Deep Analysis of Clinical Parameters and Temporal Evolution of Glycemic Parameters Based on CGM Data for the Characterization of Severe Hypoglycemia in a Cohort of Children and Adolescents with Type 1 Diabetes

Abstract

This study aims to evaluate the determinants and clinical markers of patients at risk for severe hypoglycemia (SH) in children and adolescents with type 1 diabetes. In the EPI-GLUREDIA study, clinical parameters and continuous glucose monitoring metrics from children and adolescents with type 1 diabetes were retrospectively analyzed between July 2017 and June 2022. Their clinical parameters were collected during traditional and quarterly medical consultations according to whether they experienced severe hypoglycemia or not. Then, continuous glucose monitoring metrics were analyzed on days surrounding SH during specific periods. According to the glycemic parameters, glycemic hemoglobin and glycemic mean were significantly lower in the three months preceding a SH compared with during three normal months (p < 0.05). Moreover, the time spent in hypoglycemia(time below the range, TBR<3.3) and its strong correlation (R = 0.9, p < 0.001) with the frequency of SH represent a sensitive and specific clinical parameter to predict SH (cut-off: 9%, sensitivity: 71%, specificity: 63%). The second finding of the GLUREDIA study is that SH is not an isolated event in the glycemic follow-up of our T1DM patients. Indeed, most of the glycemic parameters (i.e., glycemic mean, glycemic variability, frequency of hypoglycemia, and glycemic targets) vary considerably in the month preceding an SH (all p < 0.05), whereas most of these studied glycemic parameters remain stable in the absence of a severe acute complication (all p > 0.05). Furthermore, the use of ROC curves allowed us to determine for each glycemic parameter a sensitive or specific threshold capable of more accurately predicting SH. For example, a 10% increase in the frequency of hypoglycemia predicts a risk of near SH with good combination of sensitivity and specificity (sensitivity: 80%, specificity: 60%). The GLUREDIA study aimed to target clinical and glycemic parameters to predict patients at risk for SH. First, we identified TBR<3.3 < 9% as a sensitive and specific tool to reduce the frequency of SH. In addition, SH was not an isolated event but rather it was accompanied by glycemic disturbances in the 30 days before SH.