Is Insulin Sensitivity In Children And Their Mothers Programmed By Maternal Blood Glucose?
Funder
National Health and Medical Research Council
Funding Amount
$169,630.00
Summary
Glucose intolerance in pregnancy is associated with the birth of large-for-dates and macrosomic (>4000g) babies. The risk of type 2 diabetes is greater in babies who are small or large at birth compared to those with normal birth weight. This study will determine if treatment of mothers with glucose intolerance in pregnancy (which is intermediate between normal glucose tolerance and diabetes) alters the regulation of glucose tolerance in their children. The mothers were randomised to receive ....Glucose intolerance in pregnancy is associated with the birth of large-for-dates and macrosomic (>4000g) babies. The risk of type 2 diabetes is greater in babies who are small or large at birth compared to those with normal birth weight. This study will determine if treatment of mothers with glucose intolerance in pregnancy (which is intermediate between normal glucose tolerance and diabetes) alters the regulation of glucose tolerance in their children. The mothers were randomised to receive normal antenatal care or to have their blood sugar measured and controlled by diet and insulin as for diabetics. We will measure the insulin sensitivity of the children to a glucose load. We will also measure blood pressure and lipids in these children. Treatment of the mother during pregnancy may alter the deposition of fat in the fetus the effect of which will continue into childhood. Thus the offspring of treated mothers may remain thinner throughout childhood. Each pregnancy increases a woman's chance of developing type 2 diabetes in later life. This risk is further increased by abnormal glucose tolerance during pregnancy. This study will test the long-term benefits of treatment during pregnancy of women with impaired glucose tolerance on the subsequent regulation of glucose tolerance. We shall invite women who took part in the Australian Carbohydrate Study in Pregnancy (ACHOIS) to return and have an intravenous glucose tolerance test. Insulin sensitivity and glucose tolerance will be determined and related to treatment of the impaired glucose tolerance in pregnancy. This study will be the first follow-up of a large randomised trial of treatments of impaired glucose tolerance in pregnancy. The potential long-term benefits are strategies to reduce the future chance of developing risk factors for type 2 diabetes, obesity and abnormal blood lipids in childhood and adult life. The study will establish the benefits or otherwise of tight control of blood glucose in pregnancy.Read moreRead less
Periconceptional Nutrition And The Programming Of Obesity
Funder
National Health and Medical Research Council
Funding Amount
$468,879.00
Summary
Mothers who enter pregnancy with a high body mass index are at risk of developing diabetes in pregnancy and of having a large baby who will be at increased risk of developing obesity in childhood and later life. Heavy mothers therefore have heavy babies and these babies go on to become heavy adults. This grant will determine the separate contributions of exposure of the embryo to high nutrition and exposure of the fetus in late gestation to high maternal nutrition.
The Role Of Nutrition In Disease-linked Epigenetic Inheritance
Funder
National Health and Medical Research Council
Funding Amount
$485,412.00
Summary
This project aims to investigate one mechanism behind fetal programming, in which a suboptimal in utero environment can affect health of offspring in later life. We and others have recently shown that fetal programming can be caused by changes in the way genes behave, and we will examine how many genes are affected by these changes. We will ask whether the changes can increase in frequency with long-term exposure to nutritional stress, and become entrenched within the population.
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
In the last decade there has been a substantial increase in the number of overweight and obese individuals. Obesity is now a major public health issue in Australia and, along with its associated disorders of type 2 diabetes and heart disease, incurs significant health care costs. There is a widespread awareness of the problem, but it has proved difficult to bring this obesity epidemic under control, and unless we can understand the underlying causes, the trend seems set to continue. This researc ....In the last decade there has been a substantial increase in the number of overweight and obese individuals. Obesity is now a major public health issue in Australia and, along with its associated disorders of type 2 diabetes and heart disease, incurs significant health care costs. There is a widespread awareness of the problem, but it has proved difficult to bring this obesity epidemic under control, and unless we can understand the underlying causes, the trend seems set to continue. This research proposal seeks to define the mechanisms which lead to the development of obesity. Evidence from a large range of clinical and population-based studies has shown that infants who are exposed to an increased supply of nutrients before birth have an increased risk of being overweight or obese as children and adults. It is not however, fully understood why this occurs. In normal adults, factors released by fat cells play an important role in the maintenance of energy balance, and changes in the levels of these factors in the fat cell or in the circulation can lead to increased weight gain and the development of poor sensitivity of the body's tissues to the actions of hormones, such as insulin. Fat cells develop before birth, and therefore changes in nutrient supply to the fetus have the potential to alter the functional properties of fat cells for life. In this proposal, we will investigate the effect of being exposed to an increased supply of nutrients in fetal life on the properties of fat cells after birth and define how such changes explain the development of obesity in these individuals. Understanding the mechanisms which link the risk of obesity to events before birth will allow clinicians of the future to provide children who are born to overweight, glucose-intolerant or diabetic mothers with a healthy start to life.Read moreRead less
Liver Cell Transplantation For The Treatment Of Liver Based Metabolic Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$444,143.00
Summary
We propose to investigate the role of liver cell transplantation (LCT) for the therapy of inherited liver-based metabolic diseases using a methylmalonic aciduria (MMA) mouse model. LCT provides an exciting alternative to whole organ transplantation. Initially it was considered liver cells would be immunopriviledged. This has not proven to be the case. Immune modulation will be important. We will also examine immune modulation using antibodies to optimise longterm survival of allogeneic cells.
Genetic Dissection Of A QTL Influencing The Development Of Type 2 Diabetes And The Metabolic Syndrome.
Funder
National Health and Medical Research Council
Funding Amount
$129,875.00
Summary
Diabetes is usually associated with obesity and is often part of a wider disturbance affecting an individuals metabolism. These other factors include high blood pressure and the control of fats (eg cholesterol), and sugars (glucose) in the blood stream. Physicians have noted that these abnormalities often cluster together in individuals and have called it the metabolic syndrome, the main long term implication of which is to increase a persons risk of developing heart disease and disorders in blo ....Diabetes is usually associated with obesity and is often part of a wider disturbance affecting an individuals metabolism. These other factors include high blood pressure and the control of fats (eg cholesterol), and sugars (glucose) in the blood stream. Physicians have noted that these abnormalities often cluster together in individuals and have called it the metabolic syndrome, the main long term implication of which is to increase a persons risk of developing heart disease and disorders in blood circulation. The number of affected people with one the major components of the metabolic syndrome, type 2 diabetes, has trebled since 1981 in Australia and is still increasing. Apart from individual suffering, this presents a major public health burden for the country (approx $3 billion annually). Currently available lifestyle based and pharmaceutical therapies appear inadequate to control the increasing numbers of affected individuals. Unfortunately the cause of disease is poorly understood, although genetic factors are known to be important, in other words it runs in the family. This project proposes to identify some of these factors (genes) and how they contribute to the disease. Using molecular flags on the DNA (like DNA fingerprinting) we have previously found that a small region on chromosome 3 is likely to carry one or more of these disease genes. But there are over 100 genes in the region, so to help choose the most likely candidates first for testing, we have developed an automated computer database searching program that narrowed the list to the six most likely genes. This project will determine which if any of these genes are involved. A successful finding means we will know more about the mechanism of disease development and be able to better develop new therapies for treatment and prevention. If none of these genes are the culprit, we would continue examination of the next set of genes likely to be involved and so on until we are successful.Read moreRead less