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 for 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 for severe hypoglycemia. Design: Prospective observational trial. Setting: Outpatient clinic. Patients: One hundred fifty-three unselected patients with type 1 diabetes mellitus (T1D). Intervention: Six days of blinded continuous glucose monitoring and recording of hypoglycemia symptoms. Main Outcome Measure: Proportion of asymptomatic hypoglycemic events (glucose level <= 70 mg/dL). Results: Patients were grouped by the number of hypoglycemic events during the recording period (group 1: one event; group 2: two to three events; group 3: four to six events; group 4: seven or more events), and fractions of asymptomatic events were calculated. Across the four groups, the fraction of asymptomatic hypoglycemia increased: 57% in group 1, 61% in group 2, 65% in group 3, and 80% in group 4 (P<0.001). Higher fraction of asymptomatic hypoglycemia was positively associated with risk for severe hypoglycemia (incidence rate ratio, 1.3; 95% confidence interval, 1.1 to 1.5; P = 0.003). Group 4 consisted of patients characterized by classic risk factors of severe hypoglycemia (longer duration of diabetes, lower hemoglobin A1c, 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 for severe hypoglycemia; therefore, such patients deserve particular attention in clinical practice.