Asymptomatic Hypoglycemia Risk With Frequent Hypoglycemia in T1D

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Investigators recorded hypoglycemic symptoms and monitored blood sugar levels by continuous glucose monitoring for 6 days.

Frequent hypoglycemic exposure leads to a higher risk for asymptomatic hypoglycemia in individuals with type 1 diabetes, which in turn has a positive association with severe hypoglycemia risk, according to a study recently published in The Journal of Clinical Endocrinology & Metabolism.

This prospective observational trial included 153 adults who had type 1 diabetes for at least 1 year. Instances of severe hypoglycemia in the past year were recorded and participants filled out a questionnaire on self-estimated awareness, after which they underwent blinded, continuous interstitial glucose monitoring for 6 days.

Hypoglycemia symptoms were recorded. The primary outcome of this study was the proportion of events of asymptomatic hypoglycemia, defined as ≤70 mg/dL.

At the end of the recording period, participants were grouped according to how many hypoglycemic events they experienced: Group 1 included 1 event, Group 2 had 2 to 3 events, Group 3 had 4 to 6 events, and Group 4 had at least 7 events. This allowed proportions of asymptomatic hypoglycemic events to be calculated.

Group 1 experienced 57% asymptomatic hypoglycemia, whereas the figure rose to 61% in Group 2, 65% in Group 3, and 80% in Group 4 (<.001). An increased proportion of asymptomatic hypoglycemia positively correlated with severe hypoglycemia risk (incidence rate ratio [IRR] 1.3; 95% CI 1.1-1.5; =.003). The patients in Group 4 showed classical severe hypoglycemia risk factors such as lower glycated hemoglobin, more common lack of awareness of hypoglycemia, and a longer course of diabetes.

The recurrence of hypoglycemia in individuals with type 1 diabetes can lead to decreased awareness, which in turn can increase the risk for asymptomatic hypoglycemia.

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This develops into a dangerous cycle. Despite the high risk, there is little data on the role of asymptomatic hypoglycemia in this process or how much regular hypoglycemia is needed to start the cycle. This study sought to investigate the link between hypoglycemic exposure and frequency of asymptomatic hypoglycemia, as well as how this relates to severe hypoglycemia.

The study researchers conclude that “[patients] with [type 1 diabetes] 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.”


Henriksen MM, Andersen HU, Thorsteinsson B, Pedersen-Bjergaard U. Hypoglycemic exposure and risk of asymptomatic hypoglycemia in type 1 diabetes assessed by continuous glucose monitoring [published online March 29, 2018]. J Clin Endocrinol Metab. doi: 10.1210/jc.2018-00142