Clinical Pearls to Improve Safety and Patient Care in the ......March 2013 1 Contents Clinical Pearls to Improve Safety and Patient Care in the Hospital Setting: Addressing Challenges

Clinical Pearls to Improve Safety and Patient Care in the Hospital Setting:

A Supplement to

®

Addressing Challenges of Insulin Therapy

A supplement based on a symposium conducted at the 47th American Society of Health-System Pharmacists’ Midyear Clinical Meeting and Exhibition

This enduring activity is supported by an educational grant from Novo Nordisk Inc.

Jointly sponsored by: and

Clinical Pearls to Improve Safety and Patient Care in the Hospital Setting:Addressing Challenges of Insulin Therapy


This enduring activity is supported by an educational grant from Novo Nordisk Inc.

Jointly sponsored by: and

Release date: March 15, 2013Expiration date: March 15, 2014

Target AudienceThis educational activity has been designed to meet the educational needs of health care-system pharmacists involved in the management of hospitalized patients with diabetes and/or hyperglycemia. Other health care professionals may also participate.

Activity OverviewThis supplement focuses on the importance of addressing hyperglycemia in the inpatient setting, whether in patients with known diabetes or those without diabetes. In reviewing the most recent recommendations from major medical societies on the management of inpatient hyperglycemia, the important topic of avoiding the risks of hypoglycemia and the safe use of insulin is discussed. Central to ensuring the safe and effective balancing act of achieving normoglycemia is the need for involvement of multiple stakeholders and a multidisciplinary team, of which the pharmacist is a key player.

Learning ObjectivesAfter completing this educational activity, the learner should be better able to:

• State recent recommendations for glycemic targets for the inpatient setting and the value of glycemic control on out-comes during hospitalization

• Explain to other members of the diabetes management team why sliding scale insulin should not be the treatment of choice for insulin administration in the hospital setting

• Select appropriate types of insulin agents to meet patients’ physiologic insulin needs• Formulate a plan to improve the safe and effective use of insulin in their hospital setting

Accreditation Statement American Academy of CME, Inc, is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education.

This educational activity provides 1.25 contact hours (0.125 CEUs) of continuing education credit. ACPE Universal Activity Number: 0297-9999-13-001-H01-P, knowledge-based activity.

Instructions for Claiming CreditAfter reviewing the CPE information and activity content, please fax back the paper-based activity posttest and evaluation form at the end of this supplement. You may also complete the posttest (score 70% or greater) and evaluation online at http://tinyurl.com/PHARMACYBN. The posttest and evaluation may also be accessed online using the QR code provided.

Your statement of credit will be issued through CPE Monitor (you must provide your National Association of Boards of Pharmacy [NABP] e-Profile ID and month and day of birth) within 6 to 8 weeks following your participation in the activity.

Note: If you have not already done so, please go to the NABP website (http://mycpemonitor.net) to set up and obtain your unique NABP e-Profile ID. This ID is now required to receive pharmacy CE credits.

Time to complete: 1.25 hours.

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Contents

Clinical Pearls to Improve Safety and Patient Care in the Hospital Setting: Addressing Challenges of Insulin Therapy


Participating Faculty ............................................ 2

Articles Inpatient Management of Hyperglycemia and Diabetes: How Well Do You Know the Guidelines? .................................................................... 4 Paul M. Szumita, PharmD, BCPS

Insulin Strategies to Reduce the Risk of Hypoglycemia and Improve the Management of Hyperglycemia ............................................................ 13 Javier Morales, MD

A Snapshot of the Various Roles of Pharmacists’ Participation in Influencing Inpatient Glycemic Control .......................................................................... 21 Curtis Triplitt, PharmD, CDE; Paul M. Szumita, PharmD, BCPS; Susan Ann Cornell, BS, PharmD, CDE, FAPhA, FAADE

CE Posttest ............................................................... 26

CE Evaluation ......................................................... 28

EDITOR-IN-CHIEFFred M. Eckel, RPh, MS

GROUP EDITORIAL DIRECTORBea Riemschneider

SENIOR EDITORDaniel Weiss

ASSOCIATE EDITOREileen Oldfield

ASSOCIATE EDITOR/ONLINERandi Hernandez

PHARMACY LAW EDITORJoseph L. Fink III, BSPharm, JD

ASSOCIATE PUBLISHER Ashley Hennessy

CREATIVE DIRECTOR: PHARMACY GROUPJennifer Lynn

DESIGNERJennifer Rittmann

SENIOR VICE PRESIDENT, CLINICAL AND SCIENTIFIC AFFAIRS

Jeff Prescott, PharmD, RPh

QUALITY ASSURANCE EDITORDavid Allikas

SALES & MARKETING COORDINATORSElaine Chu, Grace Rhee

ADVERTISING REPRESENTATIVESCarmel Burke-Bonesso

[email protected]

Anthony Costella [email protected]

Chris Hennessy [email protected]

Susan Levey [email protected]

Daniel McDonough [email protected]

DIGITAL ADVERTISINGJohn Hydrusko

[email protected]

MAIN NUMBER: 609-716-7777

OPERATIONS & FINANCE

CONTROLLERJonathan Fisher, CPA

ASSISTANT CONTROLLERLeah Babitz, CPA

ACCOUNTANTAmy Wheeler

CORPORATE

CHAIRMAN/CHIEF EXECUTIVE OFFICERMike Hennessy

CHIEF OPERATING OFFICERTighe Blazier

CHIEF FINANCIAL OFFICERNeil Glasser, CPA/CFE

EXECUTIVE VICE PRESIDENT, EXECUTIVE DIRECTOR OF EDUCATION

Judy V. Lum, MPA

VICE PRESIDENT/GROUP CREATIVE DIRECTORJeff Brown

SCIENTIFIC DIRECTORElena Beyzarov, PharmD

EXECUTIVE ASSISTANTTeresa Fallon-Yandoli

PUBLISHING STAFF

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2 www.PharmacyTimes.com March 2013

DisclosureAccording to the disclosure policy of the American Academy of CME (Academy), all faculty, planning committee mem-bers, editors, managers, and other individuals who are in a position to control content are required to disclose any relevant relationships with any commercial interests related to this activity. The existence of these interests or relationships is not viewed as implying bias or decreasing the value of the presentation. All educational materials are reviewed for fair balance, scientific objectivity, and levels of evidence.

Planning Committee Disclosures

Curtis L. Triplitt, PharmD, CDEAssistant ProfessorDepartment of MedicineDivision of DiabetesUniversity of Texas Health Science Center at San AntonioTexas Diabetes InstituteSan Antonio, Texas

Curtis L. Triplitt, PharmD, CDE, discloses that he is a member of the advisory board for scientific information of Novartis and Johnson & Johnson. He is a member of the promotional speaker’s bureaus for Amylin/Lilly, Boehringer Ingelheim, and Gilead Sciences.

Susan Ann Cornell, BS, PharmD, CDE, FAPhA, FAADEAssistant Director of Experiential EducationAssociate Professor of Pharmacy PracticeMidwestern University Chicago College of PharmacyDowners Gove, Illinois

Susan Ann Cornell, BS, PharmD, CDE, FAPhA, FAADE, states that she is a member of the advisory board for marketing of Amylin and Bristol-Myers Squibb/AstraZeneca. She is a member of the promotional speaker’s bureau for Johnson & Johnson and Abbott.

Javier Morales, MDAdvanced Internal Medicine GroupNew Hyde Park, New York

Javier Morales, MD, states that he is a member of the advisory board for marketing of Novo Nordisk, Lilly, Boehringer Ingelheim, Roche, Warner Chilcott, and Ortho Biotech. He is a member of the advisory board for scientific information of Novo Nordisk and Boehringer Ingelheim. He is a consultant for marketing for Novo Nordisk, Lilly, Boehringer Ingelheim, Warner Chilcott, Roche, Ortho Biotech, and LipoScience. He is a consultant for clinical trials for Novo Nordisk. He is also a member of the promotional speaker’s bureau for Novo Nordisk, Ortho Biotech, LipoScience, and Warner Chilcott.

Paul M. Szumita, PharmD, BCPSClinical Pharmacy Practice ManagerDepartment of PharmacyBrigham and Women’s HospitalBoston, Massachusetts

Paul M. Szumita, PharmD, BCPS, states that he has no relevant financial relationships to disclose.

Laurie Ermentrout states that she has no relevant financial relationships to disclose.

John J.D. Juchniewicz, MCIS, CCMEP, states that he has no relevant financial relationships to disclose.

Katherine Mann, PharmD, states that her spouse is an employee of Otsuka Pharmaceuticals.

Edward J. Moylan, RPh, states that he has no relevant financial relationships to disclose.


Notice About Investigational or Off-Label UseThis educational activity includes discussion of drugs or devices or uses of drugs and devices that have not been approved by the FDA or have been approved by the FDA for specific uses only. It is the responsibility of the clinician to determine the FDA clearance status of each drug or device he or she wishes to use in clinical practice. The Academy is committed to the free exchange of medical education. Inclusion of any product or device discussion, including discussion of investigational or off-label uses, does not imply endorsement by the Academy of the uses, products, or techniques presented.

DisclaimerThis CPE-certified activity is designed for use by health care professionals for educational purposes only. The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or E&S MedEd Group. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information.

To contact the Academy, e-mail: [email protected].

Levels of EvidenceLevels of evidence for patient care recommendations made in this activity:

Level A (randomized controlled trial/meta-analysis): High-quality, randomized controlled trial (RCT) that considers all important outcomes. High-quality meta-analysis (quantitative systematic review) using comprehensive search strategies. Level B (other evidence): A well-designed, nonrandomized clinical trial. A nonquantitative systematic review with appro-priate search strategies and well-substantiated conclusions. Includes lower-quality RCTs, clinical cohort studies, and case-controlled studies with nonbiased selection of study participants and consistent findings. Other evidence, such as high-quality, historical, uncontrolled studies, or well-designed epidemiologic studies with compelling findings, is also included.Level C (consensus/expert opinion): Consensus viewpoint or expert opinion.

IntroductionThe number of hospital discharges with diabetes as “any-listed” diagnosis increased from 2.8 million to near-ly 5.5 million from 1988 to 2009.1 Hospitalizations account for the largest portion of the direct cost of diabetes care, or approximately 50% of the $27 billion per year (Figure 1).1 Reducing the risk of hospitalization by improv-ing outpatient diabetes care is one way that pharmacists can improve these staggering numbers. A second way is to reduce the cost of the hospitaliza-tions that do occur, through improving outcomes and reducing lengths of stay. Hospitalization also is an opportunity to identify the one-third of patients who have diabetes in the United States but may be unaware of their disease status,2 and to make improvements in the large numbers of patients who experience poor glycemic control on their current glycemic control regimens.3

Hyperglycemia is common in hos-pitalized patients (Figure 2).4 It may be present in up to 40% of patients, and 30% of those with hyperglycemia may have no prior history of diabetes.5 Whether this represents undiagnosed diabetes or stress hyperglycemia result-ing from acute illness, it is some-thing that should be ascertained before the patient is discharged. Patients who have documented hyperglyce-mia while hospitalized should have a glycated hemoglobin (A1C) test per-formed before discharge if one has not been performed in the previous 2 to 3 months; this can identify patients with diabetes (A1C >6.5%), although it is not as sensitive as the use of fasting plasma glucose levels.6

Consequence of Inpatient HyperglycemiaHistorically, hyperglycemia in hospi-talized patients was not treated until

glucose levels became very high because it was thought to be a protec-tive mechanism. However, in the last

several decades we have learned that hyperglycemia is an independent risk factor for poor outcomes in hospital-


Inpatient Management of Hyperglycemia and Diabetes: How Well Do You Know the Guidelines?

Paul M. Szumita, PharmD, BCPS

Figure 1: Economic Costs of Diabetes in the United States, 20071

24%

50%<1%

5%

3%

3%

8%6%

Hospitalizations

Nursing home

Of�ce visits

ER visits

Outpatient clinics

Home health

ER = emergency room.

Figure 2: Percentage of Patient-Days in Which Patient-Day-Weighted Mean Point-Of-Care Bedside Glucose Values Exceeded Various Cut Points in the Intensive Care Unit (ICU) (A) and the Non-ICU (B) Settings, Demonstrating the Frequency of Hyperglycemia: Data from 575 US Hospitals4

0

10

20

30

40A32.2

>180

23.1

>200

9.8

>250

4.0

>300

1.6

>350

Pat

ient

-Day

s, %

Glucose Level, mg/dL

ICU

0.6

>400

0

10

20

30

40B32.0

>180

23.0

>200

9.9

>250

4.1

>300

1.6

>350

Pat

ient

-Day

s, %


Non-ICU

0.6

>400

Fig. 2. Percentage of patient-days in which patient-day-weighted mean point-of-care bedside glucose values exceeded various cut points in the intensive care unit (ICU) (A) and the non-ICU (B) settings, demonstrating thefrequency of hyperglycemia.

Swanson CM, et al. Endocr Pract. 2011 Nov-Dec;17(6):853–861.

Reprinted with permission from reference 4.

Hospice

Other (including meds)

Inpatient Hyperglycemia Guidelines


ized patients.7 It is associated with increased morbidity and mortality,8-14 longer length of stay, increased costs,15 and higher risk of rehospitalization.16 Table 18-13 summarizes a few examples of poor outcomes observed with hyper-glycemia in different patient groups. One of the better-defined morbidities

is the increased risk of infection in patients with hyperglycemia17; this has been well documented with deep ster-nal wound infections (an infection that is very expensive) in patients under-going coronary artery bypass graft surgery.18-21 The risks associated with hyperglycemia in the hospital appear

to be greater in patients with no known history of diabetes compared with those with established diabetes (Figure 3),22,23 perhaps because these patients are not acclimated to high levels of glu-cose. This suggests that we should pay even closer attention to patients with new hyperglycemia or new diagnoses of diabetes in the hospital, and in edu-cating such patients before discharge. Persistent hyperglycemia may be a better marker for poor outcomes than admission blood glucose levels.24

Inpatient Glycemic GoalsAlthough outpatient glucose targets have been established for decades, it was not until 2004 that a professional society first established any inpatient treatment goals for hyperglycemia.25 This was in large part prompted by a randomized controlled clinical trial conducted in Belgium that showed a dramatic reduction in morbidity and mortality with the use of intravenous (IV) insulin infusions to treat hyper-glycemia in critically ill patients.26 This study, along with other retrospective or observational data,27-29 led to the first recommendations for very strict blood glucose targets in critically ill patients (80-110 mg/dL). However, the ability to achieve these goals was limited by a relatively high frequency of hypogly-cemia.26,30-33 There is indeed a J-curve for glucose—both hyperglycemia and hypoglycemia are associated with adverse outcomes.24 It became clear that there was a risk for hypoglycemia without a protocol using glucometrics to safely achieve goals, a topic we will

Table 1: Examples of Poor Outcomes Associated with Inpatient Hyperglycemia8-13

Study Patient Population Significant Hyperglycemia- Related Outcomes

Pasquel et al, 2010 Total parenteral nutrition #�Mortality, pneumonia risk, acute renal failure

Frisch et al, 2010 Noncardiac surgery #Mortality, surgery-specific risk

Schlenk et al, 2009 Aneurysmal subarachnoid hemorrhage #Mortality impaired prognosis

Bochicchio et al, 2007 Critically injured trauma patients #LOS, mortality, ventilator time, infection

Baker et al, 2006 Chronic obstructive pulmonary disease #LOS, mortality, adverse outcomes

McAllister et al, 2005 Community-acquired pneumonia #LOS, mortality, complications

LOS = length of stay.

Figure 3: In-hospital Mortality in Patients with Normoglycimia, Known Diabetes, and Newly Discovered Hyperglycemia22

0

10

20

30

0

10

20

30

0

10

20

30

FIG. 3. In-hospital mortality n patients with normoglycimia, known diabetes, and newly discovered hyperglycemia.

*P <0.01

1.7%

Normoglycemia

3.0%

KnownDiabetes

16%*

NewHyperglycemia

Mo

rtal

ity

(%)

Total In-patient Mortality

0.8%

Normoglycemia

1.7%

KnownDiabetes

10%*

NewHyperglycemia

Mo

rtal

ity

(%)

NON ICU Mortality

10%

Normoglycemia

11%

KnownDiabetes

31%*

NewHyperglycemia

Mo

rtal

ity

(%)

ICU Mortality

Umpierrez GE, Isaacs SD, Bazargan N, You X, Thaler LM, Kitabchi AE. Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab. Mar 2002;87(3):978–982.

ICU = intensive care unit.Reprinted with permission from reference 22.



return to later in this article. The results of the Normoglycaemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation study33 and 2 meta-analyses34,35 confirmed the risk of hypoglycemia with aggressive glucose goals in critically ill patients and led to the reevaluation of inpatient hyperglycemia goals. These were read-justed by the American Association of Clinical Endocrinologists (AACE) and the American Diabetes Association (ADA) in 2009 (Figure 4).7 Figure 4 also provides the treatment goals and treatment considerations for non-critically ill patients as put forth by the AACE/ADA, and those by the Endocrine Society in 2012.6,7

Insulin in Critically Ill PatientsThe AACE/ADA treatment recommen-dations provide guidance on the role of IV insulin in critically ill patients,7 as do recommendations from the Society for Hospital Medicine.36 Insulin, spe-cifically an IV insulin infusion, is the preferred method of treating hypergly-cemia in critically ill patients because it is potent, rapidly acting, easily titrated, not limited by contraindications, and without dose limits to its efficacy. It is, however, an agent with a narrow thera-

peutic index and a “high alert” medica-tion, meaning that it has a very high risk of causing injury when misused and it requires strategies to ensure that the correct drug is given in the proper dosage to the appropriate patient at the correct time, and through the proper route of administration.37 It is recom-mended that institutions use a single insulin concentration in these infusions to avoid any confusion about dose or potential errors related to having more than 1 concentration.38,39 IV insulin infusion concentrations should be stan-dardized throughout the hospital with the use of regular insulin in concentra-tions of 1 unit/mL or 0.5 unit/mL.40

There are more than 25 published insulin infusion protocols, the major-ity of which use manual blood glucose calculations and a handful of which use computerized algorithms. When evaluating protocols, features to con-sider are patient characteristics, target glucose levels, time to achieve target glucose levels, incidence of hypogly-cemia, rationale for adjusting the rates of insulin infusion, and methods of blood-glucose measurements.41 IV insu-lin is ideally administered by means of a validated protocol that allows for predefined adjustments in the insulin

infusion rate based on insulin dose and glycemic fluctuations42 as measured by glucometrics. Glucometrics is the sys-temic analysis of blood glucose data.43 Computer-directed algorithms44,45 that are flexible in blood glucose timing and advise insulin dosing in a gradu-ated manner can be simple, safe, and effective methods for maintaining gly-cemic control. These algorithms utilize a multiplication factor that takes into account the rate of insulin and rate of change in blood glucose over time. What can be problematic are “fixed” protocols that do not take into account the rate of change of blood glucose levels. For example, a patient whose blood glucose level has dropped by 70 mg/dL in an hour but is still in a “safe” range (eg, dropped from 190 mg/dL to 120 mg/dL) might stay at the same rate of insulin by a fixed protocol, but if that rate of change were to continue, in the next hour, their blood glucose level could drop to 50 mg/dL, clearly putting them in danger. In critically ill patients, accurate bedside blood glucose monitor-ing should be done frequently—rang-ing from every 30 minutes to every 2 hours.42 Automation and standardization of the glucose measurement process have the potential to greatly improve glycemic control, clinical outcomes, and safety while reducing cost.46 The resources required to monitor glycemia in hospitalized patients have thus far limited the implementation of intensive glucose management in critically ill patients. One can foresee a role for con-tinuous glucose monitoring in the hospi-tal setting much as we have continuous blood pressure monitoring now.47

Potassium should be monitored and given if necessary (consider delay-ing insulin infusion until potassium is >3.0-3.5 mEq/L). Insulin is known to drive potassium intracellularly and may exacerbate hypokalemia and lead to arrhythmias.48

When a patient is stable and trans-ferred out of a critical care unit, IV insulin is generally discontinued and the use of scheduled subcutaneous insulin is implemented.

How does one convert a patient

Figure 4: Treatment Considerations for Management of Inpatient Hyperglycemia

Non-insulin antihyperglycemic agents have a limited role in acute care settings and practitioners should consider discontinuing them in favor of insulin during acute illness.

Scheduled subcutaneous insulin injections (basal,

prandial, correction) adjusted to maintain

premeal BG <140 mg/dL and random BG <180 mg/dL

IV insulin infusion adjusted to maintain BG 140-180 mg/dL

Critically ill patientsNoncritically ill

patients

Hospitalized patients with hyperglycemia

(BG >180 mg/dL)

BG = blood glucose; IV = intraveneous.



from an IV insulin infusion to sched-uled subcutaneous insulin? The total daily dose of subcutaneous insulin is extrapolated from the average IV insu-lin rate per hour over a period of time when the patient has been stable. This is multiplied by 24 to obtain 24-hour insulin requirements. Insulin may also adsorb to plastic tubing,49 which may decrease the concentration of an insulin solution delivered from an IV infusion set. Additionally, the patient may be eating all of their meals immediately or receiving all their caloric intake pro-vided by enteral or parenteral methods. Thus, the 24-hour total daily dose is often then multiplied by a fraction (0.6 to 0.8) for a starting total daily subcu-taneous dose. This is then divided into basal and prandial components. Basal or background insulin comprises about 50% of insulin needs; the other 50% is split over 3 meals.

Because of the rapid onset of action

(and offset of action) of IV insulin, it is necessary to start subcutaneous insulin before IV insulin is discontin-ued. Generally speaking, basal insulin should be administered 2 hours before discontinuing IV insulin.50

Insulin in Non-Critically Ill PatientsIn non-critically ill patients, regularly scheduled subcutaneous insulin is the preferred method of managing hyper-glycemia. This consists of basal insulin to cover background insulin needs, prandial insulin to cover mealtime or nutritional needs (Figure 5),51 and the occasional use of supplemental or cor-rectional insulin (in the form of rapid-acting insulin) in addition to the basal and prandial insulin (insulin terminolo-gy is shown in Table 2). This is different from sliding scale insulin, which is the use of short- or rapid-acting insulin in the absence of basal insulin. Of course,

the need for prandial or nutritional insulin will depend on the patient’s status (Table 3).50 Subcutaneous insu-lin can be augmented with premeal supplemental-dose insulin to correct premeal hyperglycemia.50

Sliding scale insulin is not recom-mended by the major medical socie-ties.7 Sliding scale insulin usually con-sists of regular insulin given alone. This technique has been shown to be ineffective for several reasons. It is a reactive approach that can lead to rapid swings in blood glucose, resulting in hyperglycemia and hypoglycemia. It can increase the risk for “stacking” of insulin, which can precipitate hypogly-cemia. It is often an admission regimen that is likely to be used throughout hos-pitalization without appropriate modi-fication for changes in the patient’s health status. Clinical trials have shown that it is less effective than scheduled basal bolus insulin (Figure 6).51

How does one establish a scheduled subcutaneous insulin regimen if the patient was not receiving IV insulin? This is usually a weight-based calcu-lation, again starting with calculating a total daily dose, then dividing it into basal and prandial components. One can start higher or lower. A conservative start is between 0.5 and 0.6 units of insulin per kg of body weight per day

Case Study: Transition from IV Infusion to Scheduled Subcutaneous Insulin Injections

GH is a 68-year-old man who has had type 2 diabetes for 10 years. He was admitted to the cardiac intensive care unit for stent placement. In the past few hours, his IV insulin infusion requirements were 3 units/hour. He is now moving to a general medical floor. He is awake, alert, and eating. His 24-hour insulin requirements are determined by multiplying his calculated total daily dose of IV insulin (3 units × 24 hours = 72 units) by 0.6 (60%), which equates to roughly 40 units; half of this will meet his basal or background insulin requirements and half will meet his mealtime or prandial insulin needs. This is a conservative estimate of his insulin needs and may need to be titrated. Thus, he should receive 20 units of a long-acting basal insulin analogue at bedtime and 7 units of a rapid-acting insulin analogue 3 times a day, with the first bite of each meal. In addition, he should have correctional insulin ordered to cover unanticipated premeal hyperglycemia.

Table 2: Insulin Terminology

• Basal insulin -Controls fasting and premeal glucose - Neutral protamine Hagedorn or long-

acting basal insulin analogues

• Nutritional insulin - Controls glucose from nutritional

sources such as discrete meals, tube feeds, or total parenteral nutrition

- Short-acting (regular) insulin or rapid-acting insulin analogues

• Supplemental/correctional insulin - Used to cover unexpected hyperglyce-

mia that was not controlled by sched-uled basal and nutritional insulin

- Short-acting (regular) insulin or rapid-acting insulin analogues

• Sliding scale insulin - Usually consists of regular insulin

given in the absence of regularly scheduled insulin or any basal insulin

Figure 5: Basal, Bolus, and Correctional Insulin to Meet Physiological Insulin Needs51

Correction orSupplementalinsulin

Nutritional orMealtimeinsulin (bolus)

Normal SecretoryPattern of Insulin

Basal insulin

Breakfast Lunch Dinner Bedtime

Insu

lin



(units/kg/day) for patients with type 2 diabetes.52 If there are concerns about hypoglycemia, then a lower total daily dose may be used to start, for exam-ple, 0.3 to 0.4 units/kg/day.52 Factors such as increased age or impaired renal function may be considered risk factors for hypoglycemia.53 Best practice sug-gests to administer basal insulin once

(glargine/detemir) or twice (neutral prot-amine Hagedorn) daily, at the same time each day. Rapid-acting (prandial) insulin should be given in 3 equally divided doses before each meal. Prandial insulin should not be given if a patient is not able to eat or misses a meal due to a pro-cedure. Insulin doses should be adjusted according to the results of bedside blood

glucose measurements. Correctional insulin or supplemental

insulin should be included as a com-ponent of a scheduled insulin regimen for treatment of blood glucose values above the desired target; if high glu-cose levels persist, then doses should be adjusted the following day. The total daily dose should be adjusted up or down based on past response to insulin, presence of hyperglycemia-inducing agents (eg, corticosteroids), stress, and other factors. There are many types of insulin products avail-able. Table 4 summarizes the phar-macokinetic features of these agents.54 Long-acting basal insulin analogues provide background insulin needs that closely mimic the body’s slow steady release of insulin, more so than inter-mediate-acting insulin. Rapid-acting insulin analogues (aspart, glulisine, lis-pro) mimic the release of insulin after carbohydrate injection much more than rapid-acting insulin and do not require administration 30 minutes prior to food intake to “line up” with glucose excur-sions.55 As such, they are associated with less hypoglycemia, and thus may be preferred in the inpatient setting,

Table 3: Therapeutic Options for Glycemic Control in the Medical or Stabilized Surgical Patient50

Patient Status Basal Insulin Needs Nutritional or Prandial Insulin Needs

Supplemental-Dose Insulin Needs

Eating meals Intermediate-acting insulin twice daily or at bedtime

Long-acting insulin analogue once daily

Insulin infusion

Regular insulin 30-45 minutes before meals

Rapid-acting insulin analogue 0-15 minutes before meals

Regular or rapid-acting insulin before meals and/or at bedtime as needed

Not eating meals Intermediate-acting insulin twice daily or at bedtime

Long-acting insulin analogue once daily

Insulin infusion

Not applicable Regular insulin every 4-6 hours

Rapid-acting insulin analogue every 4 hours

Enteral tube feeding Intermediate-acting insulin twice daily

Long-acting insulin analogue at bedtime or in morning

Daytime only: Intermediate-acting insulin in morning

Regular insulin every 4-6 hours


Regular insulin every 4-6 hours


Figure 6: More Hyperglycemia with Sliding-Scale Insulin than with Basal Bolus Insulin51

*P<.01; †P<.05; ‡Long-acting insulin (glargine) once daily + short-acting insulin (glulisine) before meals, total dose 0.4 unit/kg (BG 140-200 mg/dL) or 0.5 unit/kg (BG 201-400 mg/dL)

RABBIT 2=Randomized Study of Basal-Bolus Insulin Therapy in the Inpatient Management of Patients with Type 2 Diabetes

Umpierrez GE et al. Diabetes Care. 2007;30:2181–2186.

100

120

140

160

180

200

220

240

** *

††

†

†

Basal-bolus‡

Sliding-scale

N=130 insulin-naïve hospitalizednonsurgical patients with T2DM n=9 with BG >240 mg/dL

Blo

od

glu

cose

(mg

/dL)

Admit 1 2 3 4 5 6 7 8 9 10100

140

180

220

260

300

Admit 1 2 3 4 1 2 3 4 5 6 7

Switched fromsliding-scale tobasal-bolus insulin

Days of therapy

RABBIT 2: Glycemic Control With Basal-Bolus vs Sliding-Scale Insulin

aP<.01; bP<.05; clong-acting insulin (glargine) once daily + short-acting insulin (glulisine) before meals, total dose 0.4 unit/kg (BG 14-200 mg/dL) or 0.5 unit/kg (BG 201-400 mg/dL).BG = blood glucose; RABBIT 2 = Randomized Study of Basal-Bolus Insulin Therapy in the Inpatient Management of Patients with Type 2 Diabetes; T2DM = type 2 diabetes mellitus.Reprinted with permission from reference 51.

aa a

b b

bb

c



particularly when it may be difficult to know if the patient will be eating or not.56 For more information on insulin in the inpatient setting, see the article by Morales in this supplement.

Oral Agents and Non-Insulin Antihyperglycemic AgentsThere is no extensive published expe-rience with non-insulin agents in the hospital.6,7 Each of the major classes of oral agents has features that limit its use in the hospital setting. Sulfonylureas may lead to hypoglycemia if nutrition is interrupted, and some of them are contraindicated in patients with renal impairment. Metformin is contraindicated in the setting of decreased renal blood flow, surgery, and with use of iodinated contrast dyes. Thiazolidinediones are

not rapidly effective; they also are asso-ciated with edema and heart failure. The incretin-based therapies (glucagon-like peptide-1 [GLP-1] receptor agonists, dipeptidyl peptidase-4 inhibitors) have a greater effect on postprandial glu-cose and would be effective primarily in patients who are able to eat. GLP-1 receptor agonists are associated with nausea.57

HypoglycemiaHypoglycemia is a legitimate safe-ty concern with insulin therapy. It is important to have a clear definition of hypoglycemia. In the hospital set-ting, this definition should be used as a signal to adjust or discontinue insulin therapy.7 Therefore, the threshold for altering therapy should not be set too

low. The ADA defines hypoglycemia as a blood glucose level less than 70 mg/dL58; both the AACE and ADA agree that insulin therapy should be adjusted if this occurs and that insulin regimens be reevaluated at levels of 100 mg/dL.7 There should be hypo-glycemia protocols in place that allow nurses to treat without delay (ie, with-out waiting for doctor orders). Insulin infusions should be discontinued (or reduced, if the patient is a type 1 diabetic), and glucose administered. The route, dose, and form of glu-cose administration will depend on the patient’s level of cognition (Figure 7).59 Repetition of blood glucose monitor-ing and of glucose administration is required until the patient is stabilized. Assessing causality and adjusting treat-ment is then necessary. Look for the cause of hypoglycemia and determine if other treatment changes are needed.

ConclusionAchieving glycemic control in the hospital setting remains challenging. Pharmacists are integral members of the multidisciplinary team required to implement cultural change to achieve systemwide improvements.54 Pharmacists seeking to implement the findings of published evidence into their practice face many potential bar-riers.60 For more on the role of pharma-cists, see the article by Triplitt et al in this supplement. There are no standard-ized “how to” guidelines, there are no

Table 4. Pharmacokinetics of Insulin Types54

Insulin type Onset Time to Peak Duration

Rapid acting

Aspart 5-15 min 30-90 min 4-6 hr

Glulisine 20 min 100 min 4-6 hr

Lispro 5-15 min 30-90 min 4-6 hr

Short acting

Regular 30-60 min 2-3 hr 8-10 hr

Intermediate acting

Neutral protamine Hagedorn 2-4 hr 4-10 hr 12-18 hr

Long acting

Detemir 2-4 hr Relatively flat Up to 24 hr

Glargine 2-4 hr No pronounced peak Up to 24 hr

Figure 7: Suggested Strategies for Treating Hypoglycemia59

Recheck BG in 15-20 min. If BG <70 mg/dL, then continuously repeat above until BG ≥70 mg/dL and notify provider. Once BG >70 mg/dL, repeat BG monitoring in 1 hour and check again in 2 hours. Notify provider of insulin adjustments and changes in BG monitoring. If BG level has not remained ≥70 mg/dL for both BG checks, notify provider for further insulin adjustments and changes in BG level monitoring.

If patient CAN safely swallow without aspirating

If patient CANNOT safely swallow or patient has NPO

status

If BG 50-69 mg/dL: Give 4 oz.juice or regular soda

IV access: Give 1 dose D50W IV push

If BG ≤49 mg/dL: Give 8 oz.juice or regular soda

If no IV access: Give 1 dose glucagon IM

BG = blood glucose; IM = intramuscular; IV= intravenous; NPO = nil per os (ie, nothing by mouth).



perfect protocols, and change can be slow and tedious. Glycemic control in the hospital may be improved by assess-ing current treatment approaches, mak-ing incremental changes, and looking for obvious ways to improve the safe and effective delivery of insulin therapy. Although the data continue to evolve, it is generally accepted that extremes of inpatient hyperglycemia and hypogly-cemia should be avoided. Recent data show that across the nation, hospitals are tracking their efforts and that the prevalence of severe hypoglycemia is low (Figure 8).4 Pharmacists should be aware of current treatment guidelines and insulin regimens that are physiolog-ically based with a focus on preventing hyperglycemia and hypoglycemia.

Address correspondence to: Paul M. Szumita, PharmD, BCPS, Brigham and Women’s Hospital, 75 Francis St, PBB-A4, Boston, MA 02115-6110. Phone: (617) 678-4761. E-mail: [email protected].

References1. Economic costs of diabetes in the U.S. in

2007. Diabetes Care. 2008;31(3):596-615.2. National diabetes fact sheet: national esti-

mates and general information on diabe-tes and prediabetes in the United States, 2011. Atlanta: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2011.

3. Hoerger TJ, Segel JE, Gregg EW, Saaddine JB. Is glycemic control improving in U.S. adults? Diabetes Care. 2008;31(1):81-86.

4. Swanson CM, Potter DJ, Kongable GL, Cook CB. Update on inpatient glycemic control in hospitals in the United States. Endocr Pract. 2011;17(6):853-861.

5. Umpierrez GE, Isaacs SD, Bazargan N, You X, Thaler LM, Kitabchi AE. Hyperglycemia: an independent marker of in-hospital mortal-ity in patients with undiagnosed diabetes. J Clin Endocrinol Metab. 2002;87(3):978-982.

6. Umpierrez GE, Hellman R, Korytkowski MT, et al. Management of hyperglycemia in hospitalized patients in non-critical care setting: an Endocrine Society clinical prac-tice guideline. J Clin Endocrinol Metab.

2012;97(1):16-38.7. Moghissi ES, Korytkowski MT, DiNardo

M, et al. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpa-tient glycemic control. Endocr Pract. 2009;15(4):353-369.

8. Pasquel FJ, Spiegelman R, McCauley M, et al. Hyperglycemia during total parenteral nutrition: an important marker of poor out-come and mortality in hospitalized patients. Diabetes Care. 2010;33(4):739-741.

9. Frisch A, Chandra P, Smiley D, et al. Prevalence and clinical outcome of hypergly-cemia in the perioperative period in noncardi-ac surgery. Diabetes Care. 2010;33(8):1783-1788.

10. Schlenk F, Vajkoczy P, Sarrafzadeh A. Inpatient hyperglycemia following aneurys-mal subarachnoid hemorrhage: relation to cerebral metabolism and outcome. Neurocrit Care. 2009;11(1):56-63.

11. Bochicchio GV, Joshi M, Bochicchio KM, et al. Early hyperglycemic control is impor-tant in critically injured trauma patients. J Trauma. 2007;63(6):1353-1358; discussion 1358-1359.

12. Baker EH, Janaway CH, Philips BJ, et al. Hyperglycaemia is associated with poor out-comes in patients admitted to hospital with acute exacerbations of chronic obstructive pulmonary disease. Thorax. 2006;61(4):284-289.

13. McAlister FA, Majumdar SR, Blitz S, Rowe BH, Romney J, Marrie TJ. The relation between hyperglycemia and outcomes in 2,471 patients admitted to the hospital with community-acquired pneumonia. Diabetes Care. 2005;28(4):810-815.

14. Olveira G, Tapia MJ, Ocon J, et al. Parenteral Nutrition-Associated Hyperglycemia in Noncritically Ill Inpatients Increases the Risk of In-hospital Mortality (Multicenter Study): Study Group of Hyperglycemia in Parenteral Nutrition: Nutrition Area of the Spanish Society of Endocrinology and Nutrition (SEEN) [published online December 6, 2012]. Diabetes Care.

15. Estrada CA, Young JA, Nifong LW, Chitwood WR, Jr. Outcomes and periopera-tive hyperglycemia in patients with or with-out diabetes mellitus undergoing coronary artery bypass grafting. Ann Thorac Surg.

Figure 8: Percentage of Patient-Days in Which a Hypoglycemic Event (<70 mg/dL) Occurred in the Intensive Care Unit (ICU) (A) and the Non-ICU (B) Settings: Data from 575 US Hospitals4

Fig. 8. Percentage of patient-days in which a hypoglycemic event (<70 mg/dL) occurred in the intensive care unit (ICU) (A) and the non-ICU (B) settings.

Swanson CM, et al. Endocr Pract. 2011 Nov-Dec;17(6):853–861.

0

2

4

6

8

0

2

4

6

8

A

6.3

<70

3.7

<60

2.1

<50

1.1

<40

Pat

ient

-Day

s, %


ICU

B

5.7

3.3

1.70.8

Pat

ient

-Day

s, %

Non-ICU

<70 <60 <50 <40


Reproduced with permission from reference 4.



2003;75(5):1392-1399.16. Leite SA, Locatelli SB, Niece SP, Oliveira

AR, Tockus D, Tosin T. Impact of hyper-glycemia on morbidity and mortality, length of hospitalization and rates of re-hospitaliza-tion in a general hospital setting in Brazil. Diabetol Metab Syndr. 2010;2:49.

17. Murad MH, Coburn JA, Coto-Yglesias F, et al. Glycemic control in non-critically ill hospitalized patients: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2012;97(1):49-58.

18. Furnary AP, Zerr KJ, Grunkemeier GL, Starr A. Continuous intravenous insulin infu-sion reduces the incidence of deep sternal wound infection in diabetic patients after car-diac surgical procedures. Ann Thorac Surg. 1999;67(2):352-360; discussion 360-352.

19. Furnary AP, Wu Y. Eliminating the dia-betic disadvantage: the Portland Diabetic Project. Semin Thorac Cardiovasc Surg. 2006;18(4):302-308.

20. Furnary AP, Wu Y. Clinical effects of hyper-glycemia in the cardiac surgery population: the Portland Diabetic Project. Endocr Pract. 2006;12(suppl 3):22-26.

21. Furnary AP, Wu Y, Bookin SO. Effect of hyperglycemia and continuous intravenous insulin infusions on outcomes of cardiac surgical procedures: the Portland Diabetic Project. Endocr Pract. 2004;10(suppl 2):21-33.


23. Falciglia M, Freyberg RW, Almenoff PL, D’Alessio DA, Render ML. Hyperglycemia-related mortality in critically ill patients var-ies with admission diagnosis. Crit Care Med. 2009;37(12):3001-3009.

24. Kosiborod M, Inzucchi SE, Krumholz HM, et al. Glucometrics in patients hospitalized with acute myocardial infarction: defining the optimal outcomes-based measure of risk. Circulation. 2008;117(8):1018-1027.

25. Garber AJ, Moghissi ES, Bransome ED, Jr, et al. American College of Endocrinology position statement on inpatient diabetes and metabolic control. Endocr Pract. 2004;10 (suppl 2):4-9.

26. van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill

patients. N Engl J Med. 2001;345(19):1359-1367.

27. Malmberg K, Ryden L, Efendic S, et al. Randomized trial of insulin-glucose infu-sion followed by subcutaneous insulin treat-ment in diabetic patients with acute myo-cardial infarction (DIGAMI study): effects on mortality at 1 year. J Am Coll Cardiol. 1995;26(1):57-65.

28. Furnary AP, Zerr KJ, Grunkemeier GL, Starr A. Continuous intravenous insulin infu-sion reduces the incidence of deep sternal wound infection in diabetic patients after car-diac surgical procedures. Ann Thorac Surg. 1999;67(2):352-360; discussion 360-352.

29. Krinsley JS. Effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clin Proc. 2004;79(8):992-1000.

30. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006;354(5):449-461.

31. Brunkhorst FM, Engel C, Bloos F, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med. 2008;358(2):125-139.

32. Preiser JC, Devos P, Ruiz-Santana S, et al. A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study. Intensive Care Med. 2009;35(10):1738-1748.

33. Finfer S, Chittock DR, Su SY, et al. Intensive versus conventional glucose con-trol in critically ill patients. N Engl J Med. 2009;360(13):1283-1297.

34. Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in crit-ically ill adults: a meta-analysis. JAMA. 2008;300(8):933-944.

35. Griesdale DE, de Souza RJ, van Dam RM, et al. Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data. CMAJ. 2009;180(8):821-827.

36. Ahmann AJ, Maynard G. Designing and imple-menting insulin infusion protocols and order sets. J Hosp Med. 2008;3(5 suppl):42-54.

37. Joint Commission IDs five high-alert meds. ED Manag. 2000;12(2):21-22.

38. Hellman R. A systems approach to reduc-ing errors in insulin therapy in the inpatient setting. Endocr Pract. 2004;10(suppl 2):100-108.

39. Hellman R. Patient safety and inpatient glycemic control: translating concepts into action. Endocr Pract. 2006;12(suppl 3):49-55.

40. Cohen MR. Pharmacists’ role in ensuring safe and effective hospital use of insulin. Am J Health Syst Pharm. 2010;67(16, suppl 8):S17-S21.

41. Krikorian A, Ismail-Beigi F, Moghissi ES. Comparisons of different insulin infusion protocols: a review of recent literature. Curr Opin Clin Nutr Metab Care. 2010;13(2):198-204.

42. Moghissi ES, Korytkowski MT, DiNardo M, et al. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpa-tient glycemic control. Endocr Pract. 2009;15(4):353-369.

43. Goldberg PA, Bozzo JE, Thomas PG, et al. “Glucometrics”--assessing the quality of inpatient glucose management. Diabetes Technol Ther. 2006;8(5):560-569.

44. Davidson PC, Steed RD, Bode BW. Glucommander: a computer-directed intrave-nous insulin system shown to be safe, simple, and effective in 120,618 h of operation. Diabetes Care. 2005;28(10):2418-2423.

45. Van Herpe T, Mesotten D, Wouters PJ, et al. LOGIC-Insulin Algorithm-Guided Versus Nurse-Directed Blood Glucose Control During Critical Illness: The LOGIC-1 sin-gle-center randomized, controlled clinical trial [published online September 6, 2012]. Diabetes Care. 2013;36(2):188-194.

46. Ryan EA, Germsheid J. Use of continu-ous glucose monitoring system in the man-agement of severe hypoglycemia. Diabetes Technol Ther. 2009;11(10):635-639.

47. 4oseph JI, Hipszer B, Mraovic B, Chervoneva I, Joseph M, Grunwald Z. Clinical need for continuous glucose monitoring in the hospital. J Diabetes Sci Technol. 2009;3(6):1309-1318.

48. McNaughton CD. Diabetes in the emergency department: acute care of diabetes patients. Clinical Diabetes. 2011;29(2):51-59.

49. Greenwood B. Stability of regular human insulin extemporaneously prepared in 0.9% sodium chloride in a polyvinyl chloride bag. Hosp Pharm. 2012;47(5):367-370.

50. Clement S, Braithwaite SS, Magee MF, et al. Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004;27(2):553-591.



51. Umpierrez GE, Smiley D, Zisman A, et al. Randomized study of basal-bolus insu-lin therapy in the inpatient management of patients with type 2 diabetes (RABBIT 2 trial). Diabetes Care. 2007;30(9):2181-2186.

52. Wesorick D, O’Malley C, Rushakoff R, Larsen K, Magee M. Management of dia-betes and hyperglycemia in the hospital: a practical guide to subcutaneous insulin use in the non-critically ill, adult patient. J Hosp Med. 2008;3(5 suppl):17-28.

53. Farrokhi F, Klindukhova O, Chandra P, et al. Risk factors for inpatient hypoglycemia during subcutaneous insulin therapy in non-

critically ill patients with type 2 diabetes. J Diabetes Sci Technol. 2012;6(5):1022-1029.

54. Kelly JL. Ensuring optimal insulin utilization in the hospital setting: role of the pharmacist. Am J Health Syst Pharm. 2010;67(16 suppl 8):S9-S16.

55. Hirsch IB, Bode BW, Garg S, et al. Continuous subcutaneous insulin infusion (CSII) of insu-lin aspart versus multiple daily injection of insulin aspart/insulin glargine in type 1 dia-betic patients previously treated with CSII. Diabetes Care. 2005;28(3):533-538.

56. Pollom RD. Optimizing inpatient glycemic control with basal-bolus insulin therapy.

Hosp Pract (Minneap). 2010;38(4):98-107.57. Hassan E. Hyperglycemia management in

the hospital setting. Am J Health Syst Pharm. 2007;64(10, suppl 6):S9-S14.

58. Standards of medical care in diabetes--2012. Diabetes Care. 2012;35(suppl 1):S11-S63.

59. Roe ED, Raskin P. Managing inpatient hyperglycemia in a resource-constrained county hospital: the Parkland Memorial Hospital experience. Hosp Pract (Minneap). 2012;40(3):116-125.

60. Anger KE, Szumita PM. Barriers to glu-cose control in the intensive care unit. Pharmacotherapy. 2006;26(2):214-228.

IntroductionInsulin is the cornerstone for the man-agement of inpatient hyperglycemia control for many reasons.1-5 Unlike insulin, there is little published evi-dence supporting the use of non-insulin therapies in the hospital setting. Oral therapies are not easily titrated to the changing needs of the acutely ill hospi-talized patient and many patients may have contraindications to non-insulin agents as a result of their conditions (eg, renal impairment, congestive heart failure) or medications, or they may temporarily lack the ability to take oral medications. Furthermore, insulin has distinct advantages for managing hyperglycemia in the hospital setting: it corrects hyperglycemia rapidly and effectively, its efficacy is not dose-limited, it is easily titrated, and in its modern formulations, it has no contra-indications to its use.6

Insulin does, however, have some disadvantages, including a low thera-peutic index and hypoglycemia as a dose-limiting toxicity. Additionally, it is a “high-alert” medication, mean-ing that inappropriate or unsafe use

is highly likely to cause the patient severe harm. Therefore, strategies that maximize its safe and effective use are essential to ensuring appropriate patient outcomes.7

Hyperglycemia and Hypoglycemia Definitions and ImplicationsTable 1 provides the reader with the American Association of Clinical En- docrinologists and American Diabetes Association’s recommendations for glucose levels that warrant atten-tion and action, along with physi-ologic implications of hyperglyce-mia.3 Hypoglycemia is associated with increased morbidity, mortality, and length of stay in multiple popula-tions of hospitalized patients (critically ill and noncritically ill patients).8-16 Importantly, hyperglycemia in the hos-pital setting is associated with poor outcomes in both patients with known diabetes and those without diabetes. In fact, the prognosis is worse in patients with no known diabetes,8,17 so hyper-glycemia in the hospital setting should not be ignored.

Interventional studies have shown that improving hyperglycemia improves patient outcomes,18-20 but this has to be balanced by avoiding hypoglycemia, which is also associ-ated with increased mortality in the hospital setting and after discharge (Figure 1).21 Hypoglycemia is also associated with increased length of stay and increased hospital costs (Table 222 and Table 323). Efforts to implement intensive glycemic control in critically ill patients have been asso-ciated with an increased risk of hypo-glycemia and death24,25 and have caused the reevaluation of glycemic targets in the hospital.26 The Normoglycemia in Intensive Care Evaluation–Survival Using Glucose Algorithm Regulation study was a multicenter trial involving 6104 patients wherein the intensive-control group achieved a mean blood glucose level of 115 mg/dL compared with the conventional treatment group, who achieved a mean blood glucose level of 144 mg/dL. The intensively treated group had an increase of 2.6 percentage points in the absolute risk of death at 90 days. Not surprisingly,


Javier Morales, MD

Insulin Strategies to Reduce the Risk of Hypoglycemia and Improve the

Management of Hyperglycemia

Table 1: AACE/ADA Target Inpatient Hyperglycemia and Hypoglycemia Definitions and Implications3,4

BG Value Definition Implications

Hyperglycemiaa

>140 mg/dL Hyperglycemia Pre-meal levels persistently above this level may necessitate treatment

>180 mg/dL Hyperglycemia No random blood glucose levels should be, in general, above this goal

Hypoglycemiab

<70 mg/dL Hypoglycemia Standard definition in outpatients, correlates with the initial threshold for release of counter-regulatory hormones

<40 mg/dL Severe hypoglycemia Increased mortality, cognitive impairment begins at 50 mg/dL in normal individuals

aSome patients may be maintained at a glucose range below and/or above these cut-off points.bReassess insulin regimen if BG levels fall below 100 mg/dL.AACE = American Association of Clinical Endocrinologists; ADA = American Diabetes Association; BG = blood glucose.

Safety of Insulin in Inpatient Glycemic Management

severe hypoglycemia occurred more frequently in the group of patients ran-domly assigned to intensive therapy.24 Attempts to understand the reasons for this led to a detailed assessment of data by the investigators on hypoglycemia and the risk of death from their previ-ously published study. More frequent hypoglycemia and severe hypoglyce-mia in the absence of insulin therapy were associated with a higher risk of death,27 raising the question if hypo-

glycemia is a marker for more severe underlying disease or an inappropriate counter-regulatory mechanism.28

A Brief Look at the Pathophysiology Associated with Hyperglycemia and HypoglycemiaBefore discussing approaches to improving the safety and effectiveness of inpatient insulin therapy, it is help-ful to review some of the mechanisms

that we currently understand about the pathophysiology of hyperglycemia and hypoglycemia in hospitalized patients.

The presumed links between high blood glucose levels and poor outcomes have centered on the immune sys-tem, vascular responses, mediators of inflammation, and brain cell responses, although they are by no means fully understood. Hyperglycemia causes immune suppression, although the overall magnitude and mechanism by which it does so are somewhat unclear. Acute hyperglycemia has a number of effects on the cardiovascular system. It impairs protective mechanisms against ischemic insult and may induce cardiac myocyte death by ischemia-reperfusion cellular injury or through an increased rate of apoptosis. Other effects include blood pressure changes, catecholamine abnormalities, and electrophysiolog-

Figure 1: Inpatient Hypoglycemia Was Strongly Correlated with Inpatient and Post-Discharge Death and Increased LOS in Non-ICU Settings. 4368 Admissions of 2582 Patients with Diabetes; Hypoglycemia: BG ≤50mg/dL21

0

4

12

16

8

FIG 1. P

erce

nt D

ecea

sed

D

urin

g A

dm

issi

on

(%)

Inpatient Mortality

Diabetes care by AMERICAN DIABETES ASSOCIATION Copyright 2009 Reproduced with permission of AMERICAN DIABETES ASSOCIATION in the format Republish in a journal via Copyright Clearance Center.

<30 30-39 >39Lowest BG During Admission (mg/dL)

0

4

12

16

8

Cha

nge

Fro

m E

xpec

ted

LOS

(day

s)

Inpatient LOS

Days With Hypoglycemia During Admission

0

40

60

20

Per

cent

Dec

ease

d a

t 1

Year

(%)

Postdischarge Mortality

0 1 2 >2Days With Hypoglycemia During Admission

0 1 2 >2

BG = blood glucose; ICU = intensive care unit; LOS = length of stay.Reprinted with permission from reference 21.

Table 2: Retrospective Analysis of the Length of Stay and Inpatient Mortality in Patients with Diabetes Who Had an Episode of Hypoglycemia in a Noncritical Care Setting (N = 6374 admissions)22

Lowest Recorded Blood Glucose Level

Number of Admissions

Length of Stay (Relative Risk)

Inpatient Mortality (Relative Risk)

>70 mg/dL 5726 1 (reference value) 1 (reference value)

>40-70 mg/dL 500 1.51 1.62

≤40 mg/dL 148 2.33 2.05




ic changes. Hyperglycemia may also result in effects that favor thrombosis through increased levels of plasmino-gen activator inhibitor-1 and endothe-lial dysfunction. Moderate elevations of glucose may result in the release of inflammatory cytokines such as inter-leukins and tumor-necrosis factors, among others. Acute hyperglycemia is associated with cerebral ischemic dam-age and many of the factors that link hyperglycemia to cardiovascular dys-function may also contribute to cere-brovascular dysfunction.2 Similarly, hypoglycemia is also associated with cardiac arrhythmias through calcium and potassium channel flux, tropo-nin and tropomyosin binding, inflam-mation, and central nervous system dysfunction. Like hyperglycemia, hypoglycemia appears to be a pro-inflammatory and arrhthymogenic state.29 For example, hypoglycemia can cause an acquired long QT syndrome through sympathoadrenal stimulation, which includes catecholamine-media-ted hypokalemia.30

All available evidence suggests that both hyperglycemia and hypoglycemia should be avoided in inpatients.31

Insulin Therapy in the Hospital In critically ill patients, intravenous insulin therapy is the treatment of choice to control hyperglycemia. This is generally accomplished through the use of standardized infusions of regu-lar human insulin.2,5 There are few, if

any, advantages to the use of insulin analogues in the critical care setting. Intravenous administration is not an approved indication for insulin ana-logues because of its expense and lack of favorable pharmacokinetic and phar-macodynamic profiles when infused continuously. A validated insulin infu-sion protocol that is well tolerated, and is most appropriate and practical for the respective institution (based on available resources and support), is rec-ommended, along with a hypoglycemia protocol that includes frequent blood glucose monitoring.32

The range of insulin agents needed in general medical and surgical units is greater than in the intensive care

unit. In noncritically ill hyperglycemic patients, the use of regularly scheduled basal bolus insulin (along with correc-tional insulin) is recommended, rather than sliding scale insulin regimens, for the most physiologic approach to correcting hyperglycemia (Figure 2).1-5

This requires the use of at least 2 types of insulin: a long-acting insulin to cover basal or background insulin needs between meals, and a short- or rapid-acting insulin to address pran-dial or mealtime-related glucose excur-sions. In noncritically ill patients, there are advantages to insulin analogues over regular human insulin and neutral protamine Hagedorn (NPH) insulin. As demonstrated in Figure 3, regular

Table 3: Hypoglycemia Is Associated with Increased Health Care Costs23

Hospital Outcomes, Mean

Patients with Hypoglycemia (Blood Glucose <70 mg/dL)

Patients Without Hypoglycemia Between-Group Difference or Odds Ratio (Unadjusted)

P

n Mean Value n Mean Value

Length of hospital stay, days

8234 11.7 95,579 5.1 6.6 <.001

Hospital mortal-ity, %

7994 4.8 93,012 2.3 2.12 <.001

Discharged to skilled nursing facility, %

7787 26.5 93,134 14.5 1.83 <.001

Total hospital charges, 2006 $

6020 85,905 72,681 54,038 59% <.001

Figure 2: Maintaining Physiologic Insulin Delivery in the Hospital: Scheduled Basal Bolus Subcutaneous Insulin plus Correctional Insulin

Correction orSupplementalinsulin

Nutritional orMealtimeinsulin (bolus)

Normal SecretoryPattern of Insulin

Basal insulin

Breakfast Lunch Dinner Bedtime

Insu

lin

Theoretical representation of insulin pro�les

FIG 2.



human insulin, because it has to be absorbed through the subcutis, has a longer onset of action than rapid-acting insulin analogues (aspart, glulisine, lis-pro), which were designed to be more rapidly absorbed.33 In general, regular human insulin must be injected at least 20 to 30 minutes prior to meals, which may be difficult to coordinate (whether by nursing schedule, dietary delivery, or patient activity) with food intake. In contrast, the rapid-acting analogues can be injected with the first bite of

food and still be effective. The rapid-acting analogues also have a shorter duration of action, which reduces the risks of intra-meal hypoglycemia.33

Basal Insulin AnaloguesLooking more closely at basal insulin analogues, which have been a major therapeutic advance in the management of diabetes, and have been pharma-ceutically more difficult to develop, there are many interesting aspects to consider. Some of the properties of an

ideal basal insulin analogue are sum-marized in Table 4. For a long time, NPH insulin was the only longer-acting insulin available. It is an intermediate-acting agent, however, with a pro-nounced peak, with a duration of action far less than 24 hours—typically 6 to 8 hours. This means that it may still have activity at the time a mealtime dose of insulin is administered, with the potential for insulin “stacking” and an increased risk of hypoglycemia. Additionally, NPH is associated with substantial intra- and inter-patient vari-ability. It may have a role in the hospital setting for patients receiving tube feedings or for patients receiving high-dose corticosteroids, which can result in greater postprandial glycemic excursions.5 Insulin glargine, the first long-acting basal insulin analogue, and insulin detemir, can both provide once-daily basal insulin coverage,34 and both are relatively, but not entirely, peak-less; their pharmacokinetic profiles change slightly with dose, and duration of action is dose-dependent.35 In some patients, particularly those with low insulin requirements or type 1 diabetes, there may be a need to give a long-acting insulin analogue twice a day; insulin detemir is indicated for once- or twice-daily use.36

The important benefit of long-act-ing basal insulin analogues over NPH insulin is a decreased risk of hypo-glycemia, particularly nocturnal hypo-glycemia.37-39 This safety advantage has been observed in trends of hypo-glycemia rates in the major landmark trials in diabetes—the United Kingdom Prospective Diabetes Study,40 the Diabetes Control and Complications Trial41 (when only NPH insulin was available), the Treating To Target in Type 2 diabetes study (4-T), where insulin detemir was the basal insu-lin analogue used,42,43 and Outcome Reduction with an Initial Glargine INtervention trial43 (where the insulin glargine was evaluated). Sleep marked-ly weakens the neuroendocrine defense mechanism against hypoglycemia by shifting the glycemic threshold for counter-regulatory activation to lower

Table 6: Comparison of Hypoglycemia Rates of Once-Daily Pegylated Insulin Lispro with Insulin Glargine in Patients with Type 1 Diabetes46,a

Baseline LY2605541 Insulin Glargine Relative Risk: LY2605541/Insulin Glargine (90% CI)

Total hypoglyce-miab rate per 30 days

3.78 ± 3.92 8.74 ± 7.70 7.36 ± 6.80 1.12 (1.03, 1.23)

Nocturnal hypo-glycemiac rate per 30 days

0.46 ± 1.13 0.88 ± 1.22 1.13 ± 1.42 0.75 (0.62, 0.90)

Severe hypogly-cemiad events, n (%)

— 6 (5) 6 (3) —

CI = confidence interval; SD = standard deviation.

aValues are mean ± SD unless otherwise indicated.bHypoglycemia: signs/symptoms of hypoglycemia and/or a measured blood glucose concentration of ≤70 mg/dL.cNocturnal hypoglycemia: hypoglycemia occurring between bedtime and waking.dSevere hypoglycemia: symptoms of hypoglycemia requiring the assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions.

Table 4: Characteristics of an Ideal Basal Insulin Analogue

• Steady, stable, peakless, continuous insulin concentration for at least 24 hours

• Predictable pharmacodynamics

• Low intra-individual and inter-individual variability

• Low risk of hypoglycemia and weight gain

• Equally effective in type 1 and type 2 diabetes

Table 5: Comparison of Once-Daily Pegylated Insulin Lispro with Insulin Glargine in Patients with Type 2 Diabetes45

Pegylated Insulin Lispro

Insulin Glargine P

Intraday blood glu-cose variability

34.4 mg/dL 39.1 mg/dL P = .031

Weight loss -0.6 ± 0.2 kg 0.3 ± 0.2 kg Treatment difference: -0.8 kg, P = .001



levels, making nocturnal hypoglycemia particularly worrisome.44

Emerging Basal Insulin AnaloguesThe quest continues to improve the therapeutic index of insulin therapy, particularly basal insulin replacement therapy. As stated before, hypogly-cemia is the limiting factor in the search for optimal glycemic control with insulin therapy. Efforts to reduce pharmacokinetic and pharmacody-namic variability, provide true 24-hour coverage, and reduce the risks of hypo-glycemia are ongoing. Emerging “ultra long-acting” basal insulin analogues may more closely match the desired parameters of an ideal basal insulin analogue. The investigational agent LY2605541 is a pegylated form of insulin lispro, designed to have a long-acting, once-daily profile. Currently in phase 2 development, the available data show that it has less intra-day variability to insulin glargine and may be associated with some weight loss (or at least no weight gain, which is typical of insulin therapy) in patients with type 2 diabetes (Table 5).45 More importantly, in patients with type 1 diabetes, LY2605541 is associated with an approximately 25% lower risk of nocturnal hypoglycemia compared with insulin glargine (Table 6).46 Rates of overall hypoglycemia were a bit greater (this may have to do with push-ing of the dose in these dose-finding studies, since the glycated hemoglobin reductions were also greater, which may or may not be seen when this insulin is used clinically).46 Patients receiving pegylated lispro lost weight (–0.6 kg), whereas those treated with insulin glargine gained weight ([0.3 kg]; treatment difference, –0.8 kg; P = .001). Alanine aminotransferase and aspartate aminotransferase remained within normal range but were signifi-cantly higher with pegylated lispro.46

In November 2012, an advisory panel to the FDA recommended approval of insulin degludec. In January 2013, the European Commission granted market-ing authorization for long-acting insu-

lin degludec. In a Complete Response Letter issued in February, the FDA requested data from a dedicated car-diovascular outcomes trial before the review of the New Drug Application can be completed. This basal insu-

lin, with improved pharmacokinetic properties, is produced by acylation of fatty acids that enable soluble, high-molecular weight complexes to form postinjection. These highly self-associ-ated hexamers then slowly disassemble

Figure 3: Time-Action Profiles of Insulin Products33

HoursP

lasm

a In

sulin

Lev

els

0 21 43 5 6 87 9 10 131211 14 15 16 17 18 19 2120 22 23 24

Insulin glargine; insulin detemirUp to 24 hours

NPH 12–20 hours

Regular 6–8 hours

Insulin aspart, insulin glulisine, insulin lispro4–6 hours

The New England journal of medicine by Massachusetts Medical Society Reproduced with permission of MASSACHUSETTS MEDICAL SOCIETY in the format reuse in a journal/magazine via Copyright Clearance Center.

FIG 3.

NPH = neutral protamine Hagedorn.Reprinted with permission from reference 33.

Figure 4: Formation of Insulin Degludec47

Degludec multihexamers(T6-state)

Pharm Res DOI 10.1007/s11095-012-0739-z

FIG 4.

Degludec dihexamers(T3R3-state)

Degludec dimers

Degludec monomers

Injectedformulation

Depotformation

Absorption

–phenol

–Zn2+

Zn2+

Phenol

Insulin degludec is injected subcutaneously as a zinc phenol formulation containing insulin degludec dihexamer. Rapid loss of phenol changes the degludec hexamers and multi-hexamer chains form. With slow diffusion of zinc, these chains break down into dimers, which quickly dissociate into readily absorbed monomers.

Reprinted with permission from reference 47.



to dimers, then release insulin mono-mers (Figure 4).47 Insulin clamp studies show that this insulin has an ultra-long, flat, and consistent pharmaocokinetic and pharmacodynamic profile, regard-less of dose,48 with an onset of action within hours on day 1 and achievement of steady state by day 6 (without risk of accumulation).48 It shows 4 times less pharmacodynamic variability than insulin glargine49 and in randomized clinical trials achieves comparable glu-cose lowering with a much lower risk of nocturnal hypoglycemia in insu-lin-experienced50 and insulin-naïve51 patients with type 2 diabetes. Figure 5 shows these data in patients with type 2 diabetes when insulin degludec is used as part of a basal bolus insulin strat-egy.50 Improvements in the ability to achieve glycemic control while mini-mizing the risks of hypoglycemia may benefit inpatients with hyperglycemia and outpatients with diabetes. A recent pre-planned meta-analysis of data from the phase 3 trials confirms that simi-lar glucose improvements with fewer hypoglycemic episodes, particularly nocturnal episodes, can be achieved with insulin degludec compared with insulin glargine in patients with type 1 or type 2 diabetes.52 Other analyses show that health-related quality of life

was better with insulin degludec com-pared with insulin glargine in patients with type 2 diabetes starting a basal insulin.53

ConclusionThe treatment of inpatient hyperglyce-mia has been a journey, which started with very little guidance and data, to a place where guidelines have been developed and updated as evidence and experience have emerged to better guide clinicians. The systematic review of available data and progression of practical recommendations and guid-ance on appropriate treatment goals, insulin regimens, and pharmaceutical advancements are improving the ability to achieve safe and effective manage-ment of hyperglycemia in the hospital setting. Practical attention to details such as the development and imple-mentation of protocols for treating hyperglycemia, hypoglycemia, and the use of more physiologic insulin agents and regimens supports the safe use of insulin in the hospital setting.

Address correspondence to: Javier Morales, MD, Advanced Internal Medicine Group, PC, 3003 New Hyde Park Rd, Ste 201A, New Hyde Park, NY 11042. Phone: (516) 637-4947. E-mail: [email protected].

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et al. American College of Endocrinology position statement on inpatient diabetes and metabolic control. Endocr Pract. 2004;10 (suppl 2):4-9.

2. Clement S, Braithwaite SS, Magee MF, et al. Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004;27(2):553-591.

3. Moghissi ES, Korytkowski MT, DiNardo M, et al. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpa-tient glycemic control. Endocr Pract. 2009;15(4):353-369.

4. Moghissi ES, Korytkowski MT, DiNardo M, et al. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpa-tient glycemic control. Diabetes Care. 2009;32(6):1119-1131.

5. Umpierrez GE, Hellman R, Korytkowski MT, et al. Management of hyperglycemia in hospitalized patients in non-critical care setting: an endocrine society clinical prac-tice guideline. J Clin Endocrinol Metab. 2012;97(1):16-38.

6. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: posi-tion statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35(6):1364-1379.

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10. McAlister FA, Majumdar SR, Blitz S, Rowe BH, Romney J, Marrie TJ. The relation between hyperglycemia and outcomes in

Figure 5: Insulin Degludeca Versus Insulin Glargine (Both plus Rapid-Acting Insulin) in Patients with T2DM: Confirmed Nocturnal Hypoglycemia50

Time (weeks)

Co

nfirm

ed N

oct

urna

l Hyp

og

lyce

mia

(Cum

ulat

ive

num

ber

of

even

ts p

er p

atie

nt-y

ear)

4 80 12 16

*Investigational as of 11/21/12

20 24 28 3632 40 44 48 52

25% riskreductionRR: 0.75[0.58; 0.99]signi�cant

The Lancet by LANCET PUBLISHING GROUP. Reproduced with permission of LANCET PUBLISHING GROUP in the format reuse in a journal/magazine via Copyright Clearance Center.

FIG 5.

1.2

1.4

1.8

2.0

1.6

0.2

0.4

0.8

0.0

0.0

0.6

IDeg + IAsp (n=753)

IGlar + IAsp (n=251)

RR = relative risk; T2DM = type 2 diabetes mellitus. Reprinted with permission from reference 50.

a

Insulin degludec + Insulin aspart (n=753)

Insulin glargine + Insulin aspart (n=251)



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11. Baker EH, Janaway CH, Philips BJ, et al. Hyperglycaemia is associated with poor out-comes in patients admitted to hospital with acute exacerbations of chronic obstructive pulmonary disease. Thorax. 2006;61(4):284-289.

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19. van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001;345(19):1359-1367.

20. Krinsley JS. Effect of an intensive glucose

management protocol on the mortality of critically ill adult patients. Mayo Clin Proc. 2004;79(8):992-1000.

21. Turchin A, Matheny ME, Shubina M, Scanlon JV, Greenwood B, Pendergrass ML. Hypoglycemia and clinical outcomes in patients with diabetes hospitalized in the gen-eral ward. Diabetes Care. 2009;32(7):1153-1157.

22. Nirantharakumar K, Marshall T, Kennedy A, Narendran P, Hemming K, Coleman JJ. Hypoglycaemia is associated with increased length of stay and mortality in people with diabetes who are hospitalized. Diabet Med. 2012;29(12):e445-e448.

23. Curkendall SM, Natoli JL, Alexander CM, Nathanson BH, Haidar T, Dubois RW. Economic and clinical impact of inpatient diabetic hypoglycemia. Endocr Pract. 2009;15(4):302-312.

24. Finfer S, Chittock DR, Su SY, et al. Intensive versus conventional glucose con-trol in critically ill patients. N Engl J Med. 2009;360(13):1283-1297.

25. Griesdale DE, de Souza RJ, van Dam RM, et al. Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data. CMAJ. 2009;180(8):821-827.

26. Moghissi ES. Reexamining the evidence for inpatient glucose control: new recommenda-tions for glycemic targets. Am J Health Syst Pharm. 2010;67(16, suppl 8):S3-S8.

27. Finfer S, Liu B, Chittock DR, et al. Hypoglycemia and risk of death in critically ill patients. N Engl J Med. 2012;367(12):1108-1118.

28. Hirsch IB. Understanding low sugar from NICE-SUGAR. N Engl J Med. 2012;367(12):1150-1152.

29. Razavi Nematollahi L, Kitabchi AE, Stentz FB, et al. Proinflammatory cytokines in response to insulin-induced hypoglyce-mic stress in healthy subjects. Metabolism. 2009;58(4):443-448.

30. Robinson RT, Harris ND, Ireland RH, Lee S, Newman C, Heller SR. Mechanisms of abnormal cardiac repolarization during insulin-induced hypoglycemia. Diabetes. 2003;52(6):1469-1474.

31. Bruno A, Gregori D, Caropreso A, Lazzarato F, Petrinco M, Pagano E. Normal glucose values are associated with a lower risk of mortality in hospitalized patients. Diabetes Care. 2008;31(11):2209-2210.

32. Krikorian A, Ismail-Beigi F, Moghissi ES. Comparisons of different insulin infusion protocols: a review of recent literature. Curr Opin Clin Nutr Metab Care. 2010;13(2):198-204.

33. Hirsch IB. Insulin analogues. N Engl J Med. 2005;352(2):174-183.

34. King AB. Once-daily insulin detemir is com-parable to once-daily insulin glargine in providing glycaemic control over 24 h in patients with type 2 diabetes: a double-blind, randomized, crossover study. Diabetes Obes Metab. 2009;11(1):69-71.

35. Klein O, Lynge J, Endahl L, Damholt B, Nosek L, Heise T. Albumin-bound basal insulin analogues (insulin detemir and NN344): comparable time-action profiles but less variability than insulin glargine in type 2 diabetes. Diabetes Obes Metab. 2007;9(3):290-299.

36. Home P, Bartley P, Russell-Jones D, et al. Insulin detemir offers improved glycemic control compared with NPH insulin in people with type 1 diabetes: a randomized clinical trial. Diabetes Care. 2004;27(5):1081-1087.

37. Monami M, Marchionni N, Mannucci E. Long-acting insulin analogues vs. NPH human insulin in type 1 diabetes: a meta-anal-ysis. Diabetes Obes Metab. 2009;11(4):372-378.

38. Monami M, Marchionni N, Mannucci E. Long-acting insulin analogues versus NPH human insulin in type 2 diabetes: a meta-analysis. Diabetes Res Clin Pract. 2008;81(2):184-189.

39. Home PD, Fritsche A, Schinzel S, Massi-Benedetti M. Meta-analysis of individual patient data to assess the risk of hypoglycae-mia in people with type 2 diabetes using NPH insulin or insulin glargine. Diabetes Obes Metab. 2010;12(9):772-779.

40. Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA. 1999;281(21):2005-2012.

41. The Diabetes Control and Complications (DCCT) Research Group. Effect of intensive therapy on the development and progres-sion of diabetic nephropathy in the Diabetes Control and Complications Trial. Kidney Int. 1995;47(6):1703-1720.

42. Holman RR, Farmer AJ, Davies MJ, et



al. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med. 2009;361(18):1736-1747.

43. Gerstein HC, Bosch J, Dagenais GR, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012;367(4):319-328.

44. Jauch-Chara K, Schultes B. Sleep and the response to hypoglycaemia. Best Pract Res Clin Endocrinol Metab. 2010;24(5):801-815.

45. Bergenstal RM, Rosenstock J, Arakaki RF, et al. A randomized, controlled study of once-daily LY2605541, a novel long-acting basal insulin, versus insulin glargine in basal insulin-treated patients with type 2 diabetes. Diabetes Care. 2012;35(11):2140-2147.

46. Rosenstock J, Bergenstal RM, Blevins TC, et al. Better glycemic control and weight loss with the novel long-acting basal insulin LY2605541 compared with insulin glargine in type 1 diabetes: a randomized, crossover study. Diabetes Care. 2013;36(3):522-528.

47. Jonassen I, Havelund S, Hoeg-Jensen T, Steensgaard DB, Wahlund PO, Ribel U. Design of the novel protraction mechanism of insulin degludec, an ultra-long-acting basal insulin. Pharm Res. 2012;29(8):2104-2114.

48. Heise T, Nosek L, Bottcher SG, Hastrup H, Haahr H. Ultra-long-acting insulin degludec has a flat and stable glucose-lowering effect in type 2 diabetes. Diabetes Obes Metab. 2012;14(10):944-950.

49. Heise T, Hermanski L, Nosek L, Feldman A, Rasmussen S, Haahr H. Insulin degludec: four times lower pharmacodynamic variabil-ity than insulin glargine under steady-state conditions in type 1 diabetes. Diabetes Obes Metab. 2012;14(9):859-864.

50. Garber AJ, King AB, Del Prato S, et al. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 2 diabetes (BEGIN Basal-Bolus Type 2): a phase 3, randomised, open-label,

treat-to-target non-inferiority trial. Lancet. 2012;379(9825):1498-1507.

51. Zinman B, Philis-Tsimikas A, Cariou B, et al. Insulin degludec versus insulin glargine in insulin-naive patients with type 2 dia-betes: a 1-year, randomized, treat-to-target trial (BEGIN Once Long). Diabetes Care. 2012;35(12):2464-2471.

52. Ratner R, Gough SC, Mathieu C, et al. Hypoglycaemia risk with insulin degludec compared with insulin glargine in type 2 and type 1 diabetes: a pre-planned meta-analysis of phase 3 trials. Diabetes Obes Metab. 2013;15(2):175-184.

53. Freemantle N, Meneghini L, Christensen T, Wolden ML, Jendle J, Ratner R. Insulin degludec improves health-related qual-ity of life (SF-36(®)) compared with insulin glargine in people with Type 2 diabetes start-ing on basal insulin: a meta-analysis of phase 3a trials. Diabet Med. 2013;30(2):226-232.

IntroductionThe attitude and management approach-es toward hyperglycemia in the hospi-tal setting have evolved substantially over the past decade. Prior to that, there was a general lack of recognition of the need to identify and treat hyperglyce-mia among hospitalized patients. To safely achieve recommended targets, the multidisciplinary involvement of pharmacists, nurses, and physicians, as well as other health care professionals, is needed. Pharmacists are critical to the safe and effective use of insulin in the inpatient setting and the education of patients as they are transitioned to outpatient care. The role of pharmacists varies greatly in part because hospitals vary greatly in how they have adopted recommendations for managing hyper-glycemia in the inpatient setting, their use of protocols, the resources avail-able to them, the culture within which they must work, and the nature of their patient populations. There are many opportunities for pharmacists to increase their involvement in improv-ing glycemic control, just as there are many competing priorities for their time and resources. This article pro-vides an overview of some of the different possibilities that exist and reflects the authors’ experiences.

Roles can be broadly categorized into those of systemic implementa-tion or more specific glycemic control teams or patient-specific roles (Table).

Paul M. Szumita, PharmD, BCPSClinical Pharmacy Practice Manager Director - PGY2 Critical Care Pharmacy Residency Department of Pharmacy Services Brigham and Women’s Hospital Pharmacy Administration; L-2 Boston, Massachusetts

Pharmacists have many roles in the management of glucose in the inpatient setting.1 I am an integral member of the multidisciplinary “steering committee/task force team” and manage glucose levels on an individual patient basis. At my institution, the steering commit-tee is the “Diabetes Subcommittee” of the larger Pharmacy and Therapeutics Committee with oversight of all things


Curtis Triplitt, PharmD, CDE; Paul M. Szumita, PharmD, BCPS; Susan Ann Cornell, BS, PharmD, CDE,

A Snapshot of the Various Roles of Pharmacists’ Participation in

Influencing Inpatient Glycemic Control

Table: Potential Roles for Pharmacists in Implementing Improvements in Inpatient Glycemic Control

Systematic implementation

On or lead glycemic management steer-ing committee/task forces

Develop/implement guidelines and order sets

Assessment of practice—pre and post change (PDSA [plan, do, study, act])

Edit the guidelines and order sets per feedback and metrics

Point person for any glucose-related issue in the institution

Patient care

Implementation of order sets and guide-lines on a patient-specific basis

Prioritizing glucose management in each of the sub-specialized areas of the hospital

Advocate or champion for glucose on non-glucose management teams (inten-sive care unit, internal medicine, surgical patient, transplant, oncology)

• Practices in an urban, 800-bed hospital

• Protocols for critically ill patient are fully implemented, with thresholds for intravenous (IV) insulin set at >150 mg/dL

• Hypoglycemia protocols also fully implemented (threshold set at 70 mg/dL)

• Protocols for perioperative hyper-glycemia also fully implemented, as are those for noncritically ill patients

• Institution uses computerized order entry for insulin therapy

• Integral member of diabetes man-agement team

• Barriers are numerous–daily/weekly/monthly/yearly continu-ous journey

• The key is to have a multidisci-plinary team of champions to help lead change and sustain gains

Pharmacists' Role in Inpatient Glycemic Control


related to glucose management. My fellow Brigham and Women’s Hospital pharmacists and I also manage glucose on a patient-specific basis as clinical pharmacists in the intensive care unit, general wards, and other areas of the hospital, applying the strategies recom-mended by the steering committee.

“Physical champions” refers to small group of individuals willing to accept the responsibility to encourage positive changes in clinical practice. Our mul-tidisciplinary team consists of a group of physical champions responsible for oversight, development, implementa-tion, education, and quality assess-ment of policies, order sets, protocols, and guidelines. In preparation for dis-charge, we also coordinate efforts for patients and staff to have access to critical glycemic management medica-tions and materials, including glucose monitors and test strips for patient self-testing. This steering committee/task force is crucial to ensure policies, order sets, protocols, and guidelines, which are continually critiqued, monitored, and improved. We have researched compliance with IV insulin protocols, acceptance of insulin delivery devices, glucometrics, and outcomes with both IV and subcutaneous insulin regimens.

To improve management one needs an indicator that correlates with blood glucose levels during the short interval of an inpatient stay, usually a few days; therefore, glucometrics are good mea-surements for quality in the inpatient setting. Glycated hemoglobin responds too slowly to measure glucose fluc-tuations over days. Instead, studies of inpatient glycemia have correlated outcomes with glucose measurements: both single glucose values (admission, random, fasting, and maximal glucose) and mean glucose values (admission, first 24 hours of hospitalization, fast-ing, post-operative, and overall mean).

We continue to find challenges to overcome within our institution. There are seemingly countless barriers to gly-cemic management in the inpatient set-ting that we are continually analyzing.2

One of our recent challenges has been developing guidelines for the man-

agement of glucose in the pre-, peri-, and post-procedure/operative settings. These guidelines are particularly chal-lenging given the diverse practice set-tings and lack of consensus guidelines in the literature in this setting.

Our pharmacists on various team/care areas (intensive care unit, emer-gency department, oncology, orthope-dics, general surgery, general/internal medicine, cardiology, vascular and transplant, and others) help implement the hospital guidelines in all areas of the hospital that pharmacists cover. A part of every inpatient clinical pharma-cist’s duties includes oversight of glu-cose management. Unless the patient’s admitting diagnosis is directly related to complications of diabetes, glucose management may not be an area of focus of the primary team; therefore a great opportunity for clinical pharma-cists on that team is to assist with prop-er management pathways. The Figure shows a stepwise approach that can be taken to begin to address glucose con-trol in the hospital setting.3

Curtis Triplitt, PharmD, CDEAssistant Professor, Department of MedicineDivision of DiabetesUniversity of Texas Health Science Center at San AntonioTexas Diabetes InstituteSan Antonio, Texas

As mostly an outpatient diabetes specialist pharmacist, my role is as a consultant to inpatient pharmacists. I am asked specific questions about all aspects of inpatient glycemic con-trol. Questions have ranged from those about glycemic control in the trans-plant setting, to hypoglycemia treat-ment in inpatients, to advising on how basal insulin in general medicine wards should be administered. In addition, I also serve on the Pharmacy and Therapeutics Diabetes/Endocrine sub-committee. Through this, inpatient and outpatient issues on glycemic control agents are discussed. We are current-ly involved in addressing the use of oral diabetes agents in the inpatient setting. Our general policy has been to discontinue their use in favor of insulin therapy, which is more suited to the changing needs of acutely ill patients, and who may also have tran-sient contraindications to oral agents. However, some clinicians may feel strongly about continuing oral agents, especially in stable patients ready to be discharged in the next 1 to 2 days. Through a non-formulary request, this is usually granted approval for use, but must be closely monitored. As I have traveled and spoken at many hospitals, I find our hospital is actually in the minority by not allowing oral agents to continue. Clearly, if the obvious issues of contraindications are aggressively addressed, then oral agents could be continued. Proper use, proper monitor-ing, and timely discontinuation in the event of serious adverse events are important roles for the pharmacist in developing policies and procedures.

Several years ago we had hospital-ist champions that forged consensus on implementation of inpatient gly-cemic control algorithms in surgery and critical care areas. Surprisingly, at least 3 different protocols are currently used throughout the hospital, as recom-mended by the individual hospitalists/specialists in those areas. Much work is still to be done in our institution, yet on a daily basis, the staff do an incredible job. The greatest barrier to glycemic control in our institution is

• Practices in an urban, 500-bed hospital system

• Protocols for critically ill patients are fully implemented, with thresholds for IV insulin set at >180 mg/dL

• Hypoglycemia protocols also fully implemented (threshold set at 70 mg/dL)

• Protocols for perioperative hyper-glycemia and noncritically ill patients partially implemented

• Institution uses computerized order entry for insulin therapy

• Acts as consultant for select cases from staff, as no glycemic control team exists



often time—time to gather, assess, and analyze glucometrics, find consensus, and implement change in such a rapid-ly changing environment where wards are full. This is why glycemic champi-ons are important as the driving force for change. What can pharmacists do? Pharmacists must be up-to-date with

the current evidence base about inpa-tient glycemic control. Understanding the underpinnings of currently rec-ommended glycemic control on the inpatient side is paramount. Without this knowledge, becoming an “inpa-tient glycemic champion” is unlikely. Understanding what your institution

currently does is important—are pro-tocols in place? How many protocols are in place? How closely do protocols match those suggested by national con-sensus statements? What barriers or educational gaps need to be addressed? What processes are in place? Building consensus, implementing change,

Figure: Stepwise Approach to Glucose Control Interventions

Identi�cation of the impatient population facing glucose control problems

Creation of the “physical champion”

Formation of multidisciplinary advisory committee/team

Determining target blood glucose level

Assessing existing glucose control protocols and institution resources

Synthesizing data

Implementation of protocol/intervention

Endorsement from institutional credible bodies

Publication of ef�cacy, safety, andcompliance data

Intervention/protocol selection and development

Clinician compliance assessment

Continuous education provided to all hospital clinicians and support staff

Pilot intervention/protocol

Available published literature analysis

Stepwise Approach to Glucose Control Interventions

Existing institutional guidelines

Ef�cacy and safety

Compliance assessment

Quality assessment and improvement

End-user satisfaction and feedbackIncorporation into order

entry template (paper or CPOE)

Coordination of equipment purchasing

Easy ordering

Clinical reminders

Glucometers, testing strips, Web-based programs, etc

Benchmarking against other institutions

Assistance in local and national guideline

development

CPOE = computerized physician order entry.



being reasonable in expectations, and accepting compromise are the ways to build quality improvement over time. Improving inpatient glycemic control is a process and a journey.

Susan Cornell, BS, PharmD, CDE, FAPhA, FAADEAssistant Professor, Department of Pharmacy Practice Midwestern University Chicago College of Pharmacy Downers Grove, Illinois

Transitions of care, described as situ-ations when a patient leaves one health care setting and moves to another, are challenging and have been shown to compromise patient care and safety.4 Studies have documented that medi-cation errors frequently occur during transitions of care and that medica-tion reconciliation can reduce such events.5,6 Pharmacists can have a large role in preventing medication errors and improving patient care by provid-ing medication reconciliation at vari-ous transition points.

At the DuPage Community Clinic (DCC), a free clinic for residents of DuPage County, Illinois, patients are provided primary care services by a health care team. The DCC collabo-rates with 6 area hospitals to provide health care services for the patients. My role at the DCC is to develop and oversee the clinical pharmacist–student pharmacist functions. This includes development of the program, recruit-ing, training, scheduling, pharmacist services implementation, and staffing.• Triage - After the patient is triaged and in

the exam room a student-pharmacist

will: - Perform phase 1 of a medication

reconciliation and management ser-vice:

□ Review with the patient their current medications and compare it with DCC medication sheet in the chart.

□ Assess if the patient is on other medications from another provid-er, emergency department or criti-cal care visit, or is self-treating. This should include an assessment of any over-the-counter medica-tions a patient may be taking.

□ List any discrepancies found with a patient’s medications, and report any discrepancies to DCC clinic staff and the pharmacist supervisor.

• Students also assess the patient’s adherence using the following ques-tions for each medication the patient currently takes:

- What are you taking this medicine for?

- How are you currently taking this medicine?

- What problems have you noticed since taking this medicine?

- What days of the week do you skip or not take your medication?

- How often does this happen?• Discharge - After the patient has been seen

by the primary care physician, the student with a pharmacist supervi-sor will implement phase 2 of the medication reconciliation and man-agement service:

□ Review and educate the patient on the best way to take each of their medications, including new medi-cations and OTC products.

□ Explain and discuss discontinued medications.

□ Assess and review any device tech-nique with the patient for optimal drug delivery (eg, insulin pens, self-monitoring blood glucose meters).

□ Provide a personalized medication schedule for the patient

• After their pharmacist supervisor reviews and signs the schedule form

• Diabetes services - Blood sugar monitoring – checkups □ Patients are referred to and

scheduled with a pharmacist and students for review of their BS record. The pharmacist adjusts and initiates diabetes medication dosing changes, if needed, under protocol.

- Diabetes education visits □ Pharmacists provide diabetes self-

management education and train-ing for patients with diabetes and pre-diabetes.

ConclusionPharmacists are an integral part of the multidisciplinary team ensuring the safe and effective implementation of inpatient hyperglycemic control and insulin usage and may play different roles depending on where their specific institution is in addressing the impor-tant issue of inpatient glycemic con-trol. Important questions for the reader to consider are whether or not blood glucose goals are in place for different patient populations, whether these are consistent with current medical society recommendations,7-9 if protocols are in place for the safe and effective use of insulin,10 and what role the pharmacist can play as a team member either on a system basis or in a patient-specific role.11

References1. Szumita PM. The hospital pharmacist:

an integral part of the hyperglycaemic management team. J Clin Pharm Ther. 2009;34(6):613-621.

2. Anger KE, Szumita PM. Barriers to glu-cose control in the intensive care unit. Pharmacotherapy. 2006;26(2):214-228.

3. Szumita PM. Prevention and treatment of hyperglycemia in hospitalized patients. Pharm Times. 2007:110-118.

4. Kimmel B, Sullivan MM, Rushakoff RJ. Survey on transition from inpatient to outpa-tient for patients on insulin: what really goes on at home? Endocr Pract. 2010;16(5):785-791.

5. Mueller SK, Sponsler KC, Kripalani S, Schnipper JL. Hospital-based medication reconciliation practices: a systematic review.

• Works at a community clinic that transitions patients from 6 differ-ent hospitals

• Is a fully integrated member of the team

• Has fully implemented hypogly-cemia protocol in institution, with <70 mg/dL set as threshold

• Institution uses computerized order entry for insulin orders



Arch Intern Med. 2012;172(14):1057-1069.6. Pippins JR, Gandhi TK, Hamann C, et al.

Classifying and predicting errors of inpatient medication reconciliation. J Gen Intern Med. 2008;23(9):1414-1422.

7. Moghissi ES, Korytkowski MT, DiNardo M, et al. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpa-tient glycemic control. Endocr Pract.

2009;15(4):353-369.8. Moghissi ES. Reexamining the evidence for

inpatient glucose control: new recommenda-tions for glycemic targets. Am J Health Syst Pharm. 2010;67(16, suppl 8):S3-S8.

9. Umpierrez GE, Hellman R, Korytkowski MT, et al. Management of hyperglycemia in hospitalized patients in non-critical care setting: an endocrine society clinical prac-tice guideline. J Clin Endocrinol Metab.

2012;97(1):16-38.10. Cohen MR. Pharmacists’ role in ensuring

safe and effective hospital use of insulin. Am J Health Syst Pharm. 2010;67(16, suppl 8):S17-S21.

11. Kelly JL. Ensuring optimal insulin utilization in the hospital setting: role of the pharmacist. Am J Health Syst Pharm. 2010;67(16, suppl 8):S9-S16.

Posttest


1. Which of the following statements is CORRECT about hyperglycemia/ diabetes in the hospital setting?A. Hyperglycemia may be present in

up to 50% of hospitalized patients; 20% of those may have no prior his-tory of diabetes.

B. Patients with documented hyper-glycemia while hospitalized should have an A1C test performed before discharge if one has not been performed in the previous 2 to 3 months.

C. An A1C test is as sensitive as the use of fasting plasma glucose levels.

D. Hospitalization accounts for approx-imately 30% of the direct costs of diabetes.

2. Which of the following statements is NOT correct about hyperglycemia/diabetes in the hospital setting?A. Hyperglycemia in acutely ill patients

is a protective mechanism.B. The risk of hyperglycemia is worse

in patients with no prior history of diabetes than in those with diabetes.

C. Hyperglycemia is associated with increased lengths of stay.

D. Hyperglycemia is associated with an increased risk of hospitalization.

3. Which of the following is the CURRENT recommended target blood glucose level for critically ill patients?A. 80-110 mg/dLB. 110-140 mg/dLC. 140-180 mg/dLD. 180-200 mg/dL

4. Which of the following statements is NOT correct about insulin in the hos-pital setting?A. Fixed insulin protocols are preferred

to flexible protocols in the hospital setting.

B. IV insulin infusion concentrations should be standardized throughout the hospital.

C. Insulin is a high-alert medication but it is still the preferred method of controlling glucose levels in the hospital setting.

D. Potassium should be monitored when IV insulin is being adminis-tered.

5. JL has been receiving 4 units of IV insulin per hour for the past 4 hours of his ICU stay. He is stable and will be transferred to a general medical floor. What is his 24-hour insulin requirement, using the methodology described in the first article?A. 96 unitsB. 75 unitsC. 58 unitsD. 29 units

6. When should JL receive his first dose of basal insulin?A. When his IV insulin is discontinuedB. At least 2 hours before his IV insu-

lin is discontinuedC. Two hours after his IV insulin is

discontinuedD. In the evening or at bedtime

7. What will be JL’s prandial insulin dose?A. 5 unitsB. 10 unitsC. 20 unitsD. 30 units

8. Which of the following is the defini-tion of “sliding scale” insulin?A. Controls fasting and premeal glu-

coseB. Controls glucose from nutritional

sources such as discrete meals, tube feeds, or total parenteral nutrition

C. Used to cover unexpected hyper-glycemia that was not controlled by scheduled basal and nutritional insulin

D. Usually consists of regular insulin given in the absence of regularly scheduled insulin or any basal insu-lin

9. Which of the following statements is NOT correct about hypoglycemia in the hospital setting?A. Hypoglycemia causes effects that

may favor thrombosis.B. Acute hypoglycemia has adverse

effects on the cardiovascular system.C. Hypoglycemia is associated with

cardiac arrhythmias.D. Hypoglycemia causes immune sup-

pression.

10. Which of the following is the main advantage of long-acting insulin ana-logues versus NPH insulin?

A. Greater A1C-lowering ability B. Lower cost C. Less frequent administration D. Lower risk of nocturnal

hypoglycemia

Clinical Pearls to Improve Safety and Patient Care in the Hospital Setting:Addressing Challenges of Insulin Therapy


Clinical Pearls to Improve Safety and Patient Care in the Hospital Setting: Addressing Challenges of Insulin Therapy

Instructions for Posttest and Evaluation

Two ways to claim credit:1. Go online to http://tinyurl.com/PHARMACYBN, click on the blue “Assessment” button, and register or log in (if you previously registered on the site) to complete the activity posttest and evaluation. • You must type http:// when entering this URL into the address bar at the top of your Internet browser

(do not enter this URL into your browser search box). 2. Complete the paper-based activity posttest and evaluation and fax it to 609-921-6428. Your statement of credit will be issued through CPE Monitor (you must provide your NABP e-Profile ID and Month and Day of Birth) within 6 to 8 weeks following your participation in the activity.

Please print clearly.

Name: _____________________________________________________________________________________________________

Address: ____________________________________________________________________________________________________

City: ___________________________________________State: ____________________ZIP: _______________________________

Country: ____________________________________________________________________________________________________

E-mail address: ______________________________________________________________________________________________

Reenter e-mail address: _____________________________________________________________________________________

NABP number: ______________________________________________________________________________________________

Month and day of birth (MM/DD format) _____________________________________________________________________ Signature ____________________________________________

Professional title: □ Pharmacist □ Pharmacy Technician □ Other _________________________

Practice setting: □ Hospital Pharmacy □ Other _________________________

POSTTEST FORMPlease refer to the posttest on page 26 for questions. Indicate your answers below, selecting 1 answer choice per question. A score of ≥70% is required to receive credit.

Posttest Question Number

A B C D A B C D

1. □ □ □ □ 6. □ □ □ □

2. □ □ □ □ 7. □ □ □ □

3. □ □ □ □ 8. □ □ □ □

4. □ □ □ □ 9. □ □ □ □

5. □ □ □ □ 10. □ □ □ □


EVALUATION FORM

I certify that I have participated in this activity. □

Which of the following best describes your institution?□ ≤100 beds □ 101-200 beds □ 201-300 beds □ ≥301 beds □ I don’t work in a hospital/health-system.

During a typical week, what percentage of inpatients in your institution have diabetes/hyperglycemia?□ Less than 20% □ 20-39% □ 40-59% □ 61-79% □ 80% or more □ I do not know.

This activity has or will improve my (check all that apply) □ Competence □ Performance □ Patient outcomes

Please list 1 new concept you learned in this activity. ______________________________________________________

_____________________________________________________________________________________________________________Please indicate your agreement with the following statements about this activity.

Strongly Strongly Agree Disagree

The content covered was useful and relevant to my practice. 5 4 3 2 1

The activity was fair, balanced, and free of commercial bias. 5 4 3 2 1

The information learned during this activity will help improve my skills or judgment within the next 6 months.

5 4 3 2 1

I am better able to state recent recommendations for glycemic targets for the inpatient setting and the value of glycemic control on outcomes during hospitalization.

5 4 3 2 1

I am better able to explain to other members of the diabetes management team why sliding scale insulin should not be the treatment of choice for insulin administration in the hospital setting.

5 4 3 2 1

I am better able to select appropriate types of insulin agents to meet patients’ physi-ologic insulin needs.

5 4 3 2 1

I am better able to formulate a plan to improve the safe and effective use of insulin in the hospital setting.

5 4 3 2 1

Instructional effectiveness and expertise of authors was excellent. 5 4 3 2 1

The learning method was excellent. 5 4 3 2 1

Learning assessment questions were appropriate. 5 4 3 2 1

If you selected 1 or 2 for any of above, please explain. _____________________________________________________

Based on the educational content of the activity, what will you do differently in the care of your patients? (check all that apply)□ Implement new information or skill in my practice□ Seek additional information□ Do nothing differently—Current practice reflects activity recommendations□ Do nothing differently—The content was not convincing□ Do nothing differently—System barriers prevent me from modifying my practice□ Not applicable. I have no patient contact.

Please list 1 modification you anticipate making in your practice (if none anticipated, please write “N/A”). ____________________________________________________________________________________________________ What barrier(s) have an impact on your ability to make the practice modification(s) indicated above (check all that apply)?□ Institutional □ Lack of coordination/communication among care team members□ Institutional protocols □ Team member resistance□ Administrative support □ Adverse side effects of treatment □ Time □ Other (please list) __________________________________ What information would you like to see in future activities that may help you address those barriers? ______________________________________________________________________________________________________________

Suggestions to improve this activity? _______________________________________________________________________

What patient problems/challenges related to inpatient hyperglycemia in the hospital setting do you feel you are unable to address appropriately or to your satisfaction? __________________________________________ _____________________________________________________________________________________________________________

Thank you for participating. As an added bonus, we will inform you of upcoming opportunities for future CPE-certified activities.

Documents

Clinical Pearls to Improve Safety and Patient Care in the ......March 2013 1 Contents Clinical Pearls to Improve Safety and Patient Care in the Hospital Setting: Addressing Challenges