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

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

Research output: Contribution to journalArticleResearchpeer-review

77 Citations (Scopus)


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

Original languageEnglish
Pages (from-to)562-571
Number of pages10
JournalIntensive Care Medicine
Issue number4
Publication statusPublished - Apr 2016


  • Diabetes mellitus
  • HbA1c
  • Hyperglycemia
  • Intensive care
  • Mortality

Cite this