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

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Abstract

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.

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Acknowledgments

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

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Correspondence to Moritoki Egi.

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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.

Additional information

Take-home message: Critically ill patients with higher pre-admission HbA1c levels were at significantly greater risk of hypoglycemia while in ICU. More importantly, the higher the degree of chronic hyperglycemia before ICU admission, the higher the hospital mortality among those patients who experienced hypoglycemia while in ICU.

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Egi, M., Krinsley, J.S., Maurer, P. et al. Pre-morbid glycemic control modifies the interaction between acute hypoglycemia and mortality. Intensive Care Med 42, 562–571 (2016). https://doi.org/10.1007/s00134-016-4216-8

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