Glycemic Variability Is Independently Associated With Poor Prognosis in Five Pediatric ICU Centers in Southwest China

Glucose variability (GV) is a common complication of dysglycemia in critically ill patients. However, there are few studies on the role of GV in the prognosis of pediatric patients, and there is no consensus on the appropriate method for GV measurement. The objective of this study was to determine the "optimal" index of GV in non-diabetic critically ill children in a prospective multicenter cohort observational study. Also, we aimed to confirm the potential association between GV and unfavorable outcomes and whether this association persists after controlling for hypoglycemia or hyperglycemia.

Blood glucose values were recorded for the first 72 h and were used to calculate the GV for each participant. Four different metrics [SD, glycemic lability index (GLI), mean absolute glucose (MAG), and absolute change of percentage (ACACP)] were considered and compared to identify the "best" GV index associated with poor prognosis in non-diabetic critically ill children. Among the four metrics, the SD was most commonly used in previous studies, while GLI- and MAG-integrated temporal information, that is the rate and magnitude of change and the time interval between glucose measurements. The fourth metric, the average consecutive ACACP, was introduced in our study, which can be used in real-time clinical decisions. The primary outcome of this study was the 28-day mortality. The receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive power of different metrics of GV for the primary outcome. The GV index with the largest area under ROC curve (AUC) was chosen for subsequent multivariate analyses. Multivariate Cox regression analysis was performed to identify the potential predictors of the outcome. To compare the contribution in 28-day mortality prognosis between glycemic variability and hyper- or hypoglycemia, performance metrics were calculated, which included AUC, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).

Among 780 participants, 12.4% (n = 97) died within 28 days after admission to the pediatric intensive care unit (PICU). Statistically significant differences were found between survivors and non-survivors in terms of four GV metrics (SD, GLI, MAG, and ACACP), in which MAG (AUC: 0.762, 95% CI: 0.705-0.819, p < 0.001) achieved the largest AUC and showed a strong independent association with ICU mortality. Subsequent addition of MAG to the multivariate Cox model for hyperglycemia resulted in further quantitative evolution of the model statistics (AUC = 0.651-0.681, p = 0.001; IDI: 0.017, p = 0.044; NRI: 0.224, p = 0.186). The impact of hyperglycemia (adjusted hazard ratio [aHR]: 1.419, 95% CI: 0.815-2.471, p = 0.216) on outcome was attenuated and no longer statistically relevant after adjustment for MAG (aHR: 2.455, 95% CI: 1.411-4.270, p = 0.001).

GV is strongly associated with poor prognosis independent of mean glucose level, demonstrating more predictive power compared with hypoglycemia and hyperglycemia after adjusting for confounding factors. GV metrics that contain information, such as time and rate of change, are the focus of future research; thus, the MAG may be a good choice. The findings of this study emphasize the crucial role of GVs in children in the PICU. Clinicians should pay more attention to GV for clinical glucose management.