ABSTRACT
PURPOSE: Describe the characteristics, hospital course, and outcomes of adult ICU patients receiving extremely high dose insulin infusions compared to those with lower insulin requirements. MATERIALS AND METHODS: Retrospective observational study of 128 adult ICU patients receiving IV insulin infusions at a large academic medical center. Extremely high dose insulin infusions were defined as maximum rate ≥ 35 units/h. The primary endpoint was rate of hypoglycemia (BG < 70 mg/dL) and time to glucose control. A post-hoc matching analysis was performed for baseline imbalances. RESULTS: Analysis included 32 patents with extremely high dose insulin infusions and 96 patients without, and most had a goal BG 100-150 mg/dL. Patients in the extreme group were more likely to have type 2 diabetes, a higher median hemoglobin A1c, preadmission insulin, be admitted for a medical reason, and receive inpatient steroids. The extreme group were more likely to experience hypoglycemia (<70 mg/dL, 63% v. 34%, p = 0.005), longer time to glucose control (19.8 h v. 5.7 h, p < 0.001) and higher mortality (34% v. 15%, p = 0.014). CONCLUSIONS: ICU patients with extremely high dose insulin infusions had more hypoglycemia and took longer to achieve glucose targets compared to those with lower requirements. An individualized approach may be required for appropriate management.
Subject(s)
Diabetes Mellitus, Type 2 , Adult , Blood Glucose , Humans , Hypoglycemic Agents/adverse effects , Infusions, Intravenous , Insulin/adverse effects , Intensive Care Units , Retrospective StudiesABSTRACT
Beta cell dysfunction is suggested in patients with COVID-19 infections. Poor glycemic control in ICU is associated with poor patient outcomes. This is a single center, retrospective analysis of 562 patients in an intensive care unit from 1 March to 30 April 2020. We review the time in range (70-150 mg/dL) spent by critically ill COVID-19 patients and non-COVID-19 patients, along with the daily insulin use. Ninety-three in the COVID-19 cohort and 469 in the non-COVID-19 cohort were compared for percentage of blood glucose TIR (70-150 mg/dL) and average daily insulin use. The COVID-19 cohort spent significantly less TIR (70-150 mg/dL) compared to the non-COVID-19 cohort (44.4% vs. 68.5%). Daily average insulin use in the COVID-19 cohort was higher (8.37 units versus 6.17 units). ICU COVID-19 patients spent less time in range (70-150 mg/dL) and required higher daily insulin dose. A higher requirement for ventilator and days on ventilator was associated with a lower TIR. Mortality was lower for COVID-19 patients who achieved a higher TIR.
ABSTRACT
The receptor for advanced glycation end products (RAGE) contributes to many cellular aspects of pancreatic cancer including cell proliferation, migration, and survival. Studies have shown that RAGE activation by its ligands promotes pancreatic tumor growth by stimulating both cell proliferation and migration. In this study, we investigated the effect of RAGE up-regulation on the proliferation and migration of the human pancreatic cancer Panc-1 cell-line. We show that moderate overexpression of RAGE in Panc-1 cells results in increased cell proliferation, but decreased cell migration. The observed cellular changes were confirmed to be RAGE-specific and reversible by using RAGE-specific siRNAs and the small molecule RAGE inhibitor FPS-ZM1. At the molecular level, we show that RAGE up-regulation was associated with decreased activity of FAK, Akt, Erk1/2, and NF-κB signaling pathways and greatly reduced levels of α2 and ß1 integrin expression, which is in agreement with the observed decreases in cell migration. We also demonstrate that RAGE up-regulation changes the expression of key molecular markers of epithelial-to-mesenchymal transition (EMT). Our results suggest that in the absence of stimulation by external ligands, RAGE up-regulation can differently modulate cell proliferation and migration in pancreatic cancer cells and regulates partly EMT.
