Association between acute respiratory failure requiring mechanical ventilation and the production of advanced glycation end products.

Patients with acute respiratory failure often have hyperglycemia. Elevated glucose levels could cause acute lung injury through the production of advanced glycation end products. We measured glucose, advanced glycation end products, glycated albumin, circulating glycated hemoglobin, and soluble receptor for advanced glycation end product (sRAGE) levels on admission, at 24 hours, and at 72 hours in 40 patients with acute respiratory failure requiring mechanical ventilation. We compared these values with healthy control subjects. The mean age was 63.3±11.2 years. Fifty percent of the patients were women. Thirteen patients (32.5%) died during this hospitalization. The mean maximum glucose level on the day of admission was 215.7±171.1 mg/dL. Compared with control subjects, there was a significant reduction in advanced glycation end product levels (p=0.0001) in the patients at all 3 time points. Circulating glycated hemoglobin levels were significantly higher in patients compared with control subjects. We also observed a moderate increase in glycated albumin levels on admission and at 24 hours when compared with the control samples. Overall sRAGE levels were similar to controls, but patients with dense infiltrates on chest X-ray had increased levels compared with patients who did not have these dense infiltrates on the day of admission. Patients with acute respiratory failure requiring mechanical ventilation have decreased levels of advanced glycation end products and increased levels of circulating glycated hemoglobin. The results from this pilot study suggest that the acute stress associated with respiratory failure might create glycated proteins which could contribute to disease pathogenesis.

Advanced glycation end products and glycosaminoglycans in patients with diabetic ketoacidosis.

In some patients diabetic ketoacidosis (DKA) causes acute endothelial injury and multiorgan failure. Measurement of glycosaminoglycan (GAG) and advanced glycation end products (AGE) could provide information to help understand the biochemical events associated with poor outcomes in these patients. This study included 37 patients with DKA admitted to an intensive care unit. Blood was collected from these patients during the first day of hospitalization, 24 hours after the first sample, and 72 hours after the first sample when possible. ELISA-based assays were used to measure glucose, hemoglobin A1c, AGE, glycated albumin, and GAG levels in serum. Twenty healthy control subjects with no history of diabetes donated 1 blood sample. Control subjects had a mean age of 36.3±12.1 years; patients with DKA had a mean age of 38.1±18.5 years. Admission laboratory tests in patients with DKA included glucose 546±296 mg/dL, bicarbonate 10.1±5.5 mEq/L, anion gap 31.8±7.8 mEq/L, and creatinine 1.1±1.0 mg/dL. Patients with DKA had significantly higher level glucose and free glycated hemoglobin. Control subjects had significantly higher levels of AGE and glycated albumin. There were no differences in soluble receptor for AGE levels or GAG levels between the control subjects and patients with DKA. Patients with DKA had lower circulating levels of AGE and glycated albumin than control subjects. These results may reflect absorption of these proteins to damaged capillary surfaces or loss of proteins into interstitial spaces secondary to increased endothelial permeability.