Glargine-to-intravenous insulin dose ratio, rebound hyperglycemia and hypoglycemia after discontinuation of insulin infusion in critically ill adults: a retrospective cohort study
- 1The Affiliated Taizhou People's Hospital of Nanjing Medical University
Abstract
Background When intravenous insulin is stopped in critically ill patients, the basal insulin dose that balances rebound hyperglycemia against hypoglycemia is uncertain, because randomized trials were small and not designed to quantify this trade-off. We examined how the first glargine dose, relative to the preceding intravenous insulin requirement, was associated with both outcomes. Methods In this retrospective cohort study of the Medical Information Mart for Intensive Care IV database (2008–2022), we included transitions from intravenous insulin infusions of at least 6 hours to subcutaneous glargine in adults without diabetic ketoacidosis or hyperosmolar hyperglycemic state. The exposure was the ratio of the first glargine dose to 24 times the mean infusion rate over the final 6 hours. The primary outcomes, rebound hyperglycemia (glucose >180 mg/dL within 24 hours) and hypoglycemia (glucose <70 mg/dL within 48 hours) during intensive care unit follow-up, were analyzed with multivariable Cox models after multiple imputation. Results Among 6,220 transitions in 5,924 patients (87.5% after cardiac surgery), the median ratio was 0.41 (interquartile range 0.30–0.46). Kaplan–Meier cumulative incidences were 44.4% for rebound hyperglycemia (2,109 events) and 6.4% for hypoglycemia (211 events). Each 0.1 increase in the ratio was associated with less rebound hyperglycemia (hazard ratio 0.96, 95% confidence interval 0.93–0.99) and more hypoglycemia (1.11, 1.04–1.18), consistently across 21 sensitivity analyses. Rebound within the first 6 hours (57.6% of events) was not associated with the ratio (0.99, 0.95–1.02), whereas later rebound was (0.91, 0.86–0.96). Standardized to the cohort, a ratio of 0.60 versus 0.40 corresponded to 2.7 (0.6–4.9) fewer rebound and 1.7 (−0.2 to 3.5) more hypoglycemia episodes per 100 transitions. In secondary analyses, rebound was less frequent with glargine given at least 2 hours before discontinuation (0.86, 0.77–0.96) and more frequent with an oral diet (1.49, 1.30–1.71). Conclusions In critically ill adults, mostly after cardiac surgery, higher glargine doses relative to the preceding intravenous requirement were associated with less rebound hyperglycemia after the first 6 hours and more hypoglycemia, a gradual trade-off. Which basal fraction is preferable depends on the weight given to each outcome; a randomized trial including the guideline-implied fraction of about 0.30 is warranted.
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BibTeX
@misc{shao2026glarginetointravenous,
title = {{Glargine-to-intravenous insulin dose ratio, rebound hyperglycemia and hypoglycemia after discontinuation of insulin infusion in critically ill adults: a retrospective cohort study}},
author = {L. Shao and Y. Li and L. Wang and W. Sun},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.28.26364145},
url = {https://www.medrxiv.org/content/10.64898/2026.09.28.26364145v1},
note = {Public domain},
}
RIS
TY - UNPB
TI - Glargine-to-intravenous insulin dose ratio, rebound hyperglycemia and hypoglycemia after discontinuation of insulin infusion in critically ill adults: a retrospective cohort study
AU - L. Shao
AU - Y. Li
AU - L. Wang
AU - W. Sun
PY - 2026
DA - 2026/09/28
PB - medRxiv
DO - 10.64898/2026.09.28.26364145
UR - https://www.medrxiv.org/content/10.64898/2026.09.28.26364145v1
AB - Background When intravenous insulin is stopped in critically ill patients, the basal insulin dose that balances rebound hyperglycemia against hypoglycemia is uncertain, because randomized trials were small and not designed to quantify this trade-off. We examined how the first glargine dose, relative to the preceding intravenous insulin requirement, was associated with both outcomes. Methods In this retrospective cohort study of the Medical Information Mart for Intensive Care IV database (2008–2022), we included transitions from intravenous insulin infusions of at least 6 hours to subcutaneous glargine in adults without diabetic ketoacidosis or hyperosmolar hyperglycemic state. The exposure was the ratio of the first glargine dose to 24 times the mean infusion rate over the final 6 hours. The primary outcomes, rebound hyperglycemia (glucose >180 mg/dL within 24 hours) and hypoglycemia (glucose <70 mg/dL within 48 hours) during intensive care unit follow-up, were analyzed with multivariable Cox models after multiple imputation. Results Among 6,220 transitions in 5,924 patients (87.5% after cardiac surgery), the median ratio was 0.41 (interquartile range 0.30–0.46). Kaplan–Meier cumulative incidences were 44.4% for rebound hyperglycemia (2,109 events) and 6.4% for hypoglycemia (211 events). Each 0.1 increase in the ratio was associated with less rebound hyperglycemia (hazard ratio 0.96, 95% confidence interval 0.93–0.99) and more hypoglycemia (1.11, 1.04–1.18), consistently across 21 sensitivity analyses. Rebound within the first 6 hours (57.6% of events) was not associated with the ratio (0.99, 0.95–1.02), whereas later rebound was (0.91, 0.86–0.96). Standardized to the cohort, a ratio of 0.60 versus 0.40 corresponded to 2.7 (0.6–4.9) fewer rebound and 1.7 (−0.2 to 3.5) more hypoglycemia episodes per 100 transitions. In secondary analyses, rebound was less frequent with glargine given at least 2 hours before discontinuation (0.86, 0.77–0.96) and more frequent with an oral diet (1.49, 1.30–1.71). Conclusions In critically ill adults, mostly after cardiac surgery, higher glargine doses relative to the preceding intravenous requirement were associated with less rebound hyperglycemia after the first 6 hours and more hypoglycemia, a gradual trade-off. Which basal fraction is preferable depends on the weight given to each outcome; a randomized trial including the guideline-implied fraction of about 0.30 is warranted.
ER -