The Association of Biochemical Hypoglycemia with the Subsequent Risk of a Severe Hypoglycemic Event: Analysis of the DCCT Data Set

Diabetes Technol Ther. 2019 Jan;21(1):1-5. doi: 10.1089/dia.2018.0362. Epub 2018 Dec 21.


Objective: To evaluate the association of biochemical hypoglycemia with subsequent severe hypoglycemia (SH) events using the Diabetes Control and Complications Trial (DCCT) data set.

Research design and methods: The frequency of biochemical hypoglycemia (percentage of values <70 and <54 mg/dL [3.9 and 3.0 mmol/L) was assessed using DCCT blood glucose concentrations measured at a central laboratory from seven finger-stick samples (7-point testing: pre- and 90-min postmeals and at bedtime) collected during 1 day every 3 months. SH events required a change in mental status necessitating the involvement of another individual to provide treatment. A Poisson model accounting for repeated measures from each participant was used to assess the association of biochemical hypoglycemia frequency, computed from the 7-point finger-stick data, with the development of SH events.

Results: The risk of SH during a 3-month period was substantially higher (P < 0.001) when there was at least one hypoglycemic blood glucose value in the preceding 7-point profile, with similar results seen for both the 70 mg/dL (rate ratio = 3.0 [95% confidence interval: 2.6-3.3]) and 54 mg/dL (rate ratio = 2.7 [95% confidence interval: 2.4-3.1]) thresholds.

Conclusions: The occurrence of biochemical hypoglycemia <70 or <54 mg/dL is associated with an increased risk of SH. For this reason as well as the deleterious effects of hypoglycemia on glucose counter-regulation and hypoglycemia awareness, cognition, quality of life, and arrhythmias, it is important in diabetes management to avoid hypoglycemic glucose levels as much as possible.

Keywords: Biochemical hypoglycemia; Risk assessment; Severe hypoglycemia; Type 1 diabetes..

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / analysis*
  • Blood Glucose Self-Monitoring
  • Clinical Trials as Topic
  • Diabetes Complications / blood*
  • Diabetes Complications / chemically induced
  • Female
  • Humans
  • Hypoglycemia / blood*
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / adverse effects*
  • Male
  • Poisson Distribution


  • Blood Glucose
  • Hypoglycemic Agents