Cardiometabolic SIG

SIG leaders

  • Trevor Mori, School of Medicine and Pharmacology, University of Western Australia (trevor.mori@uwa.edu.au)
  • Koya Ayonrinde, University of Western Australia, Fiona Stanley Hospital and Curtin University (oyekoya.ayonrinde@uwa.edu.au)

List of Investigators

Local

  • Ms Anahita Hamidi, The University of Western Australia
  • Dr Chi Le-Ha, The University of Western Australia
  • Professor Danny Green, The University of Western Australia
  • Ms Denise Demmer, The University of Western Australia
  • Professor Eric Moses, Curtin University and The University of Western Australia
  • Professor Gina Ambrosini, The University of Western Australia
  • Professor John Olynyk, Fiona Stanley Hospital, Edith Cowan University and Curtin University
  • Emeritus Professor Lawrie Beilin, The University of Western Australia
  • Associate Professor Leon Adams, The University of Western Australia and Sir Charles Gairdner Hospital
  • Mr Luis Calzadilla Bertot, The University of Western Australia and Sir Charles Gairdner Hospital
  • Professor Markus Schlaich, The University of Western Australia
  • Dr Phillip Melton, The University of Western Australia
  • Mr Philip Vlaskovsky, The University of Western Australia
  • Associate Professor Rae-Chi Huang, Telethon Kids Institute and The University of Western Australia
  • Ms Sally Burrows, The University of Western Australia
  • Mr Sunil Bhat, The University of Western Australia
  • Dr Therese O’Sullivan, Edith Cowan University

Industry Collaborators

  • Dr Brendan Adler, CEO Envision Medical Imaging, Wembley
  • Professor Tim St Pierre, University of Western Australia and Resonance Health, Nedlands

National

  • Dr Jun Yang, Monash University
  • Professor Martha Hickey, University of Melbourne
  • Professor Michael Stowasser, University of Queensland
  • Professor Wendy Oddy, University of Tasmania

International

  • Professor Berthold Koletzko, University of Munich, Germany
  • Professor John Blangero, Texas Biomedical Research Institute
  • Professor Paul Leeson, Oxford University, UK, GIANT & CHARGE consortia
  • Dr Siobhan Sutcliffe, Washington University School of Medicine, USA
  • Professor Vincent Jaddoe, GenR Study, The Netherlands

Overview of the current data resources available in the SIG area

Generation 1

  • Fasting bloods at 14, 17 yr & 26 yr follow-ups.  Includes lipids, glucose at 14, 17, 26 yrs; Insulin at 14 & 26 yrs; FBC, iron studies, hsCRP, electrolytes and enzymes at 26 yrs.
  • Anthropometry, blood pressure and heart rate at 14, 17, & 26 yr follow-ups

Generation 2

  • Fasting bloods at 14, 17, 20, 22, 27, 29 yr.  Includes lipids, glucose, insulin, hsCRP, electrolytes and enzymes at all ages;  Iron studies at 17, 20, 22, 27 yrs;  FBC at 17, 22, 27, 29 yrs;  Adipokines at 17, 20 yrs; Cytokines at 17 yrs; Vit D at 17, 20 & 29 yrs; Fatty acids at 14, 17 & 20 yrs
  • Spot urine at 17, 20, 22, 27 & 29 yrs
  • Liver ultrasound, visceral and subcutaneous fat thickness at 17 yr follow-up
  • Liver fibroscan at 20 yrs
  • Anthropometry, blood pressure, heart rate at 14, 17, 20, 22, 27 & 29 yrs;
  • Pulse Wave Velocity and analysis at 17, 27 and 29 yrs;  MRI at 27 yrs
  • Generation 2 gut microbiome at 27 yrs

Generation 3

  • Bloods.  Includes lipids, enzymes, insulin, hsCRP

Overview of current/recent SIG activity

The Cardiometabolic SIG is currently examining the relationship between clinical (blood pressure, heart rate, vascular function and anthropometry) and biochemical (blood and urine) biomarkers, as well as antenatal, familial, socio-behavioural & environmental factors on adolescent and adult cardiomatabolic risk and sub-clinical cardiometabolic-associated disorders, in both cross-sectional and longitudinal analyses.  Some of the current research projects are listed below:

  • Examining the genetic and Generation 2 life determinants of different ectopic fat depots using magnetic resonance imaging at 27 yrs;
  • How specific ectopic fat depots relate to age-related adiposity trajectories and cardiometabolic risk factor profiles;
  • Relating genetic determinants of ectopic fat identified from Raine young adults and major CVD events using population studies that have GWAS and CV events data;
  • Whether earlier age at menarche associates with higher risk for cardiovascular disease (CVD) later in life;
  • Examining the relationship between umbilical cord androgens and cardiovascular risk factors in adolescents and young adults;
  • Identifying pregnancy and early life factors, and offspring behaviours that may predispose to any association between adiposity and depressive tendencies at 20 yrs of age;
  • Examining the relationship between early life factors, including fetal, childhood and adolescence characteristics with impaired vascular health in young adults at 29 yrs of age;
  • Examining the relationship between Generation 1 and Generation 2 cardiometabolic risk factors at 22 yrs of age;
  • Tracking the intergenerational relationship between Generation 1 and Generation 2 cardiometabolic disease and risk factors and non-alcoholic fatty liver disease at 17 yrs;

Outline of SIG plans for next 5 years

  • Genetic and Early Life Predictors of Ectopic Fat and their Association with Cardiometabolic Health and Disease (continuation of NHMRC Project Grant)
  • Developmental Origins of Adult Cardiovascular Disease: Vascular Health in the Raine Cohort (new NHMRC Project Grant)
  • Impaired iron bio-availability and and haemoglobin production in young adults with NAFLD: determining the mechanism
  • Intergenerational heritability of NAFLD, longitudinal tracking of the NAFLD phenotype and extra-hepatic disease associations adolescents and young adults
  • Gut microbiome and NAFLD
  • The Epidemiology, Origins and Associations of Irritable Bowel Syndrome in Western Australian Adolescents
  • The effects of alcohol and cannabis during intrauterine, adolescent and young adult life on liver and cardio-metabolic health in participants from the Raine Study

Brief list of potential student/early career researcher projects

Please contact the Cardio-metabolic SIG Leaders if you are interested in a research project incorporating cardiometabolic data and they will coordinate whom to contact within the group.  There are a number of projects available within the NHMRC funded projects related to ectopic fats and vascular function.

  • Examining the relationship between umbilical cord androgens and adipokines and non-alcoholic fatty liver disease at 17 years;
  • Examining the influence of different cardio-metabolic risk trajectories on non-alcoholic fatty liver disease at 17 years;
  • Examining prospective associations between non-alcoholic fatty liver disease at 17 years and subsequent cardio-metabolic disease and risk factors and sleep disorders;
  • Examining the cross-sectional and prospective cardio-metabolic and hepatic significance of liver stiffness measurements at 17 years;
  • Examining associations between micro and macro nutrient intake and non-alcoholic fatty liver disease at 17 years;
  • Examining prospective associations between non-alcoholic fatty liver disease at 17 years and the microbiome at 27 years;
  • Examining detailed longitudinal associations between physical activity at ages 14, 17, 20, 22 and 27 years and non-alcoholic fatty liver disease at 17 years;
  • Examining associations between ultrasound measured abdominal fat measurements and cardio-metabolic risk;

Top 5-10 key findings (with reference)

  • Maternal exposure to life stresses during pregnancy predicts increased weight but lower blood pressure in offspring at 20 years of age. (Bhat SK, Beilin LJ, Robinson M, Burrows S, Mori TA. Contrasting effects of prenatal life stress on blood pressure and body mass index in young adults. J Hypertens 2015;33:711–19.
  • Passive smoking exposure over childhood and adolescence predicts reduced HDL-cholesterol during adolescence in girls but not boys. (Le-Ha C, Beilin LJ, Burrows S et al. Gender difference in the relationship between passive smoking exposure and HDL-cholesterol levels in late adolescence. J Clin Endocrinol Metab 2013;98:2126–35.
  • An adiposity trajectory characterized by an accelerated rate of growth in infancy predicts greater insulin resistance in adolescence. (Huang RC, de Klerk NH, Smith A et al. Diabetes Care 2011;34:1019–25)
  • Epigenetic studies have identified DNA methylation related to adiposity in young adulthood. (Huang RC, Galati JC, Burrows S et al.  DNA Methylation of the IGF2/H19 Imprinting Control Region and Adiposity Distribution in Young Adults.  Clin Epigenet 2012;4:21)
  • Parent pregnancy characteristics are associated with risk of non-alcoholic fatty liver disease in adolescents.  (Ayonrinde OT, Adams LA, Mori TA, Beilin LJ, de Klerk N, Pennell CE, White S, Olynyk JK.  Sex differences between parental pregnancy characteristics and non-alcoholic fatty liver disease in adolescents.  Hepatology 2018; 67: 108-122)
  • Adolescent girls with non-alcoholic fatty liver disease plus polycystic ovary syndrome have an adverse metabolic phenotype similar to boys with alcoholic fatty liver disease but worse than other adolescent girls or boys.  (Ayonrinde OT, Adams LA, Doherty D, Mori TA, Beilin LJ, Oddy WH, Hickey M, Sloboda D, Olynyk JK, Hart R.  Adverse metabolic phenotype of adolescent girls with non-alcoholic fatty liver disease plus polycystic ovary syndrome compared with other girls and boys.  J Gastroenterology Hepatology 2016; 31: 980-987)
  • Positive association between handgrip strength and back muscle endurance with systolic blood pressure throughout childhood and adolescence contrasts with beneficial effects on other related traditional cardiometabolic risk factors. (Demmer DL, Beilin LJ, Hands B, Burrows S, Cox K, Straker L, Mori TA.  Effects of muscle strength and endurance on blood pressure and related cardio-metabolic risk factors from childhood to adolescence.  Journal of Hypertension 2016, 34: 2365-2375).
  • Breastfeeding for at least six months prior to commencing infant formula milk is associated with reduced risk of non-alcoholic fatty liver disease in adolescents.  Ayonrinde OT, Oddy WH, Adams LA, Mori TA, Beilin LJ, de Klerk N, Olynyk JK.  Infant nutrition and maternal obesity prospectively influence the risk of non-aloholic fatty liver disease in adolescents.  J Hepatol.  2017;67(3):568-576.
  • Risk for non-alcoholic fatty liver disease during adolescence is identifiable from trajectories of weight and body mass index from age three years onwards.  Ayonrinde OT, Olynyk JK, Marsh JA, Beilin LJ, Mori TA, Oddy WH, Adams LA.  Childhood trajectories and risk of non-alcoholic fatty liver disease in adolescents.  J Gastroenterol Hepatol.  2015;30(1):163-171.

List of indicative recent publications

  • Ayonrinde OT, Adams LA, Mori TA, Beilin LJ, de Klerk N, Pennell CE, White S, Olynyk JK.  Sex differences between parental pregnancy characteristics and non-alcoholic fatty liver disease in adolescents.  Hepatology 2018; 67: 108-122.
  • Sarkar M, Baffy G.  Perinatal Programming of Adolescent Non-alcoholic Fatty Liver Disease: A Case for Gender Inequality?  Hepatology 2018; 67: 7-9.
  • Turcot V, Lu Y, Highland HM, Schurmann C, Justice AE, Fine RS, Bradfield JP, Esko T, Giri A, Graff M, Hendricks AE,…Mori TA, Morris AD, Morris AP, Muller-Nurasyid M, Munroe PB, Nalls MA,…Hirschhorn JN, Loos RJF.  Protein-altering variants associated with body mass index impicate pathways that control energy intake and expenditure in obesity.  Nature Genetics 2018; 50: 26-44.
  • Demmer D, Beilin LJ, Hands B, Burrows S, Cox K, Oddy WH, Mori TA.  Fatness and fitness with cardio-metabolic risk factors in adolescents.  Journal of Clinical Endocrinology and Metabolism 2018; 102: 4467-4476.
  • Oddy WH, Trapp GSA, Allen KL, Ambrosini GL, Black LJ, Huang R-C, Rzehak P, Beilin LJ, Mori TA.  Dietary patterns, body mass index and inflammation: pathways to depression and mental health problems in adolescents.  Brain, Behaviour and Immunity 2018, 69: 428-439.
  • Reynolds AC, Bucks RS, Paterson JL, Ferguson SA, Mori TA, McArdle N, Straker L, Beilin LJ, Eastwood PR.  Working (longer than) 9 to 5: Are there cardio-metabolic health risks for young Australian workers who report longer than 38 hour working weeks? International Archives of Occupational and Environmental Health 2018; 91(4): 403-412.
  • Ayonrinde OT, Oddy WH, Adams LA, Mori TA, Beilin LJ, de Klerk N, Olynyk JK.  Infant nutrition and maternal obesity influence the risk of non-alcoholic fatty liver disease in adolescents.  Journal of Hepatology 2017; 67: 568-576
  • Alisi A, Vajro P.  Pre-natal and post-natal environment monitoring to prevent non-alcoholic fatty liver disease development.  Journal of Hepatology 2017; 67: 451-453.
  • Bhat SK, Beilin LJ, Robinson M, Burrows S, Mori TA.  Relationships between Depression and Anxiety Symptoms Scores and Blood Pressure in Young Adults.  Journal of Hypertension 2017, 35(10): 1983-1991.
  • Rauschert S, Mori TA, Beilin LJ, Jacoby P, Uhl O, Koletzko B, Oddy WH, Hellmuth C.  Early life factors, obesity risk and the metabolome of young adults.  Obesity 2017; 25(9): 1549-1555.

List of current/recent grants

  • 2017-2020; D Green, L Beilin, L Straker, P Eastwood, T Mori, P Ainslie; Developmental Origins of Adult Cardiovascular Disease: Vascular Health in the Raine Cohort; NHMRC; APP1126494.
  • 2016-2010; TA Mori, LJ Beilin, E Moses, G Watts, L Adams; Genetic and Early Life Predictors of Ectopic Fat and their Association with Cardiometabolic Health and Disease; NHMRC; 1102106.
  • 2014-2018; R-C Huang, K Lillycrop, J Craig, L Beilin, T Mori, W Oddy, K Godfrey, J Holbrook, G Burdge; The Cycle Of Obesity: A two generation population study of obesity epigenetics; NHMRC; 1059711.
  • Ayonrinde OT, Sanfilippo F, Adams LA, Olynyk JK, O’Sullivan T, Robinson M.  The Epidemiology, Origins and Associations of Irritable Bowel Syndrome in Adolescents.  Western Australian Department of Health Clinician Research Fellowship.  Principal Investigator.  $232,559.00

Examples of recent media

  • Journal of Hepatology, June 2017 International Press Release: Short duration of breastfeeding and maternal obesity linked to fatty liver in adolescents.
  • European Association for the Study of Liver International Liver Congress April 13-17 2016 International Press Release; Maternal obesity and duration of breastfeeding influence the risk of non-alcoholic fatty liver disease in adolescents.
  • The West Australian Newspaper 12 July 2017, Cathy O’Leary: Teens’ liver disease link.

Other Data

The Raine Study has extensive data on genetics, phenotypes, behaviours, environment and social outcome that can be linked with Cardio-metabolic data.  For example, there is data on inflammatory markers, diet and green space.