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

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.