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The association of biochemical hypoglycemia with the subsequent risk of a severe hypoglycemic event: analysis of the DCCT data set

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Beck, Roy W., Bergenstal, Richard M., Riddlesworth, Tonya D., Kollman, Craig·2019·Diabetes Technology & Therapeutics
DOI 10.1089/dia.2018.0362PMC PMC6909677
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Abstract

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.

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  • Older and/or high-risk individuals with diabetes are at elevated risk for hypoglycemia.

    “Although there is no evidence regarding time in range for older and/or high-risk individuals, numerous studies have shown the elevated risk for hypoglycemia in these populations (54-59).”

    From Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range (2019) · cites this paper as [57]

    The Discussion reports that DCCT participants with a hypoglycemic glucose measurement had more than twice the subsequent risk of a severe hypoglycemic event. That supports elevated risk associated with biochemical hypoglycemia, but the paper does not establish that older individuals, or high-risk individuals as a population, have elevated risk compared with others. (LLM, conf=0.80)

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  • Older and/or high-risk individuals with diabetes are at notably higher risk for severe hypoglycemia due to age, duration of diabetes, duration of insulin therapy, and greater prevalence of hypoglycemia unawareness.

    “Older and/or high-risk individuals with diabetes are at notably higher risk for severe hypoglycemia due to age, duration of diabetes, duration of insulin therapy, and greater prevalence of hypoglycemia unawareness (54-58).”

    From Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range (2019) · cites this paper as [57]

    The Discussion (page not specified) says reduced hypoglycemia awareness is associated with an increased risk of severe hypoglycemic events. It does not establish that older or high-risk individuals have greater prevalence of unawareness, or that age, diabetes duration, or insulin-therapy duration account for their higher risk. The paper's analysis instead focuses on biochemical hypoglycemia preceding severe events. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • In both T1D and T2D, one or more severe hypoglycemic events over 5 years raises mortality rates ∼3.5-fold.

    “In both T1D and T2D, one or more severe hypoglycemic events over 5 years raises mortality rates ∼3.5-fold ( Beck et al., 2019 ).”

    From Pharmacologic inhibition of somatostatin receptor 2 to restore glucagon counterregulation in diabetes (2024) · cites this paper as Beck et al., 2019

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1 of the 43 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. [20]20. Heller SR, Macdonald IA: The measurement of cognitive function during acute hypoglycaemia: experimental limitations and their effect on the study of hypoglycaemia unawareness. Diabet Med 1996;13:607–615 [DOI] [PubMed] [Google Scholar]

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Authors
Beck, R. W., Bergenstal, R. M., Riddlesworth, T. D., & Kollman, C.
Affiliations
  • Jaeb Center for Health Research (US)
  • Park Nicollet Clinic (US)
Corresponding author
Beck, Roy W.
ORCID
Venue
Diabetes Technology & Therapeutics
Publisher
SAGE Publications
Published
2019-01
Volume
21
Issue
1
Pages
1-5
ISSN
  • 1520-9156 (ISSN-L)
  • 1557-8593
DOI
10.1089/dia.2018.0362
PMC
PMC6909677
OpenAlex
W2906263878
Cited by
42
References
43
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 4 · 2021: 8 · 2020: 12 · 2019: 7
FWCI
5.37
Type
journal article
Language
en
Open access
Licence
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations
  • Diabetes Technology & Therapeutics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Jaeb Center for Health Research
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • National Center for Research Resources
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Education
  • Health Sciences › Health Professions › Emergency Medical Services › Patient Safety and Medication Errors
Keywords
severe hypoglycemia, type 1 diabetes, blood glucose monitoring, hypoglycemia awareness, Diabetes Control and Complications Trial
MeSH terms
Adult, Blood Glucose, Clinical Trials as Topic, Female, Humans, Hypoglycemia, Hypoglycemic Agents, Male, Blood Glucose Self-Monitoring, Poisson Distribution, Diabetes Complications

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