Intensive Care Medicine

, Volume 42, Issue 4, pp 562–571 | Cite as

Pre-morbid glycemic control modifies the interaction between acute hypoglycemia and mortality

  • Moritoki EgiEmail author
  • James S. Krinsley
  • Paula Maurer
  • Devendra N. Amin
  • Tomoyuki Kanazawa
  • Shruti Ghandi
  • Kiyoshi Morita
  • Michael Bailey
  • Rinaldo Bellomo



To study the impact of pre-morbid glycemic control on the association between acute hypoglycemia in intensive care unit (ICU) patients and subsequent hospital mortality in critically ill patients.


We performed a multicenter, multinational, retrospective observational study of patients with available HbA1c levels within the 3-month period preceding ICU admission. We separated patients into three cohorts according to pre-admission HbA1c levels (<6.5, 6.5–7.9, ≥8.0 %, respectively). Based on published data, we defined a glucose concentration of 40–69 mg/dL (2.2–3.8 mmol/L) as moderate hypoglycemia and <40 mg/dL (<2.2 mmol/L) as severe hypoglycemia. We applied logistic regression analysis to study the impact of pre-morbid glycemic control on the relationship between acute hypoglycemia and mortality.


A total of 3084 critically ill patients were enrolled in the study. Among these patients, with increasing HbA1c levels from <6.5, to 6.5–7.9, and to ≥8.0 %, the incidence of both moderate (3.8, 11.1, and 16.4 %, respectively; p < 0.001) and severe (0.9, 2.5, and 4.3 %, respectively; p < 0.001) hypoglycemia progressively and significantly increased. The relationship between the occurrence of hypoglycemic episodes in the ICU and in-hospital mortality was independently and significantly affected by pre-morbid glucose control, as assessed by adjusted odds ratio (OR) and 95 % confidence interval (CI) for hospital mortality: (1) moderate hypoglycemia: in patients with <6.5, 6.5–7.9, and ≥8.0 % of HbA1c level—OR 0.54, 95 % CI 0.25–1.16; OR 0.82, 95 % CI 0.33–2.05; OR 3.42, 95 % CI 1.29–9.06, respectively; (2) severe hypoglycemia: OR 1.50, 95 % CI 0.42–5.33; OR 1.59, 95 % CI 0.36–7.10; OR 23.46, 95 % CI 5.13–107.28, respectively (interaction with pre-morbid glucose control, p = 0.009). We found that the higher the glucose level before admission to the ICU, the higher the mortality risk when patients experienced hypoglycemia.


In critically ill patients, chronic pre-morbid hyperglycemia increases the risk of hypoglycemia and modifies the association between acute hypoglycemia and mortality.


Diabetes mellitus Hyperglycemia HbA1c Mortality Intensive care 



This study was supported by the grants-in-aid for scientific research from the Ministry of Education, Science, and Culture of Japan.

Compliance with ethical standards

Conflicts of interest

Drs. Egi, Kanazawa, Morita, Bailey, Amin, Bellomo report no relevant disclosures. Dr. Krinsley reports receiving consultant fees from Medtronic Inc., Edwards Life Sciences, Roche Diagnostics, OptiScan Biomedical, and Alere and research support from OptiScan Biomedical. He also received royalty payments for sales of the ICU Tracker. Ms. Maurer works as a consultant for Alere, the distributor of ICU Tracker.

Supplementary material

134_2016_4216_MOESM1_ESM.docx (13 kb)
Supplementary material 1 (DOCX 14 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2016

Authors and Affiliations

  • Moritoki Egi
    • 1
    • 2
    Email author
  • James S. Krinsley
    • 3
  • Paula Maurer
    • 4
  • Devendra N. Amin
    • 5
  • Tomoyuki Kanazawa
    • 1
  • Shruti Ghandi
    • 6
  • Kiyoshi Morita
    • 1
  • Michael Bailey
    • 7
  • Rinaldo Bellomo
    • 7
  1. 1.Department of Anesthesiology and ResuscitologyOkayama University HospitalOkayamaJapan
  2. 2.Department of AnesthesiologyKobe University HospitalChuo-ku, KobeJapan
  3. 3.Division of Critical Care, Department of Medicine, Stamford HospitalColumbia University College of Physicians and SurgeonsStamfordUSA
  4. 4.BayCare Health SystemsClearwaterUSA
  5. 5.Medical/Surgical Intensive Care UnitMorton Plant HospitalClearwaterUSA
  6. 6.Department of Medicine, Stamford HospitalColumbia University College of Physicians and SurgeonsStamfordUSA
  7. 7.Australian and New Zealand Intensive Care Research Centre, School of Epidemiology and Preventive MedicineMonash UniversityMelbourneAustralia

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