Defining High Glycemic Variability in Type 1 Diabetes: Comparison of Multiple Indexes to Identify Patients at Risk of Hypoglycemia

Background: International consensus on the use of continuous glucose monitoring (CGM) recommends coefficient of variation (CV) as the metric of choice to express glycemic variability (GV) with a cutoff of 36% to define unstable diabetes. Even though, CV is associated with hypoglycemia in type 2 diabetes patients, the evidence on the use of one particular measure of GV in type 1 diabetes (T1DM) patients as a predictor of hypoglycemia is limited. Methods: A cohort of T1DM ambulatory patients was evaluated using CGM. Number and incidence rate of events <54 and <70 mg/dL were calculated. Bivariate and multivariate analysis of different glycemic indexes and clinical variables were performed to identify those associated with hypoglycemia. Receiver operating characteristic (ROC) curve analysis for each of the glycemic indexes was performed to define the best index and its optimal cutoff threshold to discriminate patients with events of hypoglycemia. Results: Seventy-three patients were included. A total of 128 events <54 mg/dL were recorded in 34 patients, and 350 events <70 mg/dL were registered in 51 patients. CV was the only variable significantly associated with hypoglycemia <54 mg/dL in the multivariate analysis (adjusted relative risk [aRR] 1.44, 95% confidence interval [CI]: 1.10-1.88, P = 0.008). CV, HbA1c (glycated hemoglobin), and mean glucose were associated with events <70 mg/dL. ROC curve analysis showed that, among GV metrics, CV had the best performance to discriminate patients with events <54 mg/dL (area under the curve [AUC] 0.87, 95% CI: 0.79-0.95) and events <70 mg/dL (AUC 0.79, 95% CI: 0.68-0.90) with optimal cutoff thresholds values of 34% and 31%, respectively. Among glycemic risk (GR) indexes, low blood glucose index (LBGI) showed the best performance. Conclusions: This analysis shows that CV is the best GV index, and LBGI the best GR index, to identify patients at risk of clinically significant hypoglycemia and hypoglycemia alert events in T1DM patients.