Downloaded from http://journals.lww.com/ccmjournal by K0BJyv8jeF7viHPjsK2H2185EViDZ6gv1oUYiABD05WaMnK6jgSJw+qHwY2Xdb+7dfWaKSG7IqIgcrVLNngrPgkjPe9roptRhAOeaGRPRLOjloEelZV7aa71OQ+EoUHYBRqS0/qwg4rbGi39EIWsIF4eMbJ7F/0oIAd/K2dHLYs= on 02/09/2022 Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. Critical Care Medicine www.ccmjournal.org 1 DOI: 10.1097/CCM.0000000000005490 Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. OBJECTIVES: To determine the associations of relative hypoglycemia and hemo- globin A1c-adjusted time in blood glucose (BG) band (HA-TIB) with mortality in critically ill patients. DESIGN: Retrospective cohort investigation. SETTING: University-affiliated adult medical-surgical ICU. PATIENTS: Three thousand six hundred fifty-five patients with at least four BG tests and hemoglobin A1c (HbA1c) level admitted between September 14, 2014, and November 30, 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were stratified for HbA1c bands of <6.5%; 6.5–7.9%; greater than or equal to 8.0% with optimal affili- ated glucose target ranges of 70–140, 140–180, and 180–250 mg/dL, respec- tively. HA-TIB, a new glycemic metric, defined the HbA1c-adjusted time in band. Relative hypoglycemia was defined as BG 70–110 mg/dL for patients with HbA1c ≥ 8.0%. Further stratification included diabetes status-no diabetes (NO-DM, n = 2,616) and preadmission treatment with or without insulin (DM-INS, n = 352; DM-No-INS, n = 687, respectively). Severity-adjusted mortality was calculated as the observed:expected mortality ratio (O:EMR), using the Acute Physiology and Chronic Health Evaluation IV prediction of mortality. Among NO-DM, mortality and O:EMR, decreased with higher TIB 70–140 mg/dL (p < 0.0001) and were lowest with TIB 90–100%. O:EMR was lower for HA-TIB greater than or equal to 50% than less than 50% and among all DM-No-INS but for DM-INS only those with HbA1 greater than or equal to 8.0%. Among all patients with hba1c greater than or equal to 8.0% And no bg less than 70 mg/dl, mortality was 18.0% For patients with relative hypoglycemia (bg, 70–110 mg/dl) (p < 0.0001) And was 0.0%, 12.9%, 13.0%, And 34.8% For patients with 0, 0.1–2.9, 3.0–11.9, And greater than or equal to 12.0 Hours of relative hypoglycemia (p < 0.0001). CONCLUSIONS: These findings have considerable bearing on interpretation of pre- vious trials of intensive insulin therapy in the critically ill. Moreover, they suggest that BG values in the 70–110 range may be deleterious for patients with HbA1c greater than or equal to 8.0% and that the appropriate target for BG should be individualized to HbA1c levels. These conclusions need to be tested in randomized trials. KEY WORDS: critically ill patients; diabetes; hemoglobin A1c; mortality; relative hypoglycemia; time in band S ince publication of the landmark single-center randomized controlled trial (RCT) of intensive insulin therapy (IIT) at Catholic University in Leuven, Belgium, in 2001 (1), a considerable literature has explored the independent James S. Krinsley, MD, FCCM, FCCP 1 Peter R. Rule, BS, MBA 2 Gregory W. Roberts, PharmD 3 Michael Brownlee, MD 4 Jean-Charles Preiser, MD, PhD 5 Sherose Chaudry, MD 6,7 Krista D. Dionne, DO 6,7 Camilla Heluey, MD 6,7 Guillermo E. Umpierrez, MD 8 Irl B. Hirsch, MD 9 Relative Hypoglycemia and Lower Hemoglobin A1c-Adjusted Time in Band Are Strongly Associated With Increased Mortality in Critically Ill Patients ONLINE CLINICAL INVESTIGATION