The Association Between Dysglycemia and Endotheliopathy in ICU Patients With and Without Diabetes: A Cohort Study

IMPORTANCE: Dysglycemia in critically ill patients is associated with endotheliopathy. This relationship may be altered in patients with diabetes.

OBJECTIVES: Dysglycemia is common in critically ill patients and associated with increased mortality. Endotheliopathy is thought to play a role in this relationship; however, evidence is scarce. The aim of this study was to investigate the associations between dysglycemia and endotheliopathy to inform future glycemic management.

DESIGN, SETTING, AND PARTICIPANTS: This prospective observational study included 577 acutely admitted adult ICU patients at Copenhagen University Hospital-North Zealand, Denmark.

MAIN OUTCOMES AND MEASURES: Up to twenty-four hours of patient glycemia was paired with same-day levels of endothelial biomarkers measured after each 24-hour period for three consecutive days. Endotheliopathy was assessed by measurement of Syndecan-1, Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1), and soluble thrombomodulin (sTM).

RESULTS: Of the included patients, a total 57.5% were males, median age was 71 yr (interquartile range [IQR], 63-79), and 24.6% had diabetes prior to admission. Median admission time was 5 d (IQR, 3-10). Time above range (TAR) greater than 13.9 mmol/L, but not TAR 10.0-13.9 mmol/L, was associated with increase in sTM (0.01 ng/mL per %-point increase in TAR, p = 0.049) and PECAM-1 (0.01 ng/mL per %-point increase, p = 0.007). Glycemic variability was associated with increases in sTM (0.24 ng/mL per mmol/L increase in sd, p = 0.001 and 0.03 ng/mL per %-point increase in coefficient of variation, p < 0.001). Hypoglycemia 3.0-3.9 mmol/L was associated with increases in sTM (3.0 ng/mL, p < 0.001) and PECAM-1 (1.54 ng/mL, p < 0.001).

CONCLUSIONS AND RELEVANCE: In acutely admitted adult ICU patients, hypoglycemia was associated with endotheliopathy regardless of preadmission diabetes status. Hyperglycemia and high glycemic variability were associated with endotheliopathy in patients without diabetes. This suggests different responses to acute dysglycemia in patients with and without diabetes and warrants further investigation in clinical trials.