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
Epigenetic Programming Of The Hypothalmo-Pituitary-Adrenal Axis
Funder
National Health and Medical Research Council
Funding Amount
$550,951.00
Summary
It has been shown that the pattern of nutrition in early pregnancy is important in determining the subsequent health of the fetus and newborn. Interestingly, the nutritional environment of the early embryo, when nutrient demands are minimal has been shown to be important in determining the development of the capacity of the fetus to respond to stress in the womb and the timing of delivery. This proposal seeks to understand the mechanisms that underlie these responses.
In the last ten years, a remarkable series of public health studies have shown that reduced birth weight is associated with an increased prevalence of high blood pressure, coronary heart disease, diabetes and obesity in adult life. These associations are independent of adult lifestyle or current size, are dependent on events initiated prenatally and are present in cohorts which have a birth weight distribution typical of urban and rural Australia. In all societies, the incidence of low birth wei ....In the last ten years, a remarkable series of public health studies have shown that reduced birth weight is associated with an increased prevalence of high blood pressure, coronary heart disease, diabetes and obesity in adult life. These associations are independent of adult lifestyle or current size, are dependent on events initiated prenatally and are present in cohorts which have a birth weight distribution typical of urban and rural Australia. In all societies, the incidence of low birth weight babies has remained above 5% and in some developing countries, it is greater than 30%. The hormonal responses which help the fetus survive periods of growth restriction in utero, result in a permanent reprogramming of the development of key fetal organs and tissues and the subsequent emergence of high blood pressure in later life. The fetal hormones which have been implicated in causing high blood pressure in adult life are known as glucocorticoids. Fetuses may be exposed to excess glucocorticoids through stress in the womb or through increased transfer of glucocorticoids across the placenta. Currently 85% of Australian obstetricians prescribe repeat courses of antenatal corticosteroids in pregnancies in which the risk of preterm birth persists or recurs. The specific long term outcomes of fetal exposure to excess glucocorticoids are unknown and may depend on the timing, route, dose and type of glucocorticoids involved. We propose to define the mechanisms by which high levels of glucocorticoids act to result in high blood pressure and hormonal disturbances in adult life.Read moreRead less
Hypertension Induced By Prenatal Glucocorticoid Exposure: Roles Of Cerebral And Renal Renin-angiotensin Systems
Funder
National Health and Medical Research Council
Funding Amount
$497,500.00
Summary
High blood pressure is a major public health problem in Australia and other developed countries as it is a common risk factor for stroke, heart failure and kidney damage. At present, there is a great interest in the possibility that high blood pressure in adults can result from stresses experienced by the fetus before birth. However, it is not known how prenatal compromise could lead to high blood pressure. We have recently established an animal model (using sheep) in which brief exposure to glu ....High blood pressure is a major public health problem in Australia and other developed countries as it is a common risk factor for stroke, heart failure and kidney damage. At present, there is a great interest in the possibility that high blood pressure in adults can result from stresses experienced by the fetus before birth. However, it is not known how prenatal compromise could lead to high blood pressure. We have recently established an animal model (using sheep) in which brief exposure to glucocorticoids - known as stress hormones - administered to the mother during early gestation results in high blood pressure in the offspring in adulthood. Increased levels of these hormones could occur in women at times when many may be unaware of their pregnancy (ie. smoking marijuana, chronic insomnia, accidents, loss of loved one, physical or mental stress or abuse). In addition, high doses of synthetic glucocorticoids might be given to pregnant patients for the treatment of asthma and acute migraine. The early origins of hypertension are of considerable importance to a large section of the community, namely the 25% who develop hypertension at the age 45 or over. If even a small proportion of hypertension can be prevented by reducing fetal exposure to excess glucocorticoids the impact on cardiovascular illness may be large. This research proposal has the potential to explain the basis for at least some of the 'essential' hypertension for which a mechanism has not been discovered after decades of research. This project will examine the separate roles of the kidney and brain, and in particular will determine whether permanent changes can be induced by exposure to stress hormones during early fetal life. Knowledge gained from this project could be used in devising strategies aimed at preventing or treating high blood pressure in adults.Read moreRead less