% of participants would be considered low-risk in diabetes screening based on low body mass index and waist circumference, approximately one-third had elevated glycated hemoglobin (≥ 5.7%). The lowest quintile of serum 25-hydroxyvitamin D was associated with an increased risk of glycated hemoglobin ≥ 5.7% (adjusted risk ratio 1.61 [95% CI 1.02, 2.56]) compared to the other quintiles, adjusting for age and trunk fat.CONCLUSIONS:Malnutrition and diabetes were prevalent in this patient population; since both can predict poor prognosis of active tuberculosis disease, including treatment outcomes and drug resistance, this emphasizes the importance of dual screening and management of under- and overnutrition-related indicators among patients with suspected or active tuberculosis disease. Further studies are needed to determine clinical implications of vitamin D as a potential modifiable risk factor in metabolic abnormalities, and whether population-specific body mass index and waist circumference cut-offs improve diabetes screening.
The First International Conference on Controversies in Vitamin D was held in Pisa, Italy, 14–16 June 2017. The meeting's purpose was to address controversies in vitamin D research, review the data available, to help resolve them, and suggest a research agenda to clarify areas of uncertainty. The serum 25‐hydroxyvitamin D [25(OH)D] concentration [i.e. the sum of 25(OH)D3 and 25(OH)D2] remains the critical measurement for defining vitamin D status. Assay variation for 25(OH)D has contributed to the current chaos surrounding efforts to define hypovitaminosis D. An essential requirement to develop a consensus on vitamin D status is that measurement of 25(OH)D and, in the future, other potential vitamin D biomarkers [e.g. 1α,25(OH)2D3, 3‐epi‐25(OH)D, 24,25(OH)2D3, vitamin D‐binding protein, free/bioavailable 25(OH)D and parathyroid hormone] be standardized/harmonized, to allow pooling of research data. Vitamin D Standardization Program tools are described and recommended for standardizing 25(OH)D measurement in research. In the future, similar methodology, based on National Institute for Standards and Technology standard reference materials, must be developed for other candidate markers of vitamin D status. Failure to standardize/harmonize vitamin D metabolite measurements is destined to promulgate continued chaos. At this time, 25(OH)D values below 12 ng ml–1 (30 nmol l–1) should be considered to be associated with an increased risk of rickets/osteomalacia, whereas 25(OH)D concentrations between 20 ng ml–1 and 50 ng ml–1 (50–125 nmol l–1) appear to be safe and sufficient in the general population for skeletal health. In an effort to bridge knowledge gaps in defining hypovitaminosis D, an international study on rickets as a multifactorial disease is proposed.
Background: Little is known about placental vitamin D metabolism and its impact on maternal circulating vitamin D concentrations in humans.Objective: This study sought to advance the current understanding of placental vitamin D metabolism and its role in modulating maternal circulating vitamin D metabolites during pregnancy.Design: Nested within a feeding study, 24 healthy pregnant women (26-29 wk of gestation) consumed a single amount of vitamin D (511 IU/d from diet and a cholecalciferol supplement) for 10 wk. Concentrations of placental and blood vitamin D metabolites and placental messenger RNA (mRNA) abundance of vitamin D metabolic pathway components were quantified. In addition, cultured human trophoblasts were incubated with 13C-cholecalciferol to examine the intracellular generation and secretion of vitamin D metabolites along with the regulation of target genes.Results: In placental tissue, 25-hydroxyvitamin D3 [25(OH)D3] was strongly correlated (r = 0.83, P < 0.001) with 24,25-dihydroxyvitamin D3 Moreover, these placental metabolites were strongly correlated (r ≤ 0.85, P ≤ 0.04) with their respective metabolites in maternal circulation. Positive associations (P ≤ 0.045) were also observed between placental mRNA abundance of vitamin D metabolic components and circulating vitamin D metabolites [i.e., LDL-related protein 2 (LRP2, also known as megalin) with 25(OH)D3 and the C3 epimer of 25(OH)D3 [3-epi-25(OH)D3]; cubilin (CUBN) with 25(OH)D3; 25-hydroxylase (CYP2R1) with 3-epi-25(OH)D3; 24-hydroxylase (CYP24A1) with 25(OH)D3, 3-epi-25(OH)D3, and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]; and 1α-hydroxylase [(CYP27B1) with 3-epi-25(OH)D3 and 1,25(OH)2D3]. Notably, in vitro experiments with trophoblasts showed increased production and secretion of 25(OH)D3 and higher CYP24A1 gene transcript abundance in response to cholecalciferol treatment.Conclusions: The numerous associations of many of the placental biomarkers of vitamin D metabolism with circulating vitamin D metabolites among pregnant women [including a CYP27B1-associated increase in 1,25(OH)2D3] and the evidence of trophoblast production and secretion of vitamin D metabolites, especially 25(OH)D3, suggest that the placenta may play an active role in modulating the vitamin D metabolite profile in maternal circulation in human pregnancy. This trial was registered at clinicaltrials.gov as NCT03051867.
Iron is particularly important in pregnancy and infancy to meet the high demands for hematopoiesis, growth and development. Much attention has been given to conditions of iron deficiency (ID) and iron deficient anemia (IDA) because of the high global prevalence estimated in these vulnerable life stages. Emerging and preliminary evidence demonstrates, however, a U-shaped risk at both low and high iron status for birth and infant adverse health outcomes including growth, preterm birth, gestational diabetes, gastrointestinal health, and neurodegenerative diseases during aging. Such evidence raises questions about the effects of high iron intakes through supplementation or food fortification during pregnancy and infancy in iron-replete individuals. This review examines the emerging as well as the current understanding of iron needs and homeostasis during pregnancy and infancy, uncertainties in ascertaining iron status in these populations, and issues surrounding U-shaped risk curves in iron-replete pregnant women and infants. Implications for research and policy are discussed relative to screening and supplementation in these vulnerable populations, especially in developed countries in which the majority of these populations are likely iron-replete.
The Vitamin D Standardization Program (VDSP) coordinated an interlaboratory study to assess the comparability of measurements of total 25-hydroxyvitamin D [25(OH)D] in human serum, which is the primary marker of vitamin D status. A set of 50 individual donor samples were analyzed by 15 different laboratories representing national nutrition surveys, assay manufacturers, and clinical and/or research laboratories to provide results for total 25(OH)D using both immunoassays (IAs) and LC tandem MS (MS/MS). The results were evaluated relative to bias compared with the target values assigned based on a combination of measurements at Ghent University (Belgium) and the U.S. National Institute of Standards and Technology using reference measurement procedures for the determination of 25(OH)D2 and 25(OH)D3. CV and mean bias for each laboratory and assay platform were assessed and compared with previously established VDSP performance criteria, namely CV ≤ 10% and mean bias ≤ 5%. Nearly all LC-MS/MS results achieved VDSP criteria, whereas only 50% of IAs met the criterion for a ≤10% CV and only three of eight IAs achieved the ≤5% bias. These results establish a benchmark for the evaluation of 25(OH)D assay performance and standardization activities in the future.
The NIH Office of Dietary Supplements convened a public workshop on iron screening and supplementation in iron-replete pregnant women and young children in 2016 in Bethesda, Maryland. The starting point for the workshop was the recent reports from the US Preventive Services Task Force concluding that there was insufficient evidence to evaluate the benefits and harms associated with iron screening and routine supplementation among asymptomatic pregnant women and young children (6-24 mo old) in the United States. The goal of the workshop was to explore and refine understanding about the existing knowledge gaps and research needs associated with these preventive services for these groups. Given the focus on the United States, planning for the workshop took into account the higher iron status in the United States compared with developing countries and, in turn, included a focus on iron-replete individuals consistent with the U-shaped risk curve for nutrient-health relations. Topic areas included adaptations in iron homeostasis associated with pregnancy and young childhood, the impact of inflammation, measurement of iron status, current estimates of iron status for pregnant women and young children in the United States and in Europe, and emerging evidence suggesting adverse effects associated with iron supplementation of iron-replete individuals. A crosscutting dialogue conducted at the close of the workshop formed the basis for a workshop summary that specified evidence gaps and research needs in a range of areas centered on the relation of these adaptations of iron homeostasis with the response to and risk from iron supplementation as well as the need for indicators informative of the full continuum of iron status and based on health outcomes, not just erythropoiesis.
Understanding the iron status in pregnant women in Europe provides a foundation for considering the role of iron screening and supplementation. However, available reports and studies have used different approaches that challenge the devising of overall summaries. Moreover, data on pregnant women are limited, and thus, data on women of reproductive age provide useful background information including baseline iron stores in pregnant women. This review considered data that are available from >15 European countries including national surveys and relevant clinical studies. In European women of reproductive age, median or geometric mean serum ferritin (SF) concentrations were estimated at 26–38 μg/L. Approximately 40–55% of this population had small or depleted iron stores (i.e., SF concentration ≤30 μg/L), and 45–60% of this population had apparently replete iron stores. The prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) was 10–32% and 2–5%, respectively, depending on the cutoffs used. Approximately 20–35% of European women of reproductive age had sufficient iron stores (SF concentration >70 μg/L) to complete a pregnancy without supplementary iron. During pregnancy, European women in controlled supplementation trials who were not receiving iron supplements displayed increasing prevalences of ID and IDA during pregnancy, which peaked in the middle to late third trimester. Available evidence has suggested that, in gestational weeks 32–39, the median or geometric mean SF concentrations were 6–21 μg/L, and prevalences of ID and IDA were 28–85% and 21–35%, respectively. Women who were taking iron supplements had higher iron status and lower prevalences of ID and IDA, which were dependent on the dose of iron and compliance. The data suggest that, in Europe, the iron status of reproductive-aged women varies by region and worsens in pregnancy without iron supplementation.
This report addresses the evidence and the uncertainties, knowledge gaps, and research needs identified by participants at the NIH workshop related to iron screening and routine iron supplementation of largely iron-replete pregnant women and young children (6-24 mo) in developed countries. The workshop presentations and panel discussions focused on current understanding and knowledge gaps related to iron homeostasis, measurement of and evidence for iron status, and emerging concerns about supplementing iron-replete members of these vulnerable populations. Four integrating themes emerged across workshop presentations and discussion and centered on 1) physiologic or developmental adaptations of iron homeostasis to pregnancy and early infancy, respectively, and their implications, 2) improvement of the assessment of iron status across the full continuum from iron deficiency anemia to iron deficiency to iron replete to iron excess, 3) the linkage of iron status with health outcomes beyond hematologic outcomes, and 4) the balance of benefit and harm of iron supplementation of iron-replete pregnant women and young children. Research that addresses these themes in the context of the full continuum of iron status is needed to inform approaches to the balancing of benefits and harms of screening and routine supplementation.
The science surrounding vitamin D presents both challenges and opportunities. Although many uncertainties are associated with the understandings concerning vitamin D, including its physiological function, the effects of excessive intake, and its role in health, it is at the same time a major interest in the research and health communities. The approach to evaluating and interpreting the available evidence about vitamin D should be founded on the quality of the data and on the conclusions that take into account the totality of the evidence. In addition, these activities can be used to identify critical data gaps and to help structure future research. The Office of Dietary Supplements (ODS) at the National Institutes of Health has as part of its mission the goal of supporting research and dialogues for topics with uncertain data, including vitamin D. This review considers vitamin D in the context of systematically addressing the uncertainty and in identifying research needs through the filter of the work of ODS. The focus includes the role of systematic reviews, activities that encompass considerations of the totality of the evidence, and collaborative activities to clarify unknowns or to fix methodological problems, as well as a case study using the relationship between cancer and vitamin D.
Background: African Americans are at increased risk of iron deficiency (ID) but also have higher serum ferritin (SF) concentrations than those of the general population. The Hemochromatosis and Iron Overload Screening (HEIRS) Study was a multicenter study of ethnically diverse participants that tested for the hemochromatosis (HFE) C282Y genotype and iron status.Objective: We sought to determine the prevalence and predictors of ID (SF concentration ≤15 μg/L) and elevated iron stores (SF concentration >300 μg/L) in HEIRS women of reproductive age (25-44 y).Design: The HEIRS Study was a cross-sectional study of iron status and HFE mutations in primary care patients at 5 centers in the United States and Canada. We analyzed data for women of reproductive age according to whether or not they were pregnant or breastfeeding at the time of the study.Results: ID was present in 12.5% of 20,080 nonpregnant and nonbreastfeeding women compared with 19.2% of 1962 pregnant or breastfeeding women (P < 0.001). Asian American ethnicity (OR ≤0.9; P ≤ 0.049) and HFE C282Y (OR ≤0.84; P ≤ 0.060) were independently associated with a decreased risk of ID in nonpregnant and nonbreastfeeding women and in pregnant or breastfeeding women. Hispanic ethnicity (OR: 1.8; P < 0.001) and African American ethnicity (OR: 1.6; P < 0.001) were associated with an increased risk of ID in nonpregnant and nonbreastfeeding women. Elevated iron stores were shown in 1.7% of nonpregnant and nonbreastfeeding women compared with 0.7% of pregnant or breastfeeding women (P = 0.001). HFE C282Y homozygosity had the most marked independent association with elevated iron stores in nonpregnant and nonbreastfeeding women and in pregnant or breastfeeding women (OR >49.0; P < 0.001), but African American ethnicity was also associated with increased iron stores in both groups of women (OR >2.0; P < 0.001). Asian American ethnicity (OR: 1.8; P = 0.001) and HFE C282Y heterozygosity (OR: 1.9; P = 0.003) were associated with increased iron stores in nonpregnant and nonbreastfeeding women.Conclusions: Both ID and elevated iron stores are present in women of reproductive age and are influenced by ethnicity and HFE C282Y. Efforts to optimize iron status should keep these findings in view. This study was registered at clinicaltrials.gov as NCT03276247.
BACKGROUND:The impact of the reproductive state on vitamin D metabolism and requirements is uncertain in part because of a lack of studies with controlled dietary intakes of vitamin D and related nutrients.OBJECTIVE:We aimed to quantify the impact of the reproductive state on a panel of vitamin D biomarkers among women of childbearing age consuming equivalent amounts of vitamin D and related nutrients.METHODS:Nested within a feeding study providing 2 doses of choline, healthy pregnant (26-29 wk gestation; n = 26), lactating (5 wk postpartum; n = 28), and control (nonpregnant/nonlactating; n = 21) women consumed a single amount of vitamin D (511 ± 48 IU/d: 311 ± 48 IU/d from diet and 200 IU/d as supplemental cholecalciferol) and related nutrients (1.6 ± 0.4 g Ca/d and 1.9 ± 0.3 g P/d) for 10 wk. Vitamin D biomarkers were measured in blood obtained at baseline and study end, and differences in biomarker response among the reproductive groups were assessed with linear mixed models adjusted for influential covariates (e.g., body mass index, season, race/ethnicity).RESULTS:At study end, pregnant women had higher (P < 0.01) circulating concentrations of 25-hydroxyvitamin D [25(OH)D; 30%], 1,25-dihydroxyvitamin D [1,25(OH)2D; 80%], vitamin D binding protein (67%), and C3 epimer of 25(OH)D3 (100%) than control women. Pregnant women also had higher (P ≤ 0.04) ratios of 25(OH)D to 24,25-dihydroxyvitamin D [24,25(OH)2D; 40%] and 1,25(OH)2D to 25(OH)D (50%) than control women. In contrast, no differences (P ≥ 0.15) in vitamin D biomarkers were detected between the lactating and control groups. Notably, the study vitamin D dose of 511 IU/d achieved vitamin D adequacy in most participants (95%) regardless of their reproductive state.CONCLUSIONS:The higher concentrations of vitamin D biomarkers among pregnant women than among control women suggest that metabolic adaptations, likely involving the placenta, transpire to enhance vitamin D supply during pregnancy. The study findings also support the adequacy of the current vitamin D RDA of 600 IU for achieving serum 25(OH)D concentrations ≥50 nmol/L among women differing in their reproductive state. This trial was registered at clinicaltrials.gov as NCT01127022.
This 10‐wk feeding study sought to advance understanding of the role of the placenta in maternal vitamin D status. To achieve this aim, we assessed associations between placental vitamin D metabolites [25‐hydroxyvitamin D3 (25[OH]D3), 24,25‐dihydroxyvitamin D3 (24,25[OH]2D3)], placental expression of vitamin D‐related genes [25‐hydroxylase (CYP2R1), 1a‐hydroxylase (CYP27B1), 24‐hydroxylase (CYP24A1)] and maternal blood vitamin D metabolites [25(OH)D3, 24,25(OH)2D3, 1,25‐dihydroxyvitamin D (1,25[OH]2D)] among healthy third‐trimester pregnant women (n=26). Participants consumed equivalent and rigorously controlled vitamin D (515 IU/d) and calcium intakes (1445 mg/d) throughout the third trimester, and blood samples were obtained at study‐baseline (beginning of third trimester) and study‐end (term), while placenta tissues were collected at delivery. Blood and placental vitamin D metabolites were measured by LC‐MS/MS, and placental gene transcript abundance was quantified by qRT‐PCR with Taqman probes. In Pearson correlation analyses, 25(OH)D3 and 24,25(OH)2D3 concentrations showed a strong positive correlation in placenta [r=0.83, P<0.001], and in maternal blood [r=0.89, P<0.001 at baseline; r=0.84, P<0.001 at study‐end]. Remarkably, placental 25(OH)D3 concentrations correlated positively with maternal serum 25(OH)D3 levels [r=0.63, P<0.001 at baseline; r=0.85, P<0.001 at study‐end], and also with maternal circulating 24,25(OH)2D3 levels [r=0.63, P=0.001 at baseline; r=0.81, P<0.001 at study‐end]. Similarly, placental 24,25(OH)2D3 concentrations were positively correlated with maternal serum 25(OH)D3 [r=0.45, P=0.03 at baseline; r=0.68, P<0.001 at study‐end] and maternal blood 24,25(OH)2D3 levels [r=0.52, P=0.01 at baseline; r=0.67, P<0.001 at study‐end]. Moreover, positive associations were observed between 25(OH)D3 and 1,25(OH)2D concentrations in maternal circulation [r=0.47, P=0.02 at baseline; r=0.36, P=0.068 at study‐end], and circulating 1,25(OH)2D and 24,25(OH)2D levels were correlated only at baseline [r=0.44, P=0.02]. Of note, in multivariate‐adjusted regression models, baseline concentrations of maternal serum 25(OH)D3 correlated positively with both placental CYP27B1 [R2=0.86 ; β=0.007; P=0.04] and CYP24A1 expression [R2 = 0.70; β=0.012; P=0.01]. In addition, maternal serum 25(OH)D at study‐end and placental CYP2R1 expression showed an inverse relationship with a borderline significance [R2=0.92; β=−0.006; P=0.06], and placental CYP24A1 expression positively correlated with 1,25(OH)2D levels at both study‐time points [R2=0.70; β=0.0022; P=0.01 at baseline; R2=0.67; β=0.0017; P=0.03 at study‐end]. To the best our knowledge, this is the first study to quantify vitamin D metabolites in human placenta tissue. The strong correlations between maternal circulating vitamin D metabolites and placental metabolic and genomic readouts suggest that the placenta may modulate the vitamin D metabolite profile in the maternal compartment.Support or Funding InformationGERBER FOUNDATION 1843‐3882, NIH R03 HD080824‐01A1
BackgroundGlobally, waist circumference (WC) and body mass index (BMI) are widely used for population screening to predict disease risk, including for diabetes. We examined the association of anthropometric measurements with diabetes and pre‐diabetes in a cohort where the majority of participants would be classified as low risk based on either BMI or WC.MethodsStudy participants were recruited from an outpatient clinic in rural South India (n=297). Concentrations of glycosylated hemoglobin (HbA1c) were measured by high‐performance liquid chromatography. Diabetes and pre‐diabetes were defined as HbA1c ≥6.5% and ≥5.7% to <6.5%, respectively. Waist circumference was measured by non‐stretch measuring tape to the nearest 0.1 cm by study staff. Whole and segmental body composition were measured by bioelectrical impedance analysis (8 electrode; Tanita BC 418 MA). Binomial regressions were used to assess the associations between diabetes (and pre‐diabetes), and anthropometric indicators (WC, BMI). Restricted cubic splines were used to evaluate non‐linearity.ResultsMean waist circumference was 73.2 cm (SD: 11.3) among males, and 69.7 cm (SD 12.1) among females. Among male study participants, more than 90% had a waist circumference < 90 cm; among females, 80% had a waist circumference <80 cm. Mean BMI was 19.2 kg/m2 (SD 4.1) among men, and 20.4 kg/m2 (SD 5.4) among women. Among males, 50.0% had BMI <18.5 kg/m2, and over 90% had BMI <25.0 kg/m2. Among females, nearly 50% of study participants had BMI <18.5 kg/m2, and more than 80% had BMI <25.0 kg/m2. Study participants with waist circumference in the two lowest tertiles had a lower risk of diabetes (Tertile 1 vs 3: RR 0.40 [95% CI 0.20–0.81]; Tertile 2 vs 3: RR 0.33 [95% CI: 0.15–0.73]), compared to those in the highest tertile (p=0.004). Waist circumference was not associated with pre‐diabetes; BMI was not associated with either diabetes or pre‐diabetes.ConclusionBased on widely used cutoffs of WC and BMI (World Health Organization, International Diabetes Federation for South Asia), nearly 90% of study participants would be considered to be at low or minimal risk for diabetes. However 13% of study participants had diabetes, and 21% had pre‐diabetes. Waist circumference was still associated with increased risk of diabetes among study participants. These findings emphasize the need for the development of population‐specific cutoffs for waist circumference in diabetes screening.Support or Funding InformationCornell University
Background: Dietary Reference Intakes (DRIs) are fundamental to inform national nutrition policy. However, a regular systematic review of the 51 nutrients that have DRIs has limited feasibility, and many DRIs have not been reviewed in >15 y.Objective: To address this issue, individuals (nutrient review group) who were members of the Food and Nutrition Board developed a streamlined, evidence-based methodology that could be used to identify nutrients potentially in need of a systematic review.Design: The proposed methodology, termed an evidence scan, comprises several steps. First, an analytic framework is developed to identify markers of associations between intake of a nutrient and a corresponding clinical outcome. Next, the framework is used to direct the identification of keywords for a scan of published research that is potentially relevant to intake requirements or upper intake levels for a nutrient. Last, a panel of content experts selects the abstracts that are likely to be relevant and reviews the full publications. The results may be used to determine whether a revision of the nutrient's DRI is an immediate priority but would not supplant a comprehensive systematic evidence review.Results: To illustrate the process, 2 nutrients were selected as case studies: thiamin and phosphorus (DRIs were last set in 1998 and 1997, respectively). Using the evidence scan for thiamin, we identified 70 potentially relevant abstracts, of which 9 full publications were reviewed. For phosphorus, 127 potentially relevant abstracts were identified, and 29 full publications were reviewed.Conclusions: From the review of these 2 nutrients, the nutrient review group concluded that there was insufficient new evidence to assign a high priority to a comprehensive systematic review for either thiamin or phosphorus. Evidence scanning is an efficient method of identifying DRI nutrients that are most in need of either a new or an updated systematic review.
Vitamin D plays a central role in calcium homeostasis; however, its relationship with bone turnover during pregnancy remains unclear due to a lack of studies that have rigorously controlled for vitamin D and other nutrients known to influence bone metabolism. Similarly, prior investigations of the effect of pregnancy on bone turnover relative to the nonpregnant state may have been confounded by varying intakes of these nutrients. Nested within a controlled intake study, the present investigation sought to quantify associations between maternal vitamin D biomarkers and biochemical markers of bone turnover among pregnant (versus nonpregnant) women and their fetuses under conditions of equivalent and adequate intakes of vitamin D and related nutrients. Changes in markers of bone turnover across the third trimester were also examined. Healthy pregnant (26-29 wk gestation; n=26) and nonpregnant (n=21) women consumed 511IU vitamin D/d, 1.6g calcium/d, and 1.9g phosphorus/d for 10weeks while participating in a controlled feeding study featuring two choline doses. Based on linear mixed models adjusted for influential covariates (e.g., BMI, ethnicity, and season), pregnant women had 50-150% higher (P<0.001) concentrations of bone resorption markers than nonpregnant women. Among pregnant women, increases in maternal 25(OH)D across the study period were associated (P<0.020) with lower osteocalcin and deoxypyridinoline at study-end, and higher fetal osteocalcin. In addition, maternal free 25(OH)D, 1,25(OH)2D and 24,25(OH)2D tended to be negatively associated (P≤0.063) with maternal NTx at study-end, and maternal free 25(OH)D and 24,25(OH)2D were positively associated (P≤0.021) with fetal CTx. Similarly, maternal 3-epi-25(OH)D3 was negatively related (P≤0.037) to maternal NTx and deoxypyridinoline at study-end. These declines in bone resorption markers resulting from higher vitamin D biomarker concentrations among pregnant women coincided with increases in their albumin-corrected serum calcium concentrations, indicating that calcium transfer to the fetus was uncompromised. Notably, none of these associations achieved statistical significance among nonpregnant women. Overall, our study findings suggest that achieving higher maternal concentrations of vitamin D biomarkers might attenuate third-trimester bone resorption while ensuring sufficient calcium delivery to the fetus.
Food insecurity (FI) during pregnancy may lead to adverse health outcomes for affected women. However, little is known on whether such effects are due to short-term within person changes (longitudi...
Objective Although obesity is an established risk factor for Type 2 diabetes mellitus (DM), our previous work has demonstrated a high prevalence of DM in populations with lower body mass index (BMI). Further, the roles of key modifiable risk factors of diabetes, such as vitamin D status, in these populations remain unclear. In this cross‐sectional study, we assessed the associations between vitamin D, diabetes, and pre‐diabetes among patients with suspected tuberculosis (TB) and low adiposity in India. Methods Study participants were recruited based on the presentation of clinical signs and symptoms of tuberculosis (n=848). Serum 25‐hydroxyvitamin D (25[OHD]) was determined by chemiluminescence immunoassay, and we defined low vitamin D with three cut‐off values (25[OH]D <40.0 nmol/L, <50.0 nmol/L, <75.0 nmol/L). Diabetes (HbA1c ≥6.5%) and pre‐diabetes (HbA1c ≥5.7% to <6.5%) were defined by concentrations of glycosylated hemoglobin (HbA1c), which was evaluated with high‐performance liquid chromatography. Whole and segmental body composition was measured by bioelectrical impedance analysis (8 electrode; Tanita BC 418 MA). Results Among study participants, median vitamin D concentrations were 49.9 nmol/L (interquartile range [IQR] 36.7–69.3). 31.7% of patients had 25(OH)D < 40.0 nmol/L, 50.2% had 25(OH)D < 50.0 nmol/L, and 81.0% had 25(OH)D < 75.0 nmol/L. Median BMI was 18.5 kg/m2 (IQR 16.3–21.3) in males and 19.0 kg/m2 (IQR 16.4–23.7) in females. Median body fat was 14.8% (IQR 9.9–20.0) in males and 26.3% (IQR 20.1–34.5) in females. 13.0% of patients had DM and 20.8% had pre‐DM. 25(OH)D concentrations (nmol/L) were similar in patients with and without diabetes (p>0.05). Fat mass (kg) was higher in individuals with low vitamin D (<50.0 nmol/L), compared to patients with higher vitamin D status (11.0 kg [SD 7.9] vs. 8.8 kg [SD 5.3]; p=0.03). Individuals with vitamin D concentrations in the lowest quintile had a 3.7 times greater odds of having pre‐diabetes (adjusted OR: 3.7 [95% CI: 1.4–9.6]) after adjusting for waist circumference and age, compared to individuals in the four highest quintiles. Conclusions Findings demonstrate that lower vitamin D status is associated with increased pre‐diabetes and higher fat mass in patients with suspected tuberculosis, despite the low BMI of this study population. Prospective studies are needed to determine the role of vitamin D in this dual epidemic of diabetes and tuberculosis. Support or Funding Information Cornell University
BackgroundAdequate gestational weight gain (GWG) and neonatal growth are important, respectively, for favorable birth outcomes and survival of infants through the first year. In sub‐Saharan Africa, underlying infections, such as HIV, may adversely impact GWG and neonatal growth. We investigated trends in GWG among HIV‐infected and ‐uninfected women in northern Uganda; and, examined growth parameters of their HIV‐exposed and ‐unexposed neonates.Methods403 (133 HIV‐infected and on treatment vs. 270 ‐uninfected) pregnant women were recruited into this study from the antenatal clinic of Gulu Hospital. Women's height and weight were measured at enrollment (mean (±SD) gestational age =19.4 (±−3.8) weeks) and weight was measured at each follow‐up visit. After delivery, a subsample (n=246) of dyads was enrolled into a postnatal cohort. At one month postpartum, length and weight were measured and growth indicators (HAZ, WAZ and WHZ) were evaluated using the 2006 WHO standards. Other important variables were documented at recruitment using a detailed questionnaire. Multivariate regression models were employed to determine whether HIV status was associated with 1) the weekly rate of GWG and 2) neonatal indicators of growth.ResultsAdjusted models indicated a quadratic trend in GWG in both HIV infected and uninfected pregnant women. The rate of GWG among HIV infected women was significantly lower than that of HIV uninfected women (p=0.001). Prenatal HIV exposure was associated with significantly lower HAZ (p=0.013) and a nonsignicant trend towards lower WAZ; but, HIV exposure was not associated with WHZ at one month postpartum. HIV‐exposed neonates were more likely to be stunted (HAZ≤−2) than those who were –unexposed (adjusted odds ratio (aOR) (95%CI): 3.48 (1.29; 9.40).ConclusionThese results provide strong justifications for studies to understand mechanisms that underlay the negative effects of HIV infection or exposure on gestational weight gain and linear growth of HIV exposed neonates in this context.Support or Funding InformationThis research was funded in part by Cornell University Weill Medical College Intercampus Seed Funds, K01 MH098902 from NIMH and USAID Cooperative Agreement AIDOAAL1000006