When critically ill patients present to the intensive care unit (ICU), they require enteral (tube) feeding to sustain their nutrient intake. Yet, the current formula contains high levels of advanced glycation end products (AGEs), potentially contributing to adverse patient outcomes in those with impaired kidney function.
Supported by the generosity of the PA Research Foundation’s donors, Dietitian Dr Ra’eesa Doola and her team are working hard to determine the effect that AGEs have on the bodies of critically ill ICU patients with reduced kidney function.
Dr Doola’s research journey began back in 2014 when she commenced her PhD at the Mater Hospital looking at low carbohydrate enteral nutrition formulae compared to standard nutrition formula.
“One of the collaborators at Mater Research, Prof Josephine Forbes, who also became her PhD supervisor, was investigating the impact of AGEs and its role in glycaemic control which is what sparked our interest in the area. Through our investigations, we found enteral nutrition formulae to be high in AGEs and given the evidence out there to suggest the implications and adverse effects of elevated AGE concentrations in non-critically ill patients, we realised that there could potentially be something promising in this avenue of research.”
“We are hypothesising that AGEs are potentially having more of an impact than we can appreciate,” Ra’eesa said.
AGEs are a group of compounds formed when carbohydrates are heated together with protein and fat. AGEs can occur naturally in the body, or they can enter circulation through exogenous sources, such as enteral nutrition feeding.
“Patients with reduced kidney function are at a greater risk of elevated circulating AGEs because AGE levels are controlled by urinary excretion.
“This is concerning because we have found that high levels of circulating AGEs in the plasma, particularly carboxymethyllysine (CML), have been linked to an increase in insulin resistance and/or an exacerbated inflammatory response. Conditions that can lead to oxidative stress, cell death, organ failure and increase mortality,” Dr Doola said.
“We are trying to determine whether AGEs consumed via enteral feeding will increase concentrations in the body and, thus, increase the risk of insulin resistance and further exacerbate the inflammatory response.”
This is a key area of research because critically ill patients in ICU are already predisposed to increased insulin resistance and a hyperinflammatory response due to the stress that their body is under.
There is also some evidence to suggest that patients who develop stress related hyperglycaemia while in ICU go on to develop diabetes (T2DM) one year later. However, Ra’eesa did say “it is difficult to determine whether they were always predisposed to T2DM or if it was due to their ICU admission.” Yet, if an association is determined than this could mean those in ICU with impaired kidney function could be at an even greater risk of developing T2DM post recovery.
Dr Doola and her team are currently sampling patients that have either a new acute kidney injury or suboptimal kidney function in the ICU. The study is now past the halfway mark of recruitment, having recruited 22 patients out of the required 40.
Ra’eesa stated, “We are testing the AGE concentration of these patients at different timepoints in their admission to determine if there is an association between what the patient is taking in nutritionally and whether that is increasing their circulating AGE levels.”
“Our hope is that we can use the data from this study to build towards advocating for a lower AGE formula, which to the best of our knowledge does not exist yet.
“But we need a lot of evidence to support our hypothesis and claims because the implications of getting companies and industry to consider this change to their products could potentially be substantial and costly,” Ra’eesa mentioned.
“We want to try our best to make a difference in terms of patient outcomes, whether that be bettering their quality of life or saving their life. At the end of the day, we just want to get people back home to their loved ones as quickly as possible.”
Ra’eesa is extremely grateful to the PA Research Foundation's donors for their support, and she is hopeful that the results from this study will lead to better outcomes for all ICU patients.
