Women's Cardiometabolic Health incl Diabetes
Evidence & Translation
Identifying key biomarkers, mechanisms and interventions to enhance risk prediction, prevention and treatment of women’s cardiometabolic disorders and reducing the burden of diabetes and gestational diabetes and its related health complications.
The research aims to translate key findings from cardiometabolic health work to policy and practice to enable women and their health care providers to make informed, evidence-based decisions regarding their health and that of their offspring. Also, examining diverse approaches to treatment and management of diabetes, ranging from pharmacological therapies to nutrition and lifestyle interventions to biomarkers and risk prediction models.
Women’s Cardiometabolic Health
Maternal disorders are the leading cause of death among children under five, and premature births alone cost the Australian economy >$1.4 billion annually. As maternal age increases, coupled with an increasing prevalence of obesity and associated metabolic disorders, this situation will escalate, with women having to make difficult decisions affecting both their own health and that of their unborn child. Currently, very little is known regarding the safety and efficacy of various interventions in metabolic and reproductive disorders, particularly when these disorders occur in, or co-exist with, pregnancy. This scarcity of information makes it difficult for patients and health professionals to weigh potential risks against benefits, particularly for women who require medications or supplements during pregnancy due to diverse risk profiles and/or comorbidities.
Through multidisciplinary collaboration, internal and external partnerships and innovative approaches to research and translation, we aim to address this evidence gap to improve our understanding of women’s cardiometabolic health during the reproductive lifespan and to facilitate informed decision-making for health professionals, patients, and communities.
Implementation & Impact
We are developing an evidence base of important biomarkers and mechanisms involved in women’s cardiometabolic disorders, and new knowledge regarding the efficacy and mechanisms of action of existing interventions on women’s cardiometabolic health and maternal and fetal outcomes. The overall research program falls into two broad categories: (1) identifying novel biomarkers and mechanisms of cardiometabolic and reproductive disorders, and (2) examining nutritional and pharmacological interventions for improving women’s cardiometabolic and reproductive health. Through collaborations with international clinical leaders in the field, we aim to translate our research findings to relevant stakeholders including clinicians, policy-makers, researchers, health professionals and communities for maximum health impact.
There is currently limited knowledge of the mechanisms underpinning metabolic and reproductive disorders and their cross-talk during the reproductive lifespan. We are utilising novel omics and mass spectrometry techniques to examine biomarkers in relation to metabolic and reproductive disorders including gestational diabetes, polycystic ovary syndrome, Turner’s syndrome, obesity and type 2 diabetes. These markers range from lipidomic, metabolomic, gut microbiota, epigenetic and genetic markers to clinical markers of hyperinsulinaemia and hyperandrogenaemia among other novel markers of metabolic risk including prolactin and human placental lactogen. Through collaborations with clinical and basic scientists and laboratories, the precise mechanisms of action of identified biomarkers or interventions of interest will be examined to facilitate our understanding of disease pathogenesis and available therapies.
Disorders of pregnancy often precede future health complications among women and their offspring. Whether these are due to perturbations during pregnancy or pre-existing genetic determinants, or a combination of both, is not currently known. The use of clinical and/or biochemical markers to predict risk of disease onset or complications has revolutionised patient care and is a fundamental aspect of diagnostic and prognostic processes to aid decision-making. Using novel machine learning and biostatistical techniques and leveraging our biobanking platform, we aim to examine the utility of specific biomarkers in risk prediction/ stratification and prevention of adverse pregnancy outcomes as well as future maternal and offspring health. Existing biobanks and datasets will also be utilised to predict treatment failure or risks associated with certain medications (eg. metformin, insulin) and identify subgroups who may benefit most from specific treatment modalities.
Currently, less than 10% of medicines have enough information to determine fetal effects, even though an estimated 44 to 93% of pregnant women use prescription medicines globally. The use of some medications in pregnancy is ad-hoc and often based on clinical experience and preference, largely due to the lack of definitive evidence for many pharmacological products. The need for further research to determine therapeutic efficacy and safety is clear, with the current scarcity of information placing a heavy onus on pregnant women and their health professionals to weigh potential risks against benefits, particularly for women at high risk and/or with comorbidities. However, pregnant women are a metabolically complex and often understudied population, largely due to ethical and safety concerns surrounding clinical trials in this group (especially for products with unknown fetal effects or known transplacental passage), posing unique challenges to this type of research. We aim to utilise innovative approaches using secondary analysis of existing individual patient data (IPD) from registries, medical and pharmaceutical records, national datasets and previous clinical trials as a pertinent first step to addressing these evidence gaps and informing future research directions. We currently have two large international studies ongoing examining the impact of metformin in pregnancy and hydroxychloroquine in pregnancy on maternal and neonatal outcomes.
Research on nutritional supplements in women’s cardiometabolic health and pregnancy remains inconclusive, despite significant strides made in this field over the last decade. Working in collaboration with clinicians, dietitians and evidence synthesis teams, we are collating and synthesizing a large body of evidence investigating the efficacy (or lack thereof) of nutritional supplements and complementary therapies in a range of metabolic and reproductive disorders, including obesity, diabetes, infertility and polycystic ovary syndrome. Findings from this work will directly inform international guidelines as well as clinical pathways within integrated health care settings.
Dr Kate Rassi
Dr Helena Neven
Dr Eveline Jona
Kushan de Silva
PhD candidate (external)
Within this stream, our work extends to examining the impact of hypoglycaemic medications in metabolically high-risk pregnancies, developing risk prediction tools for clinical use in the prediction of adverse pregnancy outcomes and future diabetes risk in women with GDM, and developing and implementing lifestyle interventions for the prevention of diabetes in high-risk women.
Gestational diabetes mellitus (GDM) is a common metabolic disorder of pregnancy, with an increasing incidence in line with obesity and advanced maternal age. Elevated maternal glucose concentrations and GDM increase the risk for adverse pregnancy outcomes including pre-eclampsia, macrosomia and fetal abnormalities, and GDM itself is the strongest population predictor of type 2 diabetes. Mounting evidence suggests that fetal exposure to a hyperglycaemic environment in utero increases susceptibility for future obesity and diabetes in adulthood, further propagating the global burden of diabetes and GDM. Therefore, effective strategies for the prevention and/or treatment of these disorders and their associated complications are of paramount importance. Through multidisciplinary collaborations, partnerships and innovative research methods, we aim to improve our understanding of the pathophysiology of GDM and diabetes, develop and implement effective interventions for prevention, management and treatment, and enhance our understanding of the facilitators and barriers to treatment success.
Implementation & Impact
Utilising clinical trials, meta-analyses, risk prediction tools and epidemiological modelling, we are generating new knowledge regarding the efficacy of interventions for the prevention, management and treatment of GDM and diabetes in pregnant women and postpartum women at high metabolic risk, while uncovering the key mechanisms and biomarkers involved. We aim to translate and implement our research to enhance evidence-based decision-making and address existing health service gaps in clinical practice.
Metformin is used to treat type 2 diabetes and to prevent diabetes in individuals at high risk (including pre-diabetes and PCOS). Although its use in the treatment of GDM (alongside lifestyle modification) is approved in the UK and New Zealand, this is not the case in Australia or the US where metformin is not approved for this indication. Reluctance around the use of metformin in pregnancy is due to a lack of definitive evidence regarding its impact on fetal health, despite a number of trials showing it to be safe, generally well-tolerated and preferred by women over insulin. We have set up an international network of collaborators from 12 countries, comprising lead investigators from the largest clinical trials worldwide examining the use of metformin for preventing or treating GDM. Using individual patient data meta-analysis, we aim to address several evidence gaps pertaining to the use of metformin in pregnancy to establish its efficacy and safety for GDM and a range of maternal and neonatal outcomes.
The pathophysiology of diabetes, gestational diabetes and associated metabolic complications (including polycystic ovary syndrome) is not well-understood. Similarly, there is conflicting evidence on whether (and how) these conditions in pregnancy can contribute to the development of adverse future metabolic outcomes in offspring. In this stream of work, we combine biomarker discovery techniques with human clinical studies, as a platform to identify key factors and mechanistic pathways underpinning diabetes and gestational diabetes. We also explore potential in utero predeterminants of metabolic risk in offspring in metabolically high-risk pregnancies. Risk prediction models, machine learning techniques and novel app technologies are developed to aid in clinical decision-and identify women with GDM who may be at highest risk of adverse outcomes during pregnancy and postpartum.
The benefits of nutritional supplements in the management of diabetes and gestational diabetes remain unclear, despite significant strides made in this field over the last few decades. Similarly, lifestyle interventions have been shown to be effective but the exact components that contribute to success and limit attrition have not been determined. In collaboration with clinicians, dietitians and evidence synthesis teams, we are collating and synthesizing a large body of evidence investigating the efficacy (or lack thereof) of nutritional supplements and complementary therapies in obesity, diabetes and other metabolic conditions. We are also examining the use of lifestyle interventions to prevent diabetes in postpartum women at high metabolic risk. Findings from this work will directly inform international guidelines as well as clinical pathways within integrated health care settings.
Dr Shamil Cooray
Clinician and Adjunct Research Fellow
Dr Eveline Jona
Mr Simon Alesi
Ms Thisara Coster
Mr Kushan de Silva
Dr Helena Neven
Clinician, PhD candidate
Dr Kate Rassie
Clinician, PhD candidate
Dr Joanne Enticott
Research fellow and biostatistician
We gratefully acknowledge the funding given to our group by the following groups:
- National Health and Medical Research Council (NHMRC)
- NHMRC Centre for Research Excellence in Polycystic Ovary Syndrome
- NHMRC Centre for Research Excellence in Women’s Health in Reproductive Life
- Monash University Research Training Stipends
- Medical Research Future Fund
- National Heart Foundation