Physical activity trajectories from childhood to late adolescence and their implications for health in young adulthood.

Physical activity has been associated with physical and mental health across the life course, yet few studies have used group-based trajectory modeling to examine the effect of longitudinal patterns of physical activity during childhood and adolescence on adult health outcomes. The Raine Study data from Gen2 follow-ups at 8, 10, 14, 17, 20, and 22 years collected between 1998 and 2014 were used. Latent class analysis identified trajectories using parent-reported physical activity for ages 8 to 17. Associations between trajectories and physical and mental health outcomes at ages 20 and 22 were explored, adjusting for current physical activity and considering sex interactions. Analysis in 2019 identified three trajectories: low (13%), mid (65%) and high (22%) physical activity (n = 1628). Compared to the low-activity trajectory, those in the high-activity trajectory had lower adiposity, insulin, HOMA-IR and fewer diagnosed disorders, higher HDL-cholesterol, and faster cognitive processing. For example, those in the high-activity trajectory had lower percent body fat at age 20 compared to those in the mid-activity (-4.2%, 95%CI: -5.8, -2.7) and low-activity (-9.5%, 95%CI: -11.7, -7.2) trajectories. Physical activity trajectories showed different associations between sexes for self-reported physical and mental health, BMI, systolic blood pressure, and depression symptoms. Being in the high- or mid-activity trajectory was associated with a more favorable cardiometabolic and mental health profile in young adulthood. Strategies are needed to help less active children to increase physical activity throughout childhood and adolescence to improve young adult health outcomes.

Features of the metabolic syndrome in late adolescence are associated with impaired testicular function at 20 years of age.

STUDY QUESTION: Are early signs of metabolic disorder in late adolescence associated with features of impaired testicular function many years before the majority seek parenthood? SUMMARY ANSWER: Adolescents with features of metabolic disorder at 17 years, or insulin resistance (IR) at 20 years of age, show impaired testicular function and altered hormone levels compared to those without metabolic disorder. WHAT IS KNOWN ALREADY: Controversial evidence suggests a recent decline in sperm production potentially linked to environmental influences, but its cause remains unclear. Concomitant increases in obesity and diabetes suggest that lifestyle factors may contribute to this decline in testicular function. Although obesity has been associated with adverse testicular function in some studies, it remains unclear whether poor testicular function merely reflects, or causes, poor metabolic health. If metabolic disorder were present in adolescence, prior to the onset of obesity, this may suggest that metabolic disorder maybe a precursor of impaired testicular function. STUDY DESIGN, SIZE, DURATION: The Western Australian Pregnancy Cohort (Raine) Study is a longitudinal study of children born in 1989-1991 who have undergone detailed physical assessments since birth (1454 male infants born). At 17 years of age, 490 boys underwent a hepatic ultrasound examination, serum cytokine assessment (n = 520) and a metabolic assessment (n = 544). A further metabolic assessment was performed at 20 years (n = 608). Testicular assessment was performed at 20 years; 609 had reproductive hormones measured, 404 underwent a testicular ultrasound and 365 produced a semen sample. PARTICIPANTS/MATERIALS, SETTING, METHODS: Testicular volume was estimated by ultrasonography, and semen analysis was performed according to World Health Organization guidelines. Concentrations of LH, FSH and inhibin B (inhB) in serum were measured by immunoassay and total testosterone by liquid chromatography-mass spectrometry.At 17 years of age, a liver ultrasound examination was performed to determine the presence of non-alcoholic fatty liver disease (NAFLD), and serum analysed for the cytokines interleukin-18 and soluble tumour necrosis factor receptor 1 and 2 (sTNFR1, sTNFR2).At 17 and 20 years of age, fasting blood samples were analysed for serum liver enzymes, insulin, glucose, triglycerides (TG), total cholesterol, high density lipoprotein and low density lipoprotein cholesterol, high sensitivity C-reactive protein and uric acid. The homoeostatic model assessment (HOMA) was calculated and approximated IR was defined by a HOMA >4. Anthropometric data was collected and dual energy X-ray absorptiometry measurement performed for lean and total fat mass. As at this young age the prevalence of metabolic syndrome was expected to be low, a two-step cluster analysis was used using waist circumference, TGs, insulin, and systolic blood pressure to derive a distinct high-risk group with features consistent with the metabolic syndrome and increased cardiometabolic risk. MAIN RESULTS AND THE ROLE OF CHANCE: Men at age 17 years with increased cardiometabolic risk had lower concentrations of serum testosterone (medians: 4.0 versus 4.9 ng/mL) and inhB (193.2 versus 221.9 pg/mL) (P < 0.001 for both) compared to those within the low risk metabolic cluster. Men with ultrasound evidence of NAFLD (n = 45, 9.8%) had reduced total sperm output (medians: 68.0 versus 126.00 million, P = 0.044), testosterone (4.0 versus 4.7 ng/mL, P = 0.005) and inhB (209.1 versus 218.4 pg/mL, P = 0.032) compared to men without NAFLD.Men with higher concentrations of sTNFR1 at 17 years of age had a lower sperm output and serum concentration of inhB, with an increase in LH and FSH (all P < 0.05 after adjustment for age, BMI, abstinence and a history of cryptorchidism, varicocele, cigarette smoking, alcohol and drug use), compared to those without an elevated sTNFR1. Multivariable regression analysis, adjusting for confounders, demonstrated that men in the high-risk metabolic cluster at 20 years had a lower serum testosterone and inhB (P = 0.003 and P = 0.001, respectively). A HOMA-IR > 4 was associated with a lower serum testosterone (P = <0.001) and inhB (P = 0.010) and an increase in serum FSH (P = 0.015). LIMITATIONS, REASONS FOR CAUTION: This study is limited by the sample size and multiple comparisons, and causality cannot be proven from an observational study. Due to a 3-year interval between some metabolic assessments and assessment of testicular function, we cannot exclude the introduction of a bias into the study, as some of the participants and their testicular function will not have been fully mature at the 17-year assessment. WIDER IMPLICATIONS OF THE FINDINGS: Irrespective of a proven causation, our study findings are important in that a significant minority of the men, prior to seeking parenthood, presented co-existent features of metabolic disorder and signs of testicular impairment. Of particular note is that the presence of NAFLD at 17 years of age, although only present in a minority of men, was associated with an almost 50% reduction in sperm output at 20 years of age, and that the presence of IR at 20 years was associated with a 20% reduction in testicular volume. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by Australian NHMRC (Grant Numbers 634457, 35351417 and 403981) and received support from the Raine Medical Research Foundation, The Telethon Kids Institute, University of Western Australia, Women and Infants Research Foundation, Curtin University and Edith Cowan University. D.A.D., J.E.D., N.M., L.A.A., R.-C.H., T.A.M., J.K.O., L.J.B. have nothing to declare. R.J.H. is Medical Director of Fertility Specialists of Western Australia, has equity interests in Western IVF, and has received grant support from MSD, Merck-Serono and Ferring Pharmaceuticals. RMcL has equity interests in the Monash IVF Group. R.J.N. has equity interests in FertilitySA, and has received grant support from Merck Serono and Ferring Pharmaceuticals. D.J.H. has received institutional grant funding (but no personal income) for investigator-initiated testosterone pharmacology studies from Lawley and Besins Healthcare and has provided expert testimony to anti-doping tribunals and for testosterone litigation.This abstract was awarded the Fertility Society of Australia clinical exchange award for the oral presentation at ESHRE, Barcelona, in 2018.

Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta-analysis of European, North American and Australian cohorts.

OBJECTIVE: To assess the separate and combined associations of maternal pre-pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact. DESIGN: Individual participant data meta-analysis of 39 cohorts. SETTING: Europe, North America, and Oceania. POPULATION: 265 270 births. METHODS: Information on maternal pre-pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used. MAIN OUTCOME MEASURES: Gestational hypertension, pre-eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth. RESULTS: Higher maternal pre-pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31- 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain. CONCLUSIONS: Maternal pre-pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications. Promoting a healthy pre-pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity. TWEETABLE ABSTRACT: Promoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications.

Associations of maternal prepregnancy body mass index and gestational weight gain with cardio-metabolic risk factors in adolescent offspring: a prospective cohort study.

OBJECTIVE: To assess the associations of maternal prepregnancy body mass index (BMI) and rates of early-pregnancy, mid-pregnancy and total gestational weight gain with adolescent body fat distribution and cardio-metabolic outcomes. DESIGN: Population-based prospective cohort study. SETTING: Western Australia. POPULATION: Thousand three hundred and ninety-two mothers and their children. METHODS: Maternal prepregnancy weight was assessed by questionnaire. Maternal weights at a mean of 16.5 ± 2.2 SD and 34.1 ± 1.5 SD weeks of gestation were obtained from medical records. Offspring adiposity and cardio-metabolic outcomes were assessed at a median age 17.0 years [95% confidence interval (CI) range: 16.7, 17.7]. MAIN OUTCOME MEASURES: Adolescent BMI, waist circumference (WC), waist-to-hip ratio (WHR), blood pressure, total and HDL-cholesterol, triglycerides, insulin, glucose and HOMA-IR. RESULTS: Higher prepregnancy BMI was associated with higher adolescent BMI, WC, WHR, systolic blood pressure, insulin, glucose and HOMA-IR levels (P-values <0.05). Adjustment for adolescent current BMI attenuated the associations of prepregnancy BMI with adolescent cardio-metabolic outcomes. Higher weight gain in early-pregnancy, but not mid-pregnancy, was associated with higher adolescent BMI, WC and WHR (P-values <0.05), but not with other cardio-metabolic risk factors. Total gestational weight gain was associated with adolescent BMI and WC (P-values <0.05). Higher prepregnancy BMI and early-pregnancy weight gain were associated with increased risks of the high-metabolic risk cluster in adolescents (OR 1.57, 95% CI 1.33, 1.85 and OR 1.23, 95% CI 1.03, 1.47 per SD increase in prepregnancy BMI and early-pregnancy weight gain, respectively). CONCLUSIONS: Higher maternal prepregnancy BMI and early-pregnancy weight gain rate are associated with an adverse adolescent cardio-metabolic profile. These associations are largely mediated by adolescent BMI.

Identification of a dietary pattern associated with greater cardiometabolic risk in adolescence.

BACKGROUND AND AIMS: Energy dense, high fat, low fibre diets may contribute to obesity in young people, however their relationships with other cardiometabolic risk factors are unclear. We examined associations between an 'energy-dense, high-fat and low-fibre' dietary pattern (DP) and cardiometabolic risk factors, and the tracking of this DP in adolescence. METHODS AND RESULTS: Data was sourced from participants in the Western Australian Pregnancy (Raine) Cohort Study. At 14 and 17 y, dietary intake, anthropometric and biochemical data were measured and z-scores for an 'energy dense, high fat and low fibre' DP were estimated using reduced rank regression (RRR). Associations between DP z-scores and cardiometabolic risk factors were examined using regression models. Tracking of DP z-scores was assessed using Pearson's correlation coefficient. A 1 SD unit increase in DP z-score between 14 and 17 y was associated with a 20% greater odds of high metabolic risk (95% CI: 1.01, 1.41) and a 0.04 mmol/L higher fasting glucose in boys (95% CI: 0.01, 0.08); a 28% greater odds of a high-waist circumference (95% CI: 1.00, 1.63) in girls. An increase of 3% and 4% was observed for insulin and HOMA (95% CI: 1%, 7%), respectively, in boys and girls, for every 1 SD increase in DP z-score and independently of BMI. The DP showed moderate tracking between 14 and 17 y of age (r = 0.51 for boys, r = 0.45 for girls). CONCLUSION: An 'energy dense, high fat, low fibre' DP is positively associated with cardiometabolic risk factors and tends to persist throughout adolescence.

Dairy product consumption, dietary nutrient and energy density and associations with obesity in Australian adolescents.

BACKGROUND: Dairy intake is likely to influence dietary energy density (ED) and nutrient density (ND), which are factors representing aspects of dietary quality. Although evidence suggests dairy intake is unlikely to contribute to obesity, intake tends to decrease over adolescence, potentially as a result of concerns around weight gain. We examined associations between dairy intake, ED and ND, and investigated relationships with obesity in adolescents. METHODS: The present study comprised a cross-sectional study of 1613 14-year-olds in the Western Australian Pregnancy Cohort (Raine) Study. Adolescents completed a 212-item food frequency questionnaire. Nutrient Rich Food index 9.3 (NRF9.3) was used to estimate ND. Age-specific body mass index (BMI) and waist-height cut-offs were used to categorise obesity risk. RESULTS: Mean (SD) dairy intake was: 2.62 (1.51) servings daily; ED was 4.53 (0.83) (food and beverage) and 6.28 (1.33) (food only); ND was 373 (109). Dairy intake was inversely associated with ED and positively associated with ND. The odds of being overweight (as assessed by BMI) increased by 1.24 (95% confidence interval = 1.09-1.42) with each 100-point increase in ND, after adjustment for potential confounders and energy intake. ED measures and dairy intake were inversely associated with obesity after adjustment for confounders; associations became nonsignificant after energy adjustment. CONCLUSIONS: The NRF9.3 was originally designed to assess foods, not diets. Further research in other cohorts to determine whether similar findings exist, or investigations into alternate measures of dietary ND, may prove useful. Our findings may be the result of factors such as an excess consumption of refined but fortified foods. Although higher dairy intakes were associated with higher ND, intakes were not associated with higher obesity risk.

Differential DNA methylation of steatosis and non-alcoholic fatty liver disease in adolescence.

BACKGROUND AND AIMS: Epigenetic modifications are associated with hepatic fat accumulation and non-alcoholic fatty liver disease (NAFLD). However, few epigenetic modifications directly implicated in such processes have been identified during adolescence, a critical developmental window where physiological changes could influence future disease trajectory. To investigate the association between DNA methylation and NAFLD in adolescence, we undertook discovery and validation of novel methylation marks, alongside replication of previously reported marks. APPROACH AND RESULTS: We performed a DNA methylation epigenome-wide association study (EWAS) on DNA from whole blood from 707 Raine Study adolescents phenotyped for steatosis score and NAFLD by ultrasound at age 17. Next, we performed pyrosequencing validation of loci within the most 100 strongly associated differentially methylated CpG sites (dmCpGs) for which ≥ 2 probes per gene remained significant across four statistical models with a nominal p value < 0.007. EWAS identified dmCpGs related to three genes (ANK1, MIR10a, PTPRN2) that met our criteria for pyrosequencing. Of the dmCpGs and surrounding loci that were pyrosequenced (ANK1 n = 6, MIR10a n = 7, PTPRN2 n = 3), three dmCpGs in ANK1 and two in MIR10a were significantly associated with NAFLD in adolescence. After adjustment for waist circumference only dmCpGs in ANK1 remained significant. These ANK1 CpGs were also associated with γ-glutamyl transferase and alanine aminotransferase concentrations. Three of twenty-two differentially methylated dmCpGs previously associated with adult NAFLD were associated with NAFLD in adolescence (all adjusted p < 2.3 × 10-3). CONCLUSIONS: We identified novel DNA methylation loci associated with NAFLD and serum liver biochemistry markers during adolescence, implicating putative dmCpG/gene regulatory pathways and providing insights for future mechanistic studies.

Adiposity associated DNA methylation signatures in adolescents are related to leptin and perinatal factors.

Epigenetics links perinatal influences with later obesity. We identifed differentially methylated CpG (dmCpG) loci measured at 17 years associated with concurrent adiposity measures and examined whether these were associated with hsCRP, adipokines, and early life environmental factors. Genome-wide DNA methylation from 1192 Raine Study participants at 17 years, identified 29 dmCpGs (Bonferroni corrected p < 1.06E-07) associated with body mass index (BMI), 10 with waist circumference (WC) and 9 with subcutaneous fat thickness. DmCpGs within Ras Association (RalGDS/AF-6), Pleckstrin Homology Domains 1 (RAPH1), Musashi RNA-Binding Protein 2 (MSI2), and solute carrier family 25 member 10 (SLC25A10) are associated with both BMI and WC. Validation by pyrosequencing confirmed these associations and showed that MSI2 , SLC25A10 , and RAPH1 methylation was positively associated with serum leptin. These were  also associated with the early environment; MSI2 methylation (ß = 0.81, p = 0.0004) was associated with pregnancy maternal smoking, SLC25A10 (CpG2 ß = 0.12, p = 0.002) with pre- and early pregnancy BMI, and RAPH1 (ß = -1.49, p = 0.036) with gestational weight gain. Adjusting for perinatal factors, methylation of the dmCpGs within MSI2, RAPH1, and SLC25A10 independently predicted BMI, accounting for 24% of variance. MSI2 methylation was additionally associated with BMI over time (17 years old ß = 0.026, p = 0.0025; 20 years old ß = 0.027, p = 0.0029) and between generations (mother ß = 0.044, p = 7.5e-04). Overall findings suggest that DNA methylation in MSI2, RAPH1, and SLC25A10 in blood may be robust markers, mediating through early life factors.

20-Hydroxyeicosatetraenoic acid synthesis is increased in human neutrophils and platelets by angiotensin II and endothelin-1.

The cytochrome P-450 arachidonic acid metabolite 20-HETE is central to the regulation of vascular tone, renal function, and blood pressure and is synthesized in the rat kidney in response to angiotensin II (ANG II) and endothelin-1 (ET-1). There are very few studies examining the cellular synthesis of 20-HETE in humans. We aimed to measure human neutrophil and platelet 20-HETE levels under basal conditions and after ANG II, ET-1, and calcium ionophore (CaI). 20-HETE was measured in human platelets and neutrophils after saline (control), CaI (2.5 µg/ml), and ANG II or ET-1 (10 nmol/l-1 µmol/l) incubations. The effect of cells, which were preincubated with the ω-hydroxylase inhibitor N-hydroxy-N'-(4-butyl-2-methylphenyl) (HET0016, 10 nM), ANG II types 1 or 2 (AT(1) or AT(2)) receptor inhibition with irbesartan (1 µmol/l) or PD-123319 (1 µmol/l), or endothelin receptor subtypes A or B (ET(A) or ET(B)) receptor inhibition with BQ-123 or BQ-778 (100 nmol/l), was studied. Neutrophil and platelet content and release of 20-HETE was significantly increased by CaI and blocked by the ω-hydroxylase inhibitor HET0016. ANG II and ET-1 significantly increased neutrophil and platelet content and release of 20-HETE. ANG II increased 20-HETE via the AT(2) receptor. ET-1 increased 20-HETE through the ET(B) receptor in platelets and both the ET(A) and ET(B) receptors in neutrophils. These studies show that human platelets and neutrophils synthesize 20-HETE in response to ANG II and ET-1. 20-HETE synthesis in both cell types was predominantly mediated via the AT(2) and ET(B) receptors. Stimulation via these receptor pathways has generally been thought to be cardioprotective and requires further studies in clinical situations associated with low-grade inflammation or where ANG II and ET-1 are elevated to clarify the role of 20-HETE.

Effects of lupin-enriched foods on body composition and cardiovascular disease risk factors: a 12-month randomized controlled weight loss trial.

BACKGROUND: Regular consumption of diets with increased protein or fibre intakes may benefit body weight and composition and cardiovascular disease risk factors. Lupin flour is a novel food ingredient high in protein and fibre. OBJECTIVE: To investigate the effects of a lupin-enriched diet, during and following energy restriction, on body weight and composition and cardiovascular disease risk factors in overweight individuals. DESIGN: Participants (n = 131) were recruited to a 12-month parallel-design trial. They were randomly assigned to consume lupin-enriched foods or matching high-carbohydrate control foods. All participants underwent 3 months of weight loss, 1 month of weight stabilization and 8 months of weight maintenance. Body weight and composition and cardiovascular disease risk factors were assessed at baseline, 4 and 12 months. RESULTS: Lupin, relative to control, did not significantly influence (mean difference (95% CI)) weight loss at 4 months (0.1 kg (-1.2, 1.4)) and 12 months (-0.6 kg (-2.0, 0.8)), maintenance of weight loss from 4 to 12 months (-0.7 kg (-1.83, 0.48)) or measures of body fat and fat-free mass. Relative to control, 24-h ambulatory systolic (-1.3 mm Hg (-2.4, -0.3), P = 0.016) and diastolic (-1.0 mm Hg (-1.9, -0.2), P = 0.021) blood pressures were lower at 12 months but not at 4 months; fasting insulin concentrations and homeostasis model assessment (HOMA) scores were significantly lower at 4 months (-1.2 mU l(-1) (-1.3, -1.1), P = 0.004 and -0.6 units (-1.0, -0.19), P = 0.004) and 12 months (-1.3 mU l(-1) (-1.4, -1.1), P < 0.001 and -0.7 units (-1.1, -0.24), P = 0.002). CONCLUSIONS: A diet higher in protein and fibre derived from lupin-enriched foods does not enhance weight loss or improve the maintenance of weight loss. However, such a diet may provide cardiovascular health benefits in terms of insulin sensitivity and blood pressure.

Body mass index, adiposity rebound and early feeding in a longitudinal cohort (Raine Study).

OBJECTIVE: This study examined the influence of type and duration of infant feeding on adiposity rebound and the tracking of body mass index (BMI) from birth to 14 years of age. METHODS: A sample of 1330 individuals over eight follows-ups was drawn from the Western Australian Pregnancy Cohort (Raine) Study. Trajectories of BMI from birth to adolescence using linear mixed model analysis investigated the influence of age at which breastfeeding was stopped and the age at which other milk was introduced (binomial 4-month cutoff point). A subsample of linear mixed model-predicted BMI was used to determine BMI and age at nadir for early infant feeding groups. RESULTS: Chi-square analysis between early feeding and weight status (normal weight, overweight and obese) groups found a significant difference between thee age at which breastfeeding was stopped (P<0.001) and the age at which other milk was introduced (P=0.011), with a higher proportion of overweight and obese in the < or = 4-month group, even after controlling for maternal education. Using the linear mixed model, the BMI determined was higher over time for the group that was breastfed for < or = 4 months (P=0.015), with a significant interaction effect with the group in which other milk was introduced at < or = 4 months (P=0.011). Using predicted BMI from the linear mixed model, significant differences for nadirs of adiposity rebound between early feeding groups were found (P<0.005). CONCLUSIONS: Early infant feeding was important in the timing of, and BMI at, adiposity rebound. The relationship between infant feeding and BMI remained up to the age of 14 years. Although confounding factors cannot be excluded, these findings support the importance of exclusive breastfeeding for longer than 4 months as a protective behaviour against the development of adolescent obesity.

Effects of increasing dietary protein and fibre intake with lupin on body weight and composition and blood lipids in overweight men and women.

BACKGROUND: Lupin kernel flour (LKF) is a novel food ingredient that is high in protein and fibre. We have previously shown that partial substitution of refined wheat-derived carbohydrate in bread with protein and fibre from LKF can reduce appetite and energy intake acutely. In addition, several studies have suggested that lupin may reduce cholesterol concentrations and benefit glucose and insulin metabolism. AIM: The aim of this study was to investigate the effects on body weight and composition and blood lipids, glucose and insulin of an ad libitum LKF-enriched diet higher in dietary protein and fibre. SUBJECTS AND METHODS: A total of 88 overweight and obese men and women were recruited for a 16-week parallel-design randomized controlled trial. Participants replaced 15-20% of their usual daily energy intake with white bread (control) or LKF-enriched bread (lupin) in an ad libitum diet. Measurements of body weight and composition, and fasting blood biochemical measurements were performed at baseline and 16 weeks. The primary analysis included 74 participants (37 per group) who completed the intervention. RESULTS: At baseline, mean (+/-s.d.) body mass index and total cholesterol were 30.6+/-3.5 kg m(-2) and 5.37+/-0.94 mmol l(-1), respectively. Estimated (mean between-group difference (95% confidence interval)) protein (13.7 (2.28, 25.0) g per day) and fibre (12.5 (8.79, 16.2) g per day) intakes were higher during the intervention with lupin than with control. For lupin relative to control, the net effects on body weight (-0.4 (-1.3, 0.6) kg), fat mass (-0.5 (-1.1, 0.2) kg) and percentage (-0.5 (-1.1, 0.1)%), plasma leptin (-1.66 (-4.91, 1.59) ng ml(-1)) and adiponectin (0.20 (-0.73, 1.13) mg l(-1), as well as serum total cholesterol (-0.08 (-0.38, 0.22) mmol l(-1)), triglycerides (0.09 (-0.10, 0.21) mmol l(-1)), glucose (0.10 (-0.11, 0.30) mmol l(-1)) and insulin (0.40 (-1.20, 2.00) mU l(-1)) were not significant. CONCLUSIONS: This study does not support the proposal that an ad libitum diet enriched in LKF resulting in moderate changes in both protein and fibre intakes can benefit body weight and composition or fasting blood lipids, glucose and insulin concentrations in overweight men and women with mildly elevated total cholesterol concentrations.

Dietary glycaemic carbohydrate in relation to the metabolic syndrome in adolescents: comparison of different metabolic syndrome definitions.

AIMS: High dietary glycaemic carbohydrate, as measured by the dietary glycaemic index and glycaemic load has been associated with increased risk of the metabolic syndrome in adults, but limited research exists for younger populations. We aimed to evaluate associations between dietary glycaemic carbohydrate and insulin resistance or the prevalence of the metabolic syndrome defined by three different criteria in a population-based adolescent cohort. METHODS: Diet was assessed using 3 day food records in 769 adolescents aged 13-15 years participating in the Western Australian Pregnancy Cohort (Raine) Study. The metabolic syndrome was identified using age-specific adolescent definitions from the International Diabetes Federation, the National Cholesterol Education Program Adult Treatment Panel III and a population-derived 'high-risk' metabolic cluster algorithm. Presence of a high waist circumference was mandatory only in the International Diabetes Federation definition. Insulin resistance was measured using homeostasis model assessment (HOMA-IR). RESULTS: The prevalence of the metabolic syndrome as defined by the International Diabetes Federation and the Adult Treatment Panel III was 3.6 and 4.0%, respectively; 25.9% of subjects were classified into the high-risk cluster. Significantly increased odds of International Diabetes Federation-defined metabolic syndrome were independently associated with a 20 unit glycaemic load increase (odds ratio 2.18; 95% confidence interval 1.26-3.78) and a 30 g carbohydrate increase (odds ratio 3.86; 95% confidence interval 1.80-8.28). No significant associations were observed when using the Adult Treatment Panel III, or the cluster-defined metabolic syndrome, or with HOMA-IR. CONCLUSIONS: This study supports the concept that high dietary glycaemic carbohydrate is associated with a higher prevalence of the metabolic syndrome in adolescents. However, relationships vary according to the definition of the metabolic syndrome used, with waist circumference a potentially relevant factor.

Dietary patterns and markers for the metabolic syndrome in Australian adolescents.

BACKGROUND AND AIMS: Overweight and other risk factors for cardiovascular disease (CVD) as well as their clustering, are increasingly prevalent among adolescents. We examined dietary patterns, CVD risk factors, and the clustering of these risk factors in 1139 14-year-olds living in Western Australia. METHODS AND RESULTS: Usual dietary intake was assessed using a food frequency questionnaire. Two dietary patterns, 'Western' and 'Healthy', were identified using factor analysis. Associations between these dietary patterns and BMI, waist circumference, systolic blood pressure, fasting levels of serum glucose, insulin, total cholesterol, HDL-C, LDL-C, triglycerides and insulin resistance were assessed using ANOVA. Cluster analysis identified a high risk group (the 'high risk metabolic cluster') with features akin to adult metabolic syndrome. Belonging to the 'high risk metabolic cluster' was examined in relation to dietary patterns using logistic regression, adjusting for aerobic fitness and socio-demographic factors. Higher 'Western' dietary pattern scores were associated with greater odds for the 'high risk metabolic cluster' (p for trend=0.02) and greater mean values for total cholesterol (p for trend=0.03), waist circumference (p for trend=0.03) and BMI (p for trend=0.02) in girls, but not boys. Scores for the 'Healthy' dietary pattern were not related to the 'high risk metabolic cluster' but were inversely associated with serum glucose in boys and girls (p for trend=0.01 and 0.04, respectively) and were positively associated with HDL-C in boys (p for trend=0.02). CONCLUSIONS: Dietary patterns are associated with CVD risk factors and the clustering of these risk factors in adolescence.

Effect of weight loss on neutrophil resolvins in the metabolic syndrome.

BACKGROUND: Non-resolving inflammation associates with obesity and insulin resistance, and may be dependent on the balance of inflammatory substances and specialised pro-resolving mediators of inflammation (SPM) that act to halt the inflammatory response. This controlled trial examined the effect of weight loss on neutrophil synthesis of SPM in volunteers with the metabolic syndrome (MetS). METHODS: Volunteers with MetS (n = 42) were matched for age and gender and randomly assigned to a 12-wk weight loss program followed by 4-wk weight stabilization or a 16-wk weight maintenance program. At baseline and 16 weeks, isolated neutrophils were stimulated with calcium ionophore and the released SPM were measured by LC-MS/MS. RESULTS: At baseline the SPM resolvin (Rv) E1, 18R-RvE3, RvD2 and Maresin-1 (MaR-1) were detected from stimulated neutrophils. The concentration of released RvE1 was at least 6-fold that of other detected SPM. Weight loss of 4.7 ±â€¯0.8 kg, led to a 2-fold increase in RvE1, P = 0.013, relative to the weight maintenance group. The increase in RvE1 after weight loss was related to, but independent of leukotriene B4. CONCLUSION: Following weight loss, human neutrophils from individuals with the metabolic syndrome are capable of releasing larger amounts of RvE1 upon stimulation.

Hospital admissions and length of stay for coronary disease in an Aboriginal cohort.

BACKGROUND AND AIMS: Coronary disease (CHD)-related hospital admission is more common among indigenous than non-indigenous Australians. We aimed to identify predictors of hospital admission potentially useful in planning prevention programs. METHODS AND RESULTS: Length of stay (LOS), interval between, and number of recurrent admissions were modelled with proportional hazards or negative binomial models using lifestyle data recorded in 1988-1989 among Aborigines (256 women, 258 men, aged 15-88years) linked to hospital records to 2002. Among 106 Aborigines with CHD, hypertension (hazard ratio (HR) 1.69, 95% CI 1.05-2.73); smoking (HR 1.90, 95% CI 1.02-3.53); consuming processed meat >4 times/month (HR 1.81, 95% CI 1.01-3.24); >6 eggs/week (HR 1.73, 95% CI 1.03-2.94); and lower intake of alcohol (HR 0.54, 95% CI 0.35-0.83) predicted LOS. Eating eggs (HR 1.05, 95% CI 1.01-1.09) and bush meats > or =7 times/month (HR 0.46, 95% CI 0.23-0.92) predicted interval between recurrent admissions. Hypertension (IRR 4.07; 95% CI 1.32-12.52), being an ex-drinker (IRR 6.60, 95% CI 2.30-19.00), eating red meat >6 times/week (IRR 0.98, 95% CI 0.97-0.99), bush meats >7 times/month (IRR 0.26, 95% CI 0.10-0.67), and adding salt to meals (IRR 3.16, 95% CI 1.12-8.92) predicted number of admissions. CONCLUSION: Hypertension, alcohol drinking, smoking, and diet influence hospital admissions for CHD in Aboriginal Australians.

Maternal smoking and low family income during pregnancy as predictors of the relationship between depression and adiposity in young adults.

There is an increasing incidence of overweight/obesity and mental health disorders in young adults and the two conditions often coexist. We aimed to investigate the influence of antenatal and postnatal factors that may underlie this association with a focus on maternal prenatal smoking, socio-economic status and gender. Data from the Western Australian Pregnancy Cohort (Raine) Study (women enrolled 1989-1991) including 1056 offspring aged 20 years (cohort recalled 2010-2012) were analyzed (2015-2016) using multivariable models for associations between offspring depression scores (DASS-21 Depression-scale) and body mass index (BMI), adjusting for pregnancy and early life factors and offspring behaviours. There was a significant positive relationship between offspring depression-score and BMI independent of gender and other psychosocial covariates. There was a significant interaction between maternal prenatal smoking and depression-score (interaction coefficient=0.096; 95% CI: 0.006, 0.19, P=0.037), indicating the relationship between depression-score and BMI differed according to maternal prenatal smoking status. In offspring of maternal prenatal smokers, a positive association between BMI and depression-score (coefficient=0.133; 95% CI: 0.05, 0.21, P=0.001) equated to 1.1 kg/m2 increase in BMI for every 1standard deviation (8 units) increase in depression-score. Substituting low family income during pregnancy for maternal prenatal smoking in the interaction (interaction coefficient=0.091; 95% CI: 0.01, 0.17, P=0.027) showed a positive association between BMI and depression score only among offspring of mothers with a low family income during pregnancy (coefficient=0.118; 95% CI: 0.06, 0.18, P<0.001). There were no significant effects of gender on these associations. Whilst further studies are needed to determine whether these associations are supported in other populations, they suggest potentially important maternal behavioural and socio-economic factors that identify individuals vulnerable to the coexistence of obesity and depression in early adulthood.

Impaired ex vivo leukotriene B4 production characterizes the metabolic syndrome and is improved after weight reduction.

CONTEXT: Neutrophil (polymorphonuclear neutrophil) production of leukotriene B4 (LTB4) may be associated with alterations in immune and inflammatory function that characterize the metabolic syndrome (MetS). OBJECTIVE: We investigated whether polymorphonuclear neutrophil production of LTB(4) and its metabolites 20-hydroxy-LTB4 (20-OH-LTB4) and 20-carboxyl-LTB4 were altered in subjects with features of the MetS before and after weight reduction. DESIGN, SETTING, PATIENTS, AND INTERVENTION: In a case-controlled comparison, men and postmenopausal women with features of the MetS were matched with controls. Subjects with MetS were then matched and randomly assigned to either a 12-wk weight reduction study followed by 4-wk weight stabilization or 16-wk weight maintenance. MAIN OUTCOME MEASURES: Measurements were performed at baseline and at the end of the 16-wk period. Stimulated neutrophil LTB4 and its metabolites were measured by HPLC. RESULTS: In the case-controlled study, body mass index, waist circumference, blood pressure, fasting triglycerides, and glucose were all significantly increased in subjects with features of the MetS (P < 0.05). Production of LTB4 and 20-OH-LTB4 was significantly lower compared with controls (P < 0.005). The weight loss intervention resulted in a 4.6-kg reduction in body weight and 6.6-cm decrease in waist circumference relative to controls and a significant increase in LTB4 and 20-OH-LTB4. CONCLUSIONS: Subjects with features of the MetS have lower stimulated LTB4, which is not due to increased metabolism of LTB4. Weight reduction restored the production of neutrophil LTB4, suggesting that in addition to modifying cardiovascular risk, weight loss may also help with the management of perturbed inflammatory responses in overweight subjects.

The frequency of high-grade intraepithelial neoplasia in anal/perianal warts is higher than previously recognized.

A retrospective review of the prevalence of intraepithelial neoplasia (IN) in surgically removed perianal/anal warts from December 1995 to December 2004 was undertaken in patients referred to the Sexual Health Clinic at Royal Perth Hospital. Data were analysed from 115 men and 38 women, 29 of whom had HIV infection (27 men and two women). Perianal/anal IN within the warts was found in 78% (52% high grade) of men with HIV infection. In men without HIV infection, the overall rate of IN within warts was 33% (20% high grade). The IN rate was 8.3% for HIV-negative women (2.8% high grade). Rates of IN within perianal/anal warts in men with or without HIV infection are higher than previously reported, and suggest the likelihood of a substantial increase in the future incidence of anal cancer. The association between IN and genital warts needs to be further studied.