Metabolic Health Outcomes Research Articles

The effects of prepartum energy intake and peripartum rumen-protected choline supplementation on hepatic genes involved in glucose and lipid metabolism

Nutritional interventions, either by controlling dietary energy (DE) or supplementing rumen-protected choline (RPC) or both, may mitigate negative postpartum metabolic health outcomes. A companion paper previously reported the effects of DE density and RPC supplementation on production and health outcomes. The objective of this study was to examine the effects of DE and RPC supplementation on the expression of hepatic oxidative, gluconeogenic, and lipid transport genes during the periparturient period. At 47 ± 6 d relative to calving (DRTC), 93 multiparous Holstein cows were randomly assigned in groups to dietary treatments in a 2 × 2 factorial of (1) excess energy (EXE) without RPC supplementation (1.63 Mcal of NEL/kg of dry matter; EXE-RPC); (2) maintenance energy (MNE) without RPC supplementation (1.40 Mcal of NEL/kg dry matter; MNE-RPC); (3) EXE with RPC supplementation (EXE+RPC); and (4) MNE with RPC supplementation (MNE+RPC). To achieve the objective of this research, liver biopsy samples were collected at -14, +7, +14, and +21 DRTC and analyzed for mRNA expression (n = 16/treatment). The interaction of DE × RPC decreased glucose-6-phosphatase and increased peroxisome proliferator-activated receptor α in MNE+RPC cows. Expression of cytosolic phosphoenolpyruvate carboxykinase was altered by the interaction of dietary treatments with reduced expression in EXE+RPC cows. A dietary treatment interaction was detected for expression of pyruvate carboxylase although means were not separated. Dietary treatment interactions did not alter expression of carnitine palmitoyltransferase 1A or microsomal triglyceride transfer protein. The 3-way interaction of DE × RPC × DRTC affected expression of carnitine palmitoyltransferase 1A, glucose-6-phosphatase, and peroxisome proliferator-activated receptor α and tended to affect cytosolic phosphoenolpyruvate carboxykinase. Despite previously reported independent effects of DE and RPC on production variables, treatments interacted to influence hepatic metabolism through altered gene expression.

The multivariate physical activity signature associated with metabolic health in children and youth: An International Children’s Accelerometry Database (ICAD) analysis

There is solid evidence for an association between physical activity and metabolic health outcomes in children and youth, but for methodological reasons most studies describe the intensity spectrum using only a few summary measures. We aimed to determine the multivariate physical activity intensity signature associated with metabolic health in a large and diverse sample of children and youth, by investigating the association pattern for the entire physical intensity spectrum. We used pooled data from 11 studies and 11,853 participants aged 5.8–18.4 years included in the International Children's Accelerometry Database. We derived 14 accelerometry-derived (ActiGraph) physical activity variables covering the intensity spectrum (from 0–99 to ≥8000 counts per minute). To handle the multicollinearity among these variables, we used multivariate pattern analysis to establish the associations with indices of metabolic health (abdominal fatness, insulin sensitivity, lipid metabolism, blood pressure). A composite metabolic health score was used as the main outcome variable. Associations with the composite metabolic health score were weak for sedentary time and light physical activity, but gradually strengthened with increasing time spent in moderate and vigorous intensities (up to 4000–5000 counts per minute). Association patterns were fairly consistent across sex and age groups, but varied across different metabolic health outcomes. This novel analytic approach suggests that vigorous intensity, rather than less intense activities or sedentary behavior, are related to metabolic health in children and youth.

Pre-operative aerobic exercise on metabolic health and surgical outcomes in patients receiving bariatric surgery: A pilot trial.

ObjectiveExamine if adding aerobic exercise to standard medical care (EX+SC) prior to bariatric surgery improves metabolic health in relation to surgical outcomes.MethodsFourteen bariatric patients (age: 42.3±2.5y, BMI: 45.1±2.5 kg/m2) met inclusion criteria and were match-paired to pre-operative SC (n = 7) or EX+SC (n = 7; walking 30min/d, 5d/wk, 65–85% HRpeak) for 30d. A 120min mixed meal tolerance test was performed pre- and post-intervention (~2d prior to surgery) to assess insulin sensitivity (Matsuda Index) and metabolic flexibility (indirect calorimetry). Aerobic fitness (VO2peak), body composition (BodPod), and adipokines (adiponectin, leptin) were also measured. Omental adipose tissue was collected during surgery to quantify gene expression of adiponectin and leptin, and operating time and length of hospital stay were recorded. ANOVA and Cohen’s d effect size (ES) was used to test group differences.ResultsSC tended to increase percent body fat (P = 0.06) after the intervention compared to EX+SC. Although SC and EX+SC tended to raise insulin sensitivity (P = 0.11), EX+SC enhanced metabolic flexibility (P = 0.01, ES = 1.55), reduced total adiponectin (P = 0.01, ES = 1.54) with no change in HMW adiponectin and decreased the length of hospital stay (P = 0.05) compared to SC. Albeit not statistically significant, EX+SC increased VO2peak 2.9% compared to a 5.9% decrease with SC (P = 0.24, ES = 0.91). This increased fitness correlated to shorter operating time (r = -0.57, P = 0.03) and length of stay (r = -0.58, P = 0.03). Less omental total adiponectin (r = 0.52, P = 0.09) and leptin (r = 0.58, P = 0.05) expression correlated with shorter operating time, and low leptin expression was linked to shorter length of stay (r = 0.70, P = 0.01), and low leptin expression was linked to shorter length of stay (r = 0.70, P = 0.01).ConclusionAdding pre-operative aerobic exercise to standard care may improve surgical outcomes through a fitness and adipose tissue derived mechanism.

Adipose depot-specific effects of 16weeks of pioglitazone on in vivo adipogenesis in women with obesity: a randomised controlled trial.

In vitro and rodent studies suggest that pioglitazone, a thiazolidinedione, can promote adipogenesis in adipose tissue (AT); however, there is a lack of in vivo studies in humans to support these findings. The objectives of this randomised, placebo-controlled, parallel-arm trial were to test if pioglitazone stimulates in vivo adipogenesis in the subcutaneous adipose tissue depots and if these measures were related to metabolic health outcomes in women with obesity. Forty-one healthy women with obesity (20 black; 21 white; 29 ± 6years; BMI 32.0 ± 1.7kg/m2; 44.0 ± 3.6% body fat) were randomised to consume 30mg/day of pioglitazone (n = 21) or placebo (n = 20) for 16weeks. SAS v9.4 was used to generate the block randomisation code sequence (stored in password-protected files) with a 1:1 allocation ratio. The participants and study staff involved in assessing and analysing data outcomes were blinded to the group assignments. The trial was conducted at Pennington Biomedical Research Center and ended in 2016. At baseline and post-intervention, subcutaneous abdominal (scABD) and femoral (scFEM) AT biopsies were collected, and in vivo cellular kinetics (primary endpoint of the trial) were assessed by an 8week labelling protocol of deuterium (2H) into the DNA of adipose cells. Body composition was measured by dual-energy x-ray absorptiometry (DXA), scABD and visceral AT (VAT) by MRI, ectopic fat by 1H-MRS, and insulin sensitivity by an OGTT. After the 16week intervention, there was a significant decrease in visceral fat (VAT:total abdominal AT [as a %]; p = 0.002) and an increase in the Matsuda index (i.e. improved insulin sensitivity; p = 0.04) in the pioglitazone group relative to the placebo group. A significant increase in the formation of new adipocytes was observed in the scFEM (Δ = 3.3 ± 1.6%; p = 0.04) but not the scABD depot (Δ = 2.0 ± 2.1%; p = 0.32) in the pioglitazone group relative to the placebo group. No serious adverse events were reported. Pioglitazone may elicit distinct differences in in vivo adipogenesis in subcutaneous adipose depots in women with obesity, with increased rates in the protective scFEM. Trial registration ClinicalTrials.gov NCT01748994 Funding This study was funded by R01DK090607, P30DK072476, and R03DK112006 from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. U54 GM104940 from the National Institute of General Medical Sciences of the National Institutes of Health. The Robert C. and Veronica Atkins Foundation. Graphical abstract.

INFANT BIRTH WEIGHT AND MATERNAL BMI: GENETIC VS EPIGENETIC CONTRIBUTIONS

The prevalence of obesity is increasing worldwide. Obesity has been shown to have a negative effect on reproductive outcomes in both spontaneous and IVF pregnancies. Studies on the effect of maternal BMI on pregnancy success rates in donor oocyte IVF cycles are conflicting. Few studies have examined the effect of maternal BMI on neonatal outcomes. While increasing maternal BMI is associated with increased infant birth weight in both spontaneous and autologous IVF pregnancies, it is unclear whether this is primarily a genetic or epigenetic phenomenon. To our knowledge, this is the first study to examine the effect of donor BMI on infant birth weight in donor oocyte IVF cycles. The purpose of this study is to assess the relationship between infant birth weight and recipient and donor BMI in donor oocyte IVF cycles in order to determine the relative genetic (oocyte) and epigenetic (endometrial) contributions. IRB-approved retrospective cohort study. We conducted a retrospective cohort study of 130 donor oocyte IVF cycles resulting in a singleton live birth at a single IVF center from 2012-2018. Pearson correlation coefficients were calculated to examine the relationship between recipient and donor BMI and infant birth weight. ANOVA was conducted to compare infant weight among various BMI subgroups. Linear regression was used to adjust for the type of embryo transfer (fresh vs frozen), diabetes or gestational diabetes status, hypertension in pregnancy, gestational age, and infant sex. Recipients were >35 years of age on average and predominantly Caucasian. Decreased ovarian reserve was the most common etiology of infertility diagnosis. Forty-four percent of recipients were normal weight and 56% were overweight or obese. The mean age of oocyte donors was 26.7 ± 3.15 (Range 20-39) years. Seventy-eight percent of oocyte donors were normal weight and oocyte donors were predominantly Caucasian. There was no correlation between recipient BMI and infant birth weight (r=0; p=0.99). In contrast, there was a weakly positive, but non-significant, correlation between donor BMI and infant birth weight (r=0.02; p=0.76). This relationship persisted after adjusting for potential confounders. Several studies have shown a clear association between maternal BMI and infant birth weight in autologous IVF cycles. In this study we examined the relative contribution of donor and recipient BMIs to infant birth weight in donor oocyte IVF cycles. The lack of correlation observed between recipient BMI and infant birth weight along with the weak although not significant correlation between donor BMI and infant birth weight suggests that oocyte or genetic components may play a greater role in infant birth weight compared to epigenetic or endometrial factors. This study is limited by the relatively small sample size and lack of information on paternal BMI. Future studies aim to examine metabolic health outcomes in oocyte donor-conceived children.

Exposures to phthalates and bisphenols in pregnancy and postpartum weight gain in a population-based longitudinal birth cohort

BackgroundExperimental evidence suggests that exposures to phthalates and bisphenols may interfere with processes related to glucose and lipid metabolism, insulin sensitivity, and body weight. Few studies have considered the possible influence of chemical exposures during pregnancy on maternal weight gain or metabolic health outcomes postpartum. ObjectiveTo examine the associations of early and mid-pregnancy bisphenol and phthalate urine concentrations with maternal weight gain 6 years postpartum. MethodsWe analyzed urine samples for bisphenol, phthalate and creatinine concentrations from early and mid-pregnancy in 1192 women in a large, population-based birth cohort in Rotterdam, the Netherlands, and examined postpartum weight gain using maternal anthropometrics before pregnancy and 6 years postpartum. We have used covariate-adjusted linear regressions to evaluate associations of early and mid-pregnancy bisphenols and phthalate metabolites with weight change. Mediator and interaction models have been used to assess the role of gestational weight gain and breastfeeding, respectively. Sensitivity analysis is performed among women without subsequent pregnancies. ResultsAmong all 1192 mothers included in the analysis, each log unit increase in the average bisphenol A and all assessed phthalate groupings were associated with increased maternal weight gain. As a proxy for phthalate exposure, each log unit increase in averaged phthalic acid was associated with 734 g weight gain (95% CI 273–1196 g) between pre-pregnancy and 6 years postpartum. Mediation by gestational weight gain was not present. Breastfeeding and ethnicity did not modify the effects. Stratification revealed these associations to be strongest among overweight and obese women. Among women without subsequent pregnancies (n = 373) associations of bisphenols, HMW phthalate metabolites and di-2-ethylhexylphthalate metabolites attenuated. For phthalic acid, LMW phthalate metabolites and di-n-octylphthalate metabolites associations increased. Similarly to the whole group, stratification yielded significant results among overweight and obese women. DiscussionIn a large population-based birth cohort, early and mid-pregnancy phthalate exposures are associated with weight gain 6 years postpartum, particularly among overweight and obese women. These data support ongoing action to replace phthalates with safer alternatives.

Patients With Prediabetes or Type 2 Diabetes Mellitus in a Medically Supervised Diet Program

The objective of this study was to examine and compare the health outcomes of patients with type 2 diabetes mellitus (DM) and patients with pre–diabetes mellitus (pre-DM) who completed a medically supervised very low calorie diet (MS-VLCD) program. A retrospective chart review was conducted to examine anthropometric, metabolic, and pharmacologic markers pre and post medically supervised program completion. Results indicated that of the 267 participants, 74.5% had pre-DM and 25.5% had type 2 DM. Both groups had a significant average reduction in clinical data points. MS-VLCDs can reduce HbA1c levels and improve metabolic health outcomes for patients with type 2 DM and pre-DM.

Non-nutritive Sweeteners and Their Associations with Obesity and Type 2 Diabetes.

Evidence linking the excessive consumption of nutritive sweeteners (NS) to adverse metabolic health outcomes has led to an increase in consumption of non-nutritive sweeteners (NNS), particularly among the obese and individuals with diabetes. NNS are characterized by having zero-to-negligible caloric load, while also having a sweet taste. They are utilized as a replacement for traditional NS to reduce energy intake and to limit carbohydrate-related negative health outcomes. However, recent studies have suggested that NNS may actually contribute to the development or worsening of metabolic diseases, including metabolic syndrome, obesity, type2 diabetes, and cardiovascular disease. Thus, it is imperative to understand the NNS efficacy and the relationship between NNS and metabolic diseases.

Metabolic Health Outcomes Following Nine Months Of Mild Caloric Restriction In Male Rats Adhering To A Western Or Vegan Diet

Metabolic Health Outcomes Following Nine Months Of Mild Caloric Restriction In Male Rats Adhering To A Western Or Vegan Diet

Healthy Eating Index, Genomics and Metabolomics; Insights into the Mechanisms Driving Dietary Pattern to Metabolic Disorders

Abstract Objectives Higher diet quality measured by healthy eating index (HEI) is associated with improved metabolic function, however the molecular basis remains unclear. We assessed associations between HEI and the metabolome in plasma and stool and explored interaction between genotype and HEI on circulating and gut metabolites. Methods We analyzed data from heathy individuals recruited to a single cross-sectional study visit (ABO Study, N = 75). HEI score was calculated from food frequency questionnaire. Metabolites in plasma (n = 800) and stool (n = 767) were measured at Metabolon Inc. Genotyping was performed by Exome chip (Illumina, CoreExome, N > 540,000 variants). Multivariable linear regression was used to assess the association of HEI score with metabolites adjusting for age, sex and body mass index. Plasma associations were replicated in the Fish oils and Adipose Inflammation Reduction (FAIR) study (N = 29). Metaboanalyst 4.0 was used to determine metabolic pathways. The interaction of single nucleotide polymorphisms (SNPs) and HEI on metabolites was tested using Plink. Results Metabolites in plasma (n = 74) and stool (n = 77) were associated with the HEI index (P < 0.05). One metabolite (N-acetyl-beta-alanine) overlapped between plasma (B = 0.003, P = 0.035) and stool (B = 0.008, P = 0.02). Glycine replicated between ABO (B = −0.001, P = 0.02) and FAIR studies (B = −0.01, P = 0.02). In plasma there was significant pathway enrichment in glycerophospholipid metabolism, glycine, serine-threonine metabolism and caffeine metabolism. In stool, histidine and caffeine metabolism pathways were significantly enriched. Significant (Pinteraction <5 × 10−8) interactions were observed between HEI and multiple independent SNPs for metabolites including circulating Valylleucine and gut Sedoheptulose-7-phosphate. Conclusions Diet quality, measured by HEI, is associated with differences in plasma and stool metabolites. The observed associations might aid understanding the link between food patterns and metabolic health outcomes. Further, our data support gene-nutrient interactions between HEI and SNPs contributing to plasma and gut metabolomic profiles. Future work will explore the relationship between HEI and gut microbiome composition. Funding Sources This project was supported by the National Institutes of Health.

Sleep Patterns in Pregnant Women with Obesity Differentially Affect Energy Intake and Metabolic Health

Abstract Objectives During pregnancy, altered glucose kinetics coupled with disrupted sleep increase the risk for adverse metabolic health outcomes. The aim of this prospective, observational study in pregnant women with obesity was to 1) examine sleep patterns in early and late pregnancy; and 2) identify how changes in sleep patterns impact gestational weight gain, energy intake and metabolic health. Methods In 52 healthy pregnant women with obesity (27.4 ± 0.6 y; BMI: 36.3 ± 0.7 kg/m,2), energy intake (intake-balance method), and changes in weight, fasting glucose, insulin, lipids and habitual sleep (5 consecutive nights via wrist worn accelerometer) were assessed from early (13,0–15,6 weeks) to late (35,0–36,6) pregnancy. A change to habitual sleep parameters (increase or decrease) was defined as ± one-half of the standard deviation of the 5-day measurement in early pregnancy. Results Results In early pregnancy, time spent in bed (TIB) was 9.40 ± 0.13 h and varied 1.61 ± 0.11 h across the 5 nights. Total sleep time (TST) and sleep efficiency (SE) significantly declined from early to late pregnancy 7.05 ± 0.13 h to 6.46 ± 0.15 h (P < 0.001) and 76 ± 0.1% to 71 ± 0.2% (P < 0.001), respectively. Women who increased TIB (11 of 52) had a significant decrease in plasma glucose −11.6 ± 4.3% (P < 0.01) and a trend towards lower insulin (−57.8 ± 33.5%; P = 0.09) and HOMA-IR (−72.4 ± 37.3%; P = 0.058) across pregnancy compared to women who decreased their TIB (13 of 52). Women who increased TIB had a significantly lower daily energy intake (−540 ± 163 kcal; P < 0.01) and tended to have less gestational weight gain (−146.7 ± 87.6 g/wk; P = 0.10). There was no difference in weight gain, energy intake or plasma markers between women who increased or decreased TST or SE. Conclusions Although sleep time and sleep quality decline throughout pregnancy, TIB had the greatest impact on metabolic health in pregnant women with obesity. Women spending more TIB consumed fewer calories. Our data suggest that the relationship between glucose metabolism and sleep during pregnancy is at least in part explained by lower energy intakes, possibly due to shorter eating windows. Studies that manipulate the eating window, independent of sleep timing are needed to understand the benefits to metabolic health for women during pregnancy. Funding Sources National Institutes of Health [R01DK099175].

0539 Are Short Sleepers Uncoupled Sleepers?

Abstract Introduction While short sleep durations (<7h/night) are associated with increased diabetes risk, there is limited evidence that increasing the habitual sleep duration of short sleepers is either feasible, or will reliably improve metabolic health outcomes. Furthermore, in the absence of insomnia disorder, it remains unclear whether habitual short sleep mainly reflects a genetic predisposition or a lifestyle choice. In a randomized controlled study we delivered a sleep extension protocol based on CBTi principles to overweight ‘short sleepers’ at increased risk of Type II diabetes. Methods 18 male short sleepers (Mage=41.4; MBMI=29.57; baseline mean TST=5.8 h/ night) with no complaints of insomnia were randomized to the sleep extension intervention or control condition (printed sleep hygiene advice). The 6-week intervention commenced with personalized sleep re-scheduling negotiated in a 60-minute 1-to-1 session, and supported by elements of sleep hygiene, stimulus control, relaxation and cognitive strategies. Outcomes included sleep duration (actigraphy), fasting insulin, Mean Amplitude of Glycemic Excursions (MAGE) from continuous glucose monitoring, and blood pressure. Data were analyzed in linear fixed effects models including time, group and baselines values. Results Adherence to the 6-week protocol was high. Relative to controls (n=8), intervention participants (n = 10) showed a significant increase in TST (95%CI 46.91min, 101.64min, p<0.001; MDiff = 79.4min, p<0.001) and significant reductions in fasting insulin (95%CI -32.08 pmol/L, -.97.0 pmol/L; p=0.04; MDiff = -10.2 pmol/L, p=0.06); MAGE (95%CI -0.77, -0.08, p=0.02; MDiff -0.35, p=0.05) and diastolic (95%CI -22, -5, p=0.004; MDiff=-12, p=0.004); and systolic blood pressure (95%CI -20, -2, p=0.03; MDiff=-10, p=0.006). Conclusion CBTi-based sleep extension protocols offer feasible and effective lifestyle interventions in the management of metabolic health in overweight short sleepers who fit published categorization of non-complaining poor sleepers with an undeveloped insomnia identity whose subjective sleep experience and objective sleep characteristics are ‘uncoupled’. Support School of Sport, Exercise and Health Sciences, Loughborough University

Individual housing of male C57BL/6J mice after weaning impairs growth and predisposes for obesity.

For (metabolic) research models using mice, singly housing is widely used for practical purposes to study e.g. energy balance regulation and derangements herein. Mouse (social) housing practices could however influence study results by modulating (metabolic) health outcomes. To study the effects of the social housing condition, we assessed parameters for energy balance regulation and proneness to (diet induced) obesity in male C57Bl/6J mice that were housed individually or socially (in pairs) directly after weaning, both at standard ambient temperature of 21°C. During adolescence, individually housed mice had reduced growth rate, while energy intake and energy expenditure were increased compared to socially housed counterparts. At 6 weeks of age, these mice had reduced lean body mass, but significantly higher white adipose tissue mass compared to socially housed mice, and higher UCP-1 mRNA expression in brown adipose tissue. During adulthood, body weight gain of individually housed animals exceeded that of socially housed mice, with elevations in both energy intake and expenditure. At 18 weeks of age, individually housed mice showed higher adiposity and higher mRNA expression of UCP-1 in inguinal white but not in brown adipose tissue. Exposure to an obesogenic diet starting at 6 weeks of age further amplified body weight gain and adipose tissue deposition and caused strong suppression of inguinal white adipose tissue mRNA UCP-1 expression. This study shows that post-weaning individual housing of male mice impairs adolescent growth and results in higher susceptibility to obesity in adulthood with putative roles for thermoregulation and/or affectiveness.

The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds.

The purpose of this project report is to introduce the European “GOLIATH” project, a new research project which addresses one of the most urgent regulatory needs in the testing of endocrine-disrupting chemicals (EDCs), namely the lack of methods for testing EDCs that disrupt metabolism and metabolic functions. These chemicals collectively referred to as “metabolism disrupting compounds” (MDCs) are natural and anthropogenic chemicals that can promote metabolic changes that can ultimately result in obesity, diabetes, and/or fatty liver in humans. This project report introduces the main approaches of the project and provides a focused review of the evidence of metabolic disruption for selected EDCs. GOLIATH will generate the world’s first integrated approach to testing and assessment (IATA) specifically tailored to MDCs. GOLIATH will focus on the main cellular targets of metabolic disruption—hepatocytes, pancreatic endocrine cells, myocytes and adipocytes—and using an adverse outcome pathway (AOP) framework will provide key information on MDC-related mode of action by incorporating multi-omic analyses and translating results from in silico, in vitro, and in vivo models and assays to adverse metabolic health outcomes in humans at real-life exposures. Given the importance of international acceptance of the developed test methods for regulatory use, GOLIATH will link with ongoing initiatives of the Organisation for Economic Development (OECD) for test method (pre-)validation, IATA, and AOP development.

MON-022 Dissecting the Interplay Between Diet and PCOS Pathology on Gut Microbiota in a PCOS Mouse Model

The gut microbiome has been implicated in the development of metabolic disorders such as obesity and type-2 diabetes, and more recently polycystic ovary syndrome (PCOS). PCOS is a heterogeneous disorder with reproductive, endocrine and metabolic irregularities, and clinical and animal studies have reported that PCOS causes a decrease in microbial diversity and composition. Diet is an important regulator of the gut microbiome, and a recent study identified that alterations in macronutrient balance impact gut microbial communities which correlate with different metabolic health outcomes (1). We have identified that macronutrient balance impacts the development of PCOS traits. Therefore, to investigate the interplay between macronutrient balance and a PCOS environment on the gut microbiome, we analyzed the intestinal microbiome from fecal pellets of control and DHT-induced PCOS mice exposed to 10 different diets that varied systematically in protein (P), carbohydrate (C) and fat (F) content. The amount of dietary P, C and F consumed significantly altered alpha and beta diversity of the gut microbiota of pooled control and PCOS mice (P<0.0001). Alpha diversity between control and PCOS mice on the same diet did not differ significantly, and hence was only affected by diet composition. However, beta diversity was significantly altered between control and PCOS mice (P<0.05). We performed DESeq2 analysis and identified an operational taxonomic unit (OTU) within Bacteroides (OTU3) to be the most differentially abundant OTU between control and PCOS mice, with a significant decrease in PCOS mice compared to controls (control: 7.88 and PCOS: 5.38; fold change = 1.464; P<0.0001). The consensus sequence of Bacteroides OTU3 was found to share 99.2% similarity to Bacteroides acidifaciens. B. acidifaciens is associated with obesity with elevated levels reported to prevent the onset of obesity (2). Thus, we then investigated the influence of P, C and F on the relative abundance of Bacteroides OTU3 and revealed an association with C consumption, with increasing levels of C leading to increased levels of Bacteroides OTU3 (Carb: r= 0.22, p=0.0028, q=0.015). These findings demonstrate that diet exerts a stronger influence over the gut microbiome than PCOS pathology. However, the hyperandrogenic PCOS environment does lead to changes in gut microbiota beta diversity, with a specific decrease in an obesity-associated (2) Bacteroides species in PCOS mice that is also responsive to levels of C consumption. Reference: (1) Holmes et al., Cell Metabolism. 2017; 25(1): 140-151. (2) Yang et al., Mucosal Immunology. 2017, 10 (1), 104-116.

Gestational Diabetes Mellitus Is Associated with Age-Specific Alterations in Markers of Adiposity in Offspring: A Narrative Review.

Maternal hyperglycemia alters an offspring’s metabolic health outcomes, as demonstrated by the increased risk for obesity, impaired glucose handling and diabetes from early childhood onwards. Infant growth patterns are associated with childhood adiposity and metabolic health outcomes and, as such, can be used as potential markers to detect suboptimal metabolic development at an early age. Hence, we aimed to assess whether gestational diabetes mellitus (GDM) has an impact on offspring growth trajectories. Outcomes included weight gain (WG), body mass index (BMI), and skin fold thickness (SFT) measured at least at two time points from birth to later childhood. In addition, we explored the role of early life pre- and post-natal nutritional modifiable factors on longitudinal growth in infants of mother with GDM (GDM–F1). Despite the large heterogeneity of the studies, we can still conclude that GDM seems to be associated with altered growth outcomes in the offspring. More specifically, these alterations in growth outcomes seem to be rather time-specific. Increased SFT were reported particularly at birth, with limited information on reporting SFT between 2–5 y, and increased adiposity, measured via SFT and BMI, appeared mainly in later childhood (5–10 y). Studies evaluating longitudinal growth outcomes suggested a potential role of early life nutritional modifiable factors including maternal nutrition and breastfeeding. These may impact the cycle of adverse metabolic health by attenuating growth outcome alterations among GDM–F1. Conclusions: Timely diagnoses of growth deviations in infancy are crucial for early identification of GDM–F1 who are at risk for childhood overweight and metabolic disease development.

Evidence Relating to Environmental Noise Exposure and Annoyance, Sleep Disturbance, Cardio-Vascular and Metabolic Health Outcomes in the Context of IGCB (N): A Scoping Review of New Evidence.

WHO published the Environmental Noise Guidelines for the European Region in 2018, based on seven systematic reviews including studies published between 2000 and 2014. Since then, new studies were published. At the request of the UK Department for Environment, Food and Rural Affairs (DEFRA), a review on annoyance, sleep disturbance, cardiovascular and metabolic effects in relation to environmental noise was prepared. The aim was to advise the Interdepartmental Group on Costs and Benefits Noise Subject Group (IGCB(N)) whether this new evidence warrants an update of their recommendations. Four databases for observational studies were screened and data were extracted on design, type and measurements of exposures and outcomes and confounders and their associations. The quality of the studies was indirectly assessed for cardiovascular and metabolic effects by only including studies with a case control or cohort design. For studies on annoyance and sleep disturbance, the risk of bias was expressed in exposure misclassification, selective participation and confounding. The update yielded 87 papers, pertaining to 108 new studies of which 40 new studies were on annoyance, 42 on sleep disturbance and 26 concerning cardiovascular and metabolic effects. The number, size and quality of the new studies suggest new meta-analyses could be undertaken over the sources and effects included in the WHO reviews.

Dietary Fibre May Mitigate Sarcopenia Risk: Findings from the NU-AGE Cohort of Older European Adults.

Sarcopenia is characterised by a progressive loss of skeletal muscle mass and physical function as well as related metabolic disturbances. While fibre-rich diets can influence metabolic health outcomes, the impact on skeletal muscle mass and function is yet to be determined, and the moderating effects by physical activity (PA) need to be considered. The aim of the present study was to examine links between fibre intake, skeletal muscle mass and physical function in a cohort of older adults from the NU-AGE study. In 981 older adults (71 ± 4 years, 58% female), physical function was assessed using the short-physical performance battery test and handgrip strength. Skeletal muscle mass index (SMI) was derived using dual-energy X-ray absorptiometry (DXA). Dietary fibre intake (FI) was assessed by 7-day food record and PA was objectively determined by accelerometery. General linear models accounting for covariates including PA level, protein intake and metabolic syndrome (MetS) were used. Women above the median FI had significantly higher SMI compared to those below, which remained in fully adjusted models (24.7 ± 0.2% vs. 24.2 ± 0.1%, p = 0.011, η2p = 0.012). In men, the same association was only evident in those without MetS (above median FI: 32.4 ± 0.3% vs. below median FI: 31.3 ± 0.3%, p = 0.005, η2p = 0.035). There was no significant impact of FI on physical function outcomes. The findings from this study suggest a beneficial impact of FI on skeletal muscle mass in older adults. Importantly, this impact is independent of adherence to guidelines for protein intake and PA, which further strengthens the potential role of dietary fibre in preventing sarcopenia. Further experimental work is warranted in order to elucidate the mechanisms underpinning the action of dietary fibre on the regulation of muscle mass.

Resistant Starch Has No Effect on Appetite and Food Intake in Individuals with Prediabetes

BackgroundType 2 resistant starch (RS2) has been shown to improve metabolic health outcomes and may increase satiety and suppress appetite and food intake in humans. ObjectiveThis study assessed whether 12 weeks of daily RS2 supplementation could influence appetite perception, food intake, and appetite-related gut hormones in adults with prediabetes, relative to the control (CTL) group. DesignThe study was a randomized controlled trial and analysis of secondary study end points. Participants/settingSixty-eight adults (body mass index ≥27) aged 35 to 75 years with prediabetes were enrolled in the study at Pennington Biomedical Research Center (2012 to 2016). Fifty-nine subjects were included in the analysis. InterventionParticipants were randomized to consume 45 g/day of high-amylose maize (RS2) or an isocaloric amount of the rapidly digestible starch amylopectin (CTL) for 12 weeks. Main outcome measuresSubjective appetite measures were assessed via visual analogue scale and the Eating Inventory; appetite-related gut hormones (glucagon-like peptide 1, peptide YY, and ghrelin) were measured during a standard mixed-meal test; and energy and macronutrient intake were assessed by a laboratory food intake (buffet) test, the Remote Food Photography Method, and SmartIntake app. Statistical analyses performedData were analyzed using linear mixed models, adjusting for treatment group and time as fixed effects, with a significance level of α=.05. ResultsRS2 had no effect on subjective measures of appetite, as assessed by visual analogue scale (P>0.05) and the Eating Inventory (P≥0.24), relative to the CTL group. There were no effects of RS2 supplementation on appetite-related gut hormones, including glucagon-like peptide 1 (P=0.61), peptide YY (P=0.34), and both total (P=0.26) and active (P=0.47) ghrelin compared with the CTL. RS2 had no effect on total energy (P=0.30), carbohydrate (P=0.11), protein (P=0.64), or fat (P=0.37) consumption in response to a buffet meal test, relative to the CTL. In addition, total energy (P=0.40), carbohydrate (P=0.15), protein (P=0.46), and fat (P=0.53) intake, as quantified by the Remote Food Photography Method, were also unaffected by RS2, relative to the CTL. ConclusionsRS2 supplementation did not increase satiety or reduce appetite and food intake in adults with prediabetes.

Deviations from normal bedtimes are associated with short-term increases in resting heart rate

Despite proper sleep hygiene being critical to our health, guidelines for improving sleep habits often focus on only a single component, namely, sleep duration. Recent works, however, have brought to light the importance of another aspect of sleep: bedtime regularity, given its ties to cognitive and metabolic health outcomes. To further our understanding of this often-neglected component of sleep, the objective of this work was to investigate the association between bedtime regularity and resting heart rate (RHR): an important biomarker for cardiovascular health. Utilizing Fitbit Charge HRs to measure bedtimes, sleep and RHR, 255,736 nights of data were collected from a cohort of 557 college students. We observed that going to bed even 30 minutes later than one’s normal bedtime was associated with a significantly higher RHR throughout sleep (Coeff +0.18; 95% CI: +0.11, +0.26 bpm), persisting into the following day and converging with one’s normal RHR in the early evening. Bedtimes of at least 1 hour earlier were also associated with significantly higher RHRs throughout sleep; however, they converged with one’s normal rate by the end of the sleep session, not extending into the following day. These observations stress the importance of maintaining proper sleep habits, beyond sleep duration, as high variability in bedtimes may be detrimental to one’s cardiovascular health.