Oral contraceptive use in girls and alcohol consumption in boys are associated with increased blood pressure in late adolescence

Aims: Lifestyle behaviours established during adolescence may adversely affect blood pressure (BP) and contribute to gender differences in cardiovascular risk in adulthood. We aimed to assess the association of health behaviours with BP in adolescents, using data from the Western Australian Pregnancy (Raine) Study. Methods: Cross-sectional analysis on 1248 Raine Study adolescents aged 17 years, to examine associations between lifestyle factors and BP. Results: Boys had 8.97 mmHg higher systolic BP, as compared with girls. The 30% of girls using oral contraceptives (OC) had 3.27 and 1.74 mmHg higher systolic and diastolic BP, respectively, compared with non-users. Alcohol consumption in boys, increasing body mass index (BMI) and the sodium-potassium ratio were associated with systolic BP. We found a continuous relationship between BMI and systolic BP in both genders; however, the gradient of this relationship was significantly steeper in boys, compared with girls not taking OC. In boys, systolic BP was 5.7 mmHg greater in alcohol consumers who were in the upper quartile of BMI and the urinary sodium-potassium ratio compared with teetotallers in the lowest quartile. In girls, systolic BP was 5.5 mmHg higher in those taking OC, in the highest BMI and urinary sodium-potassium ratio quartile as compared to those not taking the OC pill and in the lowest quartile. Conclusion: In addition to gender-related differences in the effects of adiposity on BP, we found lifestyle-related health behaviours such as high salt intake for both sexes, consumption of alcohol in boys, and OC use in girls were important factors associated with BP measurements in late adolescence. This suggests that gender-specific behavioural modification in adolescence may prevent adult hypertension

Fetal growth trajectories and measures of insulin resistance in young adults

Context: Events during gestation greatly influence the risk of cardiometabolic diseases including diabetes in offspring during later life. Objective: This study aimed to investigate relationships between serial ultrasound-derived fetal growth trajectories and markers of insulin resistance in young adults in the Raine Study, an Australian pregnancy cohort. Methods: Linear mixed modeling examined the relationship between fetal growth trajectory groups, constructed using serial ultrasound-based abdominal circumference (AC), femur length (FL), and head circumference (HC) from 1333 mother-fetal pairs, and offspring Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), as a marker of diabetes risk, at 20 (n = 414), 22 (n = 385), and 27 (n = 431) years. Analyses were adjusted for age, sex, ethnicity, socioeconomic status, adult lifestyle factors, and maternal factors during pregnancy. Results: The study identified 7 AC, 5 FL, and 5 HC growth trajectory groups. Compared to the average-stable (reference) group, a low-falling AC growth trajectory (26%; P = .005) and 2 low HC growth trajectories (20%; P = .006% and 8%; P = .021) were associated with higher adult HOMA-IR. Trajectories representing a high-stable FL and a rising HC were associated with 12% (P = .002) and 9% (P = .021) lower adult HOMA-IR, respectively, compared to the reference group. Conclusion: Restricted fetal HC and AC from early pregnancy are associated with higher relative insulin resistance in the offspring during adulthood. These data strengthen our understanding of the importance of the intrauterine environment and its effect on the risk of predisposition to adult diabetes and related metabolic disorders

Relationships between intrauterine fetal growth trajectories and markers of adiposity and inflammation in young adults

Background: There is now good evidence that events during gestation significantly influence the developmental well-being of an individual in later life. This study aimed to investigate the relationships between intrauterine growth trajectories determined by serial ultrasound and subsequent markers of adiposity and inflammation in the 27-year-old adult offspring from the Raine Study, an Australian longitudinal pregnancy cohort. Methods: Ultrasound fetal biometric measurements including abdominal circumference (AC), femur length (FL), and head circumference (HC) from 1333 mother-fetal pairs (Gen1–Gen2) in the Raine Study were used to develop fetal growth trajectories using group-based trajectory modeling. Linear mixed modeling investigated the relationship between adult body mass index (BMI), waist circumference (WC), and high-sensitivity C-reactive protein (hs-CRP) of Gen2 at 20 (n = 485), 22 (n = 421) and 27 (n = 437) years and the fetal growth trajectory groups, adjusting for age, sex, adult lifestyle factors, and maternal factors during pregnancy. Results: Seven AC, five FL and five HC growth trajectory groups were identified. Compared to the average-stable (reference) group, a lower adult BMI was observed in two falling AC trajectories: (β = −1.45 kg/m2, 95% CI: −2.43 to −0.46, P = 0.004) and (β = −1.01 kg/m2, 95% CI: −1.96 to −0.05, P = 0.038). Conversely, higher adult BMI (2.58 kg/m2, 95% CI: 0.98 to 4.18, P = 0.002) and hs-CRP (37%, 95% CI: 9–73%, P = 0.008) were observed in a rising FL trajectory compared to the reference group. A high-stable HC trajectory associated with 20% lower adult hs-CRP (95% CI: 5–33%, P = 0.011). Conclusion: This study highlights the importance of understanding causes of the unique patterns of intrauterine growth. Different fetal growth trajectories from early pregnancy associate with subsequent adult adiposity and inflammation, which predispose to the risk of diabetes and cardiometabolic disease

Association between remnant lipoprotein cholesterol levels and non-alcoholic fatty liver disease in adolescents

Background & Aims: Remnant lipoprotein cholesterol (RLP-C) is an atherogenic lipid profile associated with non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). With increased rates of CVD seen in adults with NAFLD, RLP-C has the potential to identify individuals with NAFLD who are at increased risk of CVD. This study examined in adolescents sex-different associations among RLP-C, NAFLD, and cardiometabolic risk factors, and whether RLP-C is associated with NAFLD beyond traditional cardiometabolic risk factors. Methods: Adolescents in the Raine Study had anthropometry, clinical, biochemistry and arterial stiffness measurements recorded at 17 years of age. Fatty liver, subcutaneous and visceral adipose thickness were assessed using abdominal ultrasound. Relationships among RLP-C, NAFLD, liver biochemistry, insulin resistance, adipokines, adiposity and arterial stiffness were assessed. Results: NAFLD was diagnosed in 15.1% (19.6% females and 10.7% males) of adolescents. Increasing RLP-C levels were associated with increasing severity of hepatic steatosis and metabolic syndrome. Adolescents with NAFLD and serum RLP-C levels in the highest quartile compared with the lowest quartile, had higher serum leptin, homeostatic model assessment of insulin resistance (HOMA-IR), high-sensitivity C-reactive protein, low-density-lipoprotein cholesterol, triglycerides, BMI, subcutaneous and visceral adipose thickness, systolic blood pressure and arterial stiffness, but lower adiponectin and high-density-lipoprotein cholesterol. Using multivariable logistic regression, RLP-C in the lowest quartile compared with the highest quartile was associated with 85% lower odds of NAFLD in males and 55% in females, after adjusting for waist circumference, leptin, ALT, adiponectin and HOMA-IR. Conclusions: There is an association between RLP-C and NAFLD beyond traditional risk factors of adiposity and insulin resistance in adolescents. Although raised serum RLP-C levels were associated with the severity of hepatic steatosis and markers of cardiometabolic risk, lower serum RLP-C might reflect reduced cardiovascular risk. Lay summary: Remnant lipoprotein cholesterol (RLP-C) is a part of the blood cholesterol that is linked with heart disease and non-alcoholic fatty liver disease (NAFLD) in adults. In the Raine Study, teenagers with high RLP-C levels had more severe fat accumulation in their liver. Thus, RLP-C might be the hidden link between NAFLD and future risk of heart disease

Childhood sleep health and epigenetic age acceleration in late adolescence: Cross-sectional and longitudinal analyses

Aim: Investigate if childhood measures of sleep health are associated with epigenetic age acceleration in late adolescence. Methods: Parent-reported sleep trajectories from age 5 to 17, self-reported sleep problems at age 17, and six measures of epigenetic age acceleration at age 17 were studied in 1192 young Australians from the Raine Study Gen2. Results: There was no evidence for a relationship between the parent-reported sleep trajectories and epigenetic age acceleration (p ≥ 0.17). There was a positive cross-sectional relationship between self-reported sleep problem score and intrinsic epigenetic age acceleration at age 17 (b = 0.14, p = 0.04), which was attenuated after controlling for depressive symptom score at the same age (b = 0.08, p = 0.34). Follow-up analyses suggested this finding may represent greater overtiredness and intrinsic epigenetic age acceleration in adolescents with higher depressive symptoms. Conclusion: There was no evidence for a relationship between self- or parent-reported sleep health and epigenetic age acceleration in late adolescence after adjusting for depressive symptoms. Mental health should be considered as a potential confounding variable in future research on sleep and epigenetic age acceleration, particularly if subjective measures of sleep are used

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, or the metabolic syndrome, are increasingly prevalent among children and 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 with 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

Synergy Between Adiposity, Insulin Resistance, Metabolic Risk Factors, and Inflammation in Adolescents

The purpose of this study was to investigate relationships between inflammatory markers and components of a metabolic syndrome cluster in adolescents. This was a cross-sectional analysis of an Australian childhood cohort (n = 1,377) aged 14 years. Cluster analysis defined a "high-risk" group similar to adults with metabolic syndrome. Relevant measures were anthropometry, fasting insulin, glucose, lipids, inflammatory markers, liver function, and blood pressure. Of the children, 29% fell into a high-risk metabolic cluster group compared with 2% by a pediatric metabolic syndrome definition. Relative to the "low-risk" cluster, they had higher BMI (95% CI 19.5-19.8 vs. 24.5-25.4), waist circumference (centimeters) (95% CI 71.0-71.8 vs. 83.4-85.8), insulin (units per liter) (95% CI 1.7-1.8 vs. 3.5-3.9), homeostasis model assessment (95% CI 1.7-1.8 vs. 3.5-3.9), systolic blood pressure (millimeters of mercury) (95% CI 110.8-112.1 vs. 116.7-118.9), and triglycerides (millimoles per liter) (95% CI 0.78-0.80 vs. 1.25-1.35) and lower HDL cholesterol (millimoles per liter) (95% CI 1.44-1.48 vs. 1.20-1.26). Inflammatory and liver function markers were higher in the high-risk group: C-reactive protein (CRP) (P < 0.001), uric acid (P < 0.001), alanine aminotransferase (ALT) (P < 0.001), and γ-glutamyl transferase (GGT) (P < 0.001). The highest CRP, GGT, and ALT levels were restricted to overweight children in the high-risk group. Cluster analysis revealed a strikingly high proportion of 14 year olds at risk of cardiovascular disease-related metabolic disorders. Adiposity and the metabolic syndrome cluster are synergistic in the pathogenesis of inflammation. Systemic and liver inflammation in the high-risk cluster is likely to predict diabetes, cardiovascular disease, and nonalcoholic fatty liver disease

Regular fat and reduced fat dairy products show similar associations with markers of adolescent cardiometabolic health

Reduced fat dairy products are generally recommended for adults and children over the age of two years. However, emerging evidence suggests that dairy fat may not have detrimental health effects. We aimed to investigate prospective associations between consumption of regular versus reduced fat dairy products and cardiometabolic risk factors from early to late adolescence. In the West Australian Raine Study, dairy intake was assessed using semi-quantitative food frequency questionnaires in 860 adolescents at 14 and 17-year follow-ups; 582 of these also had blood biochemistry at both points. Using generalized estimating equations, we examined associations with cardiometabolic risk factors. Models incorporated reduced fat and regular fat dairy together (in serves/day) and were adjusted for a range of factors including overall dietary pattern. In boys, there was a mean reduction in diastolic blood pressure of 0.66 mmHg (95% CI 0.23–1.09) per serve of reduced fat dairy and an independent, additional reduction of 0.47 mmHg (95% CI 0.04–0.90) per serve of regular fat dairy. Each additional serve of reduced fat dairy was associated with a 2% reduction in HDL-cholesterol (95% CI 0.97–0.995) and a 2% increase in total: HDL-cholesterol ratio (95% CI 1.002–1.03); these associations were not observed with regular fat products. In girls, there were no significant independent associations observed in fully adjusted models. Although regular fat dairy was associated with a slightly better cholesterol profile in boys, overall, intakes of both regular fat and reduced fat dairy products were associated with similar cardiometabolic associations in adolescents

DNA methylation of the IGF2/H19 imprinting control region and adiposity distribution in young adults

BACKGROUND: The insulin-like growth factor 2 (IGF2) and H19 imprinted genes control growth and body composition. Adverse in-utero environments have been associated with obesity-related diseases and linked with altered DNA methylation at the IGF2/H19 locus. Postnatally, methylation at the IGF2/H19 imprinting control region (ICR) has been linked with cerebellum weight. We aimed to investigate whether decreased IGF2/H19 ICR methylation is associated with decreased birth and childhood anthropometry and increased contemporaneous adiposity. DNA methylation in peripheral blood (n = 315) at 17 years old was measured at 12 cytosine-phosphate-guanine sites (CpGs), analysed as Sequenom MassARRAY EpiTYPER units within the IGF2/H19 ICR. Birth size, childhood head circumference (HC) at six time-points and anthropometry at age 17 years were measured. DNA methylation was investigated for its association with anthropometry using linear regression. RESULTS: The principal component of IGF2/H19 ICR DNA methylation (representing mean methylation across all CpG units) positively correlated with skin fold thickness (at four CpG units) (P-values between 0.04 to 0.001) and subcutaneous adiposity (P = 0.023) at age 17, but not with weight, height, BMI, waist circumference or visceral adiposity. IGF2/H19 methylation did not associate with birth weight, length or HC, but CpG unit 13 to 14 methylation was negatively associated with HC between 1 and 10 years. β-coefficients of four out of five remaining CpG units also estimated lower methylation with increasing childhood HC. CONCLUSIONS: As greater IGF2/H19 methylation was associated with greater subcutaneous fat measures, but not overall, visceral or central adiposity, we hypothesize that obesogenic pressures in youth result in excess fat being preferentially stored in peripheral fat depots via the IGF2/H19 domain. Secondly, as IGF2/H19 methylation was not associated with birth size but negatively with early childhood HC, we hypothesize that the HC may be a more sensitive marker of early life programming of the IGF axis and of fetal physiology than birth size. To verify this, investigations of the dynamics of IGF2/H19 methylation and expression from birth to adolescence are required

Serum 25-hydroxyvitamin D concentrations and cardiometabolic risk factors in adolescents and young adults

Evidence associating serum 25-hydroxyvitamin D (25(OH)D) concentrations and cardiometabolic risk factors is inconsistent and studies have largely been conducted in adult populations. We examined the prospective associations between serum 25(OH)D concentrations and cardiometabolic risk factors from adolescence to young adulthood in the West Australian Pregnancy Cohort (Raine) Study. Serum 25(OH)D concentrations, BMI, homoeostasis model assessment for insulin resistance (HOMA-IR), TAG, HDL-cholesterol and systolic blood pressure (SBP) were measured at the 17-year (n 1015) and 20-year (n 1117) follow-ups. Hierarchical linear mixed models with maximum likelihood estimation were used to investigate associations between serum 25(OH)D concentrations and cardiometabolic risk factors, accounting for potential confounders. In males and females, respectively, mean serum 25(OH)D concentrations were 73·6 (sd 28·2) and 75·4 (sd 25·9) nmol/l at 17 years and 70·0 (sd 24·2) and 74·3 (sd 26·2) nmol/l at 20 years. Deseasonalised serum 25(OH)D3 concentrations were inversely associated with BMI (coefficient -0·01; 95 % CI -0·03, -0·003; P=0·014). No change over time was detected in the association for males; for females, the inverse association was stronger at 20 years compared with 17 years. Serum 25(OH)D concentrations were inversely associated with log-HOMA-IR (coefficient -0·002; 95 % CI -0·003, -0·001; P<0·001) and positively associated with log-TAG in females (coefficient 0·002; 95 % CI 0·0008, 0·004; P=0·003). These associations did not vary over time. There were no significant associations between serum 25(OH)D concentrations and HDL-cholesterol or SBP. Clinical trials in those with insufficient vitamin D status may be warranted to determine any beneficial effect of vitamin D supplementation on insulin resistance, while monitoring for any deleterious effect on TAG