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)     

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.     

Adapting to the new consensus guidelines for managing hyperglycemia during critical illness: the updated Yale insulin infusion protocol

ObjectiveTo report our preliminary experience with the revised, more conservative Yale insulin infusion protocol (IIP) that targets blood glucose concentrations of 120 to 160 mg/dL.MethodsWe prospectively tracked clinical responses to the new IIP in our medical intensive care unit (ICU) by recording data on the first 115 consecutive insulin infusions that were initiated. All blood glucose values; insulin doses; nutritional support including intravenous dextrose infusions; caloric values for enteral and parenteral nutrition; and use of vasopressors, corticosteroids, and hemodialysis or continuous venovenous hemodialysis were collected from the hospital record.ResultsThe IIP was used 115 times in 90 patients (mean age, 62 [± 14 years]; 51% male; 35% ethnic minorities; 66.1% with history of diabetes). The mean admission Acute Physiology and Chronic Health Evaluation II score was 24.4 (± 7.5). The median duration of insulin infusion was 59 hours. The mean baseline blood glucose concentration was 306.1 (± 89.8) mg/dL, with the blood glucose target achieved after a median of 7 hours. Once the target was reached, the mean IIP blood glucose concentration was 155.9 (± 22.9) mg/dL (median, 150 mg/dL). The median insulin infusion rate required to reach and maintain the target range was 3.5 units/h. Hypoglycemia was rare, with 0.3% of blood glucose values recorded being less than 70 mg/dL and only 0.02% being less than 40 mg/dL. In all cases, hypoglycemia was rapidly corrected using intravenous dextrose with no evident untoward outcomes.ConclusionsThe updated Yale IIP provides effective and safe targeted blood glucose control in critically ill patients, in compliance with recent national guidelines. It can be easily implemented by hospitals now using the original Yale IIP. (Endocr Pract. 2012;18:363-370)     

Examination of Implementation of Intravenous and Subcutaneous Insulin Protocols and Glycemic Control in Heart Transplant Patients

ObjectivePerioperative glycemic management is particularly challenging in heart transplant (HT) patients who are on high-dose steroids and subject to surgical stress. The objective of the study was to examine the efficacy and safety of perioperative insulin administration in HT patients with and without diabetes.MethodsMedical records of 71 HT patients from June 1, 2005 to July 31, 2009 whose hyperglycemia was managed by our Glucose Management Service (GMS) were analyzed for up to 1 year after HT. Their daily blood glucose (BG) averages on intravenous (IV) insulin drips and subcutaneous (SQ) insulin, hypoglycemia rates, reasons for hypoglycemia, and deviations from insulin protocols were analyzed.ResultsDaily BG averages between diabetic (DM) and nondiabetic (nonDM) patients were not significantly different while on the drip but were significantly different for first 5 days on SQ (P < .05). The daily insulin glargine doses were similar. No patients developed severe hypoglycemia (BG ≤ 40 mg/dL) while on drip, and only 2.8% experienced hypoglycemia on SQ. Among 40 episodes of moderate hypoglycemia while on drip, 15 had nurse deviations from protocol prior to the episode. Posttransition day fasting glucose was at goal (mean 124.7 ± 35.4 mg/dL); however 39.4% (28/71) of patients received a transition insulin glargine dose that was different from the amount indicated by protocol. The likelihood of developing moderate hypoglycemia on SQ was associated with the glargine dose used at the time of transition (odds ratio [OR] 1.03, P = .034).ConclusionInpatient insulin protocols implemented by a GMS are successful in obtaining glycemic control with minimal side effects in patients with and without diabetes, even when they are on a high-dose steroid regimen. (Endocr Pract. 2014;20:527-535)     

Inpatient Management of Diabets Mellitus Among Noncritically Ill Patients at the University Hospital of Puerto Rico

ObjectiveTo describe the state of glycemic control in noncritically ill diabetic patients admitted to the Puerto Rico University Hospital and adherence to current standard of care guidelines for the treatment of diabetes.MethodsThis was a retrospective study of patients admitted to a general medicine ward with diabetes mellitus as a secondary diagnosis. Clinical data for the first 5 days and the last 24 hours of hospitalization were analyzed.ResultsA total of 147 noncritically ill diabetic patients were evaluated. The rates of hyperglycemia (blood glucose ≥ 180 mg/dL) and hypoglycemia (blood glucose < 70 mg/dL) were 56.7 and 2.8%, respectively. Nearly 60% of patients were hyperglycemic during the first 24 hours of hospitalization (mean random blood glucose, 226.5 mg/dL), and 54.2% were hyperglycemic during the last 24 hours of hospitalization (mean random blood glucose, 196.51 mg/dL). The mean random last glucose value before discharge was 189.6 mg/dL. Most patients were treated with subcutaneous insulin, with basal insulin alone (60%) used as the most common regimen. The proportion of patients classified as uncontrolled receiving basal-bolus therapy increased from 54.3% on day 1 to 60% on day 5, with 40% continuing to receive only basal insulin. Most of the uncontrolled patients had their insulin dose increased (70.1%); however, a substantial proportion had no change (23.7%) or even a decrease (6.2%) in their insulin dose.ConclusionThe management of hospitalized diabetic patients is suboptimal, probably due to clinical inertia, manifested by absence of appropriate modification of insulin regimen and intensification of dose in uncontrolled diabetic patients. A comprehensive educational diabetes management program, along with standardized insulin orders, should be implemented to improve the care of these patients. (Endocr Pract. 2014;20:452-460)     

Development and implementation of evidence-based guidelines for IV insulin: A statewide collaborative approach

Purpose: Recent studies have shown that the outcomes of hospitalized patients are greatly enhanced when steps are taken to improve control of their blood glucose levels. The Georgia Hospital Association Research and Education Foundation's Partnership for Health Accountability established a Diabetes Special Interest Group (D-SIG) in February 2003. Goals of the D-SIG were to enlighten health care professionals in Georgia hospitals about the benefits of controlling hyperglycemia in hospitalized patients and to develop processes to assist hospitals in the adoption of an IV insulin dosing algorithm, development of an IV insulin standing order set, and implementation of a hyperglycemia management plan.Methods: The D-SIG created an assessment tool titled “Key Elements of IV Insulin Guidelines” and evaluated numerous published IV insulin administration algorithms and protocols. After an extensive literature review, including international protocols and guidelines, user-friendly guidelines for subcutaneous and IV insulin were developed by a multidisciplinary work group, with members representing hospitals and other stakeholders from throughout the state. The group chose a well-researched method that was available in both computerized and hand-calculated formats and developed a Columnar Insulin Dosing Chart to assist with IV insulin infusions. This insulin-infusion table stems from mathematical formulas published by multiple investigators since the 1980s. The D-SIG guidelines and dosing chart were evaluated for ease of use, effectiveness, and safety in 3 settings: a small, rural critical-access hospital (CAH); an intensive care unit (ICU) in the trauma center of a large Georgia teaching hospital; and a surgical ICU in a midsize metropolitan hospital.Results: After implementation of the guidelines, the incidence of hypoglycemia (blood glucose level <60 mg/dL) was 0.9% in the trauma center ICU and 0.6% in the surgical ICU. All hypoglycemic patients in these 2 settings were asymptomatic, remained hypoglycemic only for a short time, and experienced no complications attributable to hypoglycemia. Using a moderate insulin sensitivity level for dosing initiations resulted in a time to target blood glucose level (80–110 mg/dL) of 6.4 hours, whereas using the most conservative approach required 12.8 hours to attain target range. At the CAH, time to reach the target blood glucose level (90–140 mg/dL) was 5.8 hours, and no episodes of hypoglycemia were reported. Although not part of the pilot initiative, the surgical ICU also reported a 5-fold reduction in surgical infection rates. The success of the dosing chart and standing order set paralleled that of the computerized formula when similar initiation doses were used.Conclusions: The Columnar Insulin Dosing Chart and sample clinical guidelines were piloted at 3 different settings and found to be safe and effective. Furthermore, by including the treatment for hypoglycemia in the guidelines, nurses in all patient care areas were able to manage blood glucose levels below the target range in a safe and timely manner. Use of the dosing chart and guidelines reduced blood glucose levels to the target range with no clinically significant hypoglycemia.     

Hypoglycemia: Still The Limiting Factor in the Glycemic Management of Diabetes

ObjectiveTo review the prevalence of, risk factors for, and prevention of hypoglycemia from the perspective of the pathophysiologic aspects of glucose counterregulation in diabetes.MethodsThis review is based on personal experience and research and the relevant literature.ResultsAlthough it can result from insulin excess alone, iatrogenic hypoglycemia is generally the result of the interplay of therapeutic insulin excess and compromised defenses against declining plasma glucose concentrations. Failure of β-cells of the pancreas—early in patients with type 1 diabetes mellitus but later in those with type 2 diabetes mellitus (T2DM)—causes loss of the first 2 physiologic defenses: a decrease in insulin and an increase in glucagon. Such patients are critically dependent on epinephrine, the third physiologic defense, and neurogenic symptoms that prompt the behavioral defense (carbohydrate ingestion). An attenuated sympathoadrenal response to declining glucose levels—caused by recent antecedent hypoglycemia, prior exercise, or sleep—causes hypoglycemia-associated autonomic failure (HAAF) and thus a vicious cycle of recurrent hypoglycemia. Accordingly, hypoglycemia is infrequent early in T2DM but becomes increasingly more frequent in advanced (absolutely endogenous insulin-deficient) T2DM, and risk factors for HAAF include absolute endogenous insulin deficiency; a history of severe hypoglycemia, hypoglycemia unawareness, or both; and aggressive glycemic therapy per se.ConclusionBy practicing hypoglycemia risk reduction— addressing the issue, applying the principles of aggressive glycemic therapy, and considering both the conventional risk factors and those indicative of HAAF— it is possible both to improve glycemic control and to minimize the risk of hypoglycemia in many patients. (Endocr Pract. 2008;14:750-756)     

Diabetes and Hyperglycemia Quality Improvement Efforts in Hospitals in the United States: Current Status,Practice Variation,and Barriers to Implementation

ObjectiveTo determine the status of diabetes and hyperglycemia quality improvement efforts in hospitals in the United States.MethodsWe designed and administered a survey to a convenience sample of hospitals, and the responses were analyzed statistically.ResultsWe received 269 responses from 1,151 requested surveys. The sample was similar to hospitals in the United States on the basis of hospital type and geographic region (P = no significant difference) but not on the basis of number of beds (P < .001). Among responding hospitals, 39%, 21%, and 15% had fully implemented inpatient diabetes and hyperglycemia quality improvement programs for critically ill, non-critically ill, and perioperative patients, respectively. Moreover, 77%, 44%, and 49% had fully implemented protocols for hypoglycemia, hyperglycemic crises, and diabetic ketoacidosis, respectively. Variations in glucose target ranges were noted. The responding hospitals had no standard biochemical definition of hypoglycemia; 47% defined hypoglycemia as a glucose level ≤ 70 mg/dL, but 29%, 8%, 6%, and 4% used < 60, ≤ce:hsp sp="0.10"/>50, < 40, and < 80 mg/dL, respectively. Almost a third of reporting hospitals had no metric to track the quality of inpatient diabetes and hyperglycemia care. More than half (59%) indicated that they did not have an automated capability to extract and analyze glucose data. The most frequent barrier to implementing a glycemic control program was concern regarding hypoglycemia (61%).ConclusionHospitals are addressing the issue of inpatient diabetes and glycemic control but face obstacles to implementation of quality improvement programs and vary in their approach to management. Improving the consistency of glucose control practices within hospitals in the United States should help enhance patient care and safety. Future efforts to help hospitals overcome barriers to introducing glucose control programs could include developing standardized glycemic control metrics, improving data collection and reporting methods, and providing improved tools that enable clinicians to control glucose safely. (Endocr Pract. 2010;16:219-230)     

Long-Acting Subcutaneously Administered Insulin for Glycemic Control Immediately After Cardiac Surgery

ObjectiveTo test the hypothesis that subcutaneous administration of basal insulin begun immediately after cardiac surgery can decrease the need for insulin infusion in patients without diabetes and save nursing time.MethodsAfter cardiac surgery, 36 adult patients without diabetes were randomly assigned to receive either standard treatment (control group) or insulin glargine once daily in addition to standard treatment (basal insulin group). Standard treatment included blood glucose measurements every 1 to 4 hours and intermittent insulin infusion to maintain blood glucose levels between 100 and 150 mg/dL. The study period lasted up to 72 hours.ResultsThere were no differences in demographics or baseline laboratory characteristics of the 2 study groups. Mean daily blood glucose levels were lower in the basal insulin group in comparison with the control group, but the difference was not statistically significant (129.3 ± 9.4 mg/ dL versus 132.6 ± 7.3 mg/dL; P = .25). The mean duration of insulin infusion was significantly shorter in the basal insulin group than in the control group (16.3 ± 10.7 hours versus 26.6 ± 17.3 hours; P = .04). Nurses tested blood glucose a mean of 8.3 ± 3.5 times per patient per day in the basal insulin group and 12.0 ± 4.7 times per patient per day in the control group (P = .01). There was no occurrence of hypoglycemia (blood glucose level < 60 mg/dL) in either group.ConclusionOnce-daily insulin glargine is safe and may decrease the duration of insulin infusion and reduce nursing time in patients without diabetes who have hyperglycemia after cardiac surgery. (Endocr Pract. 2011;17: 558-562)     

Inpatient Glycemic Control on the Vascular Surgery Service

ObjectiveTo describe a structured inpatient insulin management protocol and order set for glycemic control on a vascular surgery service.MethodsPatients admitted to the vascular surgery service with underlying diabetes were enrolled in a study of use of a preprinted basal-bolus insulin order set based on a total daily dose of 0.5 U/kg (0.25 U/kg of insulin glargine and 0.25 U/kg of insulin aspart divided into 3 equal mealtime doses). Outcomes included the mean glycemic control at each of 5 established time intervals, the percentage of blood glucose measurements within the target range of 70 to 180 mg/dL, the incidence of hypoglycemia, and the insulin dosages. Historical control patients with diabetes from the same hospital service were used for comparison.ResultsBoth the study group and the control group consisted of 26 patients. The number of finger-stick blood glucose measurements performed was 871 in the control group and 896 in the intervention group. The mean blood glucose level (± SD) for the intervention group was 149.4 ± 50.7 mg/dL, in comparison with 165.2 ± 64.4 mg/dL for the control group. The incidence of hypoglycemia decreased 50% in the intervention group—from 32 (4% of the finger-stick assessments in the control group) to 19 (2% of the finger-stick blood glucose measurements in the study group). The blood glucose target range of 70 to 180 mg/dL was achieved in 75% of the measurements in the study group versus 61% in the control group. The basal insulin dose was unchanged in 65% of the patients, and of the 9 patients requiring a change in the dose, 5 had the dose decreased by 10% and 4 had the dose increased by 10%.ConclusionThe use of a standardized basal-bolus weight-based insulin regimen was successful at achieving improved glycemic control as well as reducing the incidence of hypoglycemia in an inpatient population with diabetes. (Endocr Pract. 2008;14:185-192)     

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)     

Glycemic Control After Hospital Discharge in Insulin-Treated Type 2 Diabetes: A Randomized Pilot Study of Daily Remote Glucose Monitoring

ObjectiveLittle is known about glycemic control in type 2 diabetes patients treated with insulin in the high-risk period between hospital discharge and follow-up. We sought to assess the impact of remote glucose monitoring on postdischarge glycemic control and insulin titration.MethodsWe randomly assigned 28 hospitalized type 2 diabetes patients who were discharged home on insulin therapy to routine specialty care (RSC) or RSC with daily remote glucose monitoring (RGM). We compared the primary outcome of mean blood glucose and exploratory outcomes of hypoglycemia/hyperglycemia rates, change in hemoglobin A_1c and glycated albumin, and insulin titration frequency between groups.ResultsMean blood glucose was not significantly different between the treatment arms (144 ± 34 mg/dL in the RSC group and 172 ± 41 mg/dL in the RGM group; not significant), nor were there significant differences in any of the other measures of glycemia during the month after discharge. Hypoglycemia (glucometer reading < 60 mg/dL) was common, occurring in 46% of subjects, with no difference between groups. In as-treated analysis, insulin dose adjustments (29% with an increase and 43% with decrease in insulin dose) occurred more frequently in the patients who used RGM (average of 2.8 vs. 1.2 dose adjustments; P = .03).ConclusionIn this pilot trial in insulin-treated type 2 diabetes, RGM did not affect glycemic control after hospital discharge; however, the high rate of hypoglycemia in the postdischarge transition period and the higher frequency of insulin titration in patients who used RGM suggest a safety role for such monitoring in the transition from hospital to home. (Endocr Pract. 2015;21:115-121)     

Temporal Occurrences and Recurrence Patterns of Hypoglycemia During Hospitalization

Objective: To describe the temporal distribution of hypoglycemia and its rate of recurrence during hospitalization to aid in the development of strategies to prevent hypoglycemia in hospitalized patients.Methods: Retrospective review of hypoglycemia (blood glucose <50 mg/dL) audit data in adult hospitalized patients at 2 academic hospitals. Demographics, timing, and blood glucose values were recorded. Antihyperglycemic medications, number of recurrent events, and change in basal insulin dose following the hypoglycemic event were also extracted.Results: A total of 274 index occurrences of hypoglycemia were analyzed. The mean age of the patients was 53.8 years, with roughly equal gender distributions. Twenty-eight percent of the events occurred in the absence of antihyperglycemic therapy. The incidence of hypoglycemia peaked between midnight and 6 AM. There were 36 instances of recurrent hypoglycemia associated with antihyperglycemic therapy, with 78% (n = 28) cases involving basal insulin. Patients on basal insulin who developed hypoglycemia did not have their dose changed prior to the time of the next administration in 75% of the cases.Conclusion: Hypoglycemia in hospitalized patients may occur with greater frequency overnight. Although cumbersome, routine nocturnal glycemic testing should be considered. Education regarding insulin management in the hospital and improved communication between night and day staff may aid in decreasing subsequent hypoglycemic events.Abbreviations: BG = blood glucose EHR = electronic health record ICU = intensive care unit IV = intravenous     

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)     

Glycemic Control with use of Insulin Glargine after Cardiothoracic Surgery: A Retrospective Study

ObjectivePerioperative glycemic control in critically ill cardiothoracic surgery patients may improve postsurgical outcomes. The objective of the study was to compare outcomes before and after the implementation of a protocol using subcutaneous (SC) glargine at transition from intravenous insulin infusion (IVII).MethodsIn August 2006, the Cleveland Clinic began using glargine and supplemental rapid-acting sliding scale insulin (SSI) at transition from IVII (glargine-SSI group). Before August 2006, only supplemental insulin was used (SSI-only group). The primary outcome was first blood glucose (BG1) after discontinuation of IVII. Secondary outcomes included the absolute difference between the last glucose before discontinuation of IVII (BG0) and BG1, mean glucose in the first 24 hours after discontinuation of IVII (BG24), need for SSI, and hypoglycemia.ResultsMean BG0, BG1, and BG24, and the difference between BG1 and BG0 and between BG24 and BG0 were not significantly different between groups. Diabetes mellitus (DM) patients who had received glargine had a lower mean difference between BG1 and BG0 and a lower mean BG24 than those who had not received glargine (14.6 mg/dL vs. 33.1 mg/dL; P = .20, and 163.8 mg/dL vs. 177.9 mg/dL; P = .29, respectively). A higher proportion of DM patients needed SSI than did non-DM patients (82% vs. 36%; P<.001).ConclusionGlargine administered at the cessation of IVII enabled less SSI coverage in diabetic patients subsequent to transition from IVII. However, there was no significant difference in BG control between the glargine-SSI and SSI-only groups. Prospective studies involving more patients are needed to show possible clinically significant benefits of this intervention. (Endocr Pract. 2013;19:485-493)     

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.     

Comparison of 2 Intensification Regimens with Rapid-Acting Insulin Aspart in Type 2 Diabetes Mellitus Inadequately Controlled by Once-Daily Insulin Detemir and Oral Antidiabetes Drugs: The Step-Wise Randomized Study

ObjectiveTo compare the efficacy and safety of 2 intensification strategies for stepwise addition of prandial insulin aspart in patients with type 2 diabetes mellitus treated with insulin detemir.MethodsThis randomized, controlled, parallel-group, open-label, 48-week trial compared the stepwise addition of insulin aspart to either the largest meal (titration based on premeal glucose values [SimpleSTEP]) or to the meal with the largest prandial glucose increment (titration based on postmeal glucose values [ExtraSTEP]) in patients with type 2 diabetes inadequately controlled on basal insulin and oral antidiabetes drugs. After 12 weeks of basal insulin detemir dosage optimization, participants with a hemoglobin A₁ level of 7% or greater entered three 12-week treatment periods with stepwise addition of a first insulin aspart bolus, then a second, and then a third, if hemoglobin A_1c remained at 7% or greater after 12 and 24 weeks of treatment, respectively. Endpoints included hemoglobin A_1c (primary endpoint), fasting plasma glucose, self-measured plasma glucose, adverse events, and hypoglycemia.ResultsTwo hundred ninety-six patients were randomly assigned to treatment with insulin aspart in the SimpleSTEP (n = 150) and ExtraSTEP (n = 146) groups. Hemoglobin A_1c decreased by approximately 1.2% in both groups, to 7.5 ± 1.1% (SimpleSTEP) and 7.7 ± 1.2% (ExtraSTEP) at end of trial (estimated treatment difference, SimpleSTEP ExtraSTEP: -0.06% [95% confidence interval, -0.29 to 0.17]). Self-measured plasma glucose levels decreased with both regimens. At trial end, approximately 75% of patients in each group were using 3 prandial injections. The frequency of adverse events and hypoglycemia was low and similar between groups.ConclusionThe SimpleSTEP and ExtraSTEP strategies for stepwise addition of insulin aspart to 1 or more meals were equally effective at intensifying therapy in patients with type 2 diabetes not achieving glycemic control on basal insulin and oral antidiabetic drugs. (Endocr Pract. 2011;17:727-736)     

Guideline-Concordant Insulin Infusion Initiation Among Critically Ill Patients With Sepsis

ObjectiveOur objective was to benchmark rates of guideline-concordant insulin infusion initiation, identify factors associated with guideline-concordant insulin practices, and examine the association between hospital-level guideline concordance and mortality among critically ill patients with sepsis.MethodsWe performed a multicenter retrospective cohort study of intensive care patients with sepsis who were eligible for insulin infusion initiation according to American Diabetes Association and Surviving Sepsis guidelines (persistent blood sugar ≥180 mg/dL). We then identified patients who were initiated on insulin infusions within 24 hours of eligibility. We examined patient- and hospital-level factors associated with guideline-concordant insulin infusion initiation and explored the association between the hospital-level proportion of patients who received guideline-concordant insulin infusions and hospital mortality.ResultsAmong 5453 guideline-eligible patients with sepsis, 13.4% were initiated on insulin infusions. Factors most strongly associated with guideline-concordant insulin infusion initiation were mechanical ventilation and hospital of admission. The hospital-level proportion of patients who received guideline-concordant insulin infusions were not associated with mortality. Among 1501 intensive care unit patients with sepsis who were started on insulin infusions, 37.0% were initiated at a blood glucose level below 180 mg/dL, the guideline-recommended starting threshold.ConclusionGuideline-concordant insulin infusion initiation was uncommon among patients with sepsis admitted to U.S. intensive care units and was determined in large part by hospital of admission. The degree to which hospitals were guideline-concordant were not associated with mortality.     

Minimal Reduction in Insulin Dosage with Pramlintide Therapy When Pretreatment Near-Normal Glycemia is Established and Square-Wave Meal Bolus is Used

ObjectiveTo evaluate the effect of near-normal glucose control before initiation of pramlintide therapy and square-wave meal bolus on self-reported hypoglycemia and the percentage change in dosing parameters after attaining the maximum pramlintide dosage.MethodsIn this prospective study, insulin pump–treated patients with type 1 diabetes had insulin dosages optimally titrated on the basis of daily continuous glucose monitoring (CGM). Pramlintide therapy was initiated, and the dosage was increased 15 mcg/meal per week. Insulin dosage was adjusted during 30-minute visits after review of self-monitored blood glucose records, adverse effects, and hypoglycemia diary. Within 2 weeks of achieving a pramlintide dosage of 60 mcg/meal, the second CGM–guided insulin dosage adjustment was done. The primary end point was the percentage change in total basal insulin dosage (TBD) from baseline. The secondary end points were the percentage change in the insulin to carbohydrate ratio (ICR) and the assessment of symptoms of nausea and hypoglycemia during the pramlintide dosing escalation.ResultsNine patients were enrolled. The difference between before and during CGM–guided insulin dosing was a mean (± standard deviation) TBD change of -11.2 ± 13.2% (P = 0.023) and mean ICR change of 7.8 ± 13.4% (P = 0.053). Pramlintide was well tolerated and resulted in decrease in weight and hemoglobin A_1c values. Hypoglycemia occurred in 6 patients during the study; the assistance of another person was not required in any of these cases. No hypoglycemia was reported in the first week of starting pramlintide. Mild to moderate nausea was reported in 6 patients during the titration phase.ConclusionsPatients with near-normal glucose control who use a square-wave bolus may not need initial bolus dosage reduction. With weight loss, small adjustments in both TBD and ICR may be required. Greater incidence of hypoglycemia seen in previous studies may in part be due to mismatched insulin dosing. (Endocr Pract. 2009;15:229-233)