Glycemic Variability is Independently Associated with Poor Prognosis in Main PICU Centers in Southwest China

Abstract Background: Glucose variability (GV) is one of the common complications in critically ill patients, and studies investigating the role of GV in the prognosis of pediatric patients are scarce in China. And there is no consensus on the measurement of GV. Thus, this study took a prospective, multi-center cohort observational study to identify the ‘best’ index of variability in non-diabetic critically ill children and to confirm whether GV is associated with unfavorable outcomes and whether this association persists after control of hypoglycemia and hyperglycemia. Materials and Methods: Four GV indices were chosen and calculated in our study, namely, mean absolute glucose (MAG), standard deviation (SD), glycemic lability index (GLI), and another metric-average consecutive absolute change percentage (ACACP), which can be used in the real-time clinical decision. The primary outcome was 28-day mortality. Multivariate Cox regression analysis was used to identify the potential predictors for the outcome. And the area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were calculated to assess the predictability of dysglycemia (glucose variability and hypo/hyperglycemia) on the unfavorable outcome. Results: Of the total of 780 participants, 12.4% (n=97) died within 28 days after PICU admission. There were statistical differences in terms of four GV indices (SD, GLI, MAG, and ACACP) between survivors and non-survivors, in which MAG obtained the largest area under the curve and showed a strong connection to ICU mortality independently. Subsequent addition of MAG to the multivariate Cox model for hyperglycemia resulted in further quantitative evolution of the model statistics (AUC 0.651 to 0.681, P=0.001; IDI: 0.017, P=0.044; NRI:0.224, P=0.186). And the impact of hyperglycemia (adjusted HR1.419, 95% CI 0.815-2.471, p=0.216) on outcome was attenuated and no longer statistically relevant after adjustment for MAG (adjusted HR 2.455, 95%CI 1.411-4.270, p=0.001). Conclusions: GV is closely associated with unfavorable outcomes, and may be a more powerful negative predictor of outcome than hypoglycemia and hyperglycemia. These findings emphasize the crucial role of GV in PICU children. GV index that contains information such as time, rate of change, etc. is the focus of future research. MAG may be a good choice. Trial registration: Chinese clinical registration (ChiCTR), ChiCTR2000030846. Registered 15 March 2020, https://www.chictr.org.cn/showproj.aspx?proj=50760.