The Impact of Raising the Hypoglycemia Critical Value Alert Threshold at an Academic Medical Center

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To the Editor: In 2019, the American Diabetes Association (ADA) released new guidance that classified level 2 hypoglycemia as glucose values <54 mg/dL [3.0 mmol/L] (1). This threshold was adopted based on a 2017 consensus report that defined 54 mg/dL [3.0 mmol/L] as the glucose concentration requiring immediate action (1, 2). Prior clinical trials, including the Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Action in Diabetes and Vascular Disease: Preterax and Dimicron Modified Release Controlled Evaluations (ADVANCE) studies, defined 50 mg/dL [3.0 mmol/L] as the severe hypoglycemia threshold (3, 4). Since the ADA defined 54 mg/dL [3.0 mmol/L] as the actionable hypoglycemia level, some labs have proposed this as their new critical value, although adoption has varied (5). Following the release of this guidance, our laboratory conducted an internal audit based on historic data of the number of hypoglycemia critical alerts expected under different proposed thresholds at 5 mg/dL [0.28 mmol/L] increments (range: 40–60 mg/dL [2.2–3.3 mmol/L]) to assess the burden of raising the hypoglycemia critical alert threshold from 40 mg/dL [2.2 mmol/L] (data not shown). In accordance with the ACCORD and ADVANCE studies, our analysis suggested that raising our hypoglycemia critical alert threshold from 40 mg/dL [2.2 mmol/L] to 50 mg/dL [2.8 mmol/L] could capture more patients at risk of severe hypoglycemia with the least burden on laboratory staff and clinical teams (3–5). This study evaluated the impact of implementing the hypoglycemia critical value of 50 mg/dL [2.8 mmol/L] at our institution. This study qualified for exemption per §46.102(e)(1) by the institutional review board (protocol #240436). We retrospectively reviewed deidentified glucose laboratory data for the inpatient core laboratory 5 months before and after the new hypoglycemia critical value of 50 mg/dL [2.8 mmol/L] was implemented in June 2024. Formulary data, including administration of dextrose and glucagon solutions and time to intervention, were extracted from the Medication Administration Record. Fisher exact tests and Mann-Whitney U-tests were performed using Social Science Statistics (https://www.socscistatistics.com/tests/ [accessed September 25, 2025]). A P value ≤0.05 was considered statistically significant. Over the 5 months before and after the critical value change, a comparable number of glucose tests were requested in the inpatient core laboratory (pre-change: 183 607; post-change: 185 869; P = 0.90) (Table 1). Prior to implementing the new hypoglycemia critical value, there were 182 critical alerts with a median critical alert glucose result of 33 mg/dL [1.8 mmol/L] (range: 5–40 mg/dL [0.28–2.2 mmol/L]). Of the critical alerts, 20 (11%) were <20 mg/dL [1.1 mmol/L] and 74 (41%) were deemed to require administration of dextrose or glucagon solutions, with a median time to documented intervention of 22 minutes (range: 0–333 minutes) (Table 1). Following the implementation of the 50 mg/dL [2.8 mmol/L] hypoglycemia critical value, there was a statistically significant increase in both hypoglycemia critical alerts (n = 483, P < 0.01) and median critical alert glucose result (median: 43 mg/dL [2.4 mmol/L]; range: 6–50 mg/dL [0.3–2.8 mmol/L]; P < 0.01). Of the critical alerts, 22 (5%) were <20 mg/dL [1.1 mmol/L] and 167 (35%) were determined to require administration of dextrose or glucagon solutions with a median time to documented intervention of 24 min (range: 0–360 min). Neither the number of documented interventions (P = 0.15) nor the median time to documented intervention (P = 0.37) were statistically different when comparing pre- and post-implementation of the new hypoglycemia critical value (Table 1). Evaluating the impact of raising the hypoglycemia critical alert threshold from 40 mg/dL [2.2 mmol/L] (“Pre-Change”) to 50 mg/dL [2.8 mmol/L] (“Post-Change”) for the inpatient core laboratory at our institution SI unit conversion: 1 mg/dL = 0.06 mmol/L. MAR, medication administration record. a.Represents statistical significance (P value ≤0.05). Evaluating the impact of raising the hypoglycemia critical alert threshold from 40 mg/dL [2.2 mmol/L] (“Pre-Change”) to 50 mg/dL [2.8 mmol/L] (“Post-Change”) for the inpatient core laboratory at our institution SI unit conversion: 1 mg/dL = 0.06 mmol/L. MAR, medication administration record. a.Represents statistical significance (P value ≤0.05). Our data shows that increasing the hypoglycemia critical alert threshold from 40 mg/dL [2.2 mmol/L] to 50 mg/dL [2.8 mmol/L] at our institution resulted in a significant increase in the number of critical alerts and median critical alert glucose results. This suggests that the change allows us to capture more patients at risk of severe hypoglycemia while at higher glucose levels without impacting the timeliness of dextrose or glucagon solutions for patients requiring these interventions. In addition, this change added a limited burden for laboratory staff. At our institution, critical alerts for inpatient core laboratory testing utilize an automated electronic system in which the patient’s care team is paged. If the message remains unacknowledged after 2 pages (20 minutes), the hospital operator calls the patient unit to report the value. These critical value alerts are generally not handled by laboratory staff. Using shared decision-making with leadership, clinicians, and staff, our institution decided to maintain this new alert level to catch patients at higher glucose levels, allow them to be clinically assessed, and intervene if needed in hopes of promoting patient safety. This study has certain limitations as it was conducted at a single academic medical center in Tennessee and only covered the inpatient setting with a robust automated alert system. Hospital characteristics, patient demographics, and clinical alert systems may vary across institutions. Additionally, due to the nature of the Medication Administration Record, we were only able to capture formulary interventions that excluded simpler options like giving juice or a snack. For other institutions considering raising their hypoglycemia critical value, finding a balance between the potential to improve patient safety and minimize burden to staff is paramount within systems already suffering from finite human resources. Author Contributions: The corresponding author takes full responsibility that all authors on this publication have met the following required criteria of eligibility for authorship: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; (c) final approval of the published article; and (d) agreement to be accountable for all aspects of the article thus ensuring that questions related to the accuracy or integrity of any part of the article are appropriately investigated and resolved. Nobody who qualifies for authorship has been omitted from the list. Scott Nelson (Data curation-Lead, Writing—review & editing-Equal), Ryan Schell (Conceptualization-Equal, Writing—review & editing-Equal), Joe Wiencek (Conceptualization-Equal, Formal analysis-Supporting, Project administration-Lead, Writing—original draft-Supporting, Writing—review & editing-Equal), and Stephanie A. Hart (Conceptualization-Equal, Formal analysis-Lead, Investigation-Equal, Writing—original draft-Equal) Authors’ Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form. Research Funding: None declared. Disclosures: J.R. Wiencek received an honorarium for speaking at continuing education events (ADLM, Bio-Rad Laboratories, and White Hat Communications); received research support (Bio-Rad Laboratories); received travel support to attend annual meetings (ADLM, International Federation for Clinical Chemistry, and European Federation for Clinical Chemistry and

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