Intensive Insulin Therapy Group Research Articles

A retrospective comparison between intensive and nonintensive insulin regimens in type 2 diabetes mellitus.

This study compared the outcomes between intensive and nonintensive insulin regimens and assessed the predictive factors for failing to achieve the glycated hemoglobin (A1C) goals in type-2-diabetes-mellitus (T2DM) patients requiring insulin therapy. A single-center, retrospective assessment of the medical records of 125 T2DM patients undergoing intensive (46 patients) and nonintensive insulin therapy (79 patients) were conducted. No significant differences were found when the intensive and nonintensive insulin therapy groups were compared in terms of the percentage decreases of glucose and A1C levels. The mean A1C levels of the nonintensive and intensive groups declined from 11.15% and 11.30% to 7.97% and 8.06%, respectively. Both intensive and nonintensive insulin therapies improved the baseline glycemic parameters but being overweight or obese and/or being reluctant to dietary recommendations led to treatment failures regardless of the insulin regimen.

The influence of exercise training versus intensive insulin therapy on insulin resistance development in type 1 diabetes

The etiology of insulin resistance (IR) in Type 1 Diabetes (T1D) is unclear; however, intramyocellular lipids (IMCL) are likely contributors. While exercise lessens IR and IMCL content; T1D patients elevate glycemia to offset exercise-induced hypoglycemic risk. The preferred treatment for T1D patients is tight glucose management through intensive insulin therapy (IIT); however, IIT is accompanied with a sedentary lifestyle. The purpose of this study was to examine IR development and IMCL in combined exercise (DARE; aerobic/resistance) and IIT-treated T1D animals. 76 rats were divided into control sedentary (C), diabetic sedentary (CD), diabetes sedentary intensive insulin therapy (DIT) and DARE groups. Following streptozotocin (STZ), glycemia was maintained at either 9-15 mM (CD, DARE) or 5-9 mM (DIT) using insulin. DARE alternated between running and weighted climbing for 12 weeks. Results demonstrate that DARE exhibited reduced onset of IR compared with C, DIT and CD, indicated by increased glucose infusion rate (hyperinsulinemic-euglycemic-clamp). A shift in lipid metabolism was evident whereby diacylglycerol was elevated in DIT compared to DARE, while triacylglycerol was elevated in DARE. These findings indicate enhanced IMCL metabolism and the sequestration of fat as neutral triacylglycerol leads to reduced IR in DARE. In contrast, IIT and sedentary behavior leads to diacylglycerol accumulation and IR.

Effects of intensive insulin therapy on the retinal microvasculature in patients with type 2 diabetes mellitus: a prospective observational study

BackgroundWe examined the retinal microvascular changes and associated factors in type 2 diabetes mellitus (T2DM) before and after intensive insulin therapy.MethodsThis prospective observational study recruited patients with T2DM and divided them into intensive insulin therapy and oral hypoglycemic agent groups. All patients enrolled in this study had diabetes without retinopathy or non-proliferative diabetic retinopathy. Optical coherence tomography angiography (OCTA) was used in all patients before treatment and at 1, 3, and 6 months after treatment. Vessel density (VD) and thickness changes in the macular and optic disc areas were assessed.ResultsThe study included 36 eyes in the intensive insulin therapy group and 36 in the oral hypoglycemic agent group. One month after treatment, VD in the deep capillary plexus (DCP) and peripapillary capillary VD (ppVD) were significantly decreased by intensification (P = 0.009, 0.000). At three months after treatment, decreases in VD induced by intensification were found in the superficial capillary plexus (SCP), DCP, foveal density in a 300-μm-wide region around the foveal avascular area (FD-300), and ppVD (P = 0.032, 0.000, 0.039, 0.000). Six months after treatment, decreases in VD by intensification were observed in the DCP and ppVD groups (P = 0.000, 0.000). Vessel density showed no significant change in the oral hypoglycemic agent group after treatment. The amount of DCP-VD reduction was correlated with macular thickening (r = 0.348, P = 0.038; r = 0.693, P = 0.000 and r = 0.417, P = 0.011, respectively) after intensive insulin therapy.ConclusionsInsulin-intensive treatment caused a transient reduction in vessel density in the macular and optic disc areas. DCP-VD and ppVD were more susceptible at an earlier stage. Retinal microvasculature monitoring using OCTA is vital for patients with type 2 diabetes receiving intensive insulin therapy.

77-LB: A Retrospective Analysis of the Association between HbA1c and Continuous Glucose Monitor Use for U.S. Patients with Type 2 Diabetes

Background: Use of real-time continuous glucose monitoring (rtCGM) reduces HbA1c in individuals with type 2 diabetes (T2D) treated with intensive insulin regimens in randomized clinical trials. However, the effects of CGM use on glycemia in T2D patients in real world settings, particularly those treated with less intensive therapies, has not been well studied. Materials and Methods: This large retrospective, observational analysis utilized data from the Optum Research Database (ORD) to assess the glycemic effects of CGM use (any CGM or real-time CGM [rtCGM]) compared with self-monitoring of blood glucoses (SMBG) within a large T2D population treated with intensive insulin therapy (IIT) and non-intensive therapies (NIT), including basal insulin only, and non-insulin medications. Outcomes were changes from baseline in HbA1c up to 6 months post index date in all patients and by treatment regimen. The percentage of patients who achieved ≥1.0 HbA1c reductions was also assessed. Results: Data from 82,983 eligible patients were assessed (Any CGM, n=1,406; rtCGM, n=148; SMBG, n=81,575). Significant HbA1c reductions were observed with Any CGM (-0.46) and rtCGM (-0.72) vs. SMBG (-0.09), ps < 0.001. HbA1c reductions were significant in CGM vs. SMBG users in the ITT (Any CGM, -0.38%; rtCGM, -0.68%, ps<0.001) and NIT groups (Any CGM, -0.67%, p<0.001, and rtCGM, -0.87, p=0.008). Significantly higher percentages of Any CGM and rtCGM vs. SMBG users achieved ≥1.0 HbA1c reductions in the IIT and NIT groups. Effects of Any CGM and rtCGM were attenuated but remained statistically significant in multivariate adjusted models for the overall T2D cohort. Conclusions: Use of CGM (Any CGM or rtCGM) confers notable benefits in improving glycemic control regardless of therapy regimen. These findings support expanding CGM access to the broader T2D population. Disclosure G. J. Norman: Employee; Self; Dexcom, Inc. M. L. Paudel: None. T. Bancroft: None. P. M. Lynch: Employee; Self; Dexcom, Inc.

A retrospective comparison between intensive and non-intensive insulin regimens in type 2 diabetes mellitus

Background This study compared the outcomes between intensive and non-intensive insulin regimens and assessed the predictive factors for failing to achieve the glycated hemoglobin (A1C) goals in type 2 diabetes mellitus (T2DM) patients requiring insulin therapy. Methods A single-center, retrospective assessment of the medical records of 125 T2DM patients undergoing intensive (46 patients) and non-intensive insulin therapy (79 patients) were conducted. Results No significant differences were found when the intensive and non-intensive insulin therapy groups were compared in terms of the percentage decreases of glucose and A1C levels. The mean A1C levels of the non-intensive and intensive groups declined from 11.15% and 11.30% to 7.97% and 8.06%, respectively. Conclusions Both intensive and non-intensive insulin therapies improved the baseline glycemic parameters, but being overweight or obese and/or being reluctant to dietary recommendations led to treatment failures regardless of the insulin regimen.

Could the appropriate anti-diabetic therapy be mixed insulin in dialysis patients?

A good glycemic regulation should be provided to reduce mortality and morbidity in patients with end-stage renal failure due to diabetes mellitus. However, the use of insulin therapies in patients with renal failure is troublesome due to the increased rate of side effects. In our study, we investigated the frequency of hypoglycemia and its symptoms in patient groups receiving intensive and mixed insulin therapies. This prospective study included 89 hemodialysis patients with DM-related stage 5 chronic kidney disease who were followed up in a nephrology clinic of a university hospital between January 2013 and August 2015. Our study group was divided into two groups as those receiving intensive insulin therapy and mixed insulin therapy. Group 1 and group 2 consisted of 46 patients and 43 patients, respectively. Hypoglycemia (glucose 0.05). Hypoglycemia was detected in 27 patients (58.7%) in the intensive insulin therapy group and 14 patients (32.6%) in the mixed insulin therapy group. There was a significant level of hypoglycemia in the group receiving intensive insulin therapy (p < 0.05). In our study, the group receiving intensive insulin therapy had higher frequency and severity of common hypoglycemia symptoms such as confusion, sweating, weakness, dysphasia, palpitations, blurred vision, and feeling hungry. There was a higher frequency of hypoglycemia under intensive insulin therapy in patients undergoing dialysis due to chronic kidney failure, which suggests that mixed insulin therapy is the ideal treatment to avoid hypoglycemia in this group of patients.

Intensive Insulin Therapy (Basal-Bolus).

Intensive insulin therapy (IIT) aims at achieving near-normal glycemic control and usually uses a basal-bolus (BB) schema to mimic physiologic insulin secretion. The treatment burden of IIT should be outweighed by improved glycemic control and reduction of chronic complications, but reviews summarizing the effects of IIT in subjects with T1DM and T2DM in glycated hemoglobin, hypoglycemia, insulin doses, and weight are limited. We performed a PubMed search to identify relevant randomized control trials (RCTs) comparing IIT and conventional insulin treatment in T1DM and T2DM subjects and addressing glycated hemoglobin, hypoglycemia, insulin requirements, and weight. We have identified 11 RCTs in T1DM subjects, published years ago and very heterogenous in design. Throughout the studies there was a consistent superiority of IIT in glycated hemoglobin reduction, a higher rate of severe hypoglycemia and more weight gain in the IIT group without a clear effect on insulin doses. We have identified 2 RCTs in T2DM subjects, only one of them using a definite BB schema in the IIT group. IIT induced more hypoglycemia and better HbA1c, but not more weight gain. IIT is the best option for treatment of subjects with T1DM in HbA1c reduction with a cost in the rate of hypoglycemia and weight gain. In subjects with T2DM, IIT also yields improvement in HbA1c versus conventional treatment, also at the cost of more hypoglycemic episodes, but not of higher weight gain. RCT treatment arms did not only differ in the insulin schema, but also in treatment goals, therapeutic education, and frequency of clinical visits among other characteristics. However, most evidence was gained using a BB insulin schema in the intensive arm and it is likely that the insulin schema had a relevant contribution in the results.

Effect of intensive insulin therapy on high mobility group box-1/nuclear factor-ΚB pathway in severe traumatic brain injury patient with stress hyperglycemia

To explore the effect of intensive insulin therapy (IIT) on high mobility group box-1/nuclear factor-ΚB (HMGB1/NF-ΚB) signaling pathway in severe traumatic brain injury (sTBI) patient with stress hyperglycemia. Sixty-one sTBI patients with stress hyperglycemia [Glasgow coma scale (GCS) ≤ 8, three times of random blood glucose levels > 11.1 mmoL/L, glycosylated hemoglobin (HbA1c) < 0.065] admitted to the Affiliated Huaian No.1 People's Hospital of Nanjing Medical University from July 2015 to October 2017 were enrolled. Patients were divided into IIT group (29 cases, keeping blood glucose at 4.4-7.8 mmol/L) and conventional glycemic therapy (CGT) group (32 cases, keeping blood glucose at 7.8-12.2 mmo/L) according to the random number table method. Before treatment and 1, 7 and 14 days after treatment, the levels of plasma HMGB1 and tumor necrosis factor-α (TNF-α) were measured by enzyme linked immunosorbent assay (ELISA); C-reactive protein (CRP) was determined by automatic biochemical analyzer, and NF-ΚB p65 gene expression in peripheral blood mononuclear cells was detected by real-time quantitative polymerase chain reaction (PCR). Nine patients were withdrawn from the observation because the 4 consecutive blood glucose monitoring did not reach the target value, combined with severe infection, or abandoned the treatment with serious brain damage. Finally, 52 patients were enrolled in the analysis, including 28 in CGT group and 24 in IIT group. The levels of plasma HMGB1, TNF-α, CRP and the expression of NF-ΚB gene in monocytes of the two groups at 1 day after treatment were significantly higher than those before treatment, and reached the peak value, then gradually decreased. After 7 days of treatment, they were significantly lower than 1 day. The levels of plasma CRP and TNF-α in the IIT group were significantly lower than those in the CGT group [CRP (mg/L): 36.7±4.4 vs. 45.1±6.1, TNF-α (ng/L): 42.4±9.7 vs. 53.2±9.1, both P < 0.05], the level of HMGB1 in plasma and the expression of NF-ΚB p65 in monocytes were significantly lower than those in the CGT group after 14 days of treatment [HMGB1 (μg/L): 60.1±8.7 vs. 80.5±9.1, NF-ΚB p65 (ΔCt): 35.8±8.5 vs. 53.5±7.3, both P < 0.05]. IIT inhibits the inflammatory response in sTBI patients with stress hyperglycemia through HMGB1/NF-ΚB pathway.

Glycemic control and changes of inflammatory factors in severe sepsis patients and their clinical significance

Objective To investigate glycemic control, changes of inflammatory factors and their clinical significance in severe sepsis patients. Methods One hundred and three severe sepsis patients with abnormal hyperglycemia were randomly divided into the two groups and receive intensive insulin therapy (IIT) and conventional insulin therapy (CIT) respectively. According to glycosylated hemoglobin level, the two groups were further divided into stress hyperglycaemia and diabetes mellitus subgroups. The mortality and incidence of hypoglycemia were compared between the groups and subgroups. Enzyme linked immunosorbent assay was used to detect TNF-α, IL-6 levels before treatment, 3 and 7 days after treatment. Results In IIT group, the mortality in diabetes mellitus subgroup was significantly higher than that in stress hyperglycaemia subgroup (66.7% vs. 30.8%, P<0.05), while the mortality in stress hyperglycaemia subgroup significantly higher than that in diabetes mellitus subgroup (54.1% vs. 25.0%, P<0.05) in CIT group. Multivariate Logistic regression analysis revealed IIT increased the risk for death in diabetes mellitus subgroup(OR=1.221, 95%CI: 1.075-1.434), while decreased the risk for death in stress hyperglycaemia subgroup(OR=0.872, 95%CI: 0.714-0.975). The incidence of hypoglycemia was significantly higher in IIT group than that in CIT group(13.7% vs. 1.9%, P<0.05). Before treatment, the levels of TNF-α, IL-6 in stress hyperglycaemia patients were significantly higher than those in diabetes mellitus patients. After 7 day treatment, The levels of TNF-α, IL-6 decreased significantly in stress hyperglycaemia patients (P<0.01), and decreased more significantly in IIT group than that in CIT group. Conclusion Severe sepsis patients with stress hyperglycaemia can attain better glycemia control and inhibition of inflammatory factors, and clinical benefit from IIT. Key words: Severe sepsis; Stress hyperglycemia; Type 2 diabetes melittus; Intensive insulin therapy; Conventional insulin therapy; Inflammatory factors; Glycosylated hemoglobin; Prognosis

Intensive insulin therapy for preventing postoperative infection in patients with traumatic brain injury: A randomized controlled trial.

Objective:To assess the effect of intensive insulin therapy (IIT) for preventing postoperative infection in patients with traumatic brain injury (TBI).Methods:In total, 88 patients with TBI were randomly divided into 2 groups, 44 in each group. One group (group ITT) received IIT and the other group (group CIT) received conventional insulin therapy (CIT). This study was conducted between February 2013 and January 2016. Outcomes included infection rate, mortality, and neurological outcome (measured by the Glasgow Outcome Scale [GOS]).Results:A total of 81 patients completed the study. IIT showed greater efficacy than CIT, with a decreased infection rate in the IIT group compared to the CIT group (31.9% vs 52.3%, P = 0.03), and also a reduced duration of stay in intensive care unit (ICU) (IIT group, 4.5 ± 2.1 days vs CIT group, 5.7 ± 2.8 days, P = 0.02). In addition, a significant difference in scores on the GOS scale was observed between the 2 groups (P = 0.04). The mortality rates in hospital and at the 26-week follow-up were similar between the 2 groups.Conclusion:IIT leads to a reduced infection rate, shorter stays in ICU, and improved neurological outcome.

Tight glycemic control in acutely ill patients: low evidence of benefit, high evidence of harm!

In 1878 Claude Bernard described hyperglycemia during hemorrhagic shock [1]. It is now well known that acute illness or injury may result in hyperglycemia, insulin resistance, and glucose intolerance, collectively termed stress hyperglycemia [2]. Stress hyperglycemia is an evolutionarily preserved adaptive response which provides the nervous and immune system with an immediate source of energy at a time of crisis. Insects, worms, and all vertebrates develop stress hyperglycemia when exposed to stress [2]. Stress hyperglycemia is a component of the stereotypic and coordinated response to stress referred to by Hans Selye as the “general adaption syndrome” which until 2001 was believed to be a beneficial host response which enhanced the host’s chances of survival [3]. On 8 November 2001, Van den Berghe and colleagues published a study entitled “Intensive insulin therapy in critically ill patients” in which they randomized 1548 surgical ICU patients (63 % who had undergone cardiac surgery) to an intensive insulin therapy (IIT) protocol targeting a blood glucose of 80–110 mg/dl or a control arm in which patients only received insulin when the blood glucose exceeded 215 mg/dl with a target of 180–200 mg/ dl (Leuven I study) [4]. Hospital mortality was 7.2 % in the IIT group as compared to 10.9 % in the control group (p = 0.01); in addition IIT reduced length of stay and patient morbidities. This study was supported by retrospective cohort studies in acutely ill patients demonstrating an association between increasing hyperglycemia and poor clinical outcomes. The findings of the Leuven study were widely embraced and endorsed by the Institute for Health Care Improvement, the American College of Endocrinology as well as other national and international organizations and soon became considered the standard of care for ICU patients around the world. In 2006, Van den Berghe and colleagues repeated their study in medical ICU patients (Leuven II study) [5]. Although failing to reproduce the improvement in survival in the entire set of patients, this study demonstrated a reduction in morbidity in the patients randomized to IIT with a reduction in mortality in the subset of patients with an ICU stay of 3 days or more. Using a similar study design these authors repeated their study in a pediatric ICU (mostly cardiac surgery patients) and demonstrated an outcome very similar to the Leuven I study [6]. Following the Leuven I study, 14 randomized controlled trials in various patient populations including mixed ICUs, neurosurgical, neurological, coronary, trauma, and pediatric ICUs have been performed (see Table 1). Without exception all of these studies demonstrated no outcome benefit (NOB) from tight glycemic control in acutely ill patients. NICE-SUGAR, the largest trial to date (n = 6022), demonstrated a 2.6 % absolute increase in 90-day mortality in patients randomized to IIT (p = 0.02) [7]. Three of these studies demonstrated harm, with almost all of the studies demonstrating a significant increase in the risk of both moderate and severe hypoglycemia. Even mild hypoglycemia in ICU patients is associated with an increased risk of death [8]. The mechanism(s) by which hypoglycemia increases the risk of death in critically ill patients has (have) not been investigated. However, it is likely that hypoglycemia increases the risk of fatal arrhythmias [9]. Furthermore, cell death *Correspondence: marikpe@evms.edu 2 Eastern Virginia Medical School, 825 Fairfax Av, Suite 410, Norfolk, VA 23507, USA Full author information is available at the end of the article

Intensive versus nonintensive insulin therapy for hyperglycemia after traumatic brain injury: study protocol for a randomized controlled trial

Background: Hyperglycemia after traumatic brain injury is a physiological and metabolic disorder that may further aggravate secondary injury to the brain. Various experiences in the effective treatment of hyperglycemia after traumatic brain injury have been described. For example, the early use of intensive insulin therapy can control the blood glucose concentration within the target range, which has a direct protective effect on severe traumatic brain injury. However, some studies have arrived at different conclusions. Therefore, we aim to verify the therapeutic efficacy of intensive insulin therapy versus nonintensive insulin therapy on hyperglycemia after severe traumatic brain injury. Methods/Design: A randomized, controlled, double-blind study has been designed for completion at Oriental Hospital of Lianyungang, China. Sixty patients with hyperglycemia after severe closed traumatic brain injury will be randomized into an intensive insulin therapy group and a nonintensive insulin therapy group. The intensive insulin therapy group will then be divided into three subgroups based on the following target blood glucose levels: 4.4-7.0 mM (strict control group), 7.1-10.0 mM (moderate control group), and 10.1- 3.0 mM (slight control group). In the intensive insulin therapy group, the blood glucose levels will be monitored and controlled using the Yale Insulin Infusion Protocol, and a micropump will be used for intravenous injection of insulin. The nonintensive insulin therapy group will be given subcutaneous insulin injections. The primary endpoint will be the blood glucose levels, and the secondary endpoints will be mortality, activities of daily living, and prognosis. Discussion: This study will be powered to confirm the advantages of intensive insulin therapy in controlling blood glucose levels, reducing mortality, and improving prognosis in patients with hyperglycemia after severe traumatic brain injury. Trial registration: ClinicalTrials.gov identifier: NCT02161055; registered on 5 June 2014.

Effects of tight computerized glucose control on neurological outcome in severely brain injured patients: a multicenter sub-group analysis of the randomized-controlled open-label CGAO-REA study.

IntroductionHyperglycemia is a marker of poor prognosis in severe brain injuries. There is currently little data regarding the effects of intensive insulin therapy (IIT) on neurological recovery.MethodsA sub-group analysis of the randomized-controlled CGAO-REA study (NCT01002482) in surgical intensive care units (ICU) of two university hospitals. Patients with severe brain injury, with an expected ICU length of stay ≥48 hours were included. Patients were randomized between a conventional glucose management group (blood glucose target between 5.5 and 9 mmol.L−1) and an IIT group (blood glucose target between 4.4 and 6 mmol.L−1). The primary outcome was the day-90 neurological outcome evaluated with the Glasgow outcome scale.ResultsA total of 188 patients were included in this analysis. In total 98 (52%) patients were randomized in the control group and 90 (48%) in the IIT group. The mean Glasgow coma score at baseline was 7 (±4). Patients in the IIT group received more insulin (130 (68 to 251) IU versus 74 (13 to 165) IU in the control group, P = 0.01), had a significantly lower morning blood glucose level (5.9 (5.1 to 6.7) mmol.L−1 versus 6.5 (5.6 to 7.2) mmol.L−1, P <0.001) in the first 5 days after ICU admission. The IIT group experienced more episodes of hypoglycemia (P <0.0001). In the IIT group 24 (26.6%) patients had a favorable neurological outcome (good recovery or moderate disability) compared to 31 (31.6%) in the control group (P = 0.4). There were no differences in day-28 mortality. The occurrence of hypoglycemia did not influence the outcome.ConclusionsIn this sub-group analysis of a large multicenter randomized trial, IIT did not appear to alter the day-90 neurological outcome or ICU morbidity in severe brain injured patients or ICU morbidity.

Benefits of exenatide on obesity and non-alcoholic fatty liver disease with elevated liver enzymes in patients with type 2 diabetes.

The purpose of this study was to evaluate the advantages of exenatide treatment on obesity and non-alcoholic fatty liver disease (NAFLD) with elevated liver enzymes in patients with type 2 diabetes (T2D). A total of 60 newly diagnosed patients with obesity, NAFLD with elevated liver enzymes and T2D were included in the study. The patients were randomly divided into two groups. The exenatide treatment group (n = 30) were treated with exenatide and insulin glargine, and the intensive insulin therapy group (n = 30) were treated with insulin aspart and insulin glargine for 12 weeks. Selected clinical characteristics were determined, and ultrasonography was performed at both baseline and 12 weeks following treatment. At baseline, the clinical characteristics were matched between the two groups. After 12 weeks, fasting blood glucose (FBG), postprandial blood glucose (PBG), glycosylated haemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG) and total bilirubin levels were significantly decreased in the two groups (p < 0.001). Body weight and waist circumference were significantly decreased in the exenatide group but increased in the intensive insulin group (p < 0.001). The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transpeptidase (γGGT) in the exenatide group were significantly lower than in the intensive insulin group (p < 0.001). The mean body weight change correlated with the levels of ALT, AST and γGGT change (ALT, r = 0.761; AST, r = 0.733; γGGT, r = 0.752; p < 0.001). Moreover, the reversal rate of fatty liver was significantly higher in the exenatide group (93.3%) than the intensive insulin group (66.7%) (p < 0.01). Exenatide has a better hepatic-protective effect than intensive insulin therapy and perhaps represents a unique option for adjunctive therapy for patients with obesity, non-alcoholic fatty liver disease with elevated liver enzymes and T2D.

Intensive Versus Intermediate Glucose Control in Surgical Intensive Care Unit Patients

The optimal perioperative blood glucose range to improve surgical site infection (SSI) in surgical intensive care unit (ICU) patients remains unclear. We sought to determine whether the incidence of SSI is reduced by perioperative intensive insulin therapy (IT). Patients were randomly assigned to receive perioperative intensive IT, with a target blood glucose range of 4.4-6.1 mmol/L, or intermediate IT, with a target blood glucose range of 7.7-10.0 mmol/L in the surgical ICU. We defined the primary end point as the incidence of SSI. Study participants were randomly assigned to glucose control with one of two target ranges: for 225 patients in the intermediate IT group or for 222 patients in the intensive IT group, respectively. No patients in either group became hypoglycemic (<4.4 mmol/L) during their stay in the surgical ICU. In our series, the rate of SSI after hepato-biliary-pancreatic surgery was 6.7%. Patients in the intensive IT group, compared with the intermediate IT group, had fewer postoperative SSIs (9.8% vs. 4.1%, P = 0.028) and a lower incidence of postoperative pancreatic fistula after pancreatic resection (P = 0.040). The length of hospitalization required for patients in the intensive IT group was significantly shorter than that in the intermediate IT group (P = 0.017). We found that intensive IT decreased the incidence of SSI among patients who underwent hepato-biliary-pancreatic surgery: a blood glucose target of 4.4 to 6.1 mmol/L resulted in lower rate of SSI than did a target of 7.7-10.0 mmol/L.

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ASSA13-17-3 The Prospective Clinical Trial of Intensive Insulin Therapy in the Control of Perioperative Hyperglycemia For the Children Undergoing the Palliative Congenital Heart Surgeries

<h3>Objective</h3> The intensive insulin therapy (IIT) has shown great results in the therapy of acquired cardiac lesions’ surgeries during intensive care unit (ICU) while it’s unknown in the palliative operations for complex congenital heart disease (CHD). This trial was to estimate the results for controlling the hyperglycemic in the palliative heart surgeries in CHD children during the paediatric intensive care unit (PICU) stays. <h3>Methods</h3> We enrolled 79 children diagnosed with congenital complex cardiac lesions who are going through the palliative operations. They were assigned into two groups randomly by computer, the IIT (n = 39) and conventional insulin therapy (CIT) group, which blood glucose concentrations ranges were 70–130 mg/dL and 70–220 mg/dL, respectively. The insulin infusion is pumped continuously to the children once glycemic level exceeds the upper limit of their own group after the surgeries back to PICU. In this prospective clinical trial we consider the hypoglycemic as the blood glucose falls below 70mg/dL and the 50% dextrose solution will be given to deal with the hypoglycemia till the glycemic is back into the settled range of their own group with the double check of blood glucose concentration. The PICU stays, chest effusion, transfusion, blood tests and major complications were documented to analysis. <h3>Results</h3> There was no hospital death and two infants in CIT group received the secondary surgeries for post-operation bleeding. One neonate and an infant in IIT group were excluded from this study due to the cardiopulmonary resuscitation for pulmonary hypertension crisis and the use of extracorporeal membrane oxygenation (ECMO) for low cardiac output syndrome. The incidence of hypoglycemia in IIT group was 19% while the one in CIT group was 11% (p = 0.047). The mean peak blood glycemic in IIT and CIT was 161 mg/dL and 221 mg/dL, respectively, which showed significant statistical differences (p = 0.013). The mean PICU stays and ventilation hours in both groups were no significant difference. The mean chest effusion in CIT group was 312 mL in the children of Fontan circulation, which was much less than that of IIT group (p = 0.031). The total hospital days in two groups were no statistical differences (p = 0.057). <h3>Conclusions</h3> The children in IIT group got better short outcomes than that of CIT group. It’s important to enlarge the population in this trial and other complex CHD would be included to analysis to acquire more information on the controlling of hyperglycemia in the perioperative care for complex CHD children.

Influence of intensive insulin therapy on vascular endothelial growth factor in patients with severe trauma

The influence of early-stage intensive insulin therapy on the plasma levels of vascular endothelial growth factor (VEGF) and the related parameters in patients with severe trauma and the clinical implication were investigated. Sixty-four cases of severe trauma (injury severity score ≥20) with stress hyperglycemia (blood glucose >9 mmol/L) were randomly divided into intensive insulin therapy group and conventional therapy group. ELISA method, radioimmunoassay and density gradient gradation one-step process were used to determine plasma VEGF, endothelin-1 (ET-1), and the number of circulating endothelial cells (CECs) at the day of 0, 2, 3, 5 and 7 after admission. Simultaneously, the changes of CRP concentration in plasma were monitored to evaluate inflammatory response. The results showed that plasma levels of observational indexes in patients receiving early-stage intensive insulin therapy were all significantly lower than those in conventional therapy groups 2, 3, 5 and 7 days after admission [for VEGF (ng/L), 122.2±23.8 vs. 135.9±26.5, 109.6±27.3 vs. 129.0±18.4, 88.7±18.2 vs. 102.6±27.3, 54.2±26.4 vs. 85.7±35.2, P<0.05, 0.01, 0.05, 0.05 respectively; for ET-1 (ng/L), 162.8±23.5 vs. 173.7±13.2, 128.6±17.5 vs. 148.8±22.4, 96.5±14.8 vs. 125.7±14.8, 90.7±16.9 vs. 104.9±22.5, P<0.05, 0.01, 0.01, 0.01 respectively; for CRP (mg/L), 23.2±13.8 vs. 31.9±16.5, 13.6±17.3 vs. 23.5±18.4, 8.7±10.2 vs. 15.6±13.3, 5.2±9.4 vs. 10.7±11.2, all P<0.05; for CECs (/0.9 μL), 10.9±5.6 vs. 13.9±6.2, 8.5±4.9 vs. 11.3±5.3, 6.3±6.4 vs. 9.4±5.7, 4.8±7.1 vs. 7.8±4.8, all P<0.05]. It was concluded that intensive insulin therapy could antagonize the endothelium injury after trauma and reduce inflammation response quickly, which was one of important mechanisms by which intensive insulin therapy improves the prognosis of trauma patients.

Yoğun Bakım Hastalarında Yoğun İnsülin Tedavisi İle Kan Șekerinin Sıkı Kontrolünün Mortalite Ve Morbiditeye Etkileri

Amaç: Bu çalıșma, yoğun bakım (YB) hastalarında sürekli insülin infüzyonu ile kan șekerinin sıkı kontrolünün mortalite, morbidite ve immün paraliziye etkilerini araștırmak amacı ile planlandı. Materyal ve Metod: Bu prospektif, randomize ve kontrollü çalıșmaya YB’a kabul edilen hasta veya birinci derece yakınlarından onam alınan toplam 20 hasta dahil edildi. Hastalar YB’ye kabulden sonra randomize olarak, Yoğun İnsülin Tedavisi (YİT) veya Geleneksel İnsülin Tedavisi (GİT) gruplarından birine alındı. Her iki gruba 10’ar hasta dahil edildi. Sürekli insülin infüzyonu ile YİT grubunda kan șekeri 80-110 mg/dL, GİT grubunda 180-200 mg/dL arasında tutuldu. Hastalar YB’ye kabul edildikten sonra günlük APACHE II (Acute Physiology and Chronic Health Evaluation II, Akut Fizyoloji ve Kronik Sağlık Değerlendirmesi) ve TISS 28 (Therapeutic Intervention Scoring System, Tedavi Amaçlı Girișim Skorlama Sistemi) skorlamaları yapıldı. Kabul, 5, 14 ve 28’inci günde tam kan ve biyokimyasal analizler yapıldı, C-reaktif protein (CRP) ve akım sitometri yöntemi ile monositik HLA-DR düzeyi saptandı. Yoğun bakım ve hastanede kalma süreleri ile olası mortalite nedeni ve zamanı kaydedildi. İstatiksel analizde Mann Whitney U Testi ve Chi-Square Testi kullanıldı ve p

重症脑出血患者个体化血糖管理的临床意义及预后*

目的：评价标准化胰岛素强化治疗对重症脑出血患者预后的影响。方法：451例重症脑出血(GCS评分≤ 8)伴血糖异常升高患者，随机分为胰岛素强化治疗组和常规治疗组，观察治疗30天后病死率。结果：胰岛素强化治疗组和常规治疗组30天的病死率分别是47.79%和41.33%，差异没有统计学意义(P > 0.05)。接受胰岛素强化治疗的226例患者中，GHb升高组病死率明显高于GHb正常组(57.14% vs 40.63%，P = 0.01)。接受胰岛素常规治疗的225例患者中，GHb正常组病死率显著高于GHb升高组(49.65% vs 27.38%，P = 0.001)。结论：重症脑出血患者入院时就应该立即测定GHb，进而制定个体化血糖管理目标和胰岛素治疗策略。 Objective: To evaluate the effect of insulin therapy on the prognosis of patients with severe cerebral hemor- rhage. Methods: 451 patients with severe cerebral hemorrhage (GCS score ≤ 8) were randomly divided into two groups, to receive intensive insulin therapy or conventional insulin therapy. The mortality was observed in the 30th day after treatment. Results: No significant difference in the mortality was found between the intensive insulin therapy group and conventional insulin therapy group (P > 0.05). In 226 patients receiving intensive insulin treatment, a higher mortality was observed in patients with higher GHb (57.14% vs 40.63%，P = 0.01). In 225 patients receiving conventional insulin treatment, a higher mortality was found in patients with normal GHb (49.65% vs 27.38%，P = 0.001). Conclusion: GHb should be tested in the patients with severe cerebral hemorrhage at admission, to provide information for adopting individualized glycemic management and setting glycemic control targets.