Benefits Of Intensive Insulin Therapy Research Articles

Tight glycemic control in critically ill children

Hyperglycemia is a common metabolic derangement in critically ill patients. In 2001, investigators from Leuven, Belgium published results of a randomized study conducted in an adult surgical ICU testing the benefit of intensive insulin therapy, with the goal of maintaining serum glucose 80-110 mg/deciliter (N Engl J Med 2001;345:1359-67). This strategy, labelled “tight glycemic control,” resulted in a statistically detectable survival benefit compared with the more conventional approach of maintaining serum glucose values near 200 mg/deciliter. Almost from the start, however, this strategy came under scrutiny. The Leuven study was single-center, it was difficult to blind, and the physiologic basis for the benefit (prevention of hyperglycemia versus advantages of exogenous insulin versus something else) was unclear. Additionally, several subsequent attempts to replicate the Leuven experience in adult patients were met with inconsistent results. More worrisome was a hint in both the original and subsequent trials that tight glycemic control was associated with an increased incidence, albeit small, of significant hypoglycemia, which independently was associated with higher mortality. Scrupulous testing of tight glycemic control in children was particularly crucial given the vulnerability of developing brains to low serum glucose. The largest and most definitive of these studies was the HALF-PINT (Heart and Lung Failure Pediatric Insulin Titration) Trial, a 32-center federally funded project that assigned children requiring vasoactive or mechanical ventilatory support to 1 of 2 glucose targets, namely, 80-110 mg/deciliter versus 150-180 mg/deciliter. HALF-PINT enrolled children between 2012-2016 and was stopped prematurely due to a low likelihood of benefit and a signal that the lower glucose-target group experienced a higher incidence of hypoglycemia (N Engl J Med 2017;366:729-41). A critical a priori extension of HALF-PINT, measuring 1-year neurodevelopmental outcomes in enrollees, appears in this volume of The Journal. The results of extensive testing indicated similar outcomes in both groups, but they again supported that hypoglycemia from any cause had adverse effects, establishing the superiority of the higher glucose target. The HALF-PINT follow-up study has limitations: only 2- to 17-year-old subjects were tested given constraints of the instruments used, and only 60% of eligible subjects completed the 1-year follow-up testing. It should be emphasized that the HALF-PINT protocol did not test tight glycemic control versus “conventional” insulin therapy in critically ill children, but 2 different strategies of tight glycemic control differing in target serum glucose ranges. Indeed, the authors understood that hyperglycemia has its own neurotoxic effects in children and should be avoided. The HALF-PINT investigators should be commended for the commission of this difficult yet extremely important study, which likely will serve to established serum glucose levels of 150-180 mg/deciliter as the upper-limit standard in critically ill children. Article page 57▸

Strict glycemic control to prevent surgical site infections in gastroenterological surgery.

Perioperative hyperglycemia is a risk factor for surgical site infections (SSI). Although the recommended target blood glucose level (BG) is 140–180 mg/dL for critically ill patients, recent studies conducted in patients undergoing surgery showed a significant benefit of intensive insulin therapy for the management of perioperative hyperglycemia. The aim of the present review is to evaluate the benefits of strict glycemic control for reducing SSI in gastroenterological surgery. We carried out a post‐hoc analysis of the previously published data from research on the risk factors for SSI. The highest BG within 24 hours after surgery was evaluated. A total of 1555 patients were enrolled in the study. In multivariate analysis, a dose–response relationship between the level of hyperglycemia and the odds of SSI was demonstrated when compared with the reference group (≤150 mg/dL) (odds ratio [OR] = 1.68, 95% confidence interval [CI] 1.14–2.49 for 150–200 mg/dL; and OR = 2.15, 95% CI 1.40–3.29 for >200 mg/dL). Unexpectedly, hyperglycemia was not a significant risk factor for SSI among diabetes patients. By contrast, non‐diabetes patients with a BG of >150 mg/dL were found to have increased odds of SSI. In conclusion, a target BG of ≤150 mg/dL is recommended in patients without diabetes who undergo gastroenterological surgery. Additional study is required to determine an optimal target BG in diabetes patients. Because of the risk of hypoglycemia, a conventional protocol is indicated for patients admitted to the general ward where frequent glucose measurement is not assured.

Low-dose intensive insulin therapy in patients with Acute Coronary Syndrome accompanied by Left Ventricular Failure: audit of two UK hospitals.

To determine whether a low-dose intravenous insulin regimen reduces blood glucose levels at a timely rate and associated side effects among patients with Acute Coronary Syndrome and Left Ventricular Failure. Induced hypoglycaemia and the associated risks have questioned the benefits of intensive insulin therapy in patients presenting with raised blood glucose levels and Acute Coronary Syndromes. Local audit data identified that patients with Acute Coronary Syndrome and Left Ventricular Failure experienced more hypoglycaemic episodes than those with Acute Coronary Syndrome alone. Consequently, a new regimen of low-dose insulin for this group was implemented and audited over 12months. Audit. Thirty-six consecutive patient notes with a diagnosis of Acute Coronary Syndrome and blood glucose of ≥10mmol/l treated with a new insulin therapy regimen were analysed. Data were extracted using a standardised form and entered into an Excel spreadsheet for analysis. The mean age of the sample was 70years with 66% of subjects being men and 50% presenting with Acute Coronary Syndrome and Left Ventricular Failure. The low-dose regimen was effective in achieving normoglycaemia, (range 4-8mmol/l) for a consecutive six-hour period. This was achieved in 72% of patients and within a median time of 13hours. The audit suggests that a low-dose insulin regimen can effectively stabilise blood glucose in patients presenting with both Acute Coronary Syndrome and Left Ventricular Failure. The importance of regularly monitoring blood sugar levels is vital and highlights the role of nurses in minimising patient risk and promoting safety. Nurses are instrumental in the safe implementation of intensive insulin guidelines. Close monitoring of patients is essential, enabling timely adjustments to treatments and ensuring patient safety. Regular audits allow nurses to evaluate care provision and continue to drive practice forward.

Progress in Diabetes Technology: Developments in Insulin Pumps, Continuous Glucose Monitors, and Progress towards the Artificial Pancreas

Type 1 diabetes (T1D) is one of the most common chronic diseases of childhood with an estimated prevalence of more than 166 000 cases in children younger than 20 years of age in the US in 2010. 1 Pettitt D.J. Talton J. Dabelea D. Divers J. Imperatore G. Lawrence J.M. et al. Prevalence of diabetes in U.S. youth in 2009: the SEARCH for diabetes in youth study. Diabetes Care. 2014; 37: 402-408 Crossref PubMed Scopus (314) Google Scholar The rate of new-onset diabetes also is increasing worldwide, with an increased incidence of 3%-5% per year. 2 Forlenza G.P. Rewers M. The epidemic of type 1 diabetes: what is it telling us?. Curr Opin Endocrinol Diabetes Obes. 2011; 18: 248-251 Crossref PubMed Scopus (89) Google Scholar In 1993 the Diabetes Control and Complications Trial established the benefit of intensive insulin therapy in reducing long-term complications, including retinopathy, nephropathy, and neuropathy. 3 The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993; 329: 977-986 Crossref PubMed Scopus (22760) Google Scholar Despite this now longstanding knowledge, vascular complications attributable to hyperglycemia remain a significant issue in the population with T1D, even in the young-adult population. 4 James S. Gallagher R. Dunbabin J. Perry L. Prevalence of vascular complications and factors predictive of their development in young adults with type 1 diabetes: systematic literature review. BMC Res Notes. 2014; 7: 593 Crossref PubMed Scopus (33) Google Scholar , 5 Maahs D.M. Daniels S.R. de Ferranti S.D. Dichek H.L. Flynn J. Goldstein B.I. et al. Cardiovascular disease risk factors in youth with diabetes mellitus: a scientific statement from the american heart association. Circulation. 2014; 130: 1532-1558 Crossref PubMed Scopus (123) Google Scholar Recent evidence from the T1D Exchange clinic registry shows that during childhood mean hemoglobin A1c (HbA1c) remains above the target of 7.5% for all age groups, with a peak of 9.2% in the late teenage years. 6 Miller K.M. Foster N.C. Beck R.W. Bergenstal R.M. DuBose S.N. DiMeglio L.A. et al. Current state of type 1 diabetes treatment in the U.S.: updated data from the T1D Exchange Clinic Registry. Diabetes Care. 2015; 38: 971-978 Crossref PubMed Scopus (923) Google Scholar This evidence points toward the urgent need for better therapeutic interventions to improve glycemic control across the pediatric population. Innovations in diabetes care are being pursued on many fronts, including education, behavioral interventions, pharmaceutical development, beta-cell transplantation, and immunomodulation to prevent autoimmune beta-cell destruction. Although these therapies aim to provide benefit now and more so in the future, many in the diabetes community believe that the most impactful near-term benefit will be achieved by innovation in the technologies used to manage diabetes.

Vascular Glucose Sensor Symposium: Continuous Glucose Monitoring Systems (CGMS) for Hospitalized and Ambulatory Patients at Risk for Hyperglycemia, Hypoglycemia, and Glycemic Variability.

Hyperglycemia, hypoglycemia, and glycemic variability have been associated with increased morbidity, mortality, length of stay, and cost in a variety of critical care and non-critical care patient populations in the hospital. The results from prospective randomized clinical trials designed to determine the risks and benefits of intensive insulin therapy and tight glycemic control have been confusing; and at times conflicting. The limitations of point-of-care blood glucose (BG) monitoring in the hospital highlight the great clinical need for an automated real-time continuous glucose monitoring system (CGMS) that can accurately measure the concentration of glucose every few minutes. Automation and standardization of the glucose measurement process have the potential to significantly improve BG control, clinical outcome, safety and cost.

Inpatient Glycemic Control

Hyperglycemia is associated with poor outcomes in hospitalized medical and surgical patients. Although some early evidence showed benefits of intensive insulin therapy (IIT), recent evidence does not show a consistent benefit and even shows harm associated with the use of IIT. The overuse of some therapeutic interventions and the resulting harms to a patient are an important component of unnecessary health care costs. The goal of this article is to address the management of hyperglycemia and evaluate the benefits and harms associated with the use of IIT to achieve tight glycemic control in hospitalized patients with or without diabetes mellitus. This article is based on the evidence review and the guideline developed by the American College of Physicians on this topic. Best Practice Advice 1: Clinicians should target a blood glucose level of 7.8 to 11.1 mmol/L (140 to 200 mg/dL) if insulin therapy is used in SICU/MICU patients. Best Practice Advice 2: Clinicians should avoid targets less than 7.8 mmol/L (<140mg/dL) because harms are likely to increase with lower blood glucose targets.

In-Hospital Management of Diabetes.

In-Hospital Management of Diabetes.

In-hospital Management of Diabetes

In-hospital Management of Diabetes

Changing practice in the use of intensive insulin therapy

Nicola Morrell’s article on the benefits of intensive insulin therapy in post-operative intensive care patients (art&science December 5) promotes what is now generally considered to be out-of-date practice.

Benefits of intensive insulin therapy in post-operative intensive care patients

Benefits of intensive insulin therapy in post-operative intensive care patients

Benefits of intensive insulin therapy in post-operative intensive care patients

Patients without diabetes who have surgery often develop elevated blood glucose levels. This article describes the effects of stress on blood glucose levels and the importance of treating stress-induced hyperglycaemia in surgical patients. It suggests that all patients with or without diabetes could benefit from the maintenance of strict blood glucose control within set parameters during and after surgery. The evidence suggests that strict control of blood glucose levels and frequent monitoring and maintenance of normoglycaemia may reduce post-operative complications and promote better patient long-term outcomes. The use of intensive insulin therapy is recommended for all post-operative patients in intensive care.

Weighty Matters

Type 1 diabetes mellitus, characterized by a deficiency of insulin production owing to damaged pancreatic β-cells, is associated with a 10-fold increase in the risk of cardiovascular disease in comparison with the general population.1,2 Intensive insulin therapy, whether administered by multiple daily injections or continuous infusion via a pump, is the cornerstone of glycemic control in the patient with type 1 diabetes mellitus.3 Much of what we know regarding the benefits of intensive insulin therapy is derived from the Diabetes Control and Complications Trial (DCCT), a trial of patients with type 1 diabetes mellitus who were randomly assigned to either intensive or conventional insulin treatment. Article see p 180 The DCCT enrolled a total of 1441 patients with type 1 diabetes mellitus, beginning in 1983, with final closeout in 1993, for a total of 6.5 years of follow-up. Conventional therapy consisted of 1 or 2 daily injections of insulin with daily self-monitoring and examinations every 3 months, whereas intensive insulin therapy consisted of at least 3 insulin injections per day or external pump therapy with target blood glucose concentrations of 70 to 120 mg/dL fasting, postprandial glucose values of <180 mg/dL, and a target hemoglobin A1c goal in the normal range (<6.05%). The primary trial results showed that intensive therapy achieved a statistically significant lower hemoglobin A1c, evident by the first 3 months of the study, with a closeout A1c of 7.0% in the intensive therapy arm in comparison with 9.0% in the conventional arm. Importantly, those in the intensive insulin therapy arm experienced delayed progression of nephropathy, retinopathy, and neuropathy.4 In the primary trial, the risk of major cardiovascular events trended to significance, although the young age of the participants (mean age, 27 years at enrollment) rendered it difficult to detect a statistically significant …

Intensive Insulin Therapy Reduces Infections in Patients on Parenteral Nutrition: A Randomized Clinical Trial

Introduction: Hyperglycemia is a common problem encountered in hospitalized patients, especially in critically ill patients due to stress and using parenteral nutrition. Uncontrolled hyperglycemia may be associated with increased infection risk. The principal benefit of intensive insulin therapy is a decrease in infection-related complications and mortality. The aim of this study was the assessment of IIT effect on pathogen growth in ICU patients. Materials and Methods: We conducted a randomized controlled trial study where patients with brain trauma in grade 2 and 3 that received at least 50% of nutritional needs from parenteral nutrition. They randomly assigned to receive IIT or conventional glucose control. Pathogen growth, mortality, survival, APACHE II score, duration of hospital stay was assessed. Results: Of 29 patients randomized, 26 patients completed the study. Survival duration, ventilator dependency and pathogen growth was improved in tight control group but not significant between two groups due to low sample size. Conclusion: In our study, IIT reduced pathogen growth without hypoglycemic episodes in head trauma patients.[GMJ. 2012;1(1):2-7]

Perioperative Glucose Control in Neurosurgical Patients

Many neurosurgery patients may have unrecognized diabetes or may develop stress-related hyperglycemia in the perioperative period. Diabetes patients have a higher perioperative risk of complications and have longer hospital stays than individuals without diabetes. Maintenance of euglycemia using intensive insulin therapy (IIT) continues to be investigated as a therapeutic tool to decrease morbidity and mortality associated with derangements in glucose metabolism due to surgery. Suboptimal perioperative glucose control may contribute to increased morbidity, mortality, and aggravate concomitant illnesses. The challenge is to minimize the effects of metabolic derangements on surgical outcomes, reduce blood glucose excursions, and prevent hypoglycemia. Differences in cerebral versus systemic glucose metabolism, time course of cerebral response to injury, and heterogeneity of pathophysiology in the neurosurgical patient populations are important to consider in evaluating the risks and benefits of IIT. While extremes of glucose levels are to be avoided, there are little data to support an optimal blood glucose level or recommend a specific use of IIT for euglycemia maintenance in the perioperative management of neurosurgical patients. Individualized treatment should be based on the local level of blood glucose control, outpatient treatment regimen, presence of complications, nature of the surgical procedure, and type of anesthesia administered.

Effect of intensivevsconventional insulin therapy on perioperative nutritional substrates metabolism in patients undergoing gastrectomy

To investigate the effect of intensive vs conventional insulin therapy on perioperative nutritional substrates metabolism in patients undergoing radical distal gastrectomy. Within 24 h of intensive care unit management, patients with gastric cancer were enrolled after written informed consent and randomized to the intensive insulin therapy (IIT) group to keep glucose levels from 4.4 to 6.1 mmol/L or the conventional insulin therapy (CIT) group to keep levels less than 10 mmol/L. Resting energy expenditure (REE), respiratory quotient (RQ), resting energy expenditure per kilogram (REE/kg), and the lipid oxidation rate were monitored by the indirect calorimeter of calcium citrate malate nutrition metabolism investigation system. The changes in body composition were analyzed by multi-frequency bioimpedance analysis. Blood fasting glucose and insulin concentration were measured for assessment of Homeostasis model assessment of insulin resistance. Sixty patients were enrolled. Compared with preoperative baseline, postoperative REE increased by over 22.15% and 11.07%; REE/kg rose up to 27.22 ± 1.33 kcal/kg and 24.72 ± 1.43 kcal/kg; RQ decreased to 0.759 ± 0.034 and 0.791 ± 0.037; the lipid oxidation ratio was up to 78.25% ± 17.74% and 67.13% ± 12.76% supported by parenteral nutrition solutions from 37.56% ± 11.64% at the baseline; the level of Ln-HOMA-IR went up dramatically (P < 0.05, respectively) on postoperative days 1 and 3 in the IIT group. Meanwhile the concentration of total protein, albumin and triglyceride declined significantly on postoperative days 1 and 3 compared with pre-operative levels (P < 0.05, respectively). Compared with the CIT group, IIT reduced the REE/kg level (27.22 ± 1.33 kcal/kg vs 29.97 ± 1.47 kcal/kg, P = 0.008; 24.72 ± 1.43 kcal/kg vs 25.66 ± 1.63 kcal/kg, P = 0.013); and decreased the Ln-HOMA-IR score (P = 0.019, 0.028) on postoperative days 1 and 3; IIT decreased the level of CRP on postoperative days 1 and 3 (P = 0.017, 0.006); the total protein and albumin concentrations in the IIT group were greater than those in the CIT group (P = 0.023, 0.009). Postoperative values of internal cell fluid (ICF), fat mass, protein mass (PM), muscle mass, free fat mass and body weight decreased obviously on postoperative 7th day compared with the preoperative baseline in the CIT group (P < 0.05, respectively). IIT reduced markedly consumption of fat mass, PM and ICF compared with CIT (P = 0.009 to 0.026). There were some benefits of IIT in decreasing the perioperative insulin resistance state, reducing energy expenditure and consumption of proteins and lipids tissue in patients undergoing gastrectomy.

Effect of Perioperative Intensive Insulin Therapy for Liver Dysfunction After Hepatic Resection

Intensive insulin therapy (IIT) reduces morbidity and mortality in patients in surgical care units, yet the benefits of IIT during liver surgery, especially on liver function after hepatic resection, are not known. The aim of the present study was to assess the effects of IIT, with a focus on postoperative liver function, in hepatectomized patients. A total of 150 patients who underwent surgical management for hepatic diseases between September 2007 and March 2009 at Kochi Medical School were investigated. Patients were divided into two groups: (1) those receiving IIT via a closed-loop glycemic control system (i.e., an artificial pancreas; AP group; n = 74); or (2) those receiving conventional insulin therapy using the sliding scale method (SS group; n = 76). The targeted blood glucose zones in the AP and SS groups were 80–110 and 150–200 mg/dl, respectively. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels increased and prothrombin time (%) decreased immediately after surgery in both groups. There was a significant difference in postoperative ALT levels between the two groups on postoperative days 1 and 6. Hepatocyte injury and changes in AST and ALT levels after surgery (compared with preoperative levels) were significantly greater in the SS group than AP group after liver resection. During the first 18 h after hepatic resection, 174 IU of insulin was required per patient for tight glycemic control with IIT. Perioperative IIT ameliorated liver dysfunction after hepatic resection. Liver regeneration and/or an antiinflammatory effect of IIT may underlie its protective effects against hepatocyte injury in hepatectomized patients.

Have the metabolic support pendulums in the intensive care unit stopped swinging?

Have the metabolic support pendulums in the intensive care unit stopped swinging?

Glycaemic control in acute coronary syndromes: prognostic value and therapeutic options

Type 2 diabetes and acute coronary syndromes (ACS) are widely interconnected. Individuals with type 2 diabetes are more likely than non-diabetic subjects to experience silent or manifest episodes of myocardial ischaemia as the first presentation of coronary artery disease. Insulin resistance, inflammation, microvascular disease, and a tendency to thrombosis are common in these patients. Intensive blood glucose control with intravenous insulin infusion has been demonstrated to significantly reduce morbidity and mortality in critically ill hyperglycaemic patients admitted to an intensive care unit (ICU). Direct glucose toxicity likely plays a crucial role in explaining the clinical benefits of intensive insulin therapy in such critical patients. However, the difficult implementation of nurse-driven protocols for insulin infusion able to lead to rapid and effective blood glucose control without significant episodes of hypoglycaemia has led to poor implementations of insulin infusion protocols in coronary care units, and cardiologists now to consider alternative drugs for this purpose. New intravenous or oral agents include the incretin glucagon-like peptide 1 (GLP1), its analogues, and dipeptidyl peptidase-4 inhibitors, which potentiate the activity of GLP1 and thus enhance glucose-dependent insulin secretion. Improved glycaemic control with protective effects on myocardial and vascular tissues, with lesser side effects and a better therapeutic compliance, may represent an important therapeutic potential for this class of drugs in acutely ill patients in general and patients with ACS in particular. Such drugs should be known by practicing cardiologists for their possible use in ICUs in the years to come.

A Review of Perioperative Glucose Control in the Neurosurgical Population

Significant fluctuations in serum glucose levels accompany the stress response of surgery or acute injury and may be associated with vascular or neurologic morbidity. Maintenance of euglycemia with intensive insulin therapy (IIT) continues to be investigated as a therapeutic intervention to decrease morbidity associated with derangements in glucose metabolism. Hypoglycemia is a common side effect of IIT with potential for significant morbidity, especially in the neurologically injured patient. Differences in cerebral versus systemic glucose metabolism, the time course of cerebral response to injury, and heterogeneity of pathophysiology in neurosurgical patient populations are important to consider in evaluating the risks and benefits of IIT. While extremes of glucose levels are to be avoided, there are little data to support specific use of IIT for maintenance of euglycemia in the perioperative management of neurosurgical patients. Existing data are summarized and reviewed in this context.

Intensive insulin therapy confers a similar survival benefit in the burn intensive care unit to the surgical intensive care unit

In contrast to the benefits of intensive insulin therapy (IIT) in the surgical intensive care unit (SICU), its benefits in the burn ICU (BICU) remain unclear. Furthermore, IIT and tight glycemic control has received little attention in elderly ICU patients. We evaluated the normalization of blood glucose level with IIT in BICU and SICU patients. From October 2006 to July 2007, 970 patients were admitted to our BICU and our SICU. A total of 79 of these patients met criteria for initiation of IIT, 37 of who required IIT for at least 72 hours. Data were analyzed to determine if tight glycemic control (blood glucose < or =150 mg/dL by day 3) is associated with reduced morbidity and mortality. Tight control was better achieved in SICU patients (45%) than in BICU patients (33%). Daily insulin requirements were approximately 2-fold greater in SICU patients compared with BICU patients (P < .05). Tight control in both SICU and BICU patients was associated with a decreased incidence of sepsis compared with poor glycemic control (10% vs 58% and 60% vs 70%, respectively) and a decreased mortality rate (0 vs 58% and 20% vs 50%; SICU vs BICU, respectively). The percentage of total body surface area burned in BICU patients was 10% and 45% in the < or =150 and >150 mg/dL groups. Mortality rate in the poor control group was >10-fold greater than that of the tight control group; for patients > or =65 years of age, mortality was nearly double than that of patients <65 years of age. The greatest mortality rate (62%) was seen in patients >65 years of age with poor control. Tight control with IIT is associated with an increased survival rate in both BICU and SICU patients. Age is associated with survival, with patients older than 65 years of age having the greatest mortality rate.