Anthropometric measures, predicted visceral adipose tissue and biomarkers of chronic inflammation.

BACKGROUND: Evidence has linked low-grade systemic inflammation and visceral adipose tissue (VAT) with development of chronic conditions. Cytokines and select proteins released by VAT may promote a low-grade inflammatory response. A number of equations have been developed to estimate VAT levels. In this study, we compared predicted VAT equation relationships with biomarkers of inflammation. METHODS: This was a cross-sectional study of 2038 men and women aged 46-73 years. Correlation and linear regression analyses were performed to examine inflammatory biomarker relationships with four commonly assessed anthropometric measures and 10 predicted VAT equations. RESULTS: Compared with anthropometric measures, predicted VAT equations were found to explain a greater proportion of variance in CRP (R2 = .075, p = .001), IL-6 (R2 = .060, p = .001), TNF-α (R2 = .017, p = .005), resistin (R2 = .011, p = .012), monocyte (R2 = .027, p = .001), eosinophil (R2 = .012, p = .01) and basophil (R2 = .015, p = .002) levels in males, and a greater variance in concentrations of C3 (R2 = .175, p = .001), IL-6 (R2 = .090, p = .001), TNF-α (R2 = .036, p = .001), adiponectin (R2 = .121, p = .001), the adiponectin-to-leptin ratio (R2 = .444, p = .001), resistin (R2 = .025, p = .001), white blood cell count (R2 = .057, p = .001), neutrophils (R2 = .061, p = .001) and lymphocytes (R2 = .020, p = .001) in females. CONCLUSION: Equations for assessing VAT levels might be useful to characterise metabolic health. Further studies that examine predicted VAT relationships with disease and mortality outcomes are warranted.

Plant-based diet adherence is associated with metabolic health status in adults living with and without obesity.

PURPOSE: Metabolic health phenotypes exist across the body mass index spectrum. Diet may be an important modifiable risk factor, yet limited research exists on dietary patterns in this context. We investigated associations between dietary patterns, reflecting dietary quality, healthfulness and inflammatory potential, and metabolic health phenotypes in adults living with and without obesity. METHODS: This cross-sectional study included 2,040 middle- to older-aged men and women randomly selected from a large primary care centre. The Dietary Approaches to Stop Hypertension score, Healthy Eating Index, Dietary Inflammatory Index, overall, healthful and unhealthful plant-based dietary indices and Nutri-Score were derived from validated food frequency questionnaires. Descriptive and logistic regression analyses were used to examine diet score relationships with metabolic health phenotypes (Metabolically Healthy/Unhealthy Obese (MHO/MUO) and Non-Obese (MHNO/MUNO)), defined using three separate metabolic health definitions, each capturing different aspects of metabolic health. RESULTS: In fully adjusted models, higher unhealthful plant-based dietary scores were associated with a lower likelihood of MHO (OR = 0.96, 95% CI: 0.93-1.00, p = 0.038) and MHNO (OR = 0.97, 95% CI: 0.95-0.99, p = 0.006). Higher Nutri-Score values were associated with an increased likelihood of MHNO (OR = 1.06, 95% CI: 1.01-1.13, p = 0.033). CONCLUSION: These findings provide evidence that more unhealthful plant-based diets may be linked with unfavourable metabolic health status, irrespective of BMI.

Maternal and Paternal Dietary Quality and Dietary Inflammation Associations with Offspring DNA Methylation and Epigenetic Biomarkers of Aging in the Lifeways Cross-Generation Study.

BACKGROUND: Early-life nutritional exposures may contribute to offspring epigenetic modifications. However, few studies have evaluated parental dietary quality effects on offspring DNA methylation (DNAm). OBJECTIVES: We aim to fill this gap by elucidating the influence of maternal and paternal whole-diet quality and inflammatory potential on offspring DNAm in the Lifeways Cross-generation cohort. METHODS: Families (n = 1124) were recruited around 16 weeks of gestation in the Republic of Ireland between 2001 and 2003. Maternal dietary intake during the first trimester and paternal diet during the 12 previous months were assessed with an FFQ. Parental dietary inflammatory potential and quality were determined using the energy-adjusted Dietary Inflammatory Index (E-DII), the Healthy Eating Index-2015 (HEI-2015), and the maternal DASH score. DNAm in the saliva of 246 children at age nine was measured using the Illumina Infinium HumanMethylationEPIC array. DNAm-derived biomarkers of aging, the Pediatric-Buccal-Epigenetic clock and DNAm estimator of telomere length, were calculated. Parental diet associations with the DNAm concentrations of 850K Cytosine-phosphate-guanine sites (CpG sites) and with DNAm-derived biomarkers of aging were examined using an epigenome-wide association study and linear regressions, respectively. RESULTS: Maternal HEI-2015 scores were inversely associated with DNAm at CpG site (cg21840035) located near the PLEKHM1 gene, whose functions involve regulation of bone development (ß = -0.0036, per 1 point increase in the score; P = 5.6 × 10-8). Higher paternal HEI-2015 score was related to lower methylation at CpG site (cg22431767), located near cell signaling gene LUZP1 (ß = -0.0022, per 1 point increase in the score, P = 4.1 × 10-8). There were no associations with parental E-DII and DASH scores, and no evidence of major effects on biomarkers of aging. CONCLUSIONS: Parental dietary quality in the prenatal period, evaluated by the HEI-2015, may influence offspring DNAm during childhood. Further research to improve our understanding of parental nutritional programming is warranted.

Plant-based dietary indices and biomarkers of chronic low-grade inflammation: a cross-sectional analysis of adults in Ireland.

PURPOSE: There is increasing interest in the health benefits of plant-based diets (PBDs). Evidence reports favourable associations with inflammatory profiles and reduced cardiovascular disease risk. However, limited studies have examined relationships between PBD indices (PDIs) and inflammatory biomarkers. We explored overall PDI, healthful PDI (hPDI) and unhealthful PDI (uPDI) associations with inflammatory biomarker profiles. METHODS: This cross-sectional analysis included 1986 middle- to older-aged adults from the Mitchelstown Cohort. PDI scores were calculated using validated food frequency questionnaires. PDI score associations with inflammatory biomarkers were assessed via linear regression analysis, with adjustment for potential confounders. RESULTS: Comparison of quintiles (Q5 vs Q1) revealed lower concentrations of C-reactive protein (CRP), interleukin 6 (IL-6), white blood cells (WBCs), neutrophils and monocytes, and the leptin-to-adiponectin ratio (PDI and hPDI P < 0.05); lower leptin (PDI, P < 0.05), and complement component 3 (C3), tumour necrosis factor alpha (TNF-α), plasminogen activator inhibitor 1, lymphocytes and eosinophils (hPDI, P < 0.05); and higher concentrations of adiponectin (PDI and hPDI, P < 0.05). Conversely, higher concentrations of C3, CRP, IL-6, TNF-α, resistin, WBCs, neutrophils, lymphocytes, monocytes and eosinophils, and the neutrophil-to-lymphocyte ratio, and lower adiponectin concentrations were observed comparing uPDI quintiles (P < 0.05). In fully adjusted regression models, higher hPDI scores were associated with lower concentrations of C3, TNF-α, WBCs, neutrophils and monocytes (all P < 0.01). Higher uPDI scores were associated with higher C3 and TNF-α concentrations (all P < 0.01). CONCLUSION: This study provides evidence that a more healthful PBD is associated with a more favourable inflammatory profile and that a more unhealthful PBD is associated with the reverse.

Maternal diet in pregnancy and child's respiratory outcomes: an individual participant data meta-analysis of 18 000 children.

RATIONALE: Severe fetal malnutrition has been related to an increased risk of respiratory diseases later in life, but evidence for the association of a suboptimal diet during pregnancy with respiratory outcomes in childhood is conflicting. We aimed to examine whether a pro-inflammatory or low-quality maternal diet during pregnancy was associated with child's respiratory health. METHODS: We performed an individual participant meta-analysis among 18 326 mother-child pairs from seven European birth cohorts. Maternal pro-inflammatory and low-quality diets were estimated by energy-adjusted Dietary Inflammatory Index (E-DII) and Dietary Approaches to Stop Hypertension (DASH) scores. Preschool wheezing and school-age asthma were measured using questionnaires and lung function by spirometry. RESULTS: After adjustment for lifestyle and sociodemographic factors, we observed that a higher maternal E-DII score (a more pro-inflammatory diet) during pregnancy was associated only with a lower forced vital capacity (FVC) in children (z-score difference -0.05, 95% CI -0.08- -0.02, per interquartile range increase). No linear associations of the maternal E-DII or DASH score with child's wheezing or asthma were observed. In an exploratory examination of the extremes, a very low DASH score (<10th percentile) (a very low dietary quality) was associated with an increased risk of preschool wheezing and a low forced expiratory volume in 1 s/FVC (z-score <-1.64) (OR 1.20, 95% CI 1.06-1.36 and z-score difference 1.40, 95% CI 1.06-1.85, compared to ≥10th percentile), with corresponding population attributable risk fractions of 1.7% and 3.3%, respectively. CONCLUSION: The main results from this individual participant data meta-analysis do not support the hypothesis that maternal pro-inflammatory or low-quality diet in pregnancy are related to respiratory diseases in childhood.

Associations between a protective lifestyle behaviour score and biomarkers of chronic low-grade inflammation: a cross-sectional analysis in middle-to-older aged adults.

BACKGROUND/OBJECTIVES: Certain lifestyle behaviours may have a protective effect against low-grade systemic inflammation, which is linked to chronic disease. Our objective was to examine associations between a five-component protective lifestyle behaviour (PLB) score and a range of pro-inflammatory cytokines, adipocytokines, acute-phase response proteins, coagulation factors and white blood cells. SUBJECTS/METHODS: This was a cross-sectional study of 2045 middle-to-older aged men and women. Low-risk behaviours included never smoking, moderate alcohol intake, moderate-to-vigorous physical activity, a high-quality diet (upper 40% Dietary Approaches to Stop Hypertension score) and a normal body mass index (BMI) (18.5-24.9 kg/m2). Linear and logistic regression analyses tested individual protective behaviour and PLB score associations with biomarkers. RESULTS: Analysis of individual low-risk behaviours revealed varied associations depending on the biomarker, with normal BMI showing the most consistent associations. Examination of the PLB score showed that compared to subjects with 4-5 protective behaviours, those with 0-1 protective behaviours had 1.4-3.8 increased odds of having a less favourable inflammatory profile. Following adjustment for BMI, significant trend relationships were observed between the number of protective behaviours and complement component 3 (P < 0.001), c-reactive protein (P < 0.001), interleukin 6 (P < 0.001), tumour necrosis factor alpha (P < 0.001) and white blood cell count (P < 0.001) concentrations. CONCLUSIONS: These results suggest a cumulative protective effect of healthy lifestyle behaviours against systemic inflammation in middle-to-older aged adults which is independent of having a healthy body weight.

Maternal C3 complement and C-reactive protein and pregnancy and fetal outcomes: A secondary analysis of the PEARS RCT-An mHealth-supported, lifestyle intervention among pregnant women with overweight and obesity.

OBJECTIVES: Elevated circulating levels of complement component 3 (C3) and C-reactive protein (CRP) have been linked with adverse pregnancy outcomes. Lifestyle interventions may hold potential to ameliorate these effects. We investigated the effect of an antenatal healthy lifestyle intervention on maternal C3 and CRP concentrations and assessed their relationship with maternal and fetal metabolic markers and outcomes. STUDY DESIGN: Secondary analysis of data from the Pregnancy Exercise And Nutrition Research Study (PEARS) randomized controlled trial. METHODS: Women (n = 406) with C3 and CRP concentrations determined in early pregnancy (14-16 weeks) and/or late pregnancy (28-weeks) with corresponding fasting glucose, insulin, c-peptide, and lipid profiles were included in the analysis. Pregnancy outcomes included: diagnoses of gestational diabetes (GDM), pre-eclampsia (PET) or pregnancy induced hypertension (PIH), pre-term birth (delivery < 37 weeks), low birth weight (<2500 g), small-for-gestational age (SGA) defined using < 5th or 10th centile for birthweight and cord blood measures of glucose and lipid metabolism. T-tests investigated changes in C3 and CRP over time. Chi-square, Pearson's' correlations and multiple regression investigated relationships with outcomes. RESULTS: The PEARS intervention did not influence maternal C3 or CRP concentrations in pregnancy. There was no relationship between CRP concentrations and any maternal or infant outcome. Women who developed GDM had higher C3 concentrations in early (p = 0.01) and late pregnancy (p = 0.02). Women who developed PIH/PET had lower C3 concentrations in early (p = 0.02), but not late (p = 0.10) pregnancy. Maternal C3 concentrations in early pregnancy were a small but significant predictor of maternal insulin concentrations in early (ß = 0.40, 95% CI 0.27, 0.53; p < 0.001) and late (ß = 0.30, 95% CI 0.17, 0.43p < 0.001) pregnancy, early total cholesterol (TC), and both early and late triglycerides, LDL and HDL Cholesterol concentrations (all p < 0.001). Women who delivered SGA babies (<10th centile) had lower C3 concentrations than women who did not in both early (p < 0.001) and late pregnancy (p = 0.01). No relationship between maternal C3 or CRP and fetal glucose concentrations or lipid profiles was observed. CONCLUSION: Maternal C3 may play a role in multiple adverse pregnancy outcomes including cardiometabolic ill-health. Further research on this, and strategies to reduce C3 in a pregnant population, are warranted.

Dietary score associations with markers of chronic low-grade inflammation: a cross-sectional comparative analysis of a middle- to older-aged population.

PURPOSE: To assess relationships between the Dietary Approaches to Stop Hypertension (DASH), Mediterranean Diet (MD), Dietary Inflammatory Index (DII®) and Energy-adjusted DII (E-DII™) scores and pro-inflammatory cytokines, adipocytokines, acute-phase response proteins, coagulation factors and white blood cells. METHODS: This was a cross-sectional study of 1862 men and women aged 46-73 years, randomly selected from a large primary care centre in Ireland. DASH, MD, DII and E-DII scores were derived from validated food frequency questionnaires. Correlation and multivariate-adjusted linear regression analyses with correction for multiple testing were performed to examine dietary score relationships with biomarker concentrations. RESULTS: In fully adjusted models, higher diet quality or a less pro-inflammatory diet was associated with lower concentrations of c-reactive protein, neutrophils (all dietary scores), complement component 3 [C3], interleukin 6 [IL-6], tumour necrosis factor-alpha [TNF-α], white blood cell count [WBC], the neutrophil-to-lymphocyte ratio [NLR] (DASH, DII and E-DII), monocytes (DASH and DII) and resistin (DII and E-DII). After accounting for multiple testing, relationships with C3 (DASH: ß = - 2.079, p = .011 and DII: ß = 2.521, p = .036), IL-6 (DASH: ß = - 0.063, p = .011), TNF-α (DASH: ß = - 0.027, p = .034), WBC (DASH: ß = - 0.028, p = .001 and DII: ß = 0.029, p = .02), neutrophils (DASH: ß = - 0.041, p = .001; DII: ß = 0.043, p = .007; E-DII: ß = 0.029, p = .009) and the NLR (DASH: ß = - 0.035, p = .011) persisted. CONCLUSIONS: Better diet quality, determined by the DASH score, may be more closely associated with inflammatory biomarkers related to health in middle- to older-aged adults than the MD, DII and E-DII scores.

Associations of maternal dietary inflammatory potential and quality with offspring birth outcomes: An individual participant data pooled analysis of 7 European cohorts in the ALPHABET consortium.

BACKGROUND: Adverse birth outcomes are major causes of morbidity and mortality during childhood and associate with a higher risk of noncommunicable diseases in adult life. Maternal periconception and antenatal nutrition, mostly focusing on single nutrients or foods, has been shown to influence infant birth outcomes. However, evidence on whole diet that considers complex nutrient and food interaction is rare and conflicting. We aim to elucidate the influence of whole-diet maternal dietary inflammatory potential and quality during periconceptional and antenatal periods on birth outcomes. METHODS AND FINDINGS: We harmonized and pooled individual participant data (IPD) from up to 24,861 mother-child pairs in 7 European mother-offspring cohorts [cohort name, country (recruitment dates): ALSPAC, UK (1 April 1991 to 31 December 1992); EDEN, France (27 January 2003 to 6 March 2006); Generation R, the Netherlands (1 April 2002 to 31 January 2006); Lifeways, Ireland (2 October 2001 to 4 April 2003); REPRO_PL, Poland (18 September 2007 to 16 December 2011); ROLO, Ireland (1 January 2007 to 1 January 2011); SWS, United Kingdom (6 April 1998 to 17 December 2002)]. Maternal diets were assessed preconceptionally (n = 2 cohorts) and antenatally (n = 7 cohorts). Maternal dietary inflammatory potential and quality were ranked using the energy-adjusted Dietary Inflammatory Index (E-DII) and Dietary Approaches to Stop Hypertension (DASH) index, respectively. Primary outcomes were birth weight and gestational age at birth. Adverse birth outcomes, i.e., low birth weight (LBW), macrosomia, small-for-gestational-age (SGA), large-for-gestational-age (LGA), preterm and postterm births were defined according to standard clinical cutoffs. Associations of maternal E-DII and DASH scores with infant birth outcomes were assessed using cohort-specific multivariable regression analyses (adjusted for confounders including maternal education, ethnicity, prepregnancy body mass index (BMI), maternal height, parity, cigarettes smoking, and alcohol consumption), with subsequent random-effects meta-analyses. Overall, the study mothers had a mean ± SD age of 29.5 ± 4.9 y at delivery and a mean BMI of 23.3 ± 4.2 kg/m2. Higher pregnancy DASH score (higher dietary quality) was associated with higher birth weight [ß(95% CI) = 18.5(5.7, 31.3) g per 1-SD higher DASH score; P value = 0.005] and head circumference [0.03(0.01, 0.06) cm; P value = 0.004], longer birth length [0.05(0.01, 0.10) cm; P value = 0.010], and lower risk of delivering LBW [odds ratio (OR) (95% CI) = 0.89(0.82, 0.95); P value = 0.001] and SGA [0.87(0.82, 0.94); P value < 0.001] infants. Higher maternal prepregnancy E-DII score (more pro-inflammatory diet) was associated with lower birth weight [ß(95% CI) = -18.7(-34.8, -2.6) g per 1-SD higher E-DII score; P value = 0.023] and shorter birth length [-0.07(-0.14, -0.01) cm; P value = 0.031], whereas higher pregnancy E-DII score was associated with a shorter birth length [-0.06(-0.10, -0.01) cm; P value = 0.026] and higher risk of SGA [OR(95% CI) = 1.18(1.11, 1.26); P value < 0.001]. In male, but not female, infants higher maternal prepregnancy E-DII was associated with lower birth weight and head circumference, shorter birth length, and higher risk of SGA (P-for-sex-interaction = 0.029, 0.059, 0.104, and 0.075, respectively). No consistent associations were observed for maternal E-DII and DASH scores with gestational age, preterm and postterm birth, or macrosomia and LGA. Limitations of this study were that self-reported dietary data might have increased nondifferential measurement error and that causality cannot be claimed definitely with observational design. CONCLUSIONS: In this cohort study, we observed that maternal diet that is of low quality and high inflammatory potential is associated with lower offspring birth size and higher risk of offspring being born SGA in this multicenter meta-analysis using harmonized IPD. Improving overall maternal dietary pattern based on predefined criteria may optimize fetal growth and avert substantial healthcare burden associated with adverse birth outcomes.

Maternal dietary quality, inflammatory potential and childhood adiposity: an individual participant data pooled analysis of seven European cohorts in the ALPHABET consortium.

BACKGROUND: Mounting evidence suggests that maternal diet influences pregnancy and birth outcomes, but its contribution to the global epidemic of childhood obesity has not as yet been definitively characterized. We investigated whether maternal whole diet quality and inflammatory potential influence childhood adiposity. METHODS: We harmonized and pooled individual participant data from 16,295 mother-child pairs in seven European birth cohorts. Maternal pre-, early-, late-, and whole-pregnancy (any time during pregnancy) dietary quality and inflammatory potential assessed with the Dietary Approaches to Stop Hypertension (DASH) score and the energy-adjusted Dietary Inflammatory Index (E-DII™) score, respectively. Primary outcome was childhood overweight and obesity (OWOB) (age-and-sex-specific BMI z-score > 85th percentile). Secondary outcomes were sum of skinfold thickness (SST), fat mass index (FMI) and fat-free mass index (FFMI). We used multivariable regression analyses (adjusting for maternal lifestyle and sociodemographic factors) to assess the associations of maternal DASH and E-DII scores with offspring adiposity outcomes in cohort-specific analyses, with subsequent random-effect meta-analyses. RESULTS: The study mothers had a mean (SD) age of 30.2 (4.6) years and a mean BMI of 23.4 (4.2) kg/m2. Higher early-pregnancy E-DII scores (more pro-inflammatory diet) tended to be associated with a higher odds of late-childhood [10.6 (1.2) years] OWOB [OR (95% CI) 1.09 (1.00, 1.19) per 1-SD E-DII score increase], whereas an inverse association was observed for late-pregnancy E-DII score and early-childhood [2.8 (0.3) years] OWOB [0.91 (0.83, 1.00)]. Higher maternal whole pregnancy DASH score (higher dietary quality) was associated with a lower odds of late-childhood OWOB [OR (95% CI) 0.92 (0.87, 0.98) per 1-SD DASH score increase]; associations were of similar magnitude for early and late-pregnancy [0.86 (0.72, 1.04) and 0.91 (0.85, 0.98), respectively]. These associations were robust in several sensitivity analyses and further adjustment for birth weight and childhood diet did not meaningfully alter the associations and conclusions. In two cohorts with available data, a higher whole pregnancy E-DII and lower DASH scores were associated with a lower late-childhood FFMI in males and a higher mid-childhood FMI in females (P interactions < 0.10). CONCLUSIONS: A pro-inflammatory, low-quality maternal antenatal diet may adversely influence offspring body composition and OWOB risk, especially during late-childhood. Promoting an overall healthy and anti-inflammatory maternal dietary pattern may contribute to the prevention of childhood obesity, a complex health issue requiring multifaceted strategy.

Associations between a maternal healthy lifestyle score and adverse offspring birth outcomes and childhood obesity in the Lifeways Cross-Generation Cohort Study.

BACKGROUND/OBJECTIVES: Maternal adherence to healthy lifestyle behaviors during pregnancy has been associated with reduced risk of obesity in the offspring. Our objective is to examine associations between a composite healthy lifestyle score (HLS) in expectant mothers and adverse offspring birth outcomes and childhood obesity. SUBJECTS/METHODS: The Lifeways Study comprises 665 mother-child pairs. A composite HLS (scored 0-5) based on high dietary quality (top 40% of the Healthy Eating Index (HEI)-2015), moderate to vigorous physical activity (MVPA), healthy pre-pregnancy BMI (18.5-24.9 kg/m2), never smoker, and no/moderate alcohol intake was calculated. Birth outcomes were abstracted from hospital records. Offspring waist circumference (WC) and BMI was determined at age 5 and 9. Logistic regression tested HLS associations with offspring outcomes. RESULTS: Offspring birth weight, length, and head circumference were positively associated with the maternal HLS (p < 0.001), whereas child BMI and incidence of overweight/obesity at age 5 and 9 were negatively associated (p < 0.05). In multivariable models, a lower maternal HLS was associated with increased risk of low birth weight (LBW) (P trend = 0.04) and lower likelihood of macrosomia (P trend = 0.03). Examined individually, poor maternal dietary quality, smoking, and alcohol intake were associated with higher risk of LBW (p < 0.04). Likelihood of macrosomia and combined overweight/obesity at age 5 and 9 years were greater among mothers with a pre-pregnancy BMI in the range with obesity (p < 0.04). Smoking during pregnancy was also linked to greater risk of childhood overweight/obesity (OR:1.91, 95% CI:1.01-3.61, p = 0.04 at age 5 and OR: 2.14, 95% CI:1.01-4.11, p = 0.03 at age 9). CONCLUSIONS: Our findings suggest that maternal adherence to a healthy lifestyle during pregnancy, in particular having a good quality diet, not smoking, and no/low alcohol intake in combination with a healthy pre-pregnancy BMI, is associated with reduced risk of adverse offspring birth outcomes and childhood obesity.

Maternal Dietary Glycemic and Insulinemic Indexes Are Not Associated with Birth Outcomes or Childhood Adiposity at 5 Years of Age in an Irish Cohort Study.

BACKGROUND: High maternal dietary glycemic index (GI) and glycemic load (GL) may be associated with adverse offspring birth and postnatal adiposity outcomes through metabolic programming, but the evidence thus far, mainly from studies conducted in high-risk pregnant populations, has been inconclusive. No study has examined the influence of maternal insulin demand [measured by food insulinemic index (II) and insulinemic load (IL)] on offspring outcomes. OBJECTIVES: We investigated associations between maternal GI, GL, II, and IL and offspring birth outcomes and postnatal adiposity in a general pregnant population. METHODS: The study was based on data from 842 mother-child pairs from the Lifeways prospective cohort study in Ireland. Through the use of standard methodology, maternal GI, GL, II, and IL were derived from dietary information obtained via a validated food-frequency questionnaire in early pregnancy (12-16 wk). Birth outcomes were abstracted from hospital records. At 5-y follow-up, children's body mass index (BMI) and waist circumference were measured. Associations were assessed through the use of multivariable-adjusted regression analysis. RESULTS: Mothers had a mean ± SD age of 30.3 ± 5.7 y and a mean BMI (kg/m2) of 23.9 ± 4.2. The mean ± SD for dietary glycemic and insulinemic indexes were: GI = 58.9 ± 4.4; GL = 152 ± 49; II = 57.4 ± 14.5; IL = 673 ± 267. After adjustment for confounders, no consistent associations were observed between maternal GI, GL, II, and IL and birth outcomes including birth weight, macrosomia, gestational age, and postterm births. Similarly, no association was observed with BMI and waist circumference z scores and childhood obesity (general and central) at 5-y follow-up. There was no evidence of a nonlinear relation between the studied indexes and outcomes. CONCLUSIONS: We observed no clear relation between maternal GI, GL, II, and IL and offspring birth outcomes and childhood obesity in a general pregnant population.

Does replacing sedentary behaviour with light or moderate to vigorous physical activity modulate inflammatory status in adults?

BACKGROUND: Sedentary behaviour, obesity and insulin resistance are associated with pro-inflammatory status. Limited data on whether physical activity modulates inflammatory status and counteracts obesity and insulin resistance associated low-grade inflammation exist. Our objective was to investigate associations between objectively measured physical activity and inflammatory status, and specifically whether substituting daily sedentary behaviour with light activity or moderate to vigorous physical activity (MVPA), is associated with beneficial alterations to the inflammatory profile among middle-aged adults and those at increased cardiometabolic risk (obese and insulin resistant subjects). METHODS: Data are from a sub-sample of the Mitchelstown cohort; a population-based cross-sectional sample of 2047 Irish adults. Physical activity intensity and duration were measured in 396 participants for 7-consecutive days using the GENEActiv accelerometer. Isotemporal regression analysis examined the associations between replacing 30 min per day of sedentary behaviour with equal amounts of light activity and MVPA on inflammatory factors (serum acute-phase reactants, adipocytokines, pro-inflammatory cytokines and white blood cells (WBC)). RESULTS: Reallocating 30 min of sedentary time with MVPA was associated with a more favourable inflammatory profile characterized by higher adiponectin and lower complement component C3 (C3), leptin, interleukin 6 (IL-6) and WBC concentrations (P < 0.05). No significant effects were noted with substitution of sedentary time with light activity. Among the obese subjects replacing sedentary behaviour with an equivalent amount of MVPA was associated with lower WBC counts (P < 0.05); no associations were detected among the insulin resistant (HOMA-IR >75th percentile) subjects. Among the non-obese and non-insulin resistant subjects substituting 30 min of sedentary behaviour with MVPA was associated with decreased C3, IL-6 and WBC concentrations. CONCLUSIONS: Replacing sedentary behaviour with MVPA modulates pro-inflammatory status. These findings, which highlight the need for the developing randomized trials aimed at lowering cardiometabolic risk, warrant further investigation.

Nutrigenetics: bridging two worlds to understand type 2 diabetes.

The increasing global prevalence of type 2 diabetes mellitus (T2DM) is a major public health concern. Accumulating data provides strong evidence of the shared contribution of genetic and environmental factors to T2DM risk. Genome-wide association studies have hugely improved our understanding of the genetic basis of T2DM. However, it is obvious that genetics only partly account for an individuals' predisposition to T2DM. The dietary environment has changed remarkably over the last century. Examination of individual macronutrients and more recently of foods and dietary patterns is becoming increasingly important in terms of developing public health strategies. Nutrigenetics offers the potential to improve diet-related disease prevention and therapy, but is not without its own challenges. In this review we present evidence on the dietary environment and genetics as risk factors for T2DM and bridging the 2 disciplines we highlight some key gene-nutrient interactions.

Lifestyle factors and BMI attenuate relationships between biomarkers of inflammation and depressive symptoms and well-being: A cross-sectional study.

Background: Mental disorders are a growing public health concern and evidence has linked chronic low-grade inflammation with depression and well-being. Research also suggests that certain modifiable lifestyle factors such as smoking, alcohol use, physical activity, diet quality and BMI are related to psychological health. These may modulate the relationship between low-grade inflammation and mental health conditions. In this study we examined inflammatory biomarker associations with two psychological health scores and investigated whether relationships are influenced by lifestyle factors and BMI. Methods: This was a cross-sectional study of 1824 middle-to older-aged men and women randomly selected from a large primary care centre. Depressive symptoms and well-being were assessed using the 20-item Centre for Epidemiologic Studies Depression (CES-D) Scale and the World Health Organization-Five (WHO-5) Well-Being Index. Linear regression analyses were performed to examine depression and well-being score relationships with six inflammatory biomarkers, and a composite inflammatory biomarker score, adjusting for demographic characteristics, health conditions, lifestyle factors and BMI. Results: Depression and well-being score associations with complement component 3 (CES-D only) c-reactive protein, interleukin 6, leptin, white blood cell counts, neutrophils and the inflammatory biomarker score were observed. These relationships survived adjustment for demographic variables and health conditions but were attenuated in models which included lifestyle factors and BMI. In final models, only leptin (ß = 0.566, p = 0.018) and inflammatory score (ß = 0.137, p = 0.004) associations with the CES-D score remained. Conclusions: These findings suggest that the relationship between systemic low-grade inflammation and depressive symptoms and well-being may be largely explained by lifestyle factors and adiposity, highlighting the potential importance of promoting a healthy lifestyle in the treatment of depressive disorders.

Relationships between childhood adversity and inflammatory biomarkers in adulthood: A cross-sectional analysis of a middle-to older-aged population.

Background: Exposure to adverse childhood experiences (ACEs) has been linked with increased cardiometabolic risk in adulthood. Low-grade systemic inflammation may underlie this association. Thus far, however, there has been limited investigation of later life inflammatory biomarkers in the context of childhood adversity. Objectives: To assess ACE history, and ACE subcategory, relationships with a broad range of inflammatory biomarkers in middle-to older-aged adults to test the hypothesis that ACE exposure is associated with an unfavourable inflammatory profile in adulthood and determine whether associations vary by ACE subtype and sex. Methods: This study used data from a random sample of 1,839 men and women aged 46-74 years. Participant exposure to ACEs (overall and subtypes including abuse, neglect and household dysfunction) was determined using a validated 10-item ACE questionnaire. Inflammatory biomarkers (pro-inflammatory cytokines, adipocytokines, acute-phase response proteins, white blood cell counts and their constituents, coagulation factors and glycoprotein acetyl) were measured from participant blood samples. Linear regression analyses examined relationships between ACE history (overall and each subcategory) and inflammatory biomarkers in adulthood, controlling for potential confounders. Sex-stratified and mediation analyses were also conducted. Results: In age and sex-adjusted models, ACE history was significantly associated with higher c-reactive protein (p = 0.027), resistin (p = 0.024), white blood cell count (WBC) (p = 0.034), monocyte (p = 0.044), eosinophil (p = 0.031) and plasminogen activator inhibitor-1 (p = 0.047) concentrations, and lower adiponectin (p = 0.025) levels. Results from stratified analyses indicated sex differences and ACE subtype specific associations, with household dysfunction identified as the main driver of positive ACE associations with WBCs and constituents (all p < 0.05). Mediation analyses suggested that BMI and smoking mediate relationships between ACE exposures and increased inflammation. Conclusions: This study provides evidence that ACE exposure may be associated with more pro-inflammatory and pro-thrombotic profiles in adulthood. Associations differed according to ACE subtype, and sex differences exist, which may influence cardiometabolic risk.

The Nutri-Score nutrition label: Associations between the underlying nutritional profile of foods and lipoprotein particle subclass profiles in adults.

BACKGROUND AND AIMS: Lipoprotein particle concentrations and size are associated with increased risk for atherosclerosis and premature cardiovascular disease. Certain dietary behaviours may be cardioprotective and public health strategies are needed to guide consumers' dietary choices and help prevent diet-related disease. The Food Standards Agency nutrient profiling system (FSAm-NPS) constitutes the basis of the five-colour front-of-pack Nutri-Score labelling system. No study has examined FSAm-NPS index associations with a wide range of lipoprotein particle subclasses. METHODS: This was a cross-sectional study of 2006 middle-to older-aged men and women randomly selected from a large primary care centre. Individual participant FSAm-NPS dietary scores were derived from validated food frequency questionnaires. Lipoprotein particle subclass concentrations and size were determined using nuclear magnetic resonance spectroscopy. Multivariate-adjusted linear regression analyses were performed to examine FSAm-NPS relationships with lipoprotein particle subclasses. RESULTS: In fully adjusted models which accounted for multiple testing, higher FSAm-NPS scores, indicating poorer dietary quality, were positively associated with intermediate-density lipoprotein (ß = 0.096, p = 0.005) and small high-density lipoprotein (HDL) (ß = 0.492, p = 0.006) concentrations, a lipoprotein insulin resistance score (ß = 0.063, p = 0.02), reflecting greater lipoprotein-related insulin resistance, and inversely associated with HDL size (ß = -0.030, p = 0.045). CONCLUSIONS: A higher FSAm-NPS score is associated with a less favourable lipoprotein particle subclass profile in middle-to older-aged adults which may be a potential mechanism underlying reported health benefits of a healthy diet according to Nutri-Score rating.

Associations between a paternal healthy lifestyle score and its individual components with childhood overweight and obesity.

BACKGROUND: Maternal healthy lifestyle behaviors during pregnancy have been associated with reduced risk of offspring overweight and obesity (OWOB). However, there has been little investigation, in the context of the Paternal Origins of Health and Disease (POHaD) paradigm, of the potential influence of the paternal lifestyle on offspring OWOB. OBJECTIVES: To describe paternal healthy lifestyle factors around pregnancy and investigate their associations, individually and combined, with offspring risk of OWOB during childhood. MATERIALS AND METHODS: Participants included 295 father-child pairs from the Lifeways Cross-Generation Cohort Study. A composite paternal healthy lifestyle score (HLS) based on having a high dietary quality (top 40% of the Healthy Eating Index-2015), meeting physical activity guidelines (≥450 MET-min/week of moderate-to-vigorous physical activity), having a healthy body mass index (BMI) (18.5-24.9 kg/m2 ), being a non-smoker, and having no/moderate alcohol intake, was calculated (range 0-5). Paternal HLS (and individual components) associations with child BMI and waist-to-height ratio (WHtR) at age 5 and 9 years were assessed using linear (BMI z-scores and WHtR) and logistic (IOTF categories) regression analyses, adjusted for sociodemographic characteristics. RESULTS: At age 5 and 9 years, 23.5% and 16.9% of children were classified as living with OWOB, respectively. Of the 160 pairs with a complete HLS, 45.0% of the fathers had unfavorable lifestyle factors, determined by a low HLS between 0 and 2 points. Although a low paternal HLS was not significantly associated with a higher risk of childhood OWOB measured using either BMI z-scores and IOTF categories, it was associated with a greater child WHtR, an indicator of central adiposity, at 9 years of age (ß [95% CI] = 0.04 [0.01,0.07]). DISCUSSION AND CONCLUSION: Almost half of the fathers had unfavorable lifestyle factors around pregnancy. A low paternal HLS was associated with a greater child WHtR at 9 years but not with a higher risk of childhood OWOB when measured by BMI z-scores or IOTF categories.

Sociodemographic factor associations with maternal and placental outcomes: A cluster and partial least squares regression analysis.

INTRODUCTION: Maternal social disadvantage adversely affects maternal and offspring health, with limited research on placental outcomes. Therefore, we examined maternal sociodemographic factor associations with placental and birth outcomes in general (Lifeways Cross-Generation Cohort) and at-risk (PEARS Study of mothers with overweight or obesity) populations of pregnant women. METHODS: TwoStep cluster analysis profiled Lifeways mothers (n = 250) based on their age, parity, marital status, household income, private healthcare insurance, homeowner status, and education. Differences in placental and birth outcomes (untrimmed placental weight (PW), birthweight (BW) and BW:PW ratio) between clusters were assessed using one-way ANOVA and chi-square tests. Partial least squares regression analysed individual effects of sociodemographic factors on placental and birth outcomes in Lifeways and PEARS mothers (n = 461). RESULTS: Clusters were classified as "Married Homeowners" (n = 140, 56 %), "Highest Income" (n = 58, 23.2 %) and "Renters" (n = 52, 20.8 %) in the Lifeways Cohort. Renters were younger, more likely to smoke, have a means-tested medical card and more pro-inflammatory diets compared to other clusters (p < 0.01). Compared to Married Homeowners, renters' offspring had lower BW (-259.26 g, p < 0.01), shorter birth length (-1.31 cm, p < 0.01) and smaller head circumference (-0.59 cm, p = 0.02). PLS regression analyses identified nulliparity as having the greatest negative effect on PW (Lifeways and PEARS) while being a homeowner had the greatest positive effect on PW (Lifeways). CONCLUSION: Certain combinations of sociodemographic factors (particularly homeownership) were associated with less favourable lifestyle factors, and with birth, but not placental outcomes. When explored individually, parity contributed to the prediction of placental and birth outcomes in both cohorts of pregnant women.

Metabolically healthy obesity: definitions, determinants and clinical implications.

Obesity is associated with increased risk of developing metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) leading to higher all-cause mortality. However accumulating evidence suggests that not all obese subjects are at increased cardiometabolic risk and that the "metabolically healthy obese" (MHO) phenotype may exist in the absence of metabolic abnormalities. Despite the knowledge of the existence of obese metabolic phenotypes for some time now there is no standard set of criteria to define metabolic health, thus impacting on the accurate estimation of the prevalence of the MHO phenotype and making comparability between studies difficult. Furthermore prospective studies tracking the development of cardiometabolic disease and mortality in MHO have also produced conflicting results. Limited data regards the determinants of the MHO phenotype exist, particularly in relation to dietary and lifestyle behaviours. In light of the current obesity epidemic it is clear that current "one size fits all" approaches to tackle obesity are largely unsuccessful. Whether dietary, lifestyle and/or therapeutic interventions based on stratification of obese individuals according to their metabolic health phenotype are more effective remains to be seen, with limited and conflicting data available so far. This review will present the current state of the art including the epidemiology of MHO and its definitions, what factors may be important in determining metabolic health status and finally, some potential implications of the MHO phenotype in the context of obesity diagnosis, interventions and treatment.