IntroductionStudies of critically ill patients in various settings such as intensive care with mechanical ventilation, post MI, stroke and coronary bypass surgery have correlated tight glucose control with a substantial reduction in morbidity and mortality and length of hospital stay. To date the impact of hyperglycemia in the hematopoietic stem cell transplant (HSCT) population has not been studied.ObjectiveTo investigate the relationship between hyperglycemia and morbidity and mortality in HSCT patients.MethodsRetrospective chart review of 98 consecutive adult patients (age > 17) admitted between January 1, 2002, and October 31, 2003, to University of Oklahoma Health Sciences Center Bone Marrow Transplant Unit was performed. Patients who received a myeloablative regimen and then underwent an autologous (n = 48) or allogeneic (n = 47) HSCT were analyzed in separate groups. Mean plasma glucose values during hospitalization for transplant were used to stratify the patients into euglycemic (glucose < 126 mg/dL) and hyperglycemic groups (glucose > 126 mg/dL). The primary outcome measure was length of inpatient stay defined as date of HSCT, designated day 0, until discharge. Secondary outcome measures were causes of inpatient morbidity. A tertiary outcome measure was in-hospital death.ResultsLength of hospital stay for patients undergoing allogeneic HSCT was significantly longer (p = .02) in the hyperglycemic group (n = 26, mean 34.0 days) compared to the euglycemic group (n = 22, mean = 24.7 days). The hyperglycemic group also had significantly higher in-patient mortality (p = .0036), number of documented infections (p = .0015), and number of days on non-prophylactic antibiotics (p = .0078) compared to the euglycemic group. Length of hospital stay for patients undergoing autologous HSCT was also significantly longer (p = .01) in the hyperglycemic group (n = 29, mean = 31.33 days) versus the euglycemic group (n = 18, mean = 18.30 days). Hyperglycemic patients undergoing autologous HSCT also showed significantly higher number of documented infections (p = .028).ConclusionThis retrospective study indicates that hyperglycemia (blood glucose > 126 mg/dL) is strongly associated with increased mortality, morbidity and length of stay in patients undergoing HSCT. Randomized prospective studies are necessary to further elucidate the possible benefits strict glucose control may render in the setting of HSCT patients.
Thus both T-cells and E-cells show certain similarities in glucose-induced production of free radicals. We hypothesized that E-cells in high glucose media may behave similar to Tcells, induce insulin receptors and metabolize glucose since this has not been previously reported. Methods: E-cells were incubated in 5, 15, and 30 mM glucose, and 25 mM mannitol for 6, 12, 24, and 48 hours at 37ЊC. We measured 125 I insulin binding as well as uptake of 14 C deoxyglucose in response to 50 µU/mL of insulin and analyzed expression of insulin receptor (IR) and glucose transporters GLUT1 and GLUT4 by Western blotting. Results: Binding of 125 I insulin to cells incubated in 30 mM glucose (but no 5 mM) was time-and temperature-dependent and demonstrated 100% dissociation with 100 ng of insulin per mL. Uptake of 14 C deoxyglucose was also time-and glucose concentration-dependent with greatest uptake at 48 hours, but none at 6 hours. Uptake of 14 C deoxyglucose was highest at 30 mM, intermediate with 15 mM, and none at 5 mM glucose. These effects of high glucose were not attributed to hyperosmotic action of sugar, since 25 mM mannitol had no effect 14 C deoxyglucose uptake. Demonstration of time-dependent increase in insulin sensitivity was further confirmed by increased IR expression in E-cells by the use of Western blotting analysis after incubation of E-cells with 30 mM glucose, but not with 5 mM glucose. Immunoblotting experiments also showed that incubation of E-cells in 30 mM glucose was accompanied by 2-4-fold elevation in expression of GLUT1 and GLUT4 as compared with 5 mM glucose values. In conclusion, we have established certain similarities between Ecells and T-cells in which both tissues are originally insulin insensitive but become insulin sensitive and develop insulin receptors in high concentration of glucose exhibiting production of ROS and lipid peroxidation. The use of T-cells as an easily available tissue may be an attractive alternative as a surrogate biomarker to predict early atherogenic changes.
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