Benefits Of Intensive Glucose Control Research Articles

Blood glucose control in the burn intensive care unit: A narrative review of literature

Burn survivors undergoing complex glycemic derangements in the acute period after burn are at significantly increased risk of worse outcomes. Although most critical care investigations recommend intensive glycemic control to prevent morbidity and mortality, conflicting recommendations exist. To date, no literature review has studied outcomes associated with intensive glucose control in the burn intensive care unit (ICU) population. This review addresses this gap to improve practice guidelines and support further research regarding glycemic control. This is a narrative review of literature utilizing PubMed for articles published at any time. Inclusion criteria were English studies describing glucose management in ICU adult burn patients. Studies involving pediatric patients, non-human subjects, care non-ICU care, case reports, editorials, and position pieces were excluded. Our literature search identified 2154 articles. Full text review of 61 articles identified eight meeting inclusion criteria. Two studies reported mortality benefit of intensive glucose control ( mg/dL) compared to controls ( mg/dL), while two studies showed no mortality differences. Three studies reported reduced infectious complications such as pneumonia, urinary tract infection, sepsis, and bacteremia. A majority of the studies (6/8) reported higher risk for hypoglycemia with tight glucose control, but few reported instances of adverse sequela associated with hypoglycemia. Intensive glucose control may provide benefit to burn patients, but complications associated with hypoglycemia must be considered. This review recommends an individualized patient-centered approach factoring comorbidities, burn injury characteristics, and risk factors when determining whether to employ intensive glucose control.

Stress Induced Hyperglycemia in the Context of Acute Coronary Syndrome: Definitions, Interventions, and Underlying Mechanisms.

Elevation of glucose level in response to acute coronary syndrome (ACS) has been recognized as stress induced hyperglycemia (SIH). Plenty of clinical studies have documented that SIH occurs very common in patients hospitalized with ACS, even in those without previously known diabetes mellitus. The association between elevated blood glucose levels with adverse outcome in the ACS setting is well-established. Yet, the precise definition of SIH in the context of ACS remains controversial, bringing confusions about clinical management strategy. Several randomized trials aimed to evaluate the effect of insulin-based therapy on outcomes of ACS patients failed to demonstrate a consistent benefit of intensive glucose control. Mechanisms underlying detrimental effects of SIH on patients with ACS are undetermined, oxidative stress might play an important role in the upstream pathways leading to subsequent harmful effects on cardiovascular system. This review aims to discuss various definitions of SIH and their values in predicting adverse outcome in the context of ACS, as well as the effect of intensive glucose control on clinical outcome. Finally, a glimpse of the underlying mechanisms is briefly discussed.

Risk factor control and medical therapy of coronary artery disease in Taiwan - Review and Recommendations - Part III: Blood sugar management for patients with coronary artery disease

Cardiovascular disease (CVD) is the leading cause of death in the world and the second important cause of death in Taiwan. Atherosclerosis CVD (ASCVD) especially coronary artery disease (CAD) is the major cause of CVD [1]. Clinically, the presentation of CAD can be divided into acute unstable disease, so-called acute coronary syndrome (ACS) and chronic stable disease. Up to now, the main risk factors for CAD are known as hyperlipidemia, hypertension, hyperglycemia, smoking and family history. The control of the above risk factors and lifestyle modifications can improve the prognosis of CAD patients [1,2]. Here, we described the blood lipid control, blood pressure control, blood glucose control, and lifestyle modifications for CAD in Taiwan. The followings are the part III for blood glucose control. Type 2 Diabetes mellitus (T2DM) has been suggested a CAD equivalent. The risk of CAD may be correlated with the baseline HbA1c. Numerous studies have demonstrated the benefits of controlling modifiable CV risk factors in people with diabetes. Therefore, in patients with documented CAD, DM control is recommended.Because the benefits of intensive glucose control emerge slowly, while the harms can be immediate, people with longer life expectancy have more to gain from intensive glucose control. The 4 randomized clinical trials (RCTs), including UKPDS, ACCORD, ADVANCE, VADT trials, or large meta-analyses, testing intensive glucose control vs. conventional glucose control did not show positive results in reducing major adverse cardiovascular events (MACE) in individual trials. There are also lack of HbA1c target CV outcome trials in patients with CAD. The impact of glucose control on macrovascular complications is less certain. In the consensus, glycemic treatment targets should be individualized based on patient characteristic, including frailty and comorbid conditions, and risk of adverse effects of therapy (e.g., hypoglycemia and weight gain), to balance the benefit and risks of glycemic control, rather than the strengthen the HbA1c target in patients with documented CAD.

Care of Children and Adolescents with Diabetes Mellitus and Hyperglycemia in the Inpatient Setting.

Children and adolescents with acute hyperglycemia and diabetes mellitus frequently have acute, potentially life-threatening presentations which require high-acuity care in an inpatient and often intensive care setting. This review discusses the evaluation and care of hyperglycemia and diabetes mellitus in hospitalized children in both critical and non-critical care settings, highlighting important differences in their care relative to adults. Diabetic ketoacidosis remains highly prevalent at diagnosis among children with type 1 diabetes, and hyperglycemic hyperosmolar state is increasingly prevalent among children with type 2 diabetes. Recent clinical trials have investigated the potential benefits of various types of intravenous fluids and their rates of administration as well as the risks and benefits of intensive glucose control in critically ill children. The Endocrine Society has developed guidelines focused on managing hyperglycemic hyperosmolar state, outlining important aspects of care shown to decrease morbidity and mortality. In the non-critical illness setting, intensive therapy on newly diagnosed diabetes is increasingly recommended at the outset. With the increasing incidence of diabetes mellitus in children and adolescents, recent studies addressing acute diabetes emergencies help inform best practices for care of hospitalized children with hyperglycemia and diabetes.

Glycemic Control as Primary Prevention for Diabetic Kidney Disease.

Improving strategies to prevent the development and progression of CKD is a highly desirable outcome for all involved in the care of patients with diabetes. This is because CKD is a major factor contributing to morbidly and mortality in patients with diabetes. Furthermore, diabetes is the leading cause of ESRD in most developed countries. Although tight glucose control is now an established modality for preventing the development and progression of albuminuria, evidence is now accumulating to suggest that it can also ameliorate glomerular filtration rate loss and possibly progression to ESRD. These benefits of intensive glucose control appear to be most pronounced when applied to patients with the early stages of CKD. Recently, medications that belong to the sodium glucose cotransporter-type 2 inhibitor and the glucagon-like peptide-1 receptor analogue classes have been shown to reduce progression of CKD in patients with type 2 diabetes and relatively well-preserved kidney function. Here, we review the evidence from observational and interventional clinical studies that link good glucose control with the primary prevention of diabetic kidney disease with a focus on preventing early glomerular filtration rate loss.

Hypoglycaemia seriousness and weight gain as determinants of cardiovascular disease outcomes among sulfonylurea users.

Certain treatments for type 2 diabetes mellitus cause hypoglycaemia and weight gain, and thus might counteract the benefits of intensive glucose control. We quantify the association of cardiovascular disease (CVD) outcomes with hypoglycaemia and weight gain among patients with type 2 diabetes treated with sulfonylureas. This cohort study included patients from January 2009 through December 2014 who were selected from within a deidentified nationwide electronic health records repository, including multiple provider networks and electronic medical records systems. Hypoglycaemia measures from structured data fields and free text clinical notes were categorized as serious or non-serious. Covariate adjusted Poisson regression analysis was used to assess the association between frequency of hypoglycaemia (by severity), or magnitude of weight change, and incidence of acute myocardial infarction (AMI), congestive heart failure (CHF) and stroke. Among 143 635 eligible patients, we observed 5669 cases of AMI, 14 109 incident cases of CHF and 7017 cases of stroke. Overall incidence rates were 1.53, 4.26 and 1.92 per 100 person-years for AMI, CHF and stroke, respectively. The associations between overall hypoglycaemia and each of the CVD outcomes were positive, with stronger associations observed for serious hypoglycaemia and attenuated or null associations observed for non-serious hypoglycaemia. Weight change exhibited a U-shaped association with increased risks associated with both weight loss and weight gain relative to stable weight. This study provides evidence of increased CVD risk associated with hypoglycaemia, especially with serious hypoglycaemia events. While associations were attenuated with non-serious hypoglycaemia, the results were suggestive of a potential increased risk.

Intensive glycemic control and the risk of end-stage renal disease: an ADVANCE in the management of diabetes?

Posttrial follow-up of participants randomized to intensive versus standard glycemic control in the ADVANCE trial has demonstrated a significant benefit of intensive glycemic control on the risk of end-stage renal disease. In a more detailed analysis, intensive glycemic control appears to be of benefit only before the development of clinically evident kidney disease or in patients with documented early-stage chronic kidney disease.

Long-term Benefits of Intensive Glucose Control for Preventing End-Stage Kidney Disease: ADVANCE-ON.

The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial reported that intensive glucose control prevents end-stage kidney disease (ESKD) in patients with type 2 diabetes, but uncertainty about the balance between risks and benefits exists. Here, we examine the long-term effects of intensive glucose control on risk of ESKD and other outcomes. Survivors, previously randomized to intensive or standard glucose control, were invited to participate in post-trial follow-up. ESKD, defined as the need for dialysis or kidney transplantation, or death due to kidney disease, was documented overall and by baseline CKD stage, along with hypoglycemic episodes, major cardiovascular events, and death from other causes. A total of 8,494 ADVANCE participants were followed for a median of 5.4 additional years. In-trial HbA1c differences disappeared by the first post-trial visit. The in-trial reductions in the risk of ESKD (7 vs. 20 events, hazard ratio [HR] 0.35, P = 0.02) persisted after 9.9 years of overall follow-up (29 vs. 53 events, HR 0.54, P < 0.01). These effects were greater in earlier-stage CKD (P = 0.04) and at lower baseline systolic blood pressure levels (P = 0.01). The effects of glucose lowering on the risks of death, cardiovascular death, or major cardiovascular events did not differ by levels of kidney function (P > 0.26). Intensive glucose control was associated with a long-term reduction in ESKD, without evidence of any increased risk of cardiovascular events or death. These benefits were greater with preserved kidney function and with well-controlled blood pressure.

Optimizing clinical outcomes resulting from glucose‐lowering therapies in type 2 diabetes: increased confidence about the DPP‐4 inhibitors and continued concerns regarding sulphonylureas and exogenous insulin

Optimizing clinical outcomes resulting from glucose‐lowering therapies in type 2 diabetes: increased confidence about the <scp>DPP</scp>‐4 inhibitors and continued concerns regarding sulphonylureas and exogenous insulin

Effect of hypoglycaemia on thrombosis and inflammation in patients with type 2 diabetes

BackgroundIncreased cardiovascular mortality has been reported in trials of intensive glycaemic control in patients with type 2 diabetes. Evidence that hypoglycaemia predicts subsequent mortality in the weeks after a cardiovascular event is strong. Altered fibrin structure characteristics and subclinical inflammation have been implicated in the predisposition to cardiovascular events. We hypothesised that hypoglycaemia creates a thrombotic–inflammatory environment, contributing to increased mortality after the event. MethodsTen patients with type 2 diabetes were recruited (mean age 50 years [SD 8], duration of diabetes 9·5 years [4·6], and HbA1c 8·7% [2·1]). They all completed paired hyperinsulinaemic clamp studies separated by at least 4 weeks. Glucose was maintained at hypoglycaemia (2·5 mmol/L) or euglycaemia (6 mmol/L) for two 60 min periods. Four timepoints were analysed: baseline, end of clamp, and days 1 and 7 post clamp in both arms. Fibrin network properties and fibrinolysis of plasma samples were assessed with a dynamic turbidimetric assay. Plasma fibrinogen concentrations were measured with the Clauss assay, and high sensitivity CRP (hsCRP) was measured with an immunoturbidimetric assay. We also analysed heart rate variability as an indicator of vagal activity. FindingsClot maximum absorbance, a measure of clot density, increased after hypoglycaemic clamp reaching a peak at day 7, whereas a decrease occurred after euglycaemic clamp (mean change from baseline [Δ] 0·040 [SD 0·093] and −0·035 [0·080], respectively; p=0·01). Clot lysis time, an indicator of fibrinolysis potential, increased after hypoglycaemic clamp up to day 7 but decreased after euclycaemic clamp (mean Δ 64 s [SD 119] vs −51 [64], p=0·02). hsCRP increased on day 7 after hypoglycaemic clamp whereas there was a reduction after euglycaemic clamp (0·80 mg/dL [0·98] vs −0·89 [0·80], p<0·0001). Similarly, fibrinogen concentrations were higher at day 7 after hypoglycaemic clamp than after euglycaemic clamp (1·09 mg/mL [2·58] vs 0·17 [1·25], p=0·05). There were similar decreases in vagal tone as shown by high frequency heart rate variability after hypoglycaemic clamp in contrast with an increase in vagal tone after euglycaemic clamp (p=0·02) InterpretationHypoglycaemia induces prothrombotic changes in the fibrin network and aggravates subclinical inflammation, with effects that are sustained for at least 1 week. The mechanism of these changes is unclear but might involve depression of the cholinergic anti-inflammatory pathway. Hypoglycaemia might mitigate the benefits of intensive glucose control by creating a thrombotic and inflammatory milieu. Our data provide a possible explanation for the observed increase in cardiovascular mortality weeks after a hypoglycaemic event. FundingNational Institute of Health Research.

Glycemic Control and All-Cause Mortality Risk in Type 1 Diabetes Patients: The EURODIAB Prospective Complications Study

Glycemic targets and the benefit of intensive glucose control are currently under debate because intensive glycemic control has been suggested to have negative effects on mortality risk in type 2 diabetes patients. We examined the association between glycated hemoglobin (HbA1c) and all-cause mortality in patients with type 1 diabetes mellitus. A clinic-based prospective cohort study was performed in 2764 European patients with type 1 diabetes aged 15-60 years enrolled in the EURODIAB Prospective Complications Study. Possible nonlinearity of the association between HbA1c and all-cause mortality was examined using multivariable restricted cubic spline regression using three (at HbA1c 5.6%, 8.1%, and 11.8%) and five knots (additionally at HbA1c 7.1% and 9.5%). Mortality data were collected approximately 7 years after baseline examination. HbA1c was related to all-cause mortality in a nonlinear manner after adjustment for age and sex. All-cause mortality risk was increased at both low (5.6%) and high (11.8%) HbA1c compared with the reference (median HbA1c: 8.1%) following a U-shaped association [P overall effect = .008 and .04, P nonlinearity = .03 and .11 (three and five knots, respectively)]. Results from our study in type 1 diabetes patients suggest that target HbA1c below a certain threshold may not be appropriate in this population. We recognize that these low HbA1c levels may be related to anemia, renal insufficiency, infection, or other factors not available in our database. If our data are confirmed, the potential mechanisms underlying this increased mortality risk among those with low HbA1c will need further study.

PS7 - 2. Glycemic control and all-cause mortality risk in type 1 diabetes patients: the EURODIAB Prospective Complications Study

Glycemic targets and the benefit of intensive glucose control are currently under debate as intensive glycemic control has been suggested to have negative effects on mortality risk in type 2 diabetes patients. Findings in type 2 diabetes patients cannot automatically be translated to type 1 diabetes patients and need further investigation.

Focusing on Cardiovascular Disease in Type 2 Diabetes Mellitus: An Introduction to Bromocriptine QR

Cardiovascular risk reduction is a key priority in patients with diabetes. The relationship between glycemic control and macrovascular outcomes, such as the benefit of intensive glucose control and the importance of postprandial or fasting blood glucose, is still under debate. A number of pharmacologic options are available to treat type 2 diabetes mellitus and these options have differing evidence for their cardiovascular safety. In this article, the novel agent bromocriptine quick release is discussed. Recently approved, this once–daily treatment provides glycemic control as monotherapy or in combination with other antihyperglycemic medications and has been shown in a prospective phase 3 safety study to not increase cardiovascular risk. Therefore, bromocriptine quick release increases the range of options available to treat patients with type 2 diabetes mellitus without increasing cardiovascular risk.

Update in Pulmonary and Critical Care Medicine

This Update in Pulmonary and Critical Care Medicine features 12 articles published in 2009. Topics include chronic obstructive pulmonary disease, asthma, pneumonia, glucose control and mortality, e...

Implementation of an Inpatient Diabetes Management Team in the University Hospital Setting

A long history of clinical evidence points out the untoward effects of hyperglycemia in humans. Hyperglycemia acutely impairs leukocyte function, immunoglobulin action, wound healing, cardiac metabolism, glomerular filtration, and endothelial function.1 In addition, the stress of critical illness causes an increase in counterregulatory hormones. This leads to alterations in carbohydrate metabolism by increasing peripheral glucose demand and enhancing hepatic glucose production and insulin resistance, which results in a relative insulin deficiency and hyperglycemia.2 Moreover, clinical interventions also predispose patients to hyperglycemia, particularly the use of corticosteroids, vasopressors, and enteral or parenteral nutrition.3 In a study by Umpierrez et al.,4 hyperglycemia (defined as a fasting blood glucose level > 126 mg/dl or a random blood glucose level > 200 mg/dl on two separate occasions) occurred in 38% of hospitalized patients. Twenty-six percent of these patients with hyperglycemia had a known history of diabetes, but 12% had no history of diabetes. Newly discovered hyperglycemia was associated with longer hospital stays, higher admission rates to the intensive care unit, and a greater chance of being discharged to a rehabilitation facility than of being discharged home. The take-home message is that hyperglycemia is common in patients during hospitalization, and this hyperglycemia is associated with adverse outcomes. A variety of approaches, most involving development and use of intensive insulin therapy protocols to improve glucose management in the hospital setting, seem to improve metabolic outcomes. Whether these approaches improve actual outcomes of morbidity and mortality is not yet known outside of the critical care setting. Several early clinical trials suggest a benefit of intensive glucose control in the critical care setting on morbidity (especially infection), length of stay, hospital costs, and mortality in selected groups of patients.5,6 More recently, clinical trials involving intensive insulin therapy in critical care units …

Perioperative Blood Glucose Monitoring and Control in Major Vascular Surgery Patients

Diabetes mellitus (DM) is an independent predictor for morbidity and mortality in the general population, which is even more apparent in patients with concomitant cardiovascular risk factors. As the prevalence of DM is increasing, with an ageing general population, it is expected that the number of diabetic patients requiring surgical interventions will increase. Perioperative hyperglycaemia, without known DM, has been identified as a predictor for morbidity and mortality in patients undergoing surgery. Moreover, early studies showed that intensive blood-glucose-lowering therapy reduced both morbidity and mortality among patients admitted to the postoperative intensive care unit (ICU). However, later studies have doubted the benefit of intensive glucose control in medical–surgical ICU patients. This article aims to comprehensively review the evidence on the use of perioperative intensive glucose control, and to provide recommendations for current clinical practice. A systematic review was performed of the literature on perioperative intensive glucose control. Based on this literature review, we observed that intensive glucose control in the perioperative period has no clear benefit on short-term mortality. Intensive glucose control may even have a net harmful effect in selected patients. In addition, concerns on the external validity of some studies are important barriers for widespread recommendation of intensive glucose control in the perioperative setting. We propose that guidelines recommending intensive glucose control should be re-evaluated. In addition, moderate tight glucose control should currently be regarded as the safest and most efficient approach to patients undergoing major vascular surgery.

Trials Review: Cardiovascular Outcome with Intensive Glycemic Control and Implications for Patients with Type 2 Diabetes

Hyperglycemia is associated with microvascular and macrovascular complications. Intensive glucose control has been shown to reduce microvascular complications. Nevertheless, cardiovascular disease remains the leading cause of death in patients with type 2 diabetes. A positive association exists between hemoglobin A1c level and cardiovascular events, but whether reducing blood glucose will reduce cardiovascular events is still not quite clear. The benefits of intensive glucose control also remain uncertain for the heterogenous group of older patients with type 2 diabetes. This article reviews results of earlier and recently published intervention trials of intensive glucose control and their outcomes and discusses relevant recommendations for adults with type 2 diabetes.

Perioperative Blood Glucose Monitoring and Control in Major Vascular Surgery Patients

Diabetes mellitus (DM) is an independent predictor for morbidity and mortality in the general population, which is even more apparent in patients with concomitant cardiovascular risk factors. As the prevalence of DM is increasing, with an ageing general population, it is expected that the number of diabetic patients requiring surgical interventions will increase. Perioperative hyperglycaemia, without known DM, has been identified as a predictor for morbidity and mortality in patients undergoing surgery. Moreover, early studies showed that intensive blood-glucose-lowering therapy reduced both morbidity and mortality among patients admitted to the postoperative intensive care unit (ICU). However, later studies have doubted the benefit of intensive glucose control in medical-surgical ICU patients. This article aims to comprehensively review the evidence on the use of perioperative intensive glucose control, and to provide recommendations for current clinical practice. A systematic review was performed of the literature on perioperative intensive glucose control. Based on this literature review, we observed that intensive glucose control in the perioperative period has no clear benefit on short-term mortality. Intensive glucose control may even have a net harmful effect in selected patients. In addition, concerns on the external validity of some studies are important barriers for widespread recommendation of intensive glucose control in the perioperative setting. We propose that guidelines recommending intensive glucose control should be re-evaluated. In addition, moderate tight glucose control should currently be regarded as the safest and most efficient approach to patients undergoing major vascular surgery.

Cardiovascular benefit of intensive glucose control: approaching closure

Several studies have demonstrated that lower blood glucose concentrations are associated with reduced cardiovascular endpoints. The publication of intervention trials designed to investigate the impact of tighter glycaemic control on cardiovascular morbidity and mortality in type 2 diabetes have generally failed, individually, to generate statistically significant improvements in cardiovascular endpoints. This has spurred controversy regarding the role of glycaemic control within a multifactorial approach to treatment. However, a recent meta-analysis of these intervention trials showed that intensive glucose control improves cardiovascular outcomes.

Intensive glucose control after allogeneic hematopoietic stem cell transplantation: a retrospective matched-cohort study

Some studies have shown that intensive glucose control (IGC) improves outcome in the intensive care unit setting. However, it is the benefit of IGC in hematopoietic SCT (HSCT) that is not well defined. Between June 2006 and May 2007, IGC was maintained prospectively after allogeneic HSCT and clinical outcomes were compared with a cohort matched for conditioning regimen, source of stem cells, age and relation to donor. A stratified Cox regression model was used. There were no significant differences in baseline clinical characteristics. The median age was 43.5 years in both groups. The primary diagnosis was a hematologic malignancy. Patients in the IGC group had a lower glucose level (least-square mean, 116.4 vs 146.8 mg per 100 ml, P<0.001) compared to the standard glucose control group. The incidences of documented infections and bacteremia were significantly lower in the IGC group (14 vs 46%, P=0.004, 9 vs 39%, P=0.002, respectively). IGC tended to reduce the incidence of renal dysfunction (19 vs 37%, P=0.36) and the elevation of C-reactive protein (18 vs 38%, P=0.13). This study suggests that IGC has may have a beneficial effect after HSCT. IGC should be evaluated further in a large prospective, randomized study.