Gastric, Small Intestinal And Cardiovascular Mechanisms Of Postprandial Hypotension.
Funder
National Health and Medical Research Council
Funding Amount
$701,521.00
Summary
A fall in blood pressure after a meal (known as postprandial hypotension) is an important clinical problem, particularly in the elderly, and is associated with an increase in the incidence of falls, stroke, as well as mortality. The mechanisms responsible for postprandial hypotension are not well understood and current therapies are less than optimal. The studies proposed in the current application have important implications for the management of postprandial hypotension.
Pathophysiology Of Postprandial Hypotension In The Elderly - Role Of Gastric And Small Intestinal Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$471,176.00
Summary
A fall in blood pressure after a meal (known as postprandial hypotension) is an important clinical problem, particularly in the elderly, occurring in ~50% of nursing home residents and ~30% of healthy older subjects. Postprandial hypotension is associated with a substantial increase in the incidence of falls, stroke, as well as mortality. The mechanisms responsible for the fall in blood pressure after a meal are not well understood, although changes in gastrointestinal blood flow and the release ....A fall in blood pressure after a meal (known as postprandial hypotension) is an important clinical problem, particularly in the elderly, occurring in ~50% of nursing home residents and ~30% of healthy older subjects. Postprandial hypotension is associated with a substantial increase in the incidence of falls, stroke, as well as mortality. The mechanisms responsible for the fall in blood pressure after a meal are not well understood, although changes in gastrointestinal blood flow and the release of gut hormones, have been implicated. While ingestion of carbohydrate, particularly glucose, has been reported to decrease blood pressure most potently, there is inadequate and conflicting information about the effects of other nutrients such as fat and protein. Current therapies are less than optimal. Studies by our research group have established that the fall in blood pressure in response to meals is related to the rate at which nutrients enter the small intestine ie the fall in blood pressure is greater when the stomach empties more quickly. In contrast, gastric distension reduces the fall in blood pressure. Hence, treatment could be directed at facilitating gastric distension and-or slowing the rate of nutrient delivery into the small intestine. Our previous studies have not included any assessment of changes in blood flow to the gut after meals, or of the interaction between gastric distension and small intestinal mechanisms, and have involved healthy older subjects and patients with type 2 (non-insulin dependent) diabetes rather than individuals with known postprandial hypotension. We now have the capacity to measure blood flow in the gut with ultrasound. The studies proposed in the current application represent a logical development from our previous work and have important implications for the management of postprandial hypotension.Read moreRead less
Postprandial Lipid Metabolism In Familial Hypercholersterolaemia: Mechanisms And Effects Of Omega-3 Fatty Acid Ethyl Esters
Funder
National Health and Medical Research Council
Funding Amount
$616,344.00
Summary
Familial hypercholesterolaemia (FH) is the most common genetic condition known to cause premature coronary heart diseaseis (CHD). The increasd CHD risk in FH may be in part due to accumulation of fat in blood. Fish oil supplementation may be a new target, additional to standard best therapy, for reducing CHD risk in FH. Our results will add value to the science behind and clinical therapy for lipid disorders in FH, and will establish a key role for fish oils.
Insulin As A Regulator Of Postprandial Lipaemia In Obesity
Funder
National Health and Medical Research Council
Funding Amount
$226,097.00
Summary
People who are overweight often develop cardio- and peripheral-vascular disease. The reasons are multifactorial but usually involve disturbances in the metabolism of fats. Overweight subjects have a tendency to accumulate energy rich lipids in blood derived from the gut or from the liver. Chronic arterial exposure to these lipids leads to an accumulation of certain types of fats in the wall of blood vessels, which if unabated ultimately leads to an impediment in blood flow. Ongoing studies in ou ....People who are overweight often develop cardio- and peripheral-vascular disease. The reasons are multifactorial but usually involve disturbances in the metabolism of fats. Overweight subjects have a tendency to accumulate energy rich lipids in blood derived from the gut or from the liver. Chronic arterial exposure to these lipids leads to an accumulation of certain types of fats in the wall of blood vessels, which if unabated ultimately leads to an impediment in blood flow. Ongoing studies in our laboratory have found that in obesity the production of these fats and the clearance is disturbed probably because of an inability to properly respond to insulin. The hormone insulin critically regulates synthesis, secretion and clearance of lipids, however, in obese subjects the concentration of insulin is abnormally elevated. We have explored the impact of sustained weight reduction on the production and clearance of lipids from blood. Collectively, weight loss leads to an improvement in fat metabolism because of increased sensitivity to the normal effects of insulin. However, weight reduction alone is rarely able to fully correct the disturbances in fat metabolism and it is likely that the individuals are still at risk of developing vascular disease. In this proposal, we wish to explore the efficacy of two agents which could potentially ameliorate lipid disturbances in diabetes by enhancing the regulatory effects of insulin. We believe that long term correction of the lipid abnormalities in obesity will reduce the frequency and progression of cardio- and peripheral-vascular disease.Read moreRead less
Gastroduodenal Motility And Glycaemic Control In Diabetes Mellitus
Funder
National Health and Medical Research Council
Funding Amount
$393,750.00
Summary
The recent application of novel techniques to evaluate gastrointestinal motor function has established that the rate which the stomach empties food is abnormally slow in ~50% of people who have insulin-dependent (type 1) or non-insulin dependent (type 2) diabetes. Delayed stomach emptying was thought to be an infrequent complication in diabetes; much less common than damage to the eyes, kidneys or nerves. Abnormal stomach emptying may contribute to a number of problems in diabetes, including sym ....The recent application of novel techniques to evaluate gastrointestinal motor function has established that the rate which the stomach empties food is abnormally slow in ~50% of people who have insulin-dependent (type 1) or non-insulin dependent (type 2) diabetes. Delayed stomach emptying was thought to be an infrequent complication in diabetes; much less common than damage to the eyes, kidneys or nerves. Abnormal stomach emptying may contribute to a number of problems in diabetes, including symptoms such as nausea and bloating, and poor control of blood glucose concentrations. It is now recognised that the blood glucose level itself has a reversible effect on both stomach contractions and symptoms. For example, when the blood glucose is abnormally high (hyperglycaemia), the rate at which the stomach empties food into the intestine is slower and symptoms, such as fullness, are greater. The rate of stomach emptying and the absorption of glucose from the intestine affect the rise in the blood glucose level after a meal; this is an important issue because it is desirable to maintain blood glucose levels within the normal range to minimise the risk of both the development and progression of the complications of diabetes. In many people with diabetes eating a meal results in a substantial fall in blood pressure, which may cause fainting and falls. By slowing gastric emptying the magnitude of the fall in blood pressure is minimised. Our group has been the recipient of ongoing support from the NH and MRC for approximately 18 years to conduct research in this area. As a result we have performed the most comprehensive studies to date and developed new methods to evaluate stomach and intestinal function in people with diabetes, resulting in international recognition. The studies proposed in the current application represent a logical development from our previous work and have important implications for the management of diabetes.Read moreRead less
Gastric Motility And Blood Glucose Control In Diabetes Mellitus
Funder
National Health and Medical Research Council
Funding Amount
$354,947.00
Summary
The recent application of novel techniques to evaluate gastrointestinal motor function has established that the rate of which the stomach empties food is slow in up to 50% of people who have insulin-dependent (type 1) or non-insulin dependent (type 2) diabetes. Delayed stomach emptying was thought to be an infrequent complication in diabetes; much less common than damage to the eyes, kidneys or nerves. It is now recognised that disordered stomach emptying may contribute to a number of problems i ....The recent application of novel techniques to evaluate gastrointestinal motor function has established that the rate of which the stomach empties food is slow in up to 50% of people who have insulin-dependent (type 1) or non-insulin dependent (type 2) diabetes. Delayed stomach emptying was thought to be an infrequent complication in diabetes; much less common than damage to the eyes, kidneys or nerves. It is now recognised that disordered stomach emptying may contribute to a number of problems in diabetes, e.g. symptoms such as nausea and bloating and poor control of blood glucose concentrations. In some people symptoms are disabling and affect quality of life adversely. The effects of stomach emptying on blood glucose control is likely to be important, as it is desirable to maintain blood glucose levels within the normal range to minimise the risk of both the development and progression of complications of diabetes. In many people with diabetes, particularly older people with type 2 diabetes, there is a fall in blood pressure after a meal which may result in fainting and falls. The magnitude of the fall in blood pressure is determined by the rate at which the stomach empties; faster emptying results in a greater fall in blood pressure. In the past both slow stomach emptying and symptoms were assumed to result from irreversible nerve damage, however it is now recognised that the blood glucose level itself has a reversible effect on both stomach contractions and symptoms. Our group has been the recipient of ongoing support from the NH and MRC for approximately 15 years to conduct research in this area. As a result we have performed the most comprehensive studies to date and developed new methods to evaluate stomach function in people with diabetes, resulting in international recognition. The studies proposed in this current application represent a logical development from our previous work and have important implications for the management of diabetes.Read moreRead less