Principal Investigator: Prof. James Gibney
Research Title: “Intestinal gene expression and early atherosclerosis in normal and diabetic subjects”
Meath Foundation Research Funding Awarded 2014
A research project which showed that genes involved in cholesterol metabolism in the gut were associated with evidence of early vascular disease, was presented by Prof. James Gibney, Consultant Endocrinologist, Tallaght University Hospital. These genes did not differ in patients with diabetes.
Prof. Gibney said that the introduction of insulin treatment in the 1920s meant that Type 1 diabetes (T1DM) was no longer an incurable disease from which patients typically died within months of diagnosis. While this was one of the major advances in medicine in the 20th century, unfortunately patients who survived the initial stage of the disease frequently went on to develop the complications of diabetes with which we are now familiar – blindness, amputation, kidney failure. Many died in middle age. These complications were mostly explained by the effects of high blood glucose levels on small blood vessels.
Further advances in recent decades, some involving new technologies, had greatly reduced the rates of these complications. Despite this progress, however, life expectancy in T1DM remained substantially reduced; a very large recent study from Scotland had shown that at the age of 20, men and women with T1DM could still expect to live 13 and 11 years respectively less than their peers without diabetes. These findings had been substantiated by similar studies from Scandinavia.
While almost half of these deaths were attributable to cardiovascular disease, this was not explained by traditional cardiovascular risk factors and understanding why this was the case was one of the research areas of the Department of Endocrinology at Tallaght University Hospital.
“New approaches to cardiovascular disease in diabetes have explored the role of the intestine in postprandial inflammation and endothelial dysfunction and high-density lipoprotein (HDL)-cholesterol; structure and function.
“The aim of our study was to determine if genes involved in cholesterol metabolism in the gut were associated with evidence of early vascular disease, if these genes differed in patients with diabetes and to identify contributors to post-prandial vascular abnormalities in diabetes…
“In his work, Consultant Endocrinologist at Tallaght University Hospital and internationally renowned researcher in diabetes, Prof. Gerald Tomkin, paved the way and provided the background to our studies.
“Going through the routine endoscopy list, we took 100 patients, measured the expression of six genes involved in absorption of cholesterol from the gut, and divided the patients into the highest and lowest half of gene expression. Vascular ultrasound studies were carried out while fasting following a meal and two hours later.
“These studies allow early measurement of atherosclerotic disease and we showed that the genes involved in cholesterol metabolism in the gut were associated with evidence of early vascular disease. These genes, however, did not differ in patients with diabetes.
“When we tried to identify contributors to post-prandial vascular abnormalities in T1DM, we found that glucose was most important but HDL “good” cholesterol appeared to be protective.
With the support of Meath Foundation research funding, we have now moved on to carry out very detailed studies of the structure and function of HDL-cholesterol in T1DM.