Principal Investigator Prof. James Gibney
Research Title: “HDL function and HDL proteomics in type 1 diabetes mellitus (YIDM) comparison to normal subjects association with early atherosclerosis and the effects of glycaemic control.”
Meath Foundation Research Funding Awarded 2016
High-density lipoprotein (HDL) function was enhanced in Type 1 diabetes, potentially helping to reduce the progress of atherosclerosis, a significant cause of mortality among in type 1 diabetes mellitus (T1DM) patients, Prof James Gibney told the Symposium.
Prof. Gibney was speaking on “HDL function and HDL proteomics in type 1 diabetes mellitus (T1DM), comparison to normal subjects, association with early atherosclerosis and the effects of glycaemic control.”
Prof. Gibney who is a Consultant in Endocrinology & Diabetes at Tallaght University Hospital and Clinical Professor Trinity College, Dublin, was giving a progress report of his research, which is supported by the Meath Foundation.
He said January 2020 was the 100th anniversary of the discovery of insulin. This was one of the major breakthroughs of modern medicine. Prior to this discovery, patients with diabetes died within a few months. Up to the 1970s, patients with diabetes would get very inaccurate measurements of their glucose levels in urine samples, and use a disposable insulin syringe to inject insulin. Now they were using pre-loaded syringes or pens. More recent advances in technology are resulting in increasing the use of insulin pumps and continuous glucose monitoring, and it is likely that soon there will be widespread use of “closed loop systems”, where insulin infusion rates will be automatically adjusted in response to real-time glucose levels.
“We have had all these great developments, but what has not been achieved is a reduction in cardiovascular disease in patients with Type1 diabetes.
“Life expectancy in patients with Type 1 Diabetes 2008 – 2010, shows that at the age of 20, men and women with T1DM can expect to live 13 and 11 years respectively less than their peers without diabetes. Over 40 per cent of these deaths are secondary to cardiovascular disease (CVD). It is not known why CVD is so common in T1DM patients and it is not explained by conventional CVD risk factors. The reduction in life expectancy is directly due to atherosclerosis. ”
“Data from the DIAMOND database in Tallaght University Hospital has shown that those with Type 1 diabetes had total cholesterol of 4.5 compared to 5 mmol/l in non-diabetic patients, LDL-cholesterol of 2.3 compared to 2.9 mmol/l, HDL-C of 1.6 compared to 1.3 mmol/l, Triglyceride of 1.2 compared to 1.8 mmol/l; i.e. all indicating an apparently more favourable lipid profile in Type 1 diabetes.
“However, the HDL particle is much more complex than other lipid moieties and is composed of more than 100 distinct proteins and there might be more to this than meets the eye.”
Prof. Gibney said a research article published by his research group in the Journal of Diabetes Research, 2015 reported a cross sectional study which demonstrated increased serum amyloid A related inflammation in high-density lipoproteins from subjects with type 1 diabetes mellitus and that this abnormality was worsened by poor glycaemic control.
An article in the New England Journal of Medicine looked at HDL cholesterol efflux capacity and incident cardiovascular events in a large population. This provided some information that the structure of HDL particles was more predictive of cardiovascular events than HDL-C concentration, so we needed to move beyond looking at simple HDL levels and look at cholesterol efflux capacity as a better predictor of CVD.
“HDL levels are high in type1 diabetes, but we do not know if they function normally. We found HDL particle size to be greater in Type 1 diabetes, and larger particles to be associated with enhanced function. Overall, we were able to demonstrate that HDL efflux function was actually greater in Type 1 diabetes and that larger particle size was associated with early atherosclerosis assessed using carotid intima-media thickness.”
“These changes do not appear to be related to changes in the HDL proteome, which are relatively minor.”
“Ongoing studies will help to further understand what causes these changes in HDL structure and function in Type 1 diabetes, whether they help attenuate the accelerated progression of atherosclerosis that is characteristic of Type 1 diabetes and the processes that determine HDL function in non-diabetic individuals.”