Preventing Impaired Beta-cell Plasticity, Insulin Secretion And Diabetes After IUGR
Funder
National Health and Medical Research Council
Funding Amount
$760,611.00
Summary
Babies who are born small are at increased risk of later diabetes, partly because restricting growth before birth also impairs development of insulin-secreting cells in the pancreas, impairing later insulin secretion and contributing to diabetes. We will define the mechanisms underlying impaired insulin secretion in a well-established animal model of fetal growth restriction. Importantly, we will also test interventions to improve insulin secretion after intrauterine growth restriction.
Does Women's Nutrition During Pregnancy Influence Metabolic Health Of Their Children?
Funder
National Health and Medical Research Council
Funding Amount
$255,752.00
Summary
The occurrence of type 2 diabetes is increasing around the world, with the rising incidence among children and adolescents especially worrying. Widespread obesity has clearly contributed to this epidemic, but does not fully explain it. Diabetes develops over many years and obesity appears to exacerbate a pre-existing susceptibility. Our work focuses on understanding and preventing this initial susceptibility. Metabolic changes in the way the body produces and disposes of insulin, and responds to ....The occurrence of type 2 diabetes is increasing around the world, with the rising incidence among children and adolescents especially worrying. Widespread obesity has clearly contributed to this epidemic, but does not fully explain it. Diabetes develops over many years and obesity appears to exacerbate a pre-existing susceptibility. Our work focuses on understanding and preventing this initial susceptibility. Metabolic changes in the way the body produces and disposes of insulin, and responds to glucose, are seen much earlier in individuals who become diabetic. These metabolic defects are thought to be due, in part, to sub-optimal growth and development before birth (affecting the way the pancreas and liver function, for example). Poor nutrition before birth may be an important underlying cause. Animal studies reliably demonstrate that a poor quality diet of the pregnant mother can result in offspring that have impaired glucose tolerance and related metabolic problems. We now need to determine whether this occurs in humans. A limited amount of community-based research suggests this is possible. The balance between carbohydrate and protein in the mother's diet may be a key factor, and possibly the type of carbohydrate (high or low glycaemic). Weight before and during pregnancy could also be influential. We have been following a cohort of 500 children from before birth, through childhood. We collected detailed information on the mothers' diets during pregnancy. In this project, we plan to assess the glucose-insulin metabolism of the children at 8 years of age. We will then investigate whether diet of the mothers during pregnancy affects the metabolism of the children later on. Improving nutrition of pregnant women could lead to life-long improvement in metabolic health of the children. This study will contribute to the evidence-base about whether maternal diet is important, and give specific details about what kinds of changes are needed.Read moreRead less
Can Exercise And Improved Nutrition Normalise Rat Skeletal Muscle Mitochondrial Biogenesis Following Growth Restriction?
Funder
National Health and Medical Research Council
Funding Amount
$338,128.00
Summary
Being born small is associated with the development of adult diseases such as insulin resistance, cardiovascular disease and type 2 diabetes. Mitochondria are responsible for generating energy within all cells and impaired mitochondrial function is implicated in the development of these diseases. We have exciting preliminary data demonstrating that being born small impairs the synthesis of mitochondria in adult rat skeletal muscles. This project will determine if lifestyle interventions such as ....Being born small is associated with the development of adult diseases such as insulin resistance, cardiovascular disease and type 2 diabetes. Mitochondria are responsible for generating energy within all cells and impaired mitochondrial function is implicated in the development of these diseases. We have exciting preliminary data demonstrating that being born small impairs the synthesis of mitochondria in adult rat skeletal muscles. This project will determine if lifestyle interventions such as exercise and improved nutrition after birth in rats that were born small can normalise the molecular signals responsible for mitochondrial synthesis in muscle. Understanding these mechanisms responsible for mitochondrial function will provide insight into early life interventions that may lessen the adverse consequences of being born small. This research will increase the likelihood that practical public health interventions can be developed to improve adult health.Read moreRead less
Preventing Insulin Resistance And Obesity Following Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$923,510.00
Summary
Babies who are born small are at increased risk of diabetes and obesity in later life, partly because restricting growth before birth decreases the insulin sensitivity of muscle and diverts nutrients to fat deposition. We will define the mechanisms underlying impaired insulin sensitivity in fetal growth restriction. Importantly, we will also test interventions to improve insulin sensitivity after intrauterine growth restriction.
Functional And Epigenetic Consequences Of Maternal Folate Deficiency, Supplementation And Fetal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$545,183.00
Summary
Growing slowly before birth or being born early and premature are very common. Both conditions greatly increase the risk of illness or death around birth and of the infant developing major conditions such as diabetes and cardiovascular disease in later life. Despite their importance, we understand little of what causes fetal growth failure or prematurity or why they influence an individual's health throughout life. Recent findings suggest that low levels of folate in the mother, due to either di ....Growing slowly before birth or being born early and premature are very common. Both conditions greatly increase the risk of illness or death around birth and of the infant developing major conditions such as diabetes and cardiovascular disease in later life. Despite their importance, we understand little of what causes fetal growth failure or prematurity or why they influence an individual's health throughout life. Recent findings suggest that low levels of folate in the mother, due to either dietary or genetic factors, may be involved in their origins and their long-term outcomes. Folate is a nutrient required regularly in small amounts for growth and maintenance of health. Folate supplementation in women is currently recommended before and in early pregnancy, but may have a role throughout the whole of pregnancy in promoting growth and health of the infant. Using experimental models, this project will determine if too little or too much maternal folate modifies the genetic code of the infant (called epigenetic changes), which leads to later metabolic disease and high blood pressure. These epigenetic changes are mild and subtle chemical modifications of DNA that persist in the cells of the infant altering their function. The efficacy of maternal folate supplementation in improving these outcomes for the small baby will also be tested in the models. Finally, the effect of folate status in the normal and small human infant on the epigenetic state of their placenta, cord blood white blood cells and mucous cells of the mouth will be tested. These outcomes will enable the design and testing of interventions with folate and related nutrients in the mother to improve the health of their babies before birth and subsequently throughout their lives. Because these pregnancy complications of being born small or early are common and account for much of the diabetes that occurs in later life, the health benefits from development of effective interventions may be large.Read moreRead less
Investigation Of A New Hypothesis That Increased TGF? Activity In Developing Fetal Organs Predisposes A Women To Polycystic Ovary Syndrome And Associated Metabolic Disorders
Funder
National Health and Medical Research Council
Funding Amount
$583,015.00
Summary
Have you ever wondered why some people get fat and other do not, no matter how much they eat? The answer could lie in what happened before they were born. This project investigates a new hypothesis that was developed from discoveries on polycystic ovary syndrome. Women with this syndrome are at increased risk of becoming overweight and diabetic. If the hypotheses prove correct it might be possible to reduce the incidence of these metabolic disorders in the longer term.