Publications by authors named "Trevor A Mori"

236 Publications

Genome-wide analysis of thyroid function in Australian adolescents highlights SERPINA7 and NCOA3.

Eur J Endocrinol 2021 Sep 1. Epub 2021 Sep 1.

S Wilson, Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Australia.

Objective Genetic factors underpin the narrow intraindividual variability of thyroid function, although precise contributions of environmental versus genetic factors remain uncertain. We sought to clarify the heritability of thyroid function traits and thyroid peroxidase antibody (TPOAb) positivity and identify single nucleotide polymorphisms (SNPs) contributing to the trait variance. Methods Heritability of thyroid stimulating hormone (TSH), free T4 (fT4), free T3 (fT3) and TPOAb in a cohort of 2854 euthyroid, dizygous and monozygous twins (age range 11.9-16.9 years) from the Brisbane Longitudinal Twin Study (BLTS) was assessed using structural equation modelling. A genome-wide analysis was conducted on 2832 of these individuals across 7,522,526 single nucleotide polymorphisms as well as gene-based association analyses. Replication analysis of the association results was performed in the Raine Study (n= 1115) followed by meta-analysis to maximise power for discovery. Results Heritability of thyroid function parameters in the BLTS was 70.8% (95% CI: 66.7-74.9%) for TSH, 67.5% (59.8-75.3%) for fT4, 59.7% (54.4-65.0%) for fT3 and 48.8% (40.6-56.9%) for TPOAb. The genome-wide association study (GWAS) in the discovery cohort identified a novel association between rs2026401 upstream of NCOA3 and TPOAb. GWAS meta-analysis found associations between TPOAb and rs445219, also near NCOA3, and fT3 and rs12687280 near SERPINA7. Gene-based association analysis highlighted SERPINA7 for fT3 and NPAS3 for fT4. Conclusion Our findings resolve former contention regarding heritability estimates of thyroid function traits and TPOAb positivity. GWAS and gene-based association analysis identified variants accounting for a component of this heritability.
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http://dx.doi.org/10.1530/EJE-21-0614DOI Listing
September 2021

Beneficial effects of inorganic nitrate in non-alcoholic fatty liver disease.

Arch Biochem Biophys 2021 Oct 11;711:109032. Epub 2021 Sep 11.

Medical School, University of Western Australia, Perth, WA, Australia; Dobney Hypertension Centre, Medical School, University of Western Australia, Perth, WA, Australia. Electronic address:

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic representation of the metabolic disorders. Inorganic nitrate/nitrite can be converted to nitric oxide, regulate glucose metabolism, lower lipid levels, and reduce inflammation, thus raising the hypothesis that inorganic nitrate/nitrite could be beneficial for improving NAFLD. This study assessed the therapeutic effects of chronic dietary nitrate on NAFLD in a mouse model. 60 ApoE mice were fed a high-fat diet (HFD) for 12 weeks to allow for the development of atherosclerosis with associated NAFLD. The mice were then randomly assigned to different groups (20/group) for a further 12 weeks: (i) HFD + NaCl (1 mmol/kg/day), (ii) HFD + NaNO (1 mmol/kg/day), and (iii) HFD + NaNO (10 mmol/kg/day). A fourth group of ApoE mice consumed a normal chow diet for the duration of the study. At the end of the treatment, caecum contents, serum, and liver were collected. Consumption of the HFD resulted in significantly greater lipid accumulation in the liver compared to mice on the normal chow diet. Mice whose HFD was supplemented with dietary nitrate for the second half of the study, showed an attenuation in hepatic lipid accumulation. This was also associated with an increase in hepatic AMPK activity compared to mice on the HFD. In addition, a significant difference in bile acid profile was detected between mice on the HFD and those receiving the high dose nitrate supplemented HFD. In conclusion, dietary nitrate attenuates the progression of liver steatosis in ApoE mice fed a HFD.
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http://dx.doi.org/10.1016/j.abb.2021.109032DOI Listing
October 2021

The effects of perioperative dexamethasone on eicosanoids and mediators of inflammation resolution: A sub-study of the PADDAG trial.

Prostaglandins Leukot Essent Fatty Acids 2021 Aug 17;173:102334. Epub 2021 Aug 17.

Medical School, Royal Perth Hospital Unit University of Western Australia, Australia.

Introduction: Dexamethasone is an antiemetic that is frequently administered before or after the induction of anesthesia for prevention and treatment of perioperative nausea and vomiting. Dexamethasone has anti-inflammatory and immunosuppressive effects primarily via suppression of expression of inflammatory mediators. However, its effect on the eicosanoids and docosanoids that mediate the inflammatory response and inflammation resolution are unclear. We aimed to assess the effect of a single dose of intra-operative dexamethasone on peri‑operative eicosanoids involved in inflammation including leukotriene B (LTB) and 20-hydroxyeicosatetraenoic acid (20-HETE), and inflammation resolution (Specialised Proresolving Mediators (SPM)).

Patients And Methods: A subgroup of 80 patients from the randomised controlled PADDAG trial was enrolled into this substudy. They were allocated to receive 0, 4 or 8 mg dexamethasone administered intravenously at induction of anesthesia. Blood samples were collected before and 24 h after dexamethasone, for measurement of leukocytes, hs-CRP, LTB 20-HETE, the SPM pathway intermediates (14-HDHA, 18-HEPE and 17-HDHA) and SPMs (E-series resolvins, and d-series resolvins).

Results: Compared to the administration of placebo, neutrophil count was elevated (P<0.05) 24 h after administration of 4 and 8 mg dexamethasone. Dexamethasone (8 mg) resulted in increased levels of LTB (P = 0.012) and 20-HETE (P = 0.009) and reduced hs-CRP levels (P<0.001). Dexamethasone did not significantly affect plasma SPM pathway intermediates or RvE3.

Conclusion: Antiemetic doses of dexamethasone given during surgery increased plasma LTB and 20-HETE at a time when hs-CRP was significantly reduced. Plasma SPM pathway intermediates and RvE3 were unaffected.
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http://dx.doi.org/10.1016/j.plefa.2021.102334DOI Listing
August 2021

Omega-3 Index, fish consumption, use of fish oil supplements and first clinical diagnosis of central nervous system demyelination.

Mult Scler Relat Disord 2021 Aug 10;55:103210. Epub 2021 Aug 10.

Curtin School of Population Health, Curtin University, Perth, WA, Australia. Electronic address:

Higher intakes of omega-3 polyunsaturated fatty acids (n3PUFAs) have been associated with lower MS risk. We aimed to test associations between the Omega-3 Index, blood levels of n3PUFAs, fish oil supplement use, and fish consumption with a first clinical diagnosis of CNS demyelination (FCD). Cases (n = 250) had a higher Omega-3 Index compared with a matched group of controls (n = 471) (average treatment effect (ATE)=0.31, p = 0.047, based on augmented inverse probability weighting). A higher percentage of cases than controls used fish oil supplements (cases=17% vs. controls=10%). We found that Omega-3 Index increased as time between FCD and study interview increased (e.g., at or below median (112 days), based on ATE, mean=5.30, 95% CI 5.08, 5.53; above median, mean=5.90, 95% CI 5.51, 6.30). Fish oil supplement use increased in a similar manner (at or below median (112 days), based on ATE, proportion=0.12, 95% CI 0.06, 0.18; above the median, proportion=0.21, 95% CI 0.14, 0.28). Our results suggest a behaviour change post FCD with increased use of fish oil supplements.
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http://dx.doi.org/10.1016/j.msard.2021.103210DOI Listing
August 2021

The interactions between genetics and early childhood nutrition influence adult cardiometabolic risk factors.

Sci Rep 2021 Jul 21;11(1):14826. Epub 2021 Jul 21.

School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia.

It is well established that genetics, environment, and interplay between them play a crucial role in adult disease. We aimed to evaluate the role of genetics, early life nutrition, and the interaction between them, on optimal adult health. As part of a large international consortium (n ~ 154,000), we identified 60 SNPs associated with both birthweight and adult disease. Utilising the Raine Study, we developed a birthweight polygenic score (BW-PGS) based on the 60 SNPs and examined relationships between BW-PGS and adulthood cardiovascular risk factors, specifically evaluating interactions with early life nutrition. Healthy nutrition was beneficial for all individuals; longer duration of any breastfeeding was particularly associated with lower BMI and lower Systolic Blood Pressure in those with higher BW-PGS. Optimal breastfeeding offers the greatest benefit to reduce adult obesity and hypertension in those genetically predisposed to high birthweight. This provides an example of how precision medicine in early life can improve adult health.
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http://dx.doi.org/10.1038/s41598-021-94206-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295375PMC
July 2021

Relationship Between the Aldosterone-to-Renin Ratio and Blood Pressure in Young Adults: A Longitudinal Study.

Hypertension 2021 Aug 14;78(2):387-396. Epub 2021 Jun 14.

Medical School, The University of Western Australia (L.J.B., T.A.M.).

[Figure: see text].
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17336DOI Listing
August 2021

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 06 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

Participation in sport in childhood and adolescence: Implications for adult fitness.

J Sci Med Sport 2021 Sep 12;24(9):908-912. Epub 2021 May 12.

School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Australia. Electronic address:

Objectives: To investigate whether participation in sport during the developmental stages of life is associated with cardiorespiratory fitness (CRF) in adulthood.

Design: Observational longitudinal study.

Methods: Participants were Generation 2 of the Raine Study. Questionnaires related to participation in sport were administered at ages 5, 8, 10, 14 and 17 years. These data were used to develop sex-specific trajectories of sports participation: (for males) Consistent Participators, Drop-Outs and Joiners; and (females) Consistent Participators, Non-Participators and Drop-Outs. At age 28.3 ± 0.6 years, participants completed a graded maximal exercise test (i.e. V̇Opeak test). A General Linear Model assessed differences in CRF between trajectories.

Results: 402 participants n = 231 (57.5%) male, n = 171 (42.5%) female were included in the study. In males, Consistent Participators (all p < 0.001) and Joiners (p < 0.050) had greater fitness than Drop-Outs. In females, Consistent Participators had greater fitness than Non-Participators (p < 0.050), but there were no significant differences in fitness between Consistent Participators and Drop-Outs (p > 0.050) or Non-Participators and Drop-Outs (p > 0.050).

Conclusion: Participation in sport during childhood and adolescence is associated with greater fitness in adulthood, compared to individuals who never participate or those that cease participation in adolescence. A simple dichotomous question regarding sports participation over the childhood and adolescent period can be implemented to predict better fitness outcomes in young adulthood. Childhood and adolescence could be an opportune stage in life for parents, schools and governments to facilitate participation in sport and prevent drop out, as it may have an impact on long term risk reduction, with associated health and economic benefits.
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http://dx.doi.org/10.1016/j.jsams.2021.05.004DOI Listing
September 2021

Prenatal Testosterone Associates With Blood Pressure in Young Adults: A Prospective Cohort Study.

Hypertension 2021 May 29;77(5):1756-1764. Epub 2021 Mar 29.

From the Medical School, Royal Perth Hospital Campus (C.L-H, L.J.B., S.B., T.A.M.), the University of Western Australia, Perth.

[Figure: see text].
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16256DOI Listing
May 2021

Epigenome-Wide Association Study of Thyroid Function Traits Identifies Novel Associations of fT3 With KLF9 and DOT1L.

J Clin Endocrinol Metab 2021 04;106(5):e2191-e2202

Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.

Context: Circulating concentrations of free triiodothyronine (fT3), free thyroxine (fT4), and thyrotropin (TSH) are partly heritable traits. Recent studies have advanced knowledge of their genetic architecture. Epigenetic modifications, such as DNA methylation (DNAm), may be important in pituitary-thyroid axis regulation and action, but data are limited.

Objective: To identify novel associations between fT3, fT4, and TSH and differentially methylated positions (DMPs) in the genome in subjects from 2 Australian cohorts.

Method: We performed an epigenome-wide association study (EWAS) of thyroid function parameters and DNAm using participants from: Brisbane Systems Genetics Study (median age 14.2 years, n = 563) and the Raine Study (median age 17.0 years, n = 863). Plasma fT3, fT4, and TSH were measured by immunoassay. DNAm levels in blood were assessed using Illumina HumanMethylation450 BeadChip arrays. Analyses employed generalized linear mixed models to test association between DNAm and thyroid function parameters. Data from the 2 cohorts were meta-analyzed.

Results: We identified 2 DMPs with epigenome-wide significant (P < 2.4E-7) associations with TSH and 6 with fT3, including cg00049440 in KLF9 (P = 2.88E-10) and cg04173586 in DOT1L (P = 2.09E-16), both genes known to be induced by fT3. All DMPs had a positive association between DNAm and TSH and a negative association between DNAm and fT3. There were no DMPs significantly associated with fT4. We identified 23 differentially methylated regions associated with fT3, fT4, or TSH.

Conclusions: This study has demonstrated associations between blood-based DNAm and both fT3 and TSH. This may provide insight into mechanisms underlying thyroid hormone action and/or pituitary-thyroid axis function.
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http://dx.doi.org/10.1210/clinem/dgaa975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063248PMC
April 2021

Coronary F-sodium fluoride PET detects high-risk plaque features on optical coherence tomography and CT-angiography in patients with acute coronary syndrome.

Atherosclerosis 2021 02 15;319:142-148. Epub 2020 Dec 15.

Department of Cardiology, Royal Perth Hospital, Perth, Western Australia, Australia; Medical School, University of Western Australia, Perth, Western Australia, Australia. Electronic address:

Background And Aims: F-Sodium Fluoride Positron Emission Tomography (F-NaF PET) non-invasively detects micro-calcification activity, the earliest stage of atherosclerotic arterial calcification. We studied the association between coronary F-NaF uptake and high-risk plaque features on intra-coronary optical coherence tomography (OCT) and CT-angiography (CTCA) and the potential application to patient-level risk stratification.

Methods: Sixty-two prospectively recruited patients with acute coronary syndrome (ACS) underwent multi-vessel OCT, F-NaF PET and CTCA. The maximum tissue to background ratio (TBRmax = standardised uptake value (SUV)max/SUVbloodpool) was measured in each coronary segment on F-NaF PET scans. High-risk plaque features on OCT and CTCA were compared in matched coronary segments. The number of patients testing positive (>2SD above the normal range) for micro-calcification activity was determined.

Results: In 62 patients (age, mean ± standard deviation (SD) = 61 ± 9 years, 85% male) the coronary segments with elevated F-NaF uptake had higher lipid arc (LA) (median [25th-75th centile]: 74° [35°-117°] versus 48° [15°-83°], p=0.021), higher prevalence of macrophages [n(%): 37 (62%) versus 89 (39%), p=0.008] and lower plaque free wall (PFW) (50° [7°-110°] versus 94° [34°-180°], p=0.027) on OCT, and a higher total plaque burden (p=0.011) and higher dense calcified plaque burden (p= 0.001) on CTCA, when compared with F-NaF negative segments. Patients grouped by increasing number of coronary lesions positive for microcalcification activity (0,1, ≥2) showed decreasing plaque free wall, increasing calcification and increasing macrophages on OCT (respectively p=0.008, p < 0.001 and p=0.028).

Conclusions: F-NaF uptake is associated with high-risk plaque features on OCT and CTCA in a per-segment and per-patient analysis in subjects hospitalized for ACS.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.12.010DOI Listing
February 2021

Increased inspired oxygen concentration does not adversely affect oxidative stress and the resolution of inflammation during reperfusion in patients undergoing knee replacement surgery.

Free Radic Res 2021 Feb 11;55(2):131-140. Epub 2021 Jan 11.

Medical School, Royal Perth Hospital Unit, University of Western Australia, Perth, Australia.

The level of inspired oxygen during surgery may modify free radical release, and reperfusion injury. This controlled trial examined the effect of inspired oxygen on F-isoprostanes (F-IsoPs), isofurans (IsoFs), and specialized mediators of inflammation resolution (SPM) during knee replacement surgery. Patients received either 30% O (control  = 21), 50% O ( = 20), or 80% O ( = 19) O, in a parallel design. Hemoglobin (Hb) was measured throughout the surgery and F-IsoPs, IsoFs and SPM were analyzed by mass spectrometry. The effect of O on F-IsoPs and IsoFs was examined during tourniquet inflation and after tourniquet release. SPM were measured at baseline and the end of surgery. There was a significant interaction between O and Hb concentrations with plasma IsoFs during tourniquet inflation. An increase in plasma IsoFs over time was attenuated in the 80% O group (=.012) compared with the 30% O group after adjusting for Hb concentration. After tourniquet release, plasma F-IsoPs were significantly lower in the 50% and 80% O groups (=.009 and =.001, respectively) compared with the 30% O group after adjustment for Hb concentration. The SPM RvD2 and RvE2 were increased with 50% and 80% O (RvD2, =.014 and =.002, respectively; RvE2, =.032 with 50% O) compared with the 30% O group, in analyses that corrected for Hb concentration. We have shown for the first time that higher O levels may be beneficial in reducing oxidative stress and increasing resolution of inflammation during surgery that involves reperfusion after application of a tourniquet.
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http://dx.doi.org/10.1080/10715762.2020.1868451DOI Listing
February 2021

Validation of fatty liver disease scoring systems for ultrasound diagnosed non-alcoholic fatty liver disease in adolescents.

Dig Liver Dis 2021 Jun 14;53(6):746-752. Epub 2020 Dec 14.

Menzies Institute for Medical Research, University of Tasmania. Electronic address:

Background And Aims: The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing in young populations. However, there are inadequate data regarding diagnosis of NAFLD. We aimed to validate three scoring systems against a previous standard of suprailiac skinfold thickness for diagnosing NAFLD in population-based adolescents.

Methods: Seventeen-year-old adolescents (n = 899), participating in the Raine Study, attended a cross-sectional follow-up. NAFLD was diagnosed using liver ultrasound. Scores for Fatty liver index (FLI), Hepatic Steatosis Index (HSI) and Zhejiang University index (ZJU index) were calculated. Diagnostic accuracy of these diagnostic tests was evaluated through discrimination and calibration.

Results: NAFLD was diagnosed 9% in males and 15% in females. The three scoring systems demonstrated better discrimination performance for NAFLD in males (AUC was FLI:0.82, HSI: 0.83 and ZJU index: 0.83) compared to females (AUC was FLI: 0.67, HSI: 0.67 and ZJU index: 0.67). Suprailiac skinfold performed better than the scoring systems (overall AUC: 0.82; male AUC:0.88; female AUC:0.73). FLI had best calibration performance.

Conclusion: Suprailiac skinfold thickness was a better predictor of ultrasound-diagnosed NAFLD than the three diagnostic scoring systems investigated. The higher performance characteristics of the algorithmic scoring systems in males compared with females may have implications for use in population assessments.
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http://dx.doi.org/10.1016/j.dld.2020.11.037DOI Listing
June 2021

DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies.

Genome Med 2020 11 25;12(1):105. Epub 2020 Nov 25.

University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, the Netherlands.

Background: DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits.

Methods: We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment.

Results: DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P < 1.06 × 10, with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth P = 1; childhood P = 2.00 × 10; adolescence P = 2.10 × 10).

Conclusions: There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.
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http://dx.doi.org/10.1186/s13073-020-00810-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687793PMC
November 2020

Dietary management of cardiovascular risk including type 2 diabetes.

Curr Opin Endocrinol Diabetes Obes 2021 04;28(2):134-141

Medical School, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Australia.

Purpose Of Review: Recent changes or confirmations linking patterns of eating and specific dietary interventions in the management of cardiovascular risk factors including associations with prevalent and incident type 2 diabetes.

Recent Findings: Recently published guidance for dietary management of cardiovascular risk and type 2 diabetes have mostly common features. Major findings include a trend to replace strict quantitative advice on nutrients with qualitative advice on food consumption with exceptions for diabetes, global advice to increase intake of plant foods, confirmation to substitute mono and polyunsaturated oils for saturated and trans fats, new advisory on supplemental omega-3 intake, less limitation on dairy foods and fermented dairy foods encouraged, reduced emphasis on specific cholesterol-rich foods allowing greater consumption of eggs except for people with diabetes, processed meat consumption limited allowing modest intake of lean red meat, distinguishing between 'healthy' and 'unhealthy' carbohydrates including sugars, and maintaining advice on healthy bodyweight, reducing salt intake and encouraging water as preferred beverage.

Summary: The new guidance for healthier patterns of food consumption supported by evidence is more readily understood by health practitioners and translatable to consumers and patients.
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http://dx.doi.org/10.1097/MED.0000000000000589DOI Listing
April 2021

Practical Guidance for Food Consumption to Prevent Cardiovascular Disease.

Heart Lung Circ 2021 Feb 3;30(2):163-179. Epub 2020 Nov 3.

Medical School, University of Western Australia, Perth, WA, Australia.

This dietary guidance, informed by best contemporary evidence, aims to assist medical practitioners and allied health professionals in advising patients for the primary and secondary prevention of cardiovascular disease (CVD). While differing in some details from other current guidelines, the core messages accord with those published in 2019 by the American College of Cardiology/American Heart Association and the European Society of Cardiology/European Atherosclerosis Society; the National Lipid Association in 2014 and the NH&MRC Australian Dietary Guidelines in 2013. These were assessed through the Appraisal of Guidelines for Research and Evaluation (AGREE II) and the levels of evidence and classes of a recommendation developed using the GRADE system. Recommendations with high levels of evidence include increased consumption of plant based foods comprising mainly complex, fibre enriched carbohydrates (wholegrains, fruits and vegetables) while limiting intake of refined starches; partial replacement of saturated fats with monounsaturated or polyunsaturated fats and oils; reduced salt intake; achievement and maintenance of healthy weight; and low-to-moderate consumption of alcohol. Additional guidance but with moderate levels of evidence includes increased consumption of fish (and fish oils where indicated); reduction in sugar-sweetened beverages and added sugars; avoidance of butter and cream especially in those at increased CVD risk but encouragement of yoghurt; allow moderate consumption of lean meat but limit intake of processed meats; and limit cholesterol-rich foods such as eggs and crustaceans for those at increased CVD risk. Guidance has been formulated qualitatively on food categories of commonly eaten foods while avoiding prescriptive quantitative measures that are less readily translatable. This approach accords with current guidelines such as the American College of Cardiology/American Heart Association 2019 guidelines and is understandable and readily implemented.
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http://dx.doi.org/10.1016/j.hlc.2020.08.022DOI Listing
February 2021

Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.

PLoS Genet 2020 10 12;16(10):e1008718. Epub 2020 Oct 12.

Department of Public Health, Amsterdam Public Health Research Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.
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http://dx.doi.org/10.1371/journal.pgen.1008718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581004PMC
October 2020

Changing dietary approaches to prevent cardiovascular disease.

Curr Opin Lipidol 2020 12;31(6):313-323

Medical School, University of Western Australia, Perth, Australia.

Purpose Of Review: We have focused on recent research relevant to effects of dietary patterns and major food groups on cardiovascular outcomes, taking into account guidelines and position statements from expert authorities, with an emphasis on important changes in recommendations, some of which remain controversial.

Recent Findings: Major findings include: refocusing on qualitative patterns of food consumption replacing quantitative prescriptive advice on nutrients; increasing intake of plant foods; substituting saturated fats with polyunsaturated and monounsaturated oils; reducing salt intake; regular consumption of fish with a focus on omega-3 enrichment; not restricting dairy foods, other than butter and cream, with encouragement of some fermented products; reducing cholesterol intake for those at increased cardiovascular risk and diabetes, allowing 7-eggs weekly; restricting processed meats and allowing moderate lean meat consumption; preference for fiber-rich complex carbohydrates and reduced sugar intake; maintaining healthy bodyweight; and although water is the preferred beverage, allowing moderate alcohol consumption to national guidelines and avoiding alcohol in specific cardiovascular disorders.

Summary: The new approach that focuses on healthier patterns of food intake is more readily understood by health practitioners and translatable to consumers and patients.
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http://dx.doi.org/10.1097/MOL.0000000000000709DOI Listing
December 2020

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

JHEP Rep 2020 Dec 24;2(6):100150. Epub 2020 Jul 24.

Department of Gastroenterology and Hepatology, Fiona Stanley Hospital, Murdoch, WA, Australia.

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.
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http://dx.doi.org/10.1016/j.jhepr.2020.100150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495103PMC
December 2020

Machine Learning-Based DNA Methylation Score for Fetal Exposure to Maternal Smoking: Development and Validation in Samples Collected from Adolescents and Adults.

Environ Health Perspect 2020 09 15;128(9):97003. Epub 2020 Sep 15.

Telethon Kids Institute, University of Western Australia, Nedlands, Perth, Western Australia, Australia.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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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http://dx.doi.org/10.1289/EHP6076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491641PMC
September 2020

Methylome-wide association study of central adiposity implicates genes involved in immune and endocrine systems.

Epigenomics 2020 09 9;12(17):1483-1499. Epub 2020 Sep 9.

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

We conducted a methylome-wide association study to examine associations between DNA methylation in whole blood and central adiposity and body fat distribution, measured as waist circumference, waist-to-hip ratio and waist-to-height ratio adjusted for body mass index, in 2684 African-American adults in the Atherosclerosis Risk in Communities study. We validated significantly associated cytosine-phosphate-guanine methylation sites (CpGs) among adults using the Women's Health Initiative and Framingham Heart Study participants (combined n = 5743) and generalized associations in adolescents from The Raine Study (n = 820). We identified 11 CpGs that were robustly associated with one or more central adiposity trait in adults and two in adolescents, including CpG site associations near , ,  and that had not previously been associated with obesity-related traits.
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http://dx.doi.org/10.2217/epi-2019-0276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923253PMC
September 2020

rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis.

J Hepatol 2021 01 31;74(1):20-30. Epub 2020 Aug 31.

MRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, UK.

Background & Aims: A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in NAFLD; however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and to characterise its role in the regulation of related metabolic phenotypes through a meta-analysis.

Methods: We performed a meta-analysis of studies with data on the association between rs641738C>T genotype and liver fat, NAFLD histology, and serum alanine aminotransferase (ALT), lipids or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed a random effects meta-analysis using recessive, additive and dominant genetic models.

Results: Data from 1,066,175 participants (9,688 with liver biopsies) across 42 studies were included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI 0.02-0.05], p = 4.8×10) and diagnosis of NAFLD (odds ratio [OR] 1.17 [95% CI 1.05-1.3], p = 0.003) in Caucasian adults. The variant was also positively associated with presence of advanced fibrosis (OR 1.22 [95% CI 1.03-1.45], p = 0.021) in Caucasian adults using a recessive model of inheritance (CC + CT vs. TT). Meta-analysis of data from previous GWAS found the variant to be associated with higher ALT (p = 0.002) and lower serum triglycerides (p = 1.5×10). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD.

Conclusions: Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent.

Lay Summary: Fatty liver disease is a common condition where fat builds up in the liver, which can cause liver inflammation and scarring (including 'cirrhosis'). It is closely linked to obesity and diabetes, but some genes are also thought to be important. We did this study to see whether one specific change ('variant') in one gene ('MBOAT7') was linked to fatty liver disease. We took data from over 40 published studies and found that this variant near MBOAT7 is linked to more severe fatty liver disease. This means that drugs designed to work on MBOAT7 could be useful for treating fatty liver disease.
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http://dx.doi.org/10.1016/j.jhep.2020.08.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755037PMC
January 2021

Dietary fibre intake and its associations with depressive symptoms in a prospective adolescent cohort.

Br J Nutr 2021 05 3;125(10):1166-1176. Epub 2020 Sep 3.

Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS7000, Australia.

Depression is a major cause of disability in adolescents. Higher dietary fibre intake has been associated with lower depressive symptoms in adults, but there is a lack of research in adolescents. We examined the association between dietary fibre intake (Commonwealth Scientific and Industrial Research Organisation (CSIRO) FFQ) and depressive symptoms (Beck Depression Inventory for Youth) in adolescents with prospective data from the Raine Study Gen2 14- and 17-year follow-ups (n 1260 and 653). Odds of moderate/extreme (clinically relevant) depressive symptoms by quartile of fibre intake were calculated using mixed-effects logistic regression for all participants, in a paired sample without moderate/extreme depressive symptoms at 14 years and in a sub-sample of participants with available inflammatory data at the ages of 14 and 17 years (n 718 and 547). Odds of moderate/extreme depressive symptoms were lower in the fourth (highest) quartile of overall fibre intake (OR 0·273, 95 % CI 0·09, 0·81) compared with the first (lowest) quartile, adjusting for sex, age, energy intake, adiposity, and family and lifestyle factors. However, further adjustment for dietary patterns attenuated the results. Associations of depressive symptoms with cereal or fruit and vegetable fibre intake were not significant in the final model. Adjustment for inflammation had no effect on OR. The association between a higher dietary fibre intake and lower odds of clinically relevant depressive symptoms may be more reflective of a high-fibre diet with all its accompanying nutrients than of an independent effect of fibre.
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http://dx.doi.org/10.1017/S0007114520003426DOI Listing
May 2021

ApoB48-Lipoproteins Are Associated with Cardiometabolic Risk in Adolescents with and without Polycystic Ovary Syndrome.

J Endocr Soc 2020 Aug 26;4(8):bvaa061. Epub 2020 May 26.

Medical School, University of Western Australia, Royal Perth Hospital Unit, Perth, Australia.

Context: Adolescents with polycystic ovary syndrome (PCOS) have increased incidence of cardiometabolic risk factors including dyslipidemia. Atherogenic apolipoprotein (apo) B-lipoprotein remnants are associated with increased cardiovascular disease (CVD) risk.

Objective: The aim of this study was to determine the concentrations of fasting plasma apoB-lipoprotein remnants, apoB48 and apoB100, and their association with cardiometabolic risk factors and androgen indices in adolescent girls with and without PCOS.

Design Setting And Participants: Participants (n = 184) aged 17 years were recruited in the Menstruation in Teenagers Study from the Western Australian Pregnancy Cohort (Raine) Study.

The Main Outcome Measures: Fasting plasma apo-B48 and -B100 lipoprotein remnant concentrations in adolescent girls with and without PCOS.

Results: Fasting plasma apoB48-lipoprotein remnants but not apoB100-lipoprotein remnants were elevated in adolescent girls with increased cardiometabolic risk compared with those with lower cardiometabolic risk (13.91 ± 5.06 vs 12.09 ± 4.47 µg/mL, < .01). ApoB48-lipoprotein remnants were positively correlated with fasting plasma triglycerides (b = .43, < .0001). The prevalence of increased cardiometabolic risk factors was 2-fold higher in those diagnosed with PCOS (35.3%) than in those without PCOS (16.3%). Adolescents with PCOS have a 2-fold higher incidence of cardiometabolic risk factors than those without PCOS. Fasting apoB48-lipoprotein remnants are elevated in adolescent girls with a high prevalence of cardiometabolic risk factors.
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http://dx.doi.org/10.1210/jendso/bvaa061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417872PMC
August 2020

MitoQ and CoQ10 supplementation mildly suppresses skeletal muscle mitochondrial hydrogen peroxide levels without impacting mitochondrial function in middle-aged men.

Eur J Appl Physiol 2020 Jul 26;120(7):1657-1669. Epub 2020 May 26.

Discipline of Nutrition, School of Medical Sciences, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, 92019, Auckland, New Zealand.

Purpose: Excess production of reactive oxygen species (ROS) from the mitochondria can promote mitochondrial dysfunction and has been implicated in the development of a range of chronic diseases. As such there is interest in whether mitochondrial-targeted antioxidant supplementation can attenuate mitochondrial-associated oxidative stress. We investigated the effect of MitoQ and CoQ10 supplementation on oxidative stress and skeletal muscle mitochondrial ROS levels and function in healthy middle-aged men.

Methods: Skeletal muscle and blood samples were collected from twenty men (50 ± 1 y) before and following six weeks of daily supplementation with MitoQ (20 mg) or CoQ10 (200 mg). High-resolution respirometry was used to determine mitochondrial respiration and HO levels, markers of mitochondrial mass and antioxidant defences were measured in muscle samples and oxidative stress markers in urine and blood samples.

Results: Both MitoQ and CoQ10 supplementation suppressed mitochondrial net HO levels during leak respiration, while MitoQ also elevated muscle catalase expression. However, neither supplement altered urine F-isoprostanes nor plasma TBARS levels. Neither MitoQ nor CoQ10 supplementation had a significant impact on mitochondrial respiration or mitochondrial density markers (citrate synthase, mtDNA/nDNA, PPARGC1A, OXPHOS expression).

Conclusion: Our results suggest that neither MitoQ and CoQ10 supplements impact mitochondrial function, but both can mildly suppress mitochondrial ROS levels in healthy middle-aged men, with some indication that MitoQ may be more effective than CoQ10.
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http://dx.doi.org/10.1007/s00421-020-04396-4DOI Listing
July 2020

ApoB48-remnant lipoproteins are associated with increased cardiometabolic risk in adolescents.

Atherosclerosis 2020 06 4;302:20-26. Epub 2020 May 4.

Metabolic and Cardiovascular Disease Laboratory, Molecular Cell Biology of Lipids Group, University of Alberta, Edmonton, Alberta, Canada. Electronic address:

Background And Aims: Cardiovascular disease (CVD) begins in youth, and is exacerbated by obesity and metabolic syndrome. Apolipoprotein (Apo)B-remnant cholesterol is considered a primary contributor to CVD risk. Fasting plasma apoB48 can be used as a biomarker of intestinal remnant cholesterol as well as postprandial dyslipidemia. In adults, elevated fasting plasma apoB48 strongly associates with cardiometabolic risk factors and obesity, whereas in adolescents there is limited data. The aim of this study was to measure fasting plasma apoB48 and determine the relationship with cardiometabolic risk factors in adolescents.

Methods: This is a cross-sectional study of fasting plasma apoB48 from the Western Australian Pregnancy Cohort (Raine) Study. Subjects were adolescent males and females aged 17 years with complete fasting plasma apoB48, biochemical, and anthropometry data (n = 1045). The relationship between fasting plasma apoB48 and other cardiometabolic risk factors was determined. The high-risk metabolic cluster variable was defined using elevated BMI, HOMA-IR, fasting plasma triglycerides, and systolic blood pressure.

Results: Fasting plasma apoB48 was significantly higher in male (15.28 ± 2.95 μg/mL) compared to female (12.45 ± 2.43 μg/mL) adolescents (p = 0.0003), and was increased by 21% (3.60 μg/mL; p = 0.0000) in the high-risk metabolic cluster group and more pronounced in males (31%, 6.15 μg/mL; p = 0.0000). Fasting plasma apoB48 was positively associated with fasting plasma triglycerides, total-cholesterol (but not LDL-C), insulin, leptin, HOMA-IR, and the anthropometric parameters, waist-circumference and skinfold-thickness. Fasting plasma apoB48 was inversely associated with fasting plasma HDL-C, and adiponectin.

Conclusions: Plasma apoB48 remnant lipoproteins associate with cardiometabolic risk factors in adolescents and provide support for the screening of remnant cholesterol in youth.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.04.021DOI Listing
June 2020

Dietary fibre intake and its association with inflammatory markers in adolescents.

Br J Nutr 2021 02 7;125(3):329-336. Epub 2020 May 7.

Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania7000, Australia.

A high dietary fibre intake has been associated with improvements in inflammatory conditions in adults. However, little is known on whether associations between dietary fibre and inflammation are evident during adolescence. We examined the relationship between dietary fibre intake measured by FFQ and the inflammatory marker high-sensitivity C-reactive protein (hs-CRP) and the adipokines leptin and adiponectin cross-sectionally in 17-year-olds participating in the Raine Study (n 621). In weighted analysis using tobit and linear regression, and after excluding participants with hs-CRP > 10 mg/l, higher total dietary fibre intake (per 5 g/d) was significantly associated with lower leptin (β = -0·13, 95 % CI -0·17, -0·09) and adiponectin (β = -0·28, 95 % CI -0·49, -0·07), but not hs-CRP, in unadjusted analyses. These associations were no longer significant after adjustment for sex, anthropometry and a number of lifestyle factors. However, higher cereal and grain fibre intake was significantly associated with lower leptin (β = -0·06, 95 % CI -0·10, -0·01) in fully adjusted analysis. Our findings suggest that a higher intake of cereal and grain fibre may contribute to lower leptin in adolescents. This may contribute to reductions in low-grade chronic inflammation and improved health outcomes.
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http://dx.doi.org/10.1017/S0007114520001609DOI Listing
February 2021

Effects of antiemetic doses of dexamethasone on plasma mediators of inflammation resolution and pain after surgery in women.

Prostaglandins Other Lipid Mediat 2020 08 19;149:106427. Epub 2020 Feb 19.

Medical School, Royal Perth Hospital Unit, University of Western Australia, Australia.

Background: Dexamethasone is commonly given as an antiemetic during surgical procedures. It has immunosuppressive effects and can affect key enzymes involved in the synthesis of specialised lipid mediators of inflammation resolution (SPM) that direct inflammation resolution and have anti-nociceptive actions. This study examined the effect of dexamethasone on plasma SPM, and the relationship between SPM and perceived pain in women undergoing surgery.

Methods: Plasma SPM were measured in samples obtained from two double-blind controlled interventions. The first, included 51 women mean age 53 ± 1.5 years, undergoing breast surgery allocated to either intravenous saline, or dexamethasone (4 mg or 8 mg) after induction of anaesthesia. The second study included 31 women of mean age 44 ± 0.5 years undergoing laparoscopic gynecological surgery that were allocated to either saline, or dexamethasone (4 mg). SPM (18-HEPE, 17-HDHA, RvE2, RvD1 17R-RvD1 and RvD2) were measured in plasma collected prior to induction of anaesthesia and at 24 h, and 6 weeks post-surgery. Pain was assessed using a verbal analogue scale at discharge from the post-anaesthesia recovery unit. The data from each study was combined to examine the effect of dexamethasone on plasma SPM. The relationship between pain score and SPM was examined using ordinal logistic regression.

Results: The SPM 18-HEPE, 17-HDHA, RvE2, RvD1 17R-RvD1 and RvD2 were detectable in all plasma samples. There was no significant difference in any SPM due to dexamethasone over the duration of the study. There was a fall in 17-HDHA between baseline and 24 h in both the dexamethasone and saline groups (P = 0.003) but no change in the downstream SPM (RvD1, 17R-RvD1 and RvD2) or 18-HEPE and RvE2. Pain score was negatively related to levels of RvE2 measured prior to induction of anaesthesia (rho = -0.2991, P = 0.006) and positively related to BMI (rho = 0.279, P = 0.011). In ordinal logistic regression the odds ratio for RvE2 was 0.931 (CI 0.880, 0.986; P = 0.014); after adjusting for the effect of BMI indicating that an increase in RvE2 of 1 pg/ml would result in a 6.9 % fall in pain score. Allocation to a dexamethasone group did not influence the pain score or the relationship between RvE2 and pain score.

Conclusion: Dexamethasone administered as an anti-emetic does not affect plasma SPM levels. An elevated RvE2 level prior to surgery is predictive of a lower perceived pain score post-anaesthesia.
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http://dx.doi.org/10.1016/j.prostaglandins.2020.106427DOI Listing
August 2020

The effect of regular consumption of lupin-containing foods on glycaemic control and blood pressure in people with type 2 diabetes mellitus.

Food Funct 2020 Jan;11(1):741-747

School of Public Health, Curtin University, Perth, Australia.

Background: Type 2 diabetes mellitus is a metabolic disorder characterized by high glucose and insulin resistance. It is strongly linked to lifestyle, including poor diet and physical inactivity. Lupin is a novel food ingredient, rich in protein and fibre with negligible sugar and starch, which can be incorporated into various foods to reduce glycaemic load. Regular consumption of lupin-enriched foods may be a novel and easily achievable means of reducing overall glycaemic load and improving glycaemic control in diabetes.

Objective: To determine whether regular consumption of lupin-enriched foods can improve glycaemic control and lower blood pressure in people with type 2 diabetes mellitus.

Design: Fourteen men and 8 women (mean age 58.0 ± 6.6 years and BMI 29.0 ± 3.5 kg m-2) with type 2 diabetes mellitus were recruited from the general population to take part in a double-blind, randomised, controlled cross-over study. Participants consumed lupin or control foods for breakfast and lunch every day, and for dinner at least 3 days per week during the 8-week treatment periods. Lupin-enriched foods consisted of bread, pasta, Weetbix™ cereal and crumbs, with energy-matched control products. Treatments were completed in random order with an 8-week washout period. All participants monitored their blood glucose levels pre- and post-breakfast and lunch, and their blood pressure in the morning and evening, 3 days per week for the duration of each treatment period.

Results: Seventeen participants completed both treatment arms, with all 22 participants (14 males, 8 females) analysed on an intention-to-treat basis. Eight weeks consumption of lupin-enriched food had no significant effect on mean blood glucose levels (mean difference: -0.08 ± 0.06 mmol L-1, p = 0.214) or post-prandial blood glucose levels (-0.13 ± 0.10 mmol L-1, p = 0.196). There was no effect on home systolic (-0.4 ± 0.4 mmHg, p = 0.33) or diastolic (0.3 ± 0.3 mmHg, p = 0.321) blood pressure and heart rate (0.5 ± 0.3 bpm, p = 0.152), and no effect on body weight throughout the treatment periods.

Conclusion: Regular consumption of lupin-enriched foods had no significant effect on glycaemic control or blood pressure in people with type 2 diabetes mellitus.
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http://dx.doi.org/10.1039/c9fo01778jDOI Listing
January 2020

Associations of autozygosity with a broad range of human phenotypes.

Nat Commun 2019 10 31;10(1):4957. Epub 2019 Oct 31.

Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht University, Utrecht, 3584 CX, The Netherlands.

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F) for >1.4 million individuals, we show that F is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F are confirmed within full-sibling pairs, where the variation in F is independent of all environmental confounding.
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http://dx.doi.org/10.1038/s41467-019-12283-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823371PMC
October 2019
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