Increased hypoglycemia associated with renal failure during continuous intravenous insulin infusion and specialized nutritional support

Objective: To evaluate glycemic control for critically ill, hyperglycemic trauma patients with renal failure who received concurrent intensive insulin therapy and continuous enteral (EN) or parenteral nutrition (PN). Methods: Adult trauma patients with renal failure, who were given EN or PN concurrently with continuous graduated intravenous regular human insulin (RHI) infusion for at least 3 days were evaluated. Our conventional RHI algorithm was modified for those with renal failure by allowing greater changes in blood glucose concentrations (BG) before the infusion rate was escalated. BG was determined every 1-2 hours while receiving the insulin infusion. BG control was evaluated on the day prior to RHI infusion and for a maximum of 7 days while receiving RHI. Target BG during the RHI infusion was 70 to 149 mg/dL (3.9 to 8.3 mmol/L). Glycemic control and incidence of hypoglycemia for those with renal failure were compared to a historical cohort of critically ill, hyperglycemic trauma patients without renal failure given our conventional RHI algorithm. Results: Twenty-one patients with renal failure who received the modified RHI algorithm were evaluated and compared to forty patients without renal failure given our conventional RHI algorithm. Average BG was significantly greater for those with renal failure (133 + 14 mg/dL or 7.3 + 0.7 mmol/L) compared to those without renal failure (122 + 15 mg/dL or 6.8 + 0.8 mmol/L), respectively (p \u3c 0.01). Patients with renal failure experienced worsened glycemic variability with 16.1 + 3.3 hours/day within the target BG range, 6.9 + 3.2 hours/day above the target BG range, and 1.4 + 1.1 hours below the target BG range compared to 19.6 + 4.7 hours/day (p \u3c 0.001), 3.4 + 3.0 hours/day (p \u3c 0.001), and 0.7 + 0.8 hours/day (p \u3c 0.01) for those without renal failure, respectively. Moderate hypoglycemia (\u3c 60 mg/dL or \u3c 3.3 mmol/L) occurred in 76% of patients with renal failure compared to 35% without renal failure (p \u3c 0.005). Severe hypoglycemia (BG \u3c 40 mg/dL or \u3c 2.2 mmol/L) occurred in 29% of patients with renal failure compared to none of those without renal failure (p \u3c 0.001). Conclusion: Despite receiving a modified RHI infusion, critically ill trauma patients with renal failure are at higher risk for developing hypoglycemia and experience more glycemic variability than patients without renal failure

A functional and transcriptomic analysis of NET1 bioactivity in gastric cancer

<p>Abstract</p> <p>Background</p> <p>NET1, a RhoA guanine exchange factor, is up-regulated in gastric cancer (GC) tissue and drives the invasive phenotype of this disease. In this study, we aimed to determine the role of NET1 in GC by monitoring the proliferation, motility and invasion of GC cells in which NET1 has been stably knocked down. Additionally, we aimed to determine NET1-dependent transcriptomic events that occur in GC.</p> <p>Methods</p> <p>An in vitro model of stable knockdown of NET1 was achieved in AGS human gastric adenocarcinoma cells via lentiviral mediated transduction of short-hairpin (sh) RNA targeting NET1. Knockdown was assessed using quantitative PCR. Cell proliferation was assessed using an MTS assay and cell migration was assessed using a wound healing scratch assay. Cell invasion was assessed using a transwell matrigel invasion assay. Gene expression profiles were examined using affymetrix oligonucleotide U133A expression arrays. A student's t test was used to determine changes of statistical significance.</p> <p>Results</p> <p>GC cells were transduced with NET1 shRNA resulting in a 97% reduction in NET1 mRNA (p < 0.0001). NET1 knockdown significantly reduced the invasion and migration of GC cells by 94% (p < 0.05) and 24% (p < 0.001) respectively, while cell proliferation was not significantly altered following NET1 knockdown. Microarray analysis was performed on non-target and knockdown cell lines, treated with and without 10 μM lysophosphatidic acid (LPA) allowing us to identify NET1-dependent, LPA-dependent and NET1-mediated LPA-induced gene transcription. Differential gene expression was confirmed by quantitative PCR. Shortlisted NET1-dependent genes included STAT1, TSPAN1, TGFBi and CCL5 all of which were downregulatd upon NET1 downregulation. Shortlisted LPA-dependent genes included EGFR and PPARD where EGFR was upregulated and PPARD was downregulated upon LPA stimulation. Shortlisted NET1 and LPA dependent genes included IGFR1 and PIP5K3. These LPA induced genes were downregulated in NET1 knockdown cells.</p> <p>Conclusions</p> <p>NET1 plays an important role in GC cell migration and invasion, key aspects of GC progression. Furthermore, the gene expression profile further elucidates the molecular mechanisms underpinning NET1-mediated aggressive GC cell behaviour.</p

Sliding Scale Regular Human Insulin for Identifying Critically Ill Patients Who Require Intensive Insulin Therapy and for Glycemic Control in those with Mild to Moderate Hyperglycemia

Two sliding scale regular human insulin (RHI) algorithms (SSI) were retrospectively evaluated to identify those who develop severe hyperglycemia (blood glucose (BG) > 180 mg/dL) and for glycemic management of continuously-fed, critically ill trauma patients with mild to moderate hyperglycemia (BG 126 to 179 mg/dL). Assignment of low or high SSI was based upon anticipated severity of difficulty in glycemic control. BG was obtained every 3 to 6 hours. Target BG range was 70 to 149 mg/dL. Patients who were unable to achieve a BG < 150 mg/dL with SSI and who required a continuous intravenous RHI infusion were identified. Twenty-five of 121 patients (21%) failed SSI necessitating more intensive insulin therapy. The low and high intensity SSI groups exhibited a baseline BG of 123 + 33 mg/dL and 164 + 20 mg/dL (P = 0.001). Average BG for each group was 129 ± 14 mg/dL and 145 ± 21 mg/dL (P = 0.001). Each group spent 20 ± 4 and 16 ± 5 hours/day within the target BG range (P = 0.001), respectively. Mild hypoglycemia (BG 40 - 60 mg/dL) occurred in 11% and 7% of patients from each group (P = N.S.). Severe hypoglycemia (BG < 40 mg/dL) occurred in zero and two (5%) patients, respectively (P = N.S). SSI served as a useful technique to identify those requiring more intensive insulin therapy and was safe and efficacious for continuously-fed, critically ill trauma patients with mild to moderate hyperglycemia

Sliding Scale Regular Human Insulin for Identifying Critically Ill Patients Who Require Intensive Insulin Therapy and for Glycemic Control in those with Mild to Moderate Hyperglycemia

Two sliding scale regular human insulin (RHI) algorithms (SSI) were retrospectively evaluated to identify those who develop severe hyperglycemia (blood glucose (BG) > 180 mg/dL) and for glycemic management of continuously-fed, critically ill trauma patients with mild to moderate hyperglycemia (BG 126 to 179 mg/dL). Assignment of low or high SSI was based upon anticipated severity of difficulty in glycemic control. BG was obtained every 3 to 6 hours. Target BG range was 70 to 149 mg/dL. Patients who were unable to achieve a BG < 150 mg/dL with SSI and who required a continuous intravenous RHI infusion were identified. Twenty-five of 121 patients (21%) failed SSI necessitating more intensive insulin therapy. The low and high intensity SSI groups exhibited a baseline BG of 123 + 33 mg/dL and 164 + 20 mg/dL (P = 0.001). Average BG for each group was 129 ± 14 mg/dL and 145 ± 21 mg/dL (P = 0.001). Each group spent 20 ± 4 and 16 ± 5 hours/day within the target BG range (P = 0.001), respectively. Mild hypoglycemia (BG 40 - 60 mg/dL) occurred in 11% and 7% of patients from each group (P = N.S.). Severe hypoglycemia (BG < 40 mg/dL) occurred in zero and two (5%) patients, respectively (P = N.S). SSI served as a useful technique to identify those requiring more intensive insulin therapy and was safe and efficacious for continuously-fed, critically ill trauma patients with mild to moderate hyperglycemia

Increased hypoglycemia associated with renal failure during continuous intravenous insulin infusion and specialized nutritional support

Objective: To evaluate glycemic control for critically ill, hyperglycemic trauma patients with renal failure who received concurrent intensive insulin therapy and continuous enteral (EN) or parenteral nutrition (PN). Methods: Adult trauma patients with renal failure, who were given EN or PN concurrently with continuous graduated intravenous regular human insulin (RHI) infusion for at least 3 days were evaluated. Our conventional RHI algorithm was modified for those with renal failure by allowing greater changes in blood glucose concentrations (BG) before the infusion rate was escalated. BG was determined every 1-2 hours while receiving the insulin infusion. BG control was evaluated on the day prior to RHI infusion and for a maximum of 7 days while receiving RHI. Target BG during the RHI infusion was 70 to 149 mg/dL (3.9 to 8.3 mmol/L). Glycemic control and incidence of hypoglycemia for those with renal failure were compared to a historical cohort of critically ill, hyperglycemic trauma patients without renal failure given our conventional RHI algorithm. Results: Twenty-one patients with renal failure who received the modified RHI algorithm were evaluated and compared to forty patients without renal failure given our conventional RHI algorithm. Average BG was significantly greater for those with renal failure (133 + 14 mg/dL or 7.3 + 0.7 mmol/L) compared to those without renal failure (122 + 15 mg/dL or 6.8 + 0.8 mmol/L), respectively (p \u3c 0.01). Patients with renal failure experienced worsened glycemic variability with 16.1 + 3.3 hours/day within the target BG range, 6.9 + 3.2 hours/day above the target BG range, and 1.4 + 1.1 hours below the target BG range compared to 19.6 + 4.7 hours/day (p \u3c 0.001), 3.4 + 3.0 hours/day (p \u3c 0.001), and 0.7 + 0.8 hours/day (p \u3c 0.01) for those without renal failure, respectively. Moderate hypoglycemia (\u3c 60 mg/dL or \u3c 3.3 mmol/L) occurred in 76% of patients with renal failure compared to 35% without renal failure (p \u3c 0.005). Severe hypoglycemia (BG \u3c 40 mg/dL or \u3c 2.2 mmol/L) occurred in 29% of patients with renal failure compared to none of those without renal failure (p \u3c 0.001). Conclusion: Despite receiving a modified RHI infusion, critically ill trauma patients with renal failure are at higher risk for developing hypoglycemia and experience more glycemic variability than patients without renal failure