Management of Inpatient Hyperglycemia: Assessing Perceptions and Barriers to Care Among Resident Physicians

Objective:To develop insight into resident physician attitudes about inpatient hyperglycemia and determine perceived barriers to optimal management.Methods:As part of a planned educational program, a questionnaire was designed and administered to determine the opinions of residents about the importance o inpatient glucose control, their perceptions about what glucose ranges were desirable, and the problems they encountered when trying to manage hyperglycemia in hospitalized patients.ResultsOf 70 resident physicians from various services, 52 completed the survey (mean age, 31 years; 48% men; 37% in first year of residency training). Most respondents indicated that glucose control was “very important” in critically ill and perioperative patients but only “somewhat important” in non-critically ill patients. Most residents indicated that they would target a therapeutic glucose range within the recommended levels in published guidelines. Most residents also said they felt “somewhat comfortable” managing hyperglycemia and hypoglycemia and using subcutaneous insulin therapy. whereas most residents (48%) were “not at all comfortable” with use of intravenous administration of insulin. In general, respondents were not very familiar with existing institutional policies and preprinted order sets relating to glucose management. The most commonly reported barrier to management of inpatient hyperglycemia was lack of knowledge about appropriate insulin regimens and how to use them. Anxiety about hypoglycemia was only the third most frequent concern.ConclusionMost residents acknowledged the importance of good glucose control in hospitalized patients and chose target glucose ranges consistent with existing guidelines. Lack of knowledge about insulin treatment options was the most commonly cited barrier to ideal management. Educational programs should emphasize inpatient treatment strategies for glycemic control. (Endocr Pract. 2007;13:117-125)     

The Management of Hyperglycemia in Noncritically ill Hospitalized Patients Treated with Continuous Enteral or Parenteral Nutrition

Objective: Hyperglycemia is a common problem in hospitalized patients receiving artificial nutrition, and this development of hyperglycemia during parenteral nutrition therapy (PNT) and enteral nutrition therapy (ENT) increases the risks of hospital-related complications and mortality. This review aims to discuss the pathogenesis of hyperglycemia from artificial nutrition in the hospital, summarize current evidence on the treatment of hyperglycemia with insulin in these patients, and review current guidelines.Methods: A systematic literature review using PubMed and the Medical Subject Headings (MeSH) terms “hyperglycemia,” “enteral nutrition,” and “parenteral nutrition” were used to evaluate the current evidence available for treating noncritically ill patients with hyperglycemia who were receiving artificial nutrition.Results: The literature review showed that few randomized control trials exist regarding treatment of hyperglycemia in this cohort of patients, and the multiple retrospective evaluations that have addressed this topic provided varied results. In general, intravenous (IV) continuous insulin infusion offers the best glycemic control; however, this route of insulin administration is often burdensome for floor patients and their care teams. Administration of scheduled subcutaneous (SQ) insulin in patients on ENT or PNT is a safe and effective way to manage hyperglycemia, however limited data exist on an appropriate insulin regimen.Conclusion: Further prospective, randomized control trials are necessary to determine the optimal treatment of hyperglycemia for patients receiving ENT or PNT.Abbreviations: BG = blood glucose; CG = conventional glycemic control; ENT = enteral nutrition therapy; GIP = glucose-dependent insulinotropic polypeptide; GLP-1 = glucagon-like peptide 1; IG = intensive glycemic control; IV = intravenous; NPH = neutral protamine Hagedorn; PNT = parenteral nutrition therapy; SQ = subcutaneous; T2DM = type 2 diabetes mellitus; TDD = total daily dose; TPN = total parenteral nutrition     

Effects of a Computerized Order Set on the Inpatient Management of Hyperglycemia: A Cluster-Randomized Controlled Trial

ObjectiveTo determine the effects of a computerized order set on the inpatient management of diabetes and hyperglycemia.MethodsWe conducted a cluster-randomized controlled trial on the general medical service of an academic medical center staffed by residents and hospitalists. Consecutively enrolled patients with diabetes mellitus or inpatient hyperglycemia were randomized on the basis of their medical team to usual care (control group) or an admission order set built into the hospital’s computer provider order entry (CPOE) system (intervention group). All teams received a detailed subcutaneous insulin protocol and case-based education. The primary outcome was the mean percent of glucose readings per patient between 60 and 180 mg/dL.ResultsBetween April 5 and June 22, 2006, we identified 179 eligible study subjects. The mean percent of glucose readings per patient between 60 and 180 mg/dL was 75% in the intervention group and 71% in the usual care group (adjusted relative risk, 1.36; 95% confidence interval, 1.03 to 1.80). In comparison with usual care, the intervention group also had a lower patient-day weighted mean glucose (148 mg/dL versus 158 mg/dL, P = .04), less use of sliding-scale insulin by itself (25% versus 58%, P = .01), and no significant difference in the rate of severe hypoglycemia (glucose < 40 mg/dL; 0.5% versus 0.3% of patient-days, P = .58).ConclusionThe use of an order set built into a hospital’s CPOE system led to improvements in glycemic control and insulin ordering without causing a significant increase in hypoglycemia. Other institutions with CPOE should consider adopting similar order sets as part of a comprehensive inpatient glycemic management program. (Endocr Pract. 2010;16:209-218)     

Comparison of Basal Insulin Regimens on Glycemic Variability in Noncritically Ill Patients with Type 2 Diabetes

Objective: To evaluate the impact of different subcutaneous basal insulin regimens on glycemic variability (GV) and hospital complications in non-intensive care unit (ICU) patients with type 2 diabetes (T2D).Methods: This study is a post hoc analysis of 279 general medicine and surgery patients treated with either a “Basal Bolus” insulin regimen using glargine once daily and glulisine before meals or a “Basal Plus” regimen using glargine once daily plus correction doses of glulisine before meals for glucose >140 mg/dL. GV was calculated as mean delta (Δ) daily glucose, mean SD, and mean amplitude of glycemic excursions (MAGE).Results: Treatment with Basal Bolus and Basal Plus regimens resulted in similar mean daily glucose, hypoglycemia, length of stay (LOS), and hospital complications (all P>.05). There were no differences in GV between treatment groups by Δ change (72.5 ± 36 vs. 69.3 ± 34 mg/dL), SD (38.5 ± 18 vs. 37.1 ± 16 mg/dL) and MAGE (67.5 ± 34 vs. 66.1 ± 39 mg/dL) (all P>.05). Surgery patients treated with Basal Bolus had higher GV compared to those treated with Basal Plus (Δ daily glucose and SD: P = .02, MAGE: P = .009), but no difference in GV was found between treatment groups for the general medicine patients (P>.05). Patients with hypoglycemia events had higher GV compared to subjects without hypoglycemia (P<.05), but no association was found between GV and hospital complications (P>.05).Conclusion: Treating hospitalized, non-ICU, diabetic patients with Basal Plus insulin regimen resulted in similar glucose control and GV compared to the standard Basal Bolus insulin regimen. Higher GV was not associated with hospital complications.Abbreviations:BG = blood glucoseCV= coefficient of variationGV= glycemic variabilityICU = intensive care unitLOS = length of stayMAGE = mean amplitude of glycemic excursionsSSI = sliding scale insulinT2D = type 2 diabetesTDD =total daily dose     

Use Of Incretin-Based Therapy in Hospitalized Patients with Hyperglycemia

ObjectiveHyperglycemia is common in hospitalized patients with and without prior history of diabetes and is an independent marker of morbidity and mortality in critically and noncritically ill patients. Tight glycemic control using insulin has been shown to reduce cardiac morbidity and mortality in hospitalized patients, but it also results in hypoglycemic episodes, which have been linked to poor outcomes. Thus, alternative treatment options that can normalize blood glucose levels without undue hypoglycemia are being sought. Incretin-based therapies, such as glucagon-like peptide (GLP)-1 receptor agonists (RAs) and dipeptidyl peptidase (DPP)-4 inhibitors, may have this potential.MethodsA PubMed database was searched to find literature describing the use of incretins in hospital settings. Title searches included the terms “diabetes” (care, management, treatment), “hospital,” “inpatient,” “hypoglycemia,” “hyperglycemia,” “glycemic,” “incretin,” “dipeptidyl peptidase-4 inhibitor,” “glucagon-like peptide-1,” and “glucagon-like peptide-1 receptor agonist.”ResultsThe preliminary research experience with native GLP-1 therapy has shown promise, achieving improved glycemic control with a low risk of hypoglycemia, counteracting the hyperglycemic effects of stress hormones, and improving cardiac function in patients with heart failure and acute ischemia. Large, randomized controlled clinical trials are necessary to determine whether these favorable results will extend to the use of GLP-1 RAs and DPP-4 inhibitors.ConclusionsThis review offers hospitalist physicians and healthcare providers involved in inpatient diabetes care a pathophysiologic-based approach for the use of incretin agents in patients with hyperglycemia and diabetes, as well as a summary of benefits and concerns of insulin and incretin-based therapy in the hospital setting. (Endocr Pract. 2014;20:933-944)     

Standardized Glycemic Management and Perioperative Glycemic Outcomes in Patients with Diabetes Mellitus who Undergo Same-Day Surgery

ObjectiveTo assess the safety and effectiveness of a standardized glycemic management protocol in patients with diabetes mellitus who undergo same-day surgery.MethodsThe perioperative glycemic management protocol consisted of preoperative instructions and perioperative order sets for management of subcutaneous and intravenous insulin. Patients with known diabetes admitted to same-day surgery during a 10-month period were observed. Patient demographic information and all capillary blood glucose (CBG) values obtained during the sameday surgery visit were collected. Hyperglycemia, defined as a CBG concentration of 200 mg/dL or greater, prompted notification of the attending anesthesiologist. While use of the perioperative order sets was encouraged, the attending anesthesiologist retained the prerogative to treat according to these order sets or their usual care. Physician compliance with the standardized order sets was determined by chart review in the patients who had a documented blood glucose value of 200 mg/dL or greater.ResultsPatients managed with the standardized order sets had greater reductions in CBG values (percentage change, 35 ± 20.5% vs 18 ± 24%, P < .001) and lower postoperative CBG values (186 ± 53 mg/dL vs 208 ± 63 mg/dL, P < .05) than patients who received usual care. No cases of intraoperative or postoperative hypoglycemia (CBG < 70 mg/dL) were observed in either group.ConclusionsA systematic approach to glycemic management that includes instructions for preoperative adjustments to home diabetic medications and order sets for treatment of perioperative hyperglycemia is safe and can be more effective than usual care for ambulatory surgery patients with diabetes. (Endocr Pract. 2011;17:404-411)     

Insulin therapy for inpatients with diabetes: Perceptions of resident physicians from disparate geographic training programs

Background: Improving diabetes management in hospitalized patients will require educational efforts for all practitioners, particularly resident physicians. Thus, a better understanding of residents' beliefs about diabetes in the hospital must be obtained.Objective: The purpose of this article was to compare and contrast perceptions of resident physicians from 2 geographically distinct training programs regarding management of inpatients with diabetes.Methods: Residents from training programs in the southwestern and southeastern United States were surveyed in 2006 and 2007 about their views on the importance of inpatient glucose control, their perceptions about desirable target glucose ranges, and the problems they encountered when trying to manage hyperglycemia in hospitalized patients.Results: Responses were obtained from 52 of 66 residents at site 1 and from 65 of 85 residents at site 2 (N = 117 total respondents; total response, 77%; mean age, 31 years; 48% men; 61% primary care). Combined analyses revealed that respondents believed that glucose control was “very important” in critically ill patients (96%), perioperative patients (82%), and noncritically ill patients (66%). Most residents indicated that they would target a therapeutic glucose range within published recommendations. Less than half felt “very comfortable” managing inpatient hyperglycemia, hypoglycemia, subcutaneous insulin, or insulin drips. Respondents were not very familiar with existing institutional policies or preprinted order sets for insulin therapy. The most commonly reported barrier to management of inpatient hyper-glycemia was lack of knowledge about appropriate insulin regimens and their use.Conclusions: Trainees from 2 very different educational programs shared common beliefs, knowledge deficits, and perceived barriers about inpatient glucose management. Our findings indicate that trainees were uncertain about how to use insulin therapy in the hospital. Future inpatient diabetes quality-improvement efforts should focus on development of uniform educational programs targeting the management of inpatient diabetes, particularly as it relates to insulin use.     

Safety and Efficacy of a Peri-Operative Protocol for Patients with Diabetes Treated with Continuous Subcutaneous Insulin Infusion who are Admitted for Same-Day Surgery

Objective: The number of people with diabetes using continuous subcutaneous insulin infusions (CSII) with an insulin pump has risen dramatically, creating new challenges when these patients are admitted to the hospital for surgical or other procedures. There is limited literature guiding CSII use during surgical procedures.Methods: The study was carried out in a large, urban, tertiary care hospital. We enrolled 49 patients using insulin pump therapy presenting for 57 elective surgeries. We developed a CSII peri-operative glycemic management protocol (PGMP) to standardize insulin pump management in patients admitted to a same-day surgery unit (SDSU). The purpose was evaluate the safety (% capillary blood glucose (CBG) <70 mg/dL and/or pump incidents) and efficacy (first postoperative CBG ≤200 mg/dL) of the CSII PGMP. We determine the contribution of admission CBG, type of anesthesia, surgery length, and peri-operative steroid use on postoperative glycemic control.Results: Overall, 63% of patients treated according to the CSII PGMP had a first postoperative CBG ≤200 mg/dL. There were no episodes of intra- or postoperative hypoglycemia. For patients treated with the CSII PGMP, the mean postoperative CBG was lower in patients with anticipated or actual surgical length ≤120 minutes (158.1 ± 53.9 vs. 216 ± 77.7 mg/dL, P<.01). No differences were observed with admission CBG, type of anesthesia, or steroid use.Conclusions: This study demonstrates that a CSII PGMP is both safe and effective for patients admitted for elective surgical procedures and provides an example of a standardized protocol for use in clinical practice.Abbreviations: A1C = glycated hemoglobin BG = blood glucose CBG = capillary blood glucose CSII = continuous subcutaneous insulin infusion DM = diabetes mellitus EMR = electronic medical record IV = intravenous PGMP = peri-operative glycemic management protocol SDS = same-day surgery SDSU = same-day surgery unit SQ = subcutaneous UC = usual care     

Failure of Multiple Therapies in the Treatment of a Type 1 Diabetic Patient with Insulin Allergy: A Case Report

ObjectiveTo describe the clinical manifestations of insulin allergy and explain a systematic management approach.MethodsWe present the clinical, laboratory, and pathologic findings of a type 1 diabetic patient with allergy to subcutaneous insulin and briefly review the related literature.ResultsAn 18-year old woman with type 1 diabetes mellitus had an insulin allergy and developed subcutaneous nodules after insulin administration. Human and analogue insulins were used, but painful nodule formation persisted. Treatment with antihistamines, steroids, and omalizumab and insulin desensitization were ineffective. The patient required pancreatic transplant because glycemic control could not be achieved due to the insulin allergy.ConclusionsInsulin allergy is not a common condition and can be challenging in patients with type 1 diabetes. Therefore, identifying patients with true insulin allergy and applying a stepwise approach to their treatment is important. (Endocr Pract. 2011;17:91-94)     

The Association Between Glycemic Control and Clinical Outcomes after Kidney Transplantation

ObjectiveTo analyze the relationship between glycemic control after renal transplantation and subsequent graft function and complications.MethodsWe conducted a retrospective chart review of 202 consecutive patients undergoing kidney transplantation to analyze the association between perioperative and chronic glycemic control and clinical outcomes of rejection, infection, and hospital readmission during the first year after kidney transplantation.ResultsMean in-hospital blood glucose (BG) was 157 ± 34.5 mg/dL. Mean hemoglobin A1c (HbA1c) during the first 12 months posttransplantation was 6.84 ± 1.46%. Fiftyfour patients (27%) were treated for acute or chronic rejection, 88 (44%) for infection, and 149 (74%) patients were readmitted at least once within the first year after transplantation. There were no significant differences in the risks for rejection, infection, or readmission across the 5 mean initial inpatient BG or subsequent HbA1c quintiles. In addition, there was no significant relationship between the percentage of BG measurements that fell in the “tight control” range of 80 to 110 mg/dL for each patient and any of the outcomes.ConclusionWe did not find an association between glycemic control (perioperative or chronic) and the outcomes of graft rejection, infection, or hospital readmission in the first 12 months after renal transplantation. Our results suggest that “near normal” glycemic targets are not necessary for managing hyperglycemia after renal transplantation. (Endocr Pract. 2014;20:894-900)     

Glycemic Variation and Hypoglycemia in Patients with well-Controlled Type 1 Diabetes on a Multiple Daily Insulin Injection Program with use of Glargine and Ultralente as Basal Insulin

ObjectiveTo evaluate glycemic variation and hypo-glycemia in patients with well-controlled type 1 diabetes receiving multiple daily insulin injections during glargine and Ultralente use as basal insulin in a clinical trial.MethodsTwenty-two patients (12 men and 10 women, median age, 43 years), with a hemoglobin A1c level < 7.8%, were randomized in a crossover design to receive either insulin glargine or Ultralente insulin as basal insulin for 4 months each, with insulin aspart as prandial insulin. Continuous glucose monitoring and the Fear of Hypoglycemia questionnaire were used at baseline and at the end of each treatment period.ResultsWhereas the mean amplitude of glycemic excursions showed a correlation with the area under the curve of blood glucose < 3.89 mmol/L per day, the number of periods during the day with hypoglycemia was significantly correlated with the M value. Measures of glycemic variation did not differ significantly between glargine and Ultralente treatment. With use of glargine therapy, the SD of blood glucose levels showed a tendency to be lower and the SD of nocturnal blood glucose concentrations was significantly lower. Glucose concentrations were significantly lower during the 1 hour before and the 3 hours after lunch with use of Ultralente. The “Worry” scale on the Fear of Hypoglycemia questionnaire was less during Ultralente therapy and correlated with the number of times blood glucose concentrations were < 3.89 mmol/L daily.ConclusionMeasures of glycemic variability and hypoglycemia need to be studied more in clinical trials of glycemic control in patients with type 1 diabetes. Glycemic variability is less, particularly at night, with glargine as basal insulin. (Endocr Pract. 2007;13:244-250)     

Is There A “July Effect” for Inpatient Glycemic Control?

ObjectiveThe period of resident turnover in teaching hospitals is considered by some to worsen health outcomes and is called the “July effect.” We sought to study glycemic control in patients admitted to medical floors and identify any adverse outcomes related to a “July effect.”MethodsThis was a single-center retrospective cohort study that compared inpatient glycemic control at the start and end of a single academic year (July 2009 to June 2010). A total of 108 patients with a diagnosis of diabetes mellitus were included in the first group (Group 1: July to September 2009), and 134 were in the second group (Group 2: April to June 2010). Four capillary blood glucose measurements were taken from Days 2 to 6 of hospitalization, and clinical data pertinent to glycemic management were collected.ResultsData analysis showed no significant difference in the overall inpatient glycemic control between the 2 groups. The mean glucose levels were 168.67 mg/dL and 168.59 mg/dL for Groups 1 and 2, respectively. Overall, 67% of patients in Group 1 and 72.9% in Group 2 were within a blood glucose range of 70 to 179 mg/dL, and 32% of patients in Group 1 and 44.1% of patients in Group 2 were within the range of 140 to 179 mg/dL. Hypoglycemia occurred in 17% and 18.6% of Groups 1 and 2, respectively. No difference in diabetes treatment ordering practices of residents was detected.ConclusionThis study did not show any evidence to support the “July effect” on overall inpatient glycemic control. (Endocr Pract. 2014;20:919-924)     

An Update on Insulin Injection Devices

Background: Over the past 15 years, it has become clear that better glycemic control can lead to a substantial reduction in diabetic complications and that such control often requires the use of insulin therapy. However, a number of barriers exist to starting such therapy in patients with diabetes mellitus (DM). Many of these barriers to treatment are related to the use of a syringe to inject the medication. In the past ~20 years, various "pen" devices have become available that help to reduce the stigma associated with insulin injection, allowing more patients to achieve the glycemic control that they require.Objectives: This article provides an overview of the various pen devices available in the United States for subcutaneous insulin delivery and discusses the benefits these devices can provide to patients; their disadvantages are also discussed. Third-party reimbursement for these devices is highlighted.Methods: A MEDLINE search was performed (1980-2007) to identify relevant articles (English-language only) using appropriate key terms, including insulin pen and insulin delivery device. Technical specifications and availability information for the various pen devices were obtained directly from their manufacturers. Insurance coverage data were provided by major national insurance carriers.Results: There are a number of excellent pen devices available for administering each of the currently offered basal and bolus insulin analogues as well as neutral protamine Hagedorn and regular insulins. These devices range from disposable pens—which are supplied to the patient prefilled from the pharmacy, used until empty, and then discarded—to refillable digital pens, some of which have the ability to “remember” prior insulin doses. Data from various studies indicate that both patients and their physicians generally prefer insulin pens over the traditional vial and syringe delivery method. These devices are simple to use, allow patients to be more discreet in social situations, can easily be carried in a shirt pocket or purse, do not need to be refrigerated while in use, are associated with a lesser degree of injection anxiety, and may even be more accurate at lower doses. They may also be the preferred delivery system for the visually impaired, given their larger displays and the audible/tactile “click” produced each time the dose is increased by 1 U. Insulin pens lead to increased patient confidence and satisfaction and improved attitude toward insulin therapy. Most major insurance plans provide some coverage for the disposable pens as well as the cartridges for refillable pens, but this is often under tier 2 and some insurers may require prior authorization.Conclusions: Insulin pens provide DM patients with a number of advantages over a vial and syringe and can often help them overcome major barriers to the initiation of insulin therapy. The use of insulin pens leads to increased patient compliance and potential improvements in glycosylated hemoglobin, but data on glycemic control are not available. The pens should be offered to virtually all patients who require insulin therapy, except in instances in which these pens are financially prohibited.     

Impact of Multidisciplinary Process Improvement Interventions on Glucometrics in a Noncritically Ill Setting

Objective: This study aimed to assess the impact of multidisciplinary process improvement interventions on glycemic control in the inpatient setting of an urban community hospital, utilizing the daily simple average as the primary glucometric measure.Methods: From 2010–2014, five process of care interventions were implemented in the noncritical care inpatient units of the study hospital. Interventions included education of medical staff, implementation of hyperglycemia and hypoglycemia protocols, computerized insulin order entry, and coordination of meal tray delivery with finger stick and insulin administration. Unpaired t tests compared pre- and postintervention process measures. Simple average daily glucose measure was the primary glucometric outcome. Secondary outcome measures included frequency of hyperglycemia and hypoglycemia. Glucose outcomes were compared with an in-network hospital that did not implement the respective interventions.Results: A total of 180,431 glucose measurements were reported from 4,705 and 4,238 patients from the intervention and comparison hospitals, respectively. The time between bolus-insulin administration and breakfast tray delivery was significantly reduced by 81.7 minutes (P<.00005). The use of sliding scale insulin was sustainably reduced. Average daily glucose was reduced at both hospitals, and overall rates of hypoglycemia were low.Conclusion: A multidisciplinary approach at an urban community hospital with limited resources was effective in improving and sustaining processes of care for improved glycemic control in the noncritical care, inpatient setting.Abbreviations: IQR = interquartile range; JMC = Jacobi Medical Center; NCBH = North Central Bronx Hospital     

Tratamiento de la hiperglucemia en el hospital. Impresiones y conocimientos del médico residente

Background and objectiveIn many hospitals, adequate glycemic control is not achieved despite implementation of new insulin therapy protocols. Our aim was to assess resident physician’ attitudes toward inpatient hyperglycemia, barriers to achieve optimum control, and impact on them of an insulin training programMaterial and methodsA questionnaire was used to assess understanding and standard management of hyperglycemia before and six months after implementation of an inpatient insulin treatment program.ResultsTwenty-five interns completed the questionnaire. Glycemic control was considered “very important” in all admission situations, but was only considered “very important” in conventional hospitalization by 36% of interns. Most of these felt “comfortable” using sliding scales, but not with the basal/bolus regimen, which was the least commonly used. Perception of number of well-controlled patients and comfort and use of basal/bolus therapy increased at six months, but use of “sliding scales” remained high. The greatest difficulty reported for adequate management of hyperglycemia was the lack of knowledge.ConclusionsMost residents are aware of the importance of adequate glycemic control, but cannot achieve it because of inadequate knowledge. The insulin training program led to an improved perception and applicability of basal-bolus insulin regimens. However, despite all efforts, use of sliding scales remains high. Training programs should emphasize management of hyperglycemia.     

Hospital hypoglycemia: From observation to action

Background: A preponderance of evidence indicates that when treatment of hyperglycemia with insulin is provided for certain hospitalized populations, the attainment of appropriate glycemic targets improves nonglycemic outcomes such as mortality rates, morbidities (eg, wound infection, critical illness polyneuropathy, bacteremia, new renal insufficiency), duration of ventilator dependency, transfusion requirements, and length of hospital stay. Nevertheless, randomized controlled trials (RCTs) of intensive insulin therapy and studies of outcomes before and after implementation of tight glycemic control have consistently recognized an increased incidence of hypoglycemia as a complication associated with the use of lower glycemic targets and higher doses of insulin.Objectives: This commentary compares the quality of the available evidence on the clinical impact of iatrogenic hypoglycemia. We present treatment strategies designed to prevent iatrogenic hypoglycemia in the hospital setting.Methods: The PubMed database and online citations of articles tracked subsequent to publication were searched for articles on the epidemiology, clinical impact, and mechanism of harm of hypoglycemia published since 1986. In addition, we searched the literature for RCTs conducted since 2001 concerning intensive insulin therapy in the hospital critical care setting, including meta-analyses; letters to the editor were excluded. The retrieved studies were scanned and chosen selectively for full-text review based on the study size and design, novelty of findings, and evidence related to the possible clinical impact of hypoglycemia. Reference lists from the retrieved studies were searched for additional studies. Reports were summarized for the purpose of comparing and contrasting the qualitative nature of information about iatrogenic hypoglycemia in the hospital.Results: Eight RCTs of intensive glycemic management, 16 observational studies of hospitalized patients with hypoglycemia (including studies of outcomes before and after implementation of tight glycemic control), and 4 case reports on patients with hypoglycemia were selected for discussion of the incidence of hypoglycemia, significance of hypoglycemia as a marker or cause of poor prognosis, and clinical harm of hypoglycemia. Hypoglycemia was identified in clinical trials as either a category of adverse events or a complication of intensified insulin treatment. For example, a recent meta-analysis found that the incidence of severe hypoglycemia was higher among critically ill patients treated with intensive insulin therapy than among control patients, with a pooled relative risk of 6.0 (95% CI, 4.5–8.0). In the largest multisite RCT on glycemic control among patients in intensive care units (ICUs) conducted to date, deaths were reported for 27.5% (829/3010 patients) in the intensive-treatment group and 24.9% (751/3012 patients) in the conventional-treatment group (odds ratio, 1.14; 95% CI, 1.02–1.28; P = 0.02). In another multisite ICU study, although the intensive and control groups had similar mortality rates, the mortality rate was higher among hypoglycemic participants than among nonhypoglycemic participants (32.2% vs 13.6%, respectively; P < 0.01). Pooled data from 2 singlesite studies in medical and surgical ICUs revealed an increased risk of hypoglycemia in the intensive-treatment group compared with the conventional-treatment group (11.3% [154/1360] and 1.8% [25/1388], respectively; P < 0.001), but the hospital mortality rate was similar for the 2 groups (50.6% [78/154] and 52.0% [13/25], respectively). Specific sequelae of hypoglycemia affecting individual patients were described in the RCTs as well as in the observational studies. New guidelines for glycemic control have recently been issued, but results of the studies using the new targets are not yet available. We propose treatment strategies designed to prevent iatrogenic hypoglycemia in the hospital setting.Conclusions: In response to the growing evidence on the risk of hypoglycemia during intensified glycemic management of hospitalized patients, professional organizations recently revised targets for glycemic control. It is appropriate for institutions to reevaluate hospital protocols for glycemic management with intravenous insulin and, on general wards, to implement standardized order sets for use of subcutaneous insulin to achieve beneficial targets using safe strategies.     

Inpatient insulin therapy

Background: Many diabetic, as well as nondiabetic, hospitalized patients develop hyperglycemia. Numerous studies have demonstrated that critically ill, as well as noncritically ill, hospitalized patients who develop hyperglycemia are at increased risk for morbidity and mortality.Objective: The objective of this article was to review the risks associated with hyperglycemia in hospitalized patients, the biologic rationale for using insulin to prevent increases in glucose levels, and strategies for managing hyperglycemia in the hospital setting.Methods: We conducted a computerized search of biomedical journal literature from MEDLINE, PubMed, and Ovid published from 1994 to March 2008. We reviewed English-language original and review articles found under the subject headings “hospitalization and insulin therapy,” “inpatient diabetes and complications,” and “insulin and inflammation.”Results: More than 200 references were found during the literature search. According to the literature, the adverse outcomes that are associated with hyperglycemia may be attributed to the inflammatory and pro-oxidant effects of elevated glucose levels. The use of insulin, which has anti-inflammatory, vasodilatory, and antioxidant properties as well as the ability to inhibit lipolysis and platelet aggregation, can prevent many of these adverse outcomes.Conclusions: Hospitals should have protocols in place for using insulin to treat and prevent hyperglycemia. Subcutaneous insulin may be used for both purposes in most noncritically ill patients, whereas intravenous infusion of insulin is preferred in critically ill patients.     

The role of rapid-acting insulin analogues and inhaled insulin in type 2 diabetes mellitus

sBackground:The availability of rapid-acting insulin analogues and inhaled insulin gives clinicians additional treatmentoptions in the management of patients with diabetes mellitus (DM). Combining rapid-acting insulin analogues with basal insulin can more closely mimic physiologic insulin release to maximize glycemic control.Objective:The objective of this article was to discuss the role of rapid-acting insulin analogues and inhaled insulin inthe treatment of patients with type 2 DM.Methods:Materials for this article were obtained through an online search of MEDLINE/PubMed and Google(1996-2006) using the search terms bolus insulin, postprandial, rapid-acting insulin analogues, titration, hypoglycemia, glycemic control, inhaled insulin, and insulins lispro, aspart, and glulisine.Results:Glycosylated hemoglobin (A1C) levels and number of all hypoglycemic episodes were similar in patients withtype 2 DM taking either mealtime rapid-acting insulin analogues or regular human insulin (RHI). Rapid-acting insulins have been successfully used in basal-bolus regimens with a variety of long- and intermediate-acting insulins, as well as with oral hypoglycemic agents. Injectable rapid-acting insulin analogues markedly decreased postprandial glucose (PPG) levels compared with RHI. Better reduction in PPG levels may be key to achieving target A1C levels in some patients, but long-term outcome studies are needed to assess whether lowering PPG levels decreases cardiovascular risk in patients with type 2 DM. Inhaled insulin may be an option for patients who cannot inject insulin, but route of administration and dosing issues limit its use in many patients. The effect of inhaled insulin on PPG is unclear at this time.Conclusions:Although rapid-acting insulin analogues are effective in the management of patients with type 2 DM, the limited numbers of studies have yet to demonstrate that these agents have any significant long-term advantage compared with RHI. In addition, they cost more than RHI. Further studies are needed to compare the efficacy of the rapid-acting insulin analogues, to compare the different dosing regimens used with mealtime insulin administration, and to ascertain if the decrease in PPG levels seen with the use of rapid-acting insulin analogues translates into improved glycemic control and perhaps even a reduction in cardiovascular risk in patients with type 2 DM. (Insulin. 2007;2:61-67) Copyright 2007 Excerpta Medica, Inc.