Abstract
Sleep disorders in adults are associated with adverse health effects including reduced quality of life and increased mortality. However, there is little information on sleep disorders in ...young adults. A cross-sectional observational study was undertaken in 1,227 young adults participating in the Western Australian Pregnancy (Raine) Study (2012–2014) to describe the prevalence of common sleep disorders. In-laboratory polysomnography (PSG) and validated survey methods were used, including the Epworth Sleepiness Scale, Pittsburgh Sleep Symptom Questionnaire-Insomnia, and International Restless Legs Syndrome Study Group criteria. A total of 1,146 participants completed a core questionnaire, 1,051 completed a sleep-focused questionnaire and 935 had analyzable PSG data. Participants had a mean age of 22.2 years and female to male ratio of 1.1 to 1. The respective sleep disorder prevalences in females and males were: obstructive sleep apnea (OSA) (apnea-hypopnea index AHI: ≥5 events/hour) 14.9% (95% CI: 11.8–18.5) and 26.9% (95% CI: 22.9–31.2); chronic insomnia, 19.3% (95% CI: 16.7–23.9) and 10.6% (95% CI: 8.3–13.9); restless legs syndrome, 3.8% (95% CI: 2.4–5.6) and 1.9% (95% CI: 0.9–3.4); and abnormal periodic leg movements during sleep (>5 movements/hour), 8.6% (95% CI: 6.3–11.5) and 9.6% (95% CI: 7.1–12.7). There were statistically significant differences in prevalence between sexes for OSA and insomnia, which persisted after adjustment for body mass index and education. In those with complete data on all sleep-related assessments (n = 836), at least one sleep disorder was present in 41.0% of females and 42.3% of males. Sleep disorders are very common in young adults. Health practitioners should be aware of these high prevalences, as early identification and treatment can improve quality of life and may reduce later morbidity and mortality.
Studies in animal models and in cultured cells have shown that fatty acids can induce alterations in the DNA methylation of specific genes. There have been no studies of the effects of fatty acid ...supplementation on the epigenetic regulation of genes in adult humans.
We investigated the effect of supplementing renal patients with 4 g daily of either n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) or olive oil (OO) for 8 weeks on the methylation status of individual CpG loci in the 5' regulatory region of genes involved in PUFA biosynthesis in peripheral blood mononuclear cells from men and women (aged 53 to 63 years). OO and n-3 LCPUFA each altered (>10% difference in methylation) 2/22 fatty acid desaturase (FADS)-2 CpGs, while n-3 LCPUFA, but not OO, altered (>10%) 1/12 ELOVL5 CpGs in men. OO altered (>6%) 8/22 FADS2 CpGs and (>3%) 3/12 elongase (ELOVL)-5 CpGs, while n-3 LCPUFA altered (>5%) 3/22 FADS2 CpGs and 2/12 (>3%) ELOVL5 CpGs in women. FADS1 or ELOVL2 methylation was unchanged. The n-3 PUFA supplementation findings were replicated in blood DNA from healthy adults (aged 23 to 30 years). The methylation status of the altered CpGs in FADS2 and ELOVL5 was associated negatively with the level of their transcripts.
These findings show that modest fatty acid supplementation can induce altered methylation of specific CpG loci in adult humans, contingent on the nature of the supplement and on sex. This has implications for understanding the effect of fatty acids on PUFA metabolism and cell function.
Abstract
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.
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.
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and is regarded as the hepatic manifestation of the metabolic syndrome. In adults, NAFLD is a determinant of ...arterial stiffness and cardiovascular risk, independent of the metabolic syndrome. Our aim was to ascertain if NAFLD is associated with arterial stiffness, independent of cardiometabolic factors in a population‐based cohort of adolescents. The 17‐year‐olds (n = 964) from an Australian birth cohort had measures of anthropometry, blood pressure, fasting insulin, glucose, lipids, and NAFLD by ultrasound. Two‐step cluster analysis identified youth at high metabolic risk. Measures of arterial stiffness (pulse wave velocity PWV and augmentation index corrected for heart rate AI@75) were obtained using applanation tonometry. The overall prevalence of NAFLD was 13.3%. The “high risk” metabolic cluster at age 17 years included 16% males and 19% females. Compared to “low risk,” the “high risk” cluster participants had greater waist circumference, triglycerides, insulin, systolic blood pressure, and lower high‐density lipoprotein (HDL) cholesterol (all P < 0.0001). Those who had NAFLD but were not in the “high risk” metabolic cluster did not have increased PWV or AI@75. However, males and females who had NAFLD in the presence of the metabolic cluster had greater PWV (b = 0.20, 95% confidence interval CI 0.01 to 0.38, P = 0.037). Males who had NAFLD in the presence of the metabolic cluster had greater AI@75 (b = 6.3, 95% CI 1.9 to 10.7, P = 0.005). Conclusion: NAFLD is only associated with increased arterial stiffness in the presence of the “high risk” metabolic cluster. This suggests that arterial stiffness related to the presence of NAFLD is predicated on the presence of an adverse metabolic profile in adolescents. (Hepatology 2013;58:1306–1314)
ObjectivesOffspring of hypertensive pregnancies have increased cardiovascular risk factors during childhood. We hypothesised that offspring of hypertensive pregnancies would demonstrate increased ...clinical levels of hypertension by young adult life, which would be proportional to the severity of the pregnancy complication.DesignProspective birth cohort studySettingTertiary obstetric hospital.Participants2868 young adult offspring of women enrolled during pregnancy into the Western Australia Pregnancy Cohort (Raine) Study.Main outcome measuresCardiovascular risk, including incidence of hypertension and metabolic disease, in those born to hypertensive compared to normotensive pregnancies.ResultsYoung adult offspring of hypertensive pregnancies were 2.5 times (95% CI 1.32 to 4.56, p=0.004) more likely to have global lifetime risk (QRISK) scores above the 75th centile. Thirty per cent of 20 year olds with hypertensive blood pressures were born following a hypertensive pregnancy. Pre-eclampsia or hypertension resulting in preterm birth associated with a threefold (95% CI 1.3 to 7.0, p=0.01) greater risk of being hypertensive by age 20 years, with no differences in body mass index. Whereas pregnancy-induced hypertension associated with a smaller 3±1 mm Hg blood pressure rise (p=0.001) and a twofold (95% CI 1.5 to 2.8, p=0.001) greater risk of being obese or overweight. Risk factor associations were consistent throughout early life and independent of other birth-factors.ConclusionsIncidence of offspring hypertension was significantly increased in those whose mothers had a more complicated pregnancy history, including preterm birth and pre-eclampsia.
Background: High sugar-sweetened beverage (SSB) consumption is associated with cardiometabolic disturbances in adults, but this relation is relatively unexplored in children and ...adolescents.Objective: We tested the hypothesis that higher SSB intakes are associated with increases in cardiometabolic risk factors between 14 and 17 y of age.Design: Data were provided by 1433 adolescent offspring from the Western Australian Pregnancy Cohort (Raine) Study. At 14 and 17 y of age, SSB intakes were estimated by using a food-frequency questionnaire; body mass index (BMI), waist circumference, blood pressure, fasting serum lipids, glucose, and insulin were measured, and overall cardiometabolic risk was estimated. Prospective associations between cardiovascular disease risk factors and SSB intake were examined with adjustment for age, pubertal stage, physical fitness, socioeconomic status, and major dietary patterns.Results: The average SSB intake in consumers (89%) was 335 g/d or 1.3 servings/d. Girls who moved into the top tertile of SSB consumption (>1.3 servings/d) between 14 and 17 y of age had increases in BMI (3.8%; 95% CI: 1.8%, 5.7%), increased overweight and obesity risk (OR: 4.8, 95% CI: 2.1, 11.4), and greater overall cardiometabolic risk (OR: 3.2; 95% CI: 1.6, 6.2) (all P-trend ≤ 0.001). Girls and boys who moved into the top tertile of SSB intake showed increases in triglycerides (7.0–8.4%; P-trend ≤ 0.03), and boys showed reductions in HDL cholesterol (−3.1%; 95% CI: −6.2%, 0.1%; P-trend < 0.04) independent of BMI. Some associations were attenuated after adjustment for major dietary patterns.Conclusion: Increased SSB intake may be an important predictor of cardiometabolic risk in young people, independent of weight status.
Abstract
Context
“Accelerated aging,” assessed by adult DNA methylation, predicts cardiovascular disease (CVD). Adolescent accelerated aging might predict CVD earlier. We investigated whether ...epigenetic age acceleration (assessed age, 17 years) was associated with adiposity/CVD risk measured (ages 17, 20, and 22 years) and projected CVD by middle age.
Design
DNA methylation measured in peripheral blood provided two estimates of epigenetic age acceleration: intrinsic (IEAA; preserved across cell types) and extrinsic (EEAA; dependent on cell admixture and methylation levels within each cell type). Adiposity was assessed by anthropometry, ultrasound, and dual-energy x-ray absorptiometry (ages 17, 20, and 22 years). CVD risk factors lipids, homeostatic model assessment of insulin resistance (HOMA-IR), blood pressure, inflammatory markers were assessed at age 17 years. CVD development by age 47 years was calculated by Framingham algorithms. Results are presented as regression coefficients per 5-year epigenetic age acceleration (IEAA/EEAA) for adiposity, CVD risk factors, and CVD development.
Results
In 995 participants (49.6% female; age, 17.3 ± 0.6 years), EEAA (per 5 years) was associated with increased body mass index (BMI) of 2.4% (95% CI, 1.2% to 3.6%) and 2.4% (0.8% to 3.9%) at 17 and 22 years, respectively. EEAA was associated with increases of 23% (3% to 33%) in high-sensitivity C-reactive protein, 10% (4% to 17%) in interferon-γ–inducible protein of 10 kDa, and 4% (2% to 6%) in soluble TNF receptor 2, adjusted for BMI and HOMA-IR. EEAA (per 5 years) results in a 4% increase in hard endpoints of CVD by 47 years of age and a 3% increase, after adjustment for conventional risk factors.
Conclusions
Accelerated epigenetic age in adolescence was associated with inflammation, BMI measured 5 years later, and probability of middle age CVD. Irrespective of whether this is cause or effect, assessing epigenetic age might refine disease prediction.
An estimate of biological age determined from peripheral blood DNA from ∼1000 adolescents may refine prediction of cardiovascular risk above and beyond traditional risk factors.
Context:
Obesity and related diseases have become a global public health burden. Identifying biomarkers will lead to a better understanding of the underlying mechanisms associated with obesity and ...the pathways leading to insulin resistance (IR) and diabetes.
Objective:
This study aimed to identify the lipidomic biomarkers associated with obesity and IR using plasma samples from a population-based cohort of young adults.
Design and Setting:
The Western Australian Pregnancy Cohort (Raine) study enrolled 2900 pregnant women from 1989 to 1991. The 20-year follow-up was conducted between March 2010 and April 2012.
Participants and Samples:
Plasma samples from 1176 subjects aged 20 years were analyzed using mass spectrometry-based metabolomics.
Main Outcome Measures:
Associations of analytes with markers of obesity and IR including body mass index, waist circumference, homeostasis model assessment (HOMA-IR), and insulin were examined. Analyses were stratified by body mass index and adjusted for lifestyle and other factors.
Results:
Waist circumference was positively associated with seven sphingomyelins and five diacylphosphatidylcholines and negatively associated with two lysophosphatidylcholines. HOMA-IR was negatively associated with two diacylphosphatidylcholines and positively with one lysophosphatidylcholine and one diacylphosphatidylcholine. No significant association was found in the obese/overweight group of the HOMA-IR model. In the normal-weight group, one lysophosphatidylcholine was increased.
Conclusion:
A possible discriminative effect of sphingomyelins, particularly those with two double bonds, and lysophosphatidylcholines was identified between subjects with normal weight and obesity independent of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol concentrations. Our results suggest weight status-dependent mechanisms for the development of IR with lysophosphatidylcholine C14:0 as a key metabolite in nonobese IR.
Fetal exposure to maternal smoking during pregnancy is associated with the development of noncommunicable diseases in the offspring. Maternal smoking may induce such long-term effects through ...persistent changes in the DNA methylome, which therefore hold the potential to be used as a biomarker of this early life exposure. With declining costs for measuring DNA methylation, we aimed to develop a DNA methylation score that can be used on adolescent DNA methylation data and thereby generate a score for
cigarette smoke exposure.
We used machine learning methods to create a score reflecting exposure to maternal smoking during pregnancy. This score is based on peripheral blood measurements of DNA methylation (Illumina's Infinium HumanMethylation450K BeadChip). The score was developed and tested in the Raine Study with data from 995 white 17-y-old participants using 10-fold cross-validation. The score was further tested and validated in independent data from the Northern Finland Birth Cohort 1986 (NFBC1986) (16-y-olds) and 1966 (NFBC1966) (31-y-olds). Further, three previously proposed DNA methylation scores were applied for comparison. The final score was developed with 204 CpGs using elastic net regression.
Sensitivity and specificity values for the best performing previously developed classifier ("Reese Score") were 88% and 72% for Raine, 87% and 61% for NFBC1986 and 72% and 70% for NFBC1966, respectively; corresponding figures using the elastic net regression approach were 91% and 76% (Raine), 87% and 75% (NFBC1986), and 72% and 78% for NFBC1966.
We have developed a DNA methylation score for exposure to maternal smoking during pregnancy, outperforming the three previously developed scores. One possible application of the current score could be for model adjustment purposes or to assess its association with distal health outcomes where part of the effect can be attributed to maternal smoking. Further, it may provide a biomarker for fetal exposure to maternal smoking. https://doi.org/10.1289/EHP6076.
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