Novel continuous glucose monitoring-derived index may help identify hypoglycemia fragility in type 1 diabetes
Presenter: Satanay Mahmoud, MD, Tucson Medical Center, Tucson AZ
Why hypoglycemia occurs despite stable glucose patterns: a novel CGM-derived measure of hypoglycemia fragility in patients with type 1 diabetes mellitus. Presented June 14, 2026.
The novel Hypoglycemia Fragility Index measures a unique dimension of hypoglycemia risk in type 1 diabetes mellitus beyond traditional exposure- and variability-based metrics and may help inform risk stratification, personalized glycemic targets, and adaptive insulin delivery approaches, researchers reported at ENDO 2026.
Derived from a dataset of continuous glucose monitoring measurements, the Hypoglycemia Fragility Index was moderately correlated with conventional measures of hypoglycemia exposure, including the Low Blood Glucose Index and time below the normal range (< 70 mg/dL).
In contrast, correlations between the Hypoglycemia Fragility Index and glycemic variability metrics, such as coefficient of variation and standard deviation, were weak or absent. The Hypoglycemia Fragility Index also showed a weak inverse association with mean glucose levels, indicating that patients with similar average glucose control could have markedly different levels of hypoglycemia susceptibility, according to the researchers.
Novel metric evaluated against established hypoglycemia measures
Hypoglycemia is the most common acute complication of type 1 diabetes mellitus and remains a major barrier to achieving optimal glycemic control. Recurrent hypoglycemic episodes are associated with an increased risk of cognitive decline, cardiovascular morbidity, and sudden cardiac death.
Clinicians typically assess hypoglycemia risk in type 1 diabetes using exposure-based metrics such as time below range, glycemic variability, and the Low Blood Glucose Index. However, these measures do not capture an individual's intrinsic susceptibility to hypoglycemia despite otherwise stable glucose control. The term hypoglycemia fragility has emerged to describe this clinically recognized but poorly defined phenomenon.
Researchers sought to develop a novel metric to quantify the likelihood of hypoglycemia occurring following periods of low glycemic stress using hypoglycemia fragility as an investigational measure. They analyzed a synthetic continuous glucose monitoring dataset comprising 40,000 monitoring days, with glucose measurements sampled every 5 minutes (288 readings per day), using GNU Octave software. The simulated glucose profiles were designed to resemble those of individuals with type 1 diabetes and were stratified into four groups according to hemoglobin A1c range.
Hypoglycemia was defined as a glucose level below 70 mg/dL for at least two consecutive continuous glucose monitoring readings (≥ 10 minutes). At each time point, researchers assessed glycemic stress by calculating the glucose rate of change and the short-term glucose excursion during the preceding 60 minutes. Low-stress glycemic states were defined as an absolute glucose slope of 0.5 mg/dL/minute or less and a glucose excursion of 20 mg/dL or less.
For each glucose profile, the Hypoglycemia Fragility Index was calculated as the proportion of low-stress glycemic time points that were followed by hypoglycemia within 60 minutes divided by the total number of low-stress time points for that individual.
Because no established clinical thresholds exist for hypoglycemia fragility, researchers categorized Hypoglycemia Fragility Index values into low-, moderate-, and high-fragility groups using cohort-based quartiles. Associations between Hypoglycemia Fragility Index and established continuous glucose monitoring-derived measures of hypoglycemia were assessed using Spearman correlation coefficients.
Disclosures
No disclosures
References
Mahmoud S, Rivas Pajuelo C. Why hypoglycemia occurs despite stable glucose patterns: a novel CGM-derived measure of hypoglycemia fragility in patients with type 1 diabetes mellitus. Presented at ENDO 2026, June 14, 2026, Chicago, IL.
Zhang Q, Zhou H, Lin R, et al. Risk factors for hypoglycaemia in adults with type 1 diabetes: a systematic review and meta-analysis. BMC Endocr Disord 2025; 26(1):21. doi:10.1186/s12902-025-02122-9