Hypoglycemic Exposure and Risk of Asymptomatic Hypoglycemia in Type 1 Diabetes assessed by Continuous Glucose Monitoring

Context: Recurrent hypoglycemia promotes impaired awareness resulting in an increased risk of asymptomatic hypoglycemia. However, there are no firm data on the frequency of hypoglycemia in daily life needed to initiate this vicious cycle or the role of asymptomatic hypoglycemia.

Objective: To explore the association between hypoglycemic exposure and proportion of asymptomatic hypoglycemia and relation to risk of severe hypoglycemia.

Design: Prospective observational trial.

Setting: Outpatient clinic.

Patients: 153 unselected subjects with type 1 diabetes mellitus (T1D).

Intervention: Six days of blinded continuous glucose monitoring (CGM) and recording of hypoglycemia symptoms.

Main Outcome Measure: Proportion of asymptomatic hypoglycemic events (≤70 mg/dl).

Results: Patients were grouped by the number of hypoglycemic events during the recording period (group 1: 1 event, group 2: 2-3 events, group 3: 4-6 events, group 4: ≥7 events) and fractions of asymptomatic events were calculated. In the four groups, the fraction of asymptomatic hypoglycemia increased from 57% in group 1 to 61%, 65%, and 80% in group 2, 3, and 4, respectively (p<0.001). Higher fraction of asymptomatic hypoglycemia were positively associated with risk of severe hypoglycemia (incidence rate ratio (IRR) 1.3 (95% CI 1.1-1.5); p=0.003). Group 4 consisted of patients characterized by classical risk factors of severe hypoglycemia (longer duration of diabetes, lower HbA1c and more frequent impaired awareness of hypoglycemia).

Conclusions: Patients with T1D with hypoglycemic rates corresponding to daily exposure had an increased fraction of asymptomatic events, which was positively associated with risk of severe hypoglycemia; therefore, such patients deserve particular attention in clinical practice.