Biomarkers Of Metabolic Health Research Articles

Effects of weight-loss on adipokines, total and regional body composition and markers of metabolic syndrome in women who are overweight and obese

Obesity among aging women is associated with increased risk for metabolic and cardiovascular diseases. Weight-loss has been shown to reduce disease risk; however, it remains unclear how changes in adipokines following weight-loss are associated with markers of metabolic and cardiovascular health in women. The aim of this study was to determine the effects of a 3-month intensive lifestyle management-focused weight-loss program on the interactions between adipokines, total and regional body composition, and biomarkers of cardiovascular and metabolic health. Women who were overweight or obese (n = 43, age = 49.2 ± 1.5 years, body mass index (BMI) = 34.5 ± 0.9 kg/m2; waist circumference (WC) = 99.8 ± 2.2 cm) completed a 3-month weight-loss program consisting of a reduced energy intake to 1200–1500 kcals/day combined with a progressive walking program targeting 300 min/wk. At 3-months, average body mass was reduced 8.3 % (ΔBMI −8.0 %; ΔWC −6.6 %). Weight-loss lowered fasting glucose (−12.1 %), insulin (−23.2 %), total cholesterol (−11.0 %), and LDL-C (−12.2 %) concentrations, and HOMA-IR (−32.4 %). Leptin was decreased 32.6 %, high molecular weight (HMW) adiponectin increased 25.0 %, and adiponectin:leptin ratio increased 1.27-fold. The change in fat mass was positively correlated with Δleptin (r = 0.527) and inversely correlated with Δadiponectin:leptin ratio (r = −0.547). The ΔHMW adiponectin inversely correlated with Δinsulin (r = −0.360) and ΔHOMA-IR (r = −0.304), and ΔLDL-C (r = −0.305), whereas Δleptin correlated with Δtriglyceride (r = 0.366) and Δtotal cholesterol (r = 0.402). Weight-loss in women who were overweight and obese was associated with a reduction in leptin and increase in HMW adiponectin and adiponectin:leptin ratio. Correlations revealed that changes in these adipokines were uniquely associated with improvements in select markers of metabolic and cardiovascular disease risk.

Genome-Wide Placental Gene Methylations in Gestational Diabetes Mellitus, Fetal Growth and Metabolic Health Biomarkers in Cord Blood.

Gestational diabetes mellitus (GDM) “program” an elevated risk of metabolic syndrome in the offspring. Epigenetic alterations are a suspected mechanism. GDM has been associated with placental DNA methylation changes in some epigenome-wide association studies. It remains unclear which genes or pathways are affected, and whether any placental differential gene methylations are correlated to fetal growth or circulating metabolic health biomarkers. In an epigenome-wide association study using the Infinium MethylationEPIC Beadchip, we sought to identify genome-wide placental differentially methylated genes and enriched pathways in GDM, and to assess the correlations with fetal growth and metabolic health biomarkers in cord blood. The study samples were 30 pairs of term placentas in GDM vs. euglycemic pregnancies (controls) matched by infant sex and gestational age at delivery in the Shanghai Birth Cohort. Cord blood metabolic health biomarkers included insulin, C-peptide, proinsulin, IGF-I, IGF-II, leptin and adiponectin. Adjusting for maternal age, pre-pregnancy BMI, parity, mode of delivery and placental cell type heterogeneity, 256 differentially methylated positions (DMPs,130 hypermethylated and 126 hypomethylated) were detected between GDM and control groups accounting for multiple tests with false discovery rate <0.05 and beta-value difference >0.05. WSCD2 was identified as a differentially methylated gene in both site- and region-level analyses. We validated 7 hypermethylated (CYP1A2, GFRA1, HDAC4, LIMS2, NAV3, PAX6, UPK1B) and 10 hypomethylated (DPP10, CPLX1, CSMD2, GPR133, NRXN1, PCSK9, PENK, PRDM16, PTPRN2, TNXB) genes reported in previous epigenome-wide association studies. We did not find any enriched pathway accounting for multiple tests. DMPs in 11 genes (CYP2D7P1, PCDHB15, ERG, SIRPB1, DKK2, RAPGEF5, CACNA2D4, PCSK9, TSNARE1, CADM2, KCNAB2) were correlated with birth weight (z score) accounting for multiple tests. There were no significant correlations between placental gene methylations and cord blood biomarkers. In conclusions, GDM was associated with DNA methylation changes in a number of placental genes, but these placental gene methylations were uncorrelated to the observed metabolic health biomarkers (fetal growth factors, leptin and adiponectin) in cord blood. We validated 17 differentially methylated placental genes in GDM, and identified 11 differentially methylated genes relevant to fetal growth.

Relationships between physical function, body composition and metabolic health in Pacific Island youth.

The Pacific Islands Families (PIF) study is a birth cohort study designed to increase knowledge about the growth and development of Pacific children living in Auckland, New Zealand. Adolescence is a critical time of growth and development, yet the roles of physical function and body composition in metabolic health at this life stage are not clear. We aimed to investigate associations between measures of physical function (the 6-minute-walk-test (6MWT)), heart rate changes before and after the 6MWT, handgrip strength, body composition including appendicular skeletal muscle mass (ASMM) measured by dual-energy X-ray absorptiometry and biomarkers of metabolic health from a fasting blood sample.A total of 200 youth (98 girls, 102 boys) aged 14–15 years, from the birth-cohort of children in the Pacific Islands families study were measured. In girls, the proportion of ASMM was lower and fat higher than in boys. Controlling for age, a 1% increase in ASMM predicted a longer walk distance (+6.3, 95%CI 2.2, 10.4 m in girls; +7.1, 95%CI 4.4, 9.1 m in boys) and lower heart rate following the 6MWT. ASMM and fat mass were independently predictive of maximal handgrip strength which was increased by 1.4 (1.0,1.8) kg in girls and 1.7 (1.3, 2.0) kg in boys for each kg increase in ASMM and reduced by 0.23 (0.08, 0.38) kg in girls and 0.26 (0.14, 0.37) kg in boys for each kg increase in fat mass. Lower total cholesterol and LDL were associated with an increase in distance walked in boys only. For each year of age, distance walked was reduced by 34 (15, 53) m in girls and 59 (36,84) m in boys. These findings should be explored further in the context of other influences such as food security, opportunities for physical activity and cultural expectations.

Four-Week Supplementation with Multi-Ingredient Nutrition Supplement Affects Biomarkers of Metabolic Health in Metabolically Healthy Adults: A Randomized-Controlled Cross-Over Pilot Trial

Multicomponent nutritional formulas are rarely evaluated for their effectiveness and safety to protect metabolic health. We analyzed the effects of short-term supplementation with a multicomponent formula, AGELess DefenseTM, on blood pressure, clinical chemistry, and body composition in non-diabetic, non-hypertensive adults. Ten healthy mid-age adults (aged 47.5 ± 8.5 years; 7 women) volunteered to take part in this randomized, placebo-controlled cross-over pilot trial. The participants were allocated in a double-blind design to receive AGELess DefenseTM or placebo (inulin) during a 4-week intervention period. At the 4-week follow-up, AGELess DefenseTM reduced serum total and low-density lipoprotein cholesterol significantly more than the placebo (P = 0.05). Serum insulin levels increased significantly after consuming AGELess DefenseTM (P = 0.03), with AGELess DefenseTM having a medium-to-large effect size (d = 0.71). These preliminary findings suggest that AGELess DefenseTM is an effective nutritional intervention for protecting metabolic health; additional studies are warranted to corroborate this effect in metabolically compromised individuals.

Myo-Inositol Supplementation in Suckling Rats Protects against Adverse Programming Outcomes on Hypothalamic Structure Caused by Mild Gestational Calorie Restriction, Partially Comparable to Leptin Effects.

We studied whether myo-inositol supplementation throughout lactation, alone and combined with leptin, may reverse detrimental effects on hypothalamic structure and function caused by gestational calorie gestation (CR) in rats. Candidate early transcript-based biomarkers of metabolic health in peripheral blood mononuclear cells (PBMC) were also studied. Offspring of dams exposed to 25% gestational CR and supplemented during lactation with physiological doses of leptin (CR-L), myo-inositol (CR-M), the combination (CR-LM), or the vehicle (CR-V) as well as control rats (CON-V) were followed and sacrificed at postnatal day 25. Myo-inositol and the combination increased the number of neurons in arcuate nucleus (ARC) (only in females) and paraventricular nucleus, and myo-inositol (alone) restored the number of αMSH+ neurons in ARC. Hypothalamic mRNA levels of Lepr in CR-M and Insr in CR-M and CR-LM males were higher than in CR-V and CON-V, respectively. In PBMC, increased expression levels of Lrp11 and Gls in CR-V were partially normalized in all supplemented groups (but only in males for Gls). Therefore, myo-inositol supplementation throughout lactation, alone and combined with leptin, reverts programmed alterations by fetal undernutrition on hypothalamic structure and gene expression of potential early biomarkers of metabolic health in PBMC, which might be attributed, in part, to increased leptin sensitivity.

Endogenous circadian regulation and phase resetting of clinical metabolic biomarkers.

Shiftwork and circadian disruption are associated with adverse metabolic effects. Therefore, we examined whether clinical biomarkers of metabolic health are under endogenous circadian regulation using a 40hours constant routine protocol (CR; constant environmental and behavioral conditions) and evaluated the impact of typical daily conditions with periodic sleep and meals (baseline; 8hours sleep at night, four meals during a 16hour wake episode) on the phase and amplitude of these rhythms. Additionally, we tested whether these circadian rhythms are reset during simulated shiftwork. Under CR (n=16 males, mean age±SD=23.4±2.3years), we found endogenous circadian rhythms in cholesterol, HDL and LDL, albumin and total protein, and VLDL and triglyceride. The rhythms were masked under baseline conditions except for cholesterol, which had near-identical phases under both conditions. Resetting of the cholesterol rhythm and Dim Light Melatonin Onset (DLMO) was then tested in a study of simulated shiftwork (n=25, 14 females, 36.3±8.9years) across four protocols; two with abrupt 8hour delay shifts and exposure to either blue-enriched or standard white light; and either an abrupt or gradual 8hour advance (1.6hours/day over 5days) both with exposure to blue-enriched white light. In the delay protocols, the cholesterol rhythm shifted later by -3.7hours and -4.2hours, respectively, compared to -6.6hours and -4.7hours, for DLMO. There was a significant advance in cholesterol in the abrupt (+5.1hours) but not the gradual (+2.1hours) protocol, compared to +3.1hours and +2.8hours in DLMO, respectively. Exploratory group analysis comparing the phases of all metabolic biomarkers under both studies showed evidence of phase shifts due to simulated shiftwork. These results show that clinical biomarkers of metabolic health are under endogenous circadian regulation but that the expression of these rhythms is substantially influenced by environmental factors. These rhythms can also be reset, which has implications for understanding how both behavioral changes and circadian shifts due to shiftwork may disrupt metabolic function.

A Comprehensive Review of Almond Clinical Trials on Weight Measures, Metabolic Health Biomarkers and Outcomes, and the Gut Microbiota.

This comprehensive narrative review of 64 randomized controlled trials (RCTs) and 14 systematic reviews and/or meta-analyses provides an in-depth analysis of the effect of almonds on weight measures, metabolic health biomarkers and outcomes, and the colonic microbiota, with extensive use of figures and tables. Almonds are a higher energy-dense (ED) food that acts like a lower ED food when consumed. Recent systematic reviews and meta-analyses of nut RCTs showed that almonds were the only nut that had a small but significant decrease in both mean body mass and fat mass, compared to control diets. The biological mechanisms for almond weight control include enhanced displacement of other foods, decreased macronutrient bioavailability for a lower net metabolizable energy (ME), upregulation of acute signals for reduced hunger, and elevated satiety and increased resting energy expenditure. The intake of 42.5 g/day of almonds significantly lowered low-density lipoprotein cholesterol (LDL-C), 10-year Framingham estimated coronary heart disease (CHD) risk and associated cardiovascular disease (CVD) medical expenditures. Diastolic blood pressure (BP) was modestly but significantly lowered when almonds were consumed at >42.5 g/day or for >6 weeks. Recent RCTs suggest possible emerging health benefits for almonds such as enhanced cognitive performance, improved heart rate variability under mental stress, and reduced rate of facial skin aging from exposure to ultraviolet (UV) B radiation. Eight RCTs show that almonds can support colonic microbiota health by promoting microflora richness and diversity, increasing the ratio of symbiotic to pathogenic microflora, and concentrations of health-promoting colonic bioactives. Almonds are a premier healthy snack for precision nutrition diet plans.

Objectively Measured Physical Activity Is Associated With Body Composition and Metabolic Profiles of Pacific and New Zealand European Women With Different Metabolic Disease Risks.

Objective: To assess associations between physical activity (PA), body composition, and biomarkers of metabolic health in Pacific and New Zealand European (NZE) women who are known to have different metabolic disease risks.Methods: Pacific (n = 142) or NZE (n = 162) women aged 18–45 years with a self-reported body mass index (BMI) of either 18.5–25.0 kg⋅m–2 or ≥30.0 kg⋅m–2 were recruited and subsequently stratified as either low (<35%) or high (≥35%) BF%, with approximately half of each group in either category. Seven-day accelerometery was used to assess PA levels. Fasting blood was analysed for biomarkers of metabolic health, and whole body dual-energy X-ray absorptiometry (DXA) was used to estimate body composition.Results: Mean moderate-to-vigorous physical activity (MVPA; min⋅day–1) levels differed between BF% (p < 0.05) and ethnic (p < 0.05) groups: Pacific high- 19.1 (SD 15.2) and low-BF% 26.3 (SD 15.6) and NZE high- 30.5 (SD 19.1) and low-BF% 39.1 (SD 18.4). On average Pacific women in the low-BF% group engaged in significantly less total PA when compared to NZE women in the low-BF% group (133 cpm); no ethnic difference in mean total PA (cpm) between high-BF% groups were observed: Pacific high- 607 (SD 185) and low-BF% 598 (SD 168) and NZE high- 674 (SD 210) and low-BF% 731 (SD 179). Multiple linear regression analysis controlling for age and deprivation showed a significant inverse association between increasing total PA and fasting plasma insulin among Pacific women; every 100 cpm increase in total PA was associated with a 6% lower fasting plasma insulin; no significant association was observed in NZE women. For both Pacific and NZE women, there was an 8% reduction in fasting plasma insulin for every 10-min increase in MVPA (p ≤ 0.05).Conclusion: Increases in total PA and MVPA are associated with lower fasting plasma insulin, thus indicating a reduction in metabolic disease risk. Importantly, compared to NZE, the impact of increased total PA on fasting insulin may be greater in Pacific women. Considering Pacific women are a high metabolic disease risk population, these pre-clinical responses to PA may be important in this population; indicating promotion of PA in Pacific women should remain a priority.

The associations of phthalate biomarkers during pregnancy with later glycemia and lipid profiles

BackgroundPregnancy induces numerous cardiovascular and metabolic changes. Alterations in these sensitive processes may precipitate long-term post-delivery health consequences. Studies have reported associations between phthalates and metabolic complications of pregnancy, but no study has investigated metabolic outcomes beyond pregnancy. ObjectivesTo examine associations of exposure to phthalates during pregnancy with post-delivery metabolic health. DesignWe quantified 15 urinary phthalate biomarker concentrations during the second and third trimesters among 618 pregnant women from Mexico City. Maternal metabolic health biomarkers included fasting blood measures of glycemia [glucose, insulin, Homeostatic Model Assessment of Insulin Resistance [HOMA-IR], % hemoglobin A1c (HbA1c%)] and lipids (total, high-density lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol, triglycerides), at 4–5 and 6–8 years post-delivery. To estimate the influence of the phthalates mixture, we used Bayesian weighted quantile sum regression and Bayesian kernel machine regression; for individual biomarkers, we used linear mixed models. ResultsAs a mixture, higher urinary phthalate biomarker concentrations during pregnancy were associated with post-delivery concentrations of plasma glucose (interquartile range [IQR] difference: 0.13 SD, 95%CrI: 0.05, 0.20), plasma insulin (IQR difference: 0.06 SD, 95%CrI: −0.02, 0.14), HOMA-IR (IQR difference: 0.08 SD, 95% CrI: 0.01, 0.16), and HbA1c% (IQR difference: 0.15 SD, 95%CrI: 0.05, 0.24). Associations were primarily driven by mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) and the sum of dibutyl phthalate biomarkers (∑DBP). The phthalates mixture was associated with lower HDL (IQR difference: −0.08 SD, 95%CrI: −0.16, −0.01), driven by ∑DBP and monoethyl phthalate (MEP), and higher triglyceride levels (IQR difference: 0.15 SD, 95%CrI: 0.08, 0.22), driven by MECPTP and MEP. The overall mixture was not associated with total cholesterol and LDL. However, ∑DBP and MEP were associated with lower and higher total cholesterol, respectively, and MECPTP and ∑DBP were associated with lower LDL. ConclusionsPhthalate exposure during pregnancy is associated with adverse long-term changes in maternal metabolic health. A better understanding of timing of the exact biological changes and their implications on metabolic disease risk is needed.

Cesarean delivery and metabolic health and inflammation biomarkers during mid-childhood and early adolescence

BackgroundWe assessed differences in plasma levels of metabolic health and inflammation biomarkers during mid-childhood and early adolescence between children born by cesarean section vs. vaginal delivery.MethodsMother–child pairs (N = 942) enrolled during pregnancy in obstetric practices and child follow-up started at birth. Risk biomarkers were assessed in blood samples collected at the mild-childhood (median = 7 years) and early adolescence (median = 13 years) in-person visits.ResultsTwo hundred and six children (22%) were born by cesarean section. There were no significant differences in biomarker levels between children born by cesarean and children born vaginally in mid-childhood. However, adolescents born by cesarean section had significantly lower adiponectin [% difference (95% confidence interval (CI)) = −11.3 (−18.1, −4.0) µg/mL] compared to vaginal delivery. We also found some suggestion of higher insulin resistance [insulin levels % difference (95% CI) = 11.5 (−0.40, 25.0) µU/mL and HOMA-IR (homeostatic model assessment of insulin resistance) % difference (95% CI) = 9.1 (−2.30, 21.8) U] in adolescents born by cesarean section compared to those born vaginally.ConclusionsWe found suggestive evidence that adolescents born by cesarean section show differences in certain metabolic health biomarkers relative to adolescents born by vaginal delivery. Further studies are needed to reevaluate these associations since the clinical significance of these differences is unclear.ImpactMultiple studies show that children born by cesarean section are at higher risk of obesity compared to those born vaginally.It is unclear yet to what extent this elevated risk may extend to a more adverse profile of biomarkers of metabolic health and inflammation.Adolescents born by cesarean section show small differences in adiponectin and insulin relative to adolescents born by vaginal delivery.Adolescents born by cesarean section may be at higher risk to a more adverse profile of biomarkers of metabolic health and inflammation, but the clinical significance of these differences is uncertain.

A preconception intervention targeted at women with modifiable risk factors before pregnancy to improve outcomes; protocol for the Get Ready! feasibility trial

BackgroundThe health of a woman before conception not only influences the outcome of her pregnancy but also the lifelong health of mother and child. Many women in the UK are inadequately prepared for pregnancy, with reports of a high prevalence of smoking, low folic acid supplement use, and suboptimal diet and physical activity. Get Ready! will link an online digital tool to identify women planning pregnancy most at risk of complications with a personalised intervention to improve health behaviours and biomarkers of metabolic health.MethodsWomen planning pregnancy will be identified from a free and widely used online preconception tool. A short online screening questionnaire will then be used to recruit women considered to be at high metabolic risk. Eligibility criteria include resident in the UK, age > 18–< 50 years, BMI ≥ 23 kg/m2 (South Asian) or ≥ 25 kg/m2 (all other ethnicities), and plus one or more of the following: 1st degree relative with type 2 diabetes, previous gestational diabetes (GDM), previous baby > 4 kg, or high risk ethnicity for GDM. Eligible women who consent to participate will be enrolled in a commercially available preconception intervention (Prepare Plans, LiveSmart UK Ltd). Following an online health assessment and home blood test, women will be provided with individualised lifestyle advice and coaching by dietitians. Process evaluation will provide an assessment of implementation of the intervention. Change in health behaviours and biomarkers of metabolic health will also be examined.DiscussionSuboptimal health behaviours amongst women planning pregnancy are widely prevalent in the UK. Personalised health checks and coaching are especially important for women at risk of pregnancy complications. Get Ready! introduces a novel approach to identifying high risk women planning pregnancy and provision of a targeted intervention.RegistrationTrial sponsor: King’s College London.

Cord Blood IGF-I, Proinsulin, Leptin, HMW Adiponectin, and Ghrelin in Short or Skinny Small-for-Gestational-Age Infants.

Small-for-gestational-age (SGA) is an indicator of poor fetal growth "programming" an elevated risk of type 2 diabetes in adulthood. Little is known about early-life endocrine characteristics in SGA subtypes. Stunting (short) and wasting (skinny) are considered distinct SGA phenotypes in neonatal prognosis. This work aimed to assess whether SGA infants with stunting or wasting have similar alterations in neonatal endocrine metabolic health biomarkers. This was a nested case-control study based on the 3D (Design, Develop, and Discover) birth cohort in Canada. The study subjects were 146 SGA (birth weight < 10th percentile) and 155 optimal-for-gestational age (OGA, 25th-75th percentiles) infants. Stunting was defined as birth length less than the 10th percentile, and wasting as body mass index less than the 10th percentile for sex and gestational age, respectively. Main outcome measures included cord plasma concentrations of insulin-like growth factor I (IGF-I), proinsulin, leptin, high-molecular-weight (HMW) adiponectin, and ghrelin. Comparing to OGA infants adjusted for maternal and neonatal characteristics, SGA infants with either stunting only or wasting only had lower cord plasma IGF-I and leptin concentrations. HMW adiponectin concentrations were lower in SGA infants with wasting only (P = .004), but similar in SGA infants with stunting only (P = .816). Only SGA infants with both stunting and wasting had substantially lower proinsulin (P < .001) and higher ghrelin concentrations (P < .001) than OGA infants. This study is the first to demonstrate that SGA infants with wasting only are characterized by low HMW adiponectin concentrations, whereas those with stunting only are not. SGA with both stunting and wasting are characterized by low proinsulin and high ghrelin concentrations.

A ketogenic diet consumed during radiotherapy improves several aspects of quality of life and metabolic health in women with breast cancer

Ketogenic diets (KDs) have been proposed as complementary nutritional treatments for cancer patients. Because it is important to gain knowledge about the safety of KDs adopted during cancer therapy, we studied the effects of KDs on quality of life and blood parameters in women with early-stage breast cancer undergoing radiotherapy. A total of 29 patients consuming a KD were compared to 30 patients consuming their standard diet (SD) with respect to EORTC-QLQ30 questionnaire scores and different metabolic and hormonal blood parameters that were obtained prior to, in the middle of and at the end of radiotherapy. Baseline-to-end differences were assessed using Wilcoxon tests, and longitudinal changes were analyzed using linear mixed effects models. Compared to the SD, women consuming a KD experienced significant improvements in emotional functioning, social functioning, sleep quality, future perspectives and systemic therapy side effects (all p-values <0.01). While breast symptoms increased significantly in both groups, the increase was less pronounced in the KD group. There was no hint of a detrimental effect of the KDs on either liver or kidney function; in contrast, biomarkers of metabolic health (gamma-glutamyl-transpeptidase, creatinine, triglycerides, IGF-1, free T3) significantly improved in the KD, but not the SD group. These data support the hypothesis that consuming a KD during radiotherapy is safe for women with breast cancer and has the potential to improve quality of life and metabolic health. CLINICALTRIALS. NCT02516501.

331 Dietary methionine restriction: an approach to treating obesity that does not involve food restriction

Abstract Dietary methionine restriction (MR) produces an integrated series of metabolic and physiological responses that develop quickly after introducing the diet. Collectively, these responses to the diet improve many biomarkers of metabolic health. Two prominent physiological responses are increases in energy intake and expenditure, with the larger effect on energy expenditure slowing ongoing fat deposition by increasing the proportion of total energy intake required for maintenance of existing tissue. A significant remaining obstacle in implementing dietary MR in a translational context will be to develop methionine-restricted diets that are palatable to higher metazoans.

Prenatal urinary phthalates and postpartum metabolic health in Women from Mexico City

Studies have reported associations between phthalates, a family of ubiquitous environmental contaminants, and metabolic complications of pregnancy, but no study has considered these outcomes beyond pregnancy. We examined associations of prenatal phthalates exposure with postpartum metabolic health biomarkers in the PROGRESS cohort.The longitudinal PROGRESS cohort includes 948 pregnant women recruited during the second trimester from 2007 to 2011. We quantified 15 phthalate metabolites from spot urines collected during the second and third trimesters. Maternal metabolic health biomarkers were fasting blood measures of glycemia [glucose, insulin, %glycated hemoglobin (HbA1C%)] and lipids (total, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) cholesterol, and triglycerides], collected at 48 and 72 months postpartum. We used linear mixed models, weighted quantile sum regression, and Bayesian Kernel Machine Regression to estimate associations of geometric mean urinary phthalate metabolite concentrations (between 2nd/3rd trimesters) and metabolic health biomarkers.In multivariable-adjusted linear mixed models, each doubling of mean urinary mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) was associated with 0.12 uIU/L greater plasma insulin (95%CI: 0.0, 0.25) and 0.06% greater HbA1C% (95%CI: 0.03, 0.09). Mixtures analyses indicated that phthalate mixtures were positively associated with plasma insulin and HbA1c% and MECPTP and diisobutyl phthalate metabolites were the primary drivers. Mediation analyses found that greater gestational weight retention (GWR) mediated 29% of the observed association between urinary MECPTP and plasma insulin. No mediation by GWR was observed for HbA1C%.We found that prenatal MECPTP concentrations were positively associated with plasma insulin and HbA1C% up to 72 months postpartum. In previous analyses of this cohort, we found that prenatal MECPTP was associated with greater GWR and blood pressure. Collectively, these findings suggest that exposure to di-2-ethylhexyl terephthalate, parent compound of MECPTP, may contribute to poorer metabolic health among women. GWR may be one mediator of later metabolic dysfunction; other underlying mechanisms and clinical implications are unknown.

Sex dimorphism in the associations of gestational diabetes with cord blood adiponectin and retinol-binding protein 4

IntroductionGestational diabetes (GD) is associated with impaired insulin sensitivity in newborns. Adiponectin and retinol-binding protein 4 (RBP-4) are involved in regulating insulin sensitivity. Females are more likely to develop diabetes...

Facial appearance and metabolic health biomarkers in women

Facial appearance has been suggested to provide an honest cue of an individual’s biological condition. However, there is little direct evidence that facial attractiveness reflects actual health. Here we tested if facial appearance is related with metabolic health biomarkers. Face photographs of 161 healthy, young women (Mage = 28.59, SDage = 2.34) were assessed in terms of perceived attractiveness and health. Metabolic health was evaluated based on levels of markers of lipid and glucose metabolism balance, liver functioning, and inflammation. BMI, testosterone (T), and estradiol (E2) levels were controlled. Facial attractiveness, but not health, was negatively related with lipid profile components detrimental to health (total cholesterol, LDL, triglycerides) but not with relatively protective for health HDL. When controlled for BMI, E2, and T, only the relationship between attractiveness and triglycerides remained significant. Facial appearance was unrelated with glucose metabolism, liver functioning, and inflammatory markers. The results suggest, that for healthy women of reproductive age, such measures as BMI and sex hormone levels may be better predictors of attractiveness, compared to measures of metabolic health. Markers of lipid, glucose homeostasis, liver functioning or low-grade inflammation may be rather indicators of future health, of lesser importance in mating context, thus only modestly reflected in facial appearance.

Exploring the Antihypertensive and Vascular-Protective Effects of Blueberries in Middle-Aged/Older Men: Study Protocol

Abstract Objectives Previous research has demonstrated the antihypertensive and vascular-protective effects of blueberries in postmenopausal women with elevated blood pressure (BP) or stage 1-hypertension (HTN). However, this has not been explored in men with elevated BP or HTN. The objective of the present study is to examine effects of blueberry (BB) on BP, endothelial function, and arterial stiffness in men with elevated BP or stage 1-HTN, and baseline endothelial dysfunction, as well as to investigate possible mechanisms involved with BB on vascular health. Methods In a randomized, double-blind, placebo-controlled, parallel-arm trial, men with elevated BP or stage 1-HTN (systolic BP of 120–139 mmHg, and a diastolic BP &amp;lt; 90 mmHg), and endothelial dysfunction (reactive hyperemia index, RHI) &amp;lt;1.67, but otherwise healthy, will be randomized to receive either 22 g/day of freeze-dried wild BB powder or 22 g/day of placebo powder for 12 weeks. Primary outcomes for this study are BP and RHI, which is a measure of vascular endothelial function assessed using peripheral arterial tonometry. Secondary outcomes include analysis of arterial stiffness, measured by pulse wave velocity (PWV), as well as blood biomarkers of cardiovascular and metabolic health that include blood lipids, hemoglobin A1c, oxidized LDL, nitric oxide, and adhesion molecules. Furthermore, endothelial cells will be biopsied to provide mechanistic insight on how BB consumption might affect the vascular system by utilizing quantitative immunofluorescence. Results We hypothesize that 22 g/day of BB consumption (∼1 cup) for 12 weeks will improve endothelial function, arterial stiffness, and BP in men with elevated BP and/or stage 1-HTN. We also hypothesize that these improvements will be mediated by reductions in vascular oxidative stress and inflammation, and increased nitric oxide bioavailability. Conclusions This study has potential to provide unique in vivo (functional) and ex vivo (molecular) support for the hypothesis that BB consumption may attenuate endothelial dysfunction, arterial stiffness, and high BP that occurs with aging. Funding Sources Wild Blueberry Association of North America.

Evaluating the Impact of an Aronia Berry Dietary Supplement on Vascular Endothelial Function and the Gut Microbiota in Healthy Middle-Aged/Older Adults: Study Protocol

Abstract Objectives Aging is the primary risk factor for cardiovascular disease (CVD) largely due to vascular endothelial dysfunction, an initiating step in the development of atherosclerosis. The gut microbiota has emerged as an important regulator of cardiovascular health. Aronia berries are rich in polyphenols such as anthocyanins, proanthocyanidins, and phenolic acids. These compounds, and metabolites resulting from gut microbial and phase II metabolism, have been shown to improve endothelial function. The primary objective of this study is to assess the dose-dependent efficacy of an aronia berry full spectrum dietary supplement to improve vascular endothelial function in middle-aged/older men and postmenopausal women. A secondary goal is to determine whether aronia full spectrum modulation of the gut microbiota is associated with improvements in vascular endothelial function. Methods Healthy men and postmenopausal women (n = 28) aged 45–75 years are being recruited for this randomized, double-blind, placebo-controlled, crossover trial. In random order, participants take a placebo, 500 mg aronia full spectrum, or 1000 mg aronia full spectrum daily for a 6-week period. Each treatment period is separated by a 6-week washout period. The primary outcome is reactive hyperemia index (RHI), a validated measure of vascular endothelial function assessed using peripheral arterial tonometry. Secondary outcome measures include analysis of the gut microbiota in stool samples, hemodynamic parameters including blood pressure and augmentation index, arterial stiffness, and blood biomarkers of cardiovascular and metabolic health including blood lipids, hemoglobin a1c, oxidized LDL, and adhesion molecules. Other outcome measures will include plasma, fecal, and urine polyphenol metabolites. Gut microbial populations will be statistically compared with RHI. Results To date, a total of 22 individuals (11 men/11 women) have been enrolled in the trial and randomized to their intervention order. Of these, 3 have completed the study, 1 was lost to follow-up, and 18 are currently enrolled. Conclusions We hypothesize that this aronia berry dietary supplement will dose-dependently improve vascular endothelial function in healthy middle-aged/older adults, and that improvements will be linked to modulation of the gut microbiota. Funding Sources Naturex.

Fatty acid profile and estimated desaturase activities in whole blood are associated with metabolic health

BackgroundThe aim was to investigate if fatty acid profile and estimated desaturase activities; stearoyl CoA-desaturase (SCD), delta-5-desaturase and delta-6-desaturase (D5D; D6D), differ between individuals with metabolically healthy (MH) and unhealthy (MU) phenotypes. We also explored these associations according to BMI categories.MethodsMen and women at moderately elevated risk of cardiovascular disease were included in this cross-sectional study (n = 321). If subjects met ≥4 out of 5 criteria (elevated triglycerides, total and LDL-cholesterol, HbA1c and low HDL-cholesterol), they were classified as MU (n = 52). If levels were within reference ranges for ≥3 of the same criteria, subjects were classified as MH (n = 150). Utilizing the entire population, a score ranging from 0 to 5 denoting the number of MU criteria met was computed. Estimated desaturase activities were calculated as product-to-precursor ratio of fatty acids in whole blood (SCD16 [16:1n7/16:0], SCD18 [18:1n9/18:0], D5D [18:3n6/18:2n6], D6D [20:4n6/20:3n6]).ResultsIndividuals with MH had lower estimated SCD16 and SCD18 activities, whereas estimated D6D activity was higher compared to MU. Similar, SCD16 and SCD18 increased, whereas D6D decreased with increasing criteria of MU. Trends were similar across BMI categories.ConclusionsThis study supports the notion of estimated desaturase activities as possible novel biomarkers of metabolic health irrespectively of BMI.