Association between enteral carboxymethyllysine intake and daily glycemic variability in critically ill adults: A retrospective cohort study

BACKGROUND: Advanced glycation end-products (AGEs) can enter patients' circulation through exogenous sources, such as enteral nutrition formulae. Circulating AGEs, specifically carboxymethyllysine, can promote insulin resistance and activation of pro-inflammatory pathways leading to oxidative stress, cell death, and organ failure. Suboptimal kidney function increases the risk of elevated circulating AGEs because levels are controlled through urinary excretion. Our aim was to determine associations between carboxymethyllysine intake and glycemic control as well as clinical outcomes in critically ill patients and explore these in the subset of patients with an acute kidney injury (AKI). METHODS: This was a retrospective cohort study. Data were extracted from electronic medical records. Patients were eligible if they were =18 years and received enteral nutrition, with known carboxymethyllysine content, for =3 days. AKI was defined using the Kidney Disease: Improving Global Outcomes guidelines. Linear and logistic regression models were used to determine adjusted associations. RESULTS: Between 2015 and 2021, 2636 patients met the eligibility criteria, with 848 (32%) patients having an AKI. Most were male (n = 1752, 67%) with a median (interquartile range) Acute Physiology And Chronic Health Evaluation III score of 59 (45-77). For every 10-µmol increase in carboxymethyllysine provision, mean blood glucose increased by 0.05 mmol (95% CI, 0.03-0.07), and the odds of dying increased by 16% (odds ratio = 1.16; 95% CI, 1.06-1.27). A subgroup analysis indicated these associations persisted in patients with AKI but not in those without. CONCLUSION: Carboxymethyllysine intake was associated with increased mean blood glucose and odds of dying in our study cohort.