Efficacy Of Intensive Insulin Therapy Research Articles

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.

Benefits of subcutaneous continuous insulin infusion in type 1 diabetic patients with high glycemic variability

BackgroundHypoglycemia limits the efficacy of intensive insulin therapy, especially in patients with great glucose variability. The extent to which continuous subcutaneous insulin infusion (CSII) overcomes this limitation is unclear. Our aim was to determine whether CSII is helpful for decreasing glucose variability and hypoglycemia, mainly in patients with the greatest variability. MethodTwenty-four patients with type 1 diabetes wore a continuous glucose monitoring system sensor for 3 days before starting therapy with CSII and 6 months later. Glucose variability (SD, MAGE, M) and hypoglycemia duration (area under the curve (AUC) <70mg/dL) were compared in all patients and in those with the greatest MAGE (highest quartile). ResultsAt 6 months, a decreased glucose variability was seen, as measured by MAGE, M, and SD (median: −28mg/dL (interquartile range, −48 to 1), p=0.03; −22 (−40 to 0), p=0.04; −11 (−23 to 0), p=0.009; respectively). Patients with the greatest initial glucose variability (MAGE quartile 4) showed a greater decrease in both MAGE (−47mg/dL (−103 to −34) vs −20 (−36 to 17), p=0.01) and AUC <70 (−10.7mg/dL×day (−15 to 0) vs −1.1 (−4.7 to 3.8), p=0.03) as compared to all others. Patients with longer initial hypoglycemia (AUC quartile 4) achieved a greater reduction in AUC <70 (−9.7mg/dL×day (−15 to −6.5) vs −0.08 (−2.9 to 3.8), p=0.003). A correlation was found between ΔMAGE–ΔAUC (r 0.4, p=0.03). ConclusionsDuring CSII, glucose variability significantly decreased, especially in patients with the greatest initial variability. Hypoglycemia was also markedly less in patients with greater variability, with the greatest reduction occurring in those who experienced more marked hypoglycemia with CSII.

Beneficios de la terapia con infusión subcutánea continua de insulina en pacientes diabéticos tipo 1 que presentan gran variabilidad glucémica

BackgroundHypoglycemia limits the efficacy of intensive insulin therapy, especially in patients with great glucose variability. The extent to which continuous subcutaneous insulin infusion (CSII) overcomes this limitation is unclear. Our aim was to determine whether CSII is helpful for decreasing glucose variability and hypoglycemia, mainly in patients with the greatest variability. MethodTwenty-four patients with type 1 diabetes wore a continuous glucose monitoring system sensor for three days before starting therapy with CSII and 6 months later. Glucose variability (SD, MAGE, M) and hypoglycemia duration (area under the curve (AUC) <70mg/dL) were compared in all patients and in those with the greatest MAGE (highest quartile). ResultsAt 6 months, a decreased glucose variability was seen, as measured by MAGE, M, and SD (median: -28mg/dL (interquartile range, -48 to 1), p=0.03; -22(-40 to 0), p=0.04; -11(-23 to 0), p=0.009; respectively). Patients with the greatest initial glucose variability (MAGE quartile 4) showed a greater decrease in both MAGE (-47mg/dL (-103 to -34) vs -20 (-36 to 17), p=0.01) and AUC <70 (-10.7mg/dL x day (-15 to 0) vs -1.1 (-4.7 to 3.8), p=0.03) as compared to all others. Patients with longer initial hypoglycemia (AUC quartile 4) achieved a greater reduction in AUC <70 (-9.7mg/dL x day(-15 to -6.5) vs -0.08 (-2.9 to 3.8), p=0.003). A correlation was found between ΔMAGE-ΔAUC (r 0.4, p=0.03). ConclusionsDuring CSII, glucose variability significantly decreased, especially in patients with the greatest initial variability. Hypoglycemia was also markedly less in patients with greater variability, with the greatest reduction occurring in those who experienced more marked hypoglycemia with CSII.

A critical appraisal of Vlasselaers D, Milants I, Desmet L, et al: Intensive insulin therapy for patients in paediatric intensive care: A prospective, randomised controlled study. Lancet 2009; 373:547–556

To review findings and discuss implications of strict glycemic control in children. Critical appraisal of a randomized controlled trial. This is the largest prospective randomized controlled trial to date, comparing intensive insulin therapy (glycemic targets: 50.4-79.2 mg/dL [2.8-4.4 mmol/L] and 70.2-99 mg/dL [3.9-5.5 mmol/L] [for infants and children, respectively]) and conventional insulin therapy (target: 180-215 mg/dl [10-11.9 mmol/L]) among critically ill children. Groups were similar at enrollment and had comparable forms of nutrition and glucose infusion rates. Steroid use and vasoactive-inotrope scores were not compared. Intensive insulin therapy reduced pediatric intensive care unit length of stay (primary outcome measure) and attenuated C-reactive protein concentrations >5 days. The effect of intensive insulin therapy on secondary outcome measures was precise in regards to significant reductions in secondary infection occurrence (absolute risk reduction = 7.6% [95% confidence interval: 0.6-14.4], number needed to treat = 14 [95% confidence interval: 7-179]) and need for vasoactive support beyond 2 days (absolute risk reduction = 10.4% [95% confidence interval: 3-17], number needed to treat = 10 [95% confidence interval: 6-30]). Mortality decreased with intensive insulin therapy (p = .038); however, this finding was imprecise (absolute risk reduction = 3.1% [95% confidence interval: 0.2-5.4], number needed to treat = 33 [95% confidence interval: 18.6-597.3]). The incidence of hypoglycemia was significantly higher with intensive insulin therapy (absolute risk increase = 23.5% [95% confidence interval: 20-25%], number needed to harm = 4 [95% confidence interval: 4-5]). Long-term effects on outcomes were not evaluated, and the authors recognize the need for such follow-up studies. This study demonstrated efficacy of intensive insulin therapy at the same institution where the original adult intensive insulin therapy trial was conducted, but it may not demonstrate effectiveness in populations other than postoperative cardiac patients, which composed the majority of patients enrolled or in institutions without a highly experienced nursing staff to manage intensive insulin therapy. This was a well-designed single-center trial that serves as proof of concept. The effects of intensive insulin therapy on mortality require further investigation, and its practice may need refinement to reduce the risk of hypoglycemia. In the meantime, targeting age-adjusted fasting glucose ranges cannot be routinely recommended in critically ill children.

Treating Hyperglycemia in Neurocritical Patients: Benefits and Perils

There is growing debate over the value of intensive insulin therapy (IIT) in critically ill patients. Available trials have been performed in general medical or surgical intensive care units, and the results may not be directly applicable to patients with severe acute brain disease because these patients may have heightened susceptibility to hyperglycemia (HyperG) and hypoglycemia. Our objective was to review the pathophysiology and effects of HyperG and hypoglycemia in neurocritical patients and to analyze the potential role of IIT in this population. Source data were obtained from a PubMed search of the medical literature combining the terms HyperG, hypoglycemia, insulin, stroke, intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), traumatic brain injury (TBI), spinal cord injury (SCI), and related diagnoses. Brain metabolism is highly dependent on constant supply of glucose. As a consequence, the acutely injured brain is particularly sensitive to hypoglycemia, which can induce a state of energy failure (metabolic crisis). Meanwhile, neurocritical patients have a high prevalence of HyperG, and its occurrence is associated with poor outcome after acute ischemic stroke, ICH, SAH, and TBI. It is unclear whether this association is due to direct detrimental effects exerted by HyperG or simply represents a marker of severe brain injury. Insulin has been shown to have various potentially pleiotropic neuroprotective properties in experimental models. However, the safety and efficacy of IIT in patients with critical brain disease have not been well studied. Available results do not support the use of IIT to maintain strict normoglycemia in this population. Patients with critical brain disease should have frequent glucose monitoring because severe HyperG and even modest hypoglycemia may be detrimental. Careful use of insulin infusion protocols appears advisable, but maintenance of strict normoglycemia cannot be recommended. Rigorous studies must be conducted to assess the value of insulin therapy and to determine the optimal blood glucose targets in patients with the most common acute vascular and traumatic brain insults.

Safety and Efficacy of Intensive Insulin Therapy in Critical Neurosurgical Patients

Survey of Anesthesiology: December 2009 - Volume 53 - Issue 6 - p 257-258 doi: 10.1097/01.SA.0000360628.41394.3c

2009 in Review

2009 in Review

Safety and Efficacy of Intensive Insulin Therapy in Critical Neurosurgical Patients

Intensive insulin therapy to maintain blood glucose at or below 6.11 mM reduces morbidity and mortality after cardiac surgery and morbidity in medical intensive care unit (ICU) patients. The authors investigated the clinical safety and outcome effects of intensive insulin therapy compared to conventional insulin therapy in patients receiving postoperative intensive care after neurosurgical procedures. In this prospective randomized controlled trial, 483 patients undergoing elective or emergency brain surgery were prospectively and randomly assigned either to intensive insulin therapy (241 patients), receiving insulin titrated to maintain blood glucose levels within the range of 4.44-6.11 mM, or to conventional insulin therapy (242 patients), receiving insulin to maintain blood glucose levels below 11.94 mM. Primary endpoint was incidence of hypoglycemia (defined as blood glucose < 2.78 mM). Efficacy measures included the length of ICU stay, infection rate, and 6 months follow-up Glasgow outcome scale score and overall survival. Hypoglycemia episodes were more frequent in patients receiving intensive insulin therapy, median (min-max): 8 (0-23) versus 3 (0-4); P < 0.0001. The length of stay in the ICU was shorter (6 vs. 8 days; P = 0.0001), and the infection rate was lower (25.7% vs. 39.3%; P = 0.0018). Glasgow outcome scale score and overall survival at 6 months were similar in the two groups. Intensive insulin therapy in patients admitted to a postoperative neurosurgical ICU after brain surgery is associated with iatrogenic hypoglycemia, but it can also reduce the infection rate and shorten the ICU stay.

Safety and Efficacy of Intensive Insulin Therapy in Patients with Thermal Injury

Purpose To evaluate the safety and efficacy of intensive insulin therapy (IIT) versus traditional corrective insulin management (CIM) for the treatment of hyperglycemia in adult patients with thermal injury who are under intensive care. Methods Using a searchable pharmacy database, a retrospective, observational chart review was conducted of adult patients who were admitted to the surgical burn service intensive care unit (ICU) at the University of North Carolina Hospitals (UNCH) from January 2004 through December 2005 and who had received insulin therapy. Results Seventy-one patients qualified for analysis. The average morning serum blood glucose value while patients were receiving IIT, defined as 80 to 110 mg/dL, was 107 mg/dL compared with 124 mg/dL while patients were receiving CIM ( P &lt; 0.001). Of morning serum blood glucose values taken, 49% were within the target range in patients receiving IIT compared with 34% in patients receiving CIM ( P &lt; 0.001). No significant differences were found between the 2 groups with regard to mortality, ICU stay, or hospital stay. More patients experienced hypoglycemia (blood glucose value less than 50 mg/dL) while receiving IIT compared with CIM (36.4% vs 31.3%; P = 0.732); however, none of the patients had symptomatic hypoglycemia. There was a significantly higher rate of hypoglycemia among nonsurvivors compared with survivors (66.7% vs 26.4%; P = 0.006). Conclusion IIT lowers average morning blood glucose in the thermal injury population when compared with CIM. Differences in hypoglycemic events were observed in this review; however, none of the episodes were symptomatic. Although further study is needed, IIT appears to be a safe and effective method of controlling serum blood glucose values in this specialized population.

Hypoglycemia with Intensive Insulin Therapy: A Systematic Review and Meta-Analyses of Randomized Trials of Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Injections

Hypoglycemia limits the efficacy of intensive insulin therapy. The extent to which continuous insulin infusion (CSII) overcomes this limitation is unclear. The aim was to summarize evidence on the effect of CSII and multiple daily injections (MDIs) on glycemic control and hypoglycemia. We searched electronic databases between 2002 and March 2008. We selected published randomized trials of CSII vs. MDI. Reviewers working in duplicate and independently extracted study characteristics and quality and differences in glycosylated hemoglobin (HbA1c) and hypoglycemic events. We found 15 eligible randomized trials of moderate quality, with elevated baseline and end-of-study HbA1c levels. Patients with type 1 diabetes using CSII had slightly lower HbA1c [random-effects weighted mean difference, -0.2%; 95% confidence interval (CI), -0.3, -0.1, compared with MDI], with no significant difference in severe (pooled odds ratio, 0.48; 95% CI, 0.23, 1.00) or nocturnal hypoglycemia (pooled odds ratio 0.82, 95% CI 0.33, 2.03). Adolescents and adults with type 1 diabetes enrolled in crossover trials had nonsignificantly fewer minor hypoglycemia episodes per patient per week (-0.08; 95% CI, -0.21, 0.06) with CSII than MDI; children enrolled in parallel trials had significantly more episodes (0.68; 95% CI, 0.16, 1.20; P(interaction) = 0.03). Outcomes were not different in patients with type 2 diabetes. Contemporary evidence indicates that compared to MDI, CSII slightly reduced HbA1c in adults with type 1 diabetes, with unclear impact on hypoglycemia. In type 2 diabetes, CSII and MDI had similar outcomes. The effect in patients with hypoglycemia unawareness or recurrent severe hypoglycemia remains unclear because of lack of data.

Achieving glycemic control with intensive insulin therapy in the ICU

Hyperglycemia is common in critically ill patients and is associated with increased mortality. The aim of our study was to test the efficacy of intensive insulin therapy in maintaining blood glucose levels within the target range.

Hyperglycemia may alter cytokine production and phagocytosis by means other than hyperosmotic stress

In the previous issue of Critical Care, Otto and colleagues used in vitro studies to explore the theory that immunomodulation, by correction of hyperglycemia, may be a contributing factor to the reported efficacy of intensive insulin therapy (IIT) in critically ill patients. They suggested that hyperglycemia via hyperosmolarity at supra-physiological levels potentiates the production of cytokines by peripheral blood mononuclear cells in response to lipopolysaccharide (LPS) stimulation and that it also reduces the responses of phagocytosis and oxidative burst in human granulocytes. The efficacy of IIT, they concluded, may be partially due to the correction of hyperosmolality. Other studies, however, have suggested that immunological responses to LPS in the presence of hyperglycemia are mediated by a mechanism other than hyperosmolality.

Feasibility and Efficacy of Intensive Insulin Therapy in Type 1 Diabetes Mellitus in Primary Care

To determine the feasibility and efficacy of structured education in intensive insulin therapy (IIT) in patients with Type 1 diabetes mellitus commonly attended by primary care physicians, a prospective case-control study was carried out in co-operation with 26 general practitioners in rural Alpine region and the diabetes service at the University of Vienna, Medical School, Austria. From 89 rural Type 1 diabetic patients on conventional insulin therapy (CIT), those volunteering for better diabetes care (n = 52) were trained in IIT in the diabetes education centre and subsequently received their outpatient service by their general practitioners, as did those remaining on CIT (n = 37). Patients were matched as case-controls (n = 36 in each therapy group) for metabolic control at baseline (IIT/CIT: HbA1c 8.2 +/- 1.8 vs 8.1 +/- 2.0%, ns), age, duration of diabetes, incidence of retinopathy and nephropathy. Analysing an observation period of > 4.5 years, patients trained in IIT presented with improved metabolic control as compared to those on CIT (Mean HbA1c: IIT, 6.9 +/- 1.0%; CIT, 7.9 +/- 1.3%, p < 0.05, ANOVA). No difference between groups was, however, observed at the end-point of the study in HbA1c (IIT, 7.3 +/- 1.3%; CIT, 7.8 +/- 1.4%; IIT vs CIT, p = 0.14) and in the development of diabetic microangiopathy, frequency of reported severe hypoglycaemic episodes, and increase in body weight.(ABSTRACT TRUNCATED AT 250 WORDS)