getting to goal in glycemic control: practical strategies for improved outcomes … ·...

A SUPPLEMENT TO THE CLINICAL ADVISOR FEBRUARY 2009

GETTING TO GOAL IN GLYCEMIC CONTROL:Practical Strategies for Improved

Outcomes in Type 2 Diabetes

This activity is supported by an educational grant from Takeda Pharmaceuticals North America, Inc. Produced by

Sponsored by Boston UniversitySchool of Medicine

GETTING TO GOAL IN GLYCEMIC CONTROL:

Practical Strategies for Improved Outcomes in Type 2 Diabetes

STATEMENT OF NEEDAs rates of type 2 diabetes continue to soar and the number of endocrinologistsin the United States remains relatively low, primary care clinicians are beingcalled upon to treat increasing numbers of these patients. A number of trialshave shown that aggressive efforts to achieve and maintain A1C target levels significantly decrease the risk for adverse events in patients with type 2 diabetes.Indeed, the 2007 Physician Quality Reporting Initiative (PQRI) listed control ofA1C in patients with diabetes as the number-one target for Physician QualityMeasures.1

Many patients in primary care are not meeting the recommended AmericanDiabetes Association (ADA) target of A1C <7%, and overall compliance with ADAguidelines for the management of diabetes is poor.2,3 Failure to treat patients togoal subjects them to prolonged exposure to elevated glucose levels, increasingtheir potential for serious adverse outcomes.

Importantly, poor glycemic control often reflects the failure of health careproviders to intensify diabetes therapy when indicated.4

This clinical monograph will help increase the primary care clinician’s confi-dence and ability in improving glycemic control in patients with type 2 diabetes,reducing risk for morbidity and mortality, and fostering the positive results thatcan be obtained through timely and sustained intervention. Useful strategies forpractice improvement will be presented, drawing on the expertise of type 2 dia-betes experts.

REFERENCES1. Centers for Medicare and Medicaid Services. Physician Quality Reporting Initiative, 2007. Available at: http://www.cms.hhs.gov/pqri/. Accessed October 23, 2008.2. Resnick HE, Foster GL, Bardsley J, Ratner RE. Achievement of American DiabetesAssociation clinical practice recommendations among U.S. adults with diabetes,1999-2002: the National Health and Nutrition Examination Survey. Diabetes Care.2006;29:531-537.3. Putzer GJ, Ramirez AM, Sneed K, et al. Prevalence of patients with type 2 diabetes melli-tus reaching the American Diabetes Association’s target guidelines in a university primarycare setting. South Med J. 2004;97:145-148.4. Calvert MJ, McManus RJ, Freemantle N. The management of people with type 2 diabeteswith hypoglycaemic agents in primary care: retrospective cohort study. Fam Pract. 2007;24:224-229.

LEARNING OBJECTIVESAfter participating in this activity, clinicians should be better able to:• Identify at least one barrier in their practice to the effective treatment of

their patients with type 2 diabetes• Establish a plan to implement improvements in their office-wide systems

for the case management of patients with type 2 diabetes• Outline a systematic approach in their practice to the diagnosis and treatment

of type 2 diabetes that leads to improved long-term outcomes

TARGET AUDIENCEPrimary care clinicians who manage patients with type 2 diabetes.

DISCLOSURE POLICYBoston University School of Medicine asks all individuals involved in the develop-ment of Continuing Medical Education (CME) activities to disclose all relationshipswith commercial interests. This information is disclosed to CME activity partici-pants. Boston University School of Medicine has procedures to resolve apparentconflicts of interest. In addition, faculty members are asked to disclose when anydiscussion of unapproved use of pharmaceuticals and devices is being discussed.

FACULTY/REVIEWER DISCLOSURESElaine Fleck, MD, has received grant and research support from AccordPharmaceutical Co., Ltd.

Jane Seley, MPH, MSN, GNP, CDE, BC-ADM, is a consultant for Abbott DiabetesCare, Amylin Pharmaceuticals, Inc., Roche Diabetes Care, and Sanofi-AventisPharmaceuticals. Ms. Seley is on the advisory boards for Abbott Diabetes Care,Amylin Pharmaceuticals, Inc., and Sanofi-Aventis Pharmaceuticals and is on thespeaker’s bureaus for Amylin Pharmaceuticals, Inc. and Sanofi-AventisPharmaceuticals.

Elliot Sternthal, MD, is on the speaker’s bureaus for Amylin Pharmaceuticals,Inc., AstraZeneca, Eli Lilly and Co., and Merck & Co., Inc.

John R. White, Jr., PA-C, PharmD, has nothing to disclose with regard to com-mercial interests.

BUSM PROGRAM DEVELOPMENT/PUBLISHING STAFF DISCLOSURESJason Worcester, MD, BUSM CME Reviewer, has nothing to disclose withregard to commercial interests.

Julie White, Lara Zisblatt, and Elizabeth Gifford, BUSM, have nothing to disclose with regard to commercial interests.

Sally Farrand and Krista Sierra, Haymarket Medical Education, have nothingto disclose with regard to commercial interests.

Unlabeled/investigational use of commercial products is not discussed in thisactivity.

Cover Image: Photo Researchers

©2009 Haymarket Medical Education LP, 25 Philips Parkway, Montvale, NJ 07645 (201) 799-4800.

Release date: February 2009Expiration date: February 28, 2010

2 FEBRUARY 2009

ACCREDITATIONThis activity has been planned and implemented in accordance withthe essential areas and policies of the Accreditation Council forContinuing Medical Education through the joint sponsorship ofBoston University School of Medicine and Haymarket MedicalEducation. Boston University School of Medicine is accredited bythe ACCME to provide continuing medical education for physicians.Boston University School of Medicine designates this educationalactivity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™.Physicians should only claim credit commensurate with the extentof their participation in the activity. This program has been approved for 1.0 contact hour of continuingeducation by the American Academy of Nurse Practitioners. ProgramID 0812574

Review Date: December 2008 Release Date: February 2009. Creditavailable through February 28, 2010.

CME/CE credit will be awarded provided this activity is used andcompleted according to instructions and a score of 70% or better isachieved. A certificate of credit will be sent within six weeks ofreceipt of the test answers to those who successfully complete theexamination.

DISCLAIMERTHESE MATERIALS AND ALL OTHER MATERIALS PROVIDED IN CON-JUNCTION WITH CONTINUING MEDICAL EDUCATION ACTIVITIESARE INTENDED SOLELY FOR PURPOSES OF SUPPLEMENTING CONTIN-UING MEDICAL EDUCATION PROGRAMS FOR QUALIFIED HEALTHCARE PROFESSIONALS. ANYONE USING THE MATERIALS ASSUMESFULL RESPONSIBILITY AND ALL RISK FOR THEIR APPROPRIATE USE.TRUSTEES OF BOSTON UNIVERSITY MAKES NO WARRANTIES ORREPRESENTATIONS WHATSOEVER REGARDING THE ACCURACY, COM-PLETENESS, CURRENTNESS, NONINFRINGEMENT, MERCHANTABILITY,OR FITNESS FOR A PARTICULAR PURPOSE OF THE MATERIALS. IN NOEVENT WILL TRUSTEES OF BOSTON UNIVERSITY BE LIABLE TO ANY-ONE FOR ANY DECISION MADE OR ACTION TAKEN IN RELIANCE ONTHE MATERIALS. IN NO EVENT SHOULD THE INFORMATION IN THEMATERIALS BE USED AS A SUBSTITUTE FOR PROFESSIONAL CARE.

©2009 Haymarket Medical Education LP

A SUPPLEMENT TO THE CLINICAL ADVISOR

FEBRUARY 2009 3



Elaine Fleck, MDAssociate Clinical Professor of MedicineDepartment of Internal MedicineNew York Presbyterian Hospital-

Columbia University Medical CenterNew York, NY

Jane Seley, MPH, MSN, GNP,CDE, BC-ADMDiabetes Nurse PractitionerDivision of EndocrinologyNew York Presbyterian-Weill Cornell Medical Center

New York, NY

Elliot Sternthal, MD Assistant Professor of Medicine

Endocrinology, Diabetes, and NutritionBoston University School of MedicineClinical Director of Diabetes ServicesBoston Medical CenterBoston, MA

John R. White, Jr., PA-C, PharmDProfessor of PharmacotherapyWashington State University,

College of PharmacySpokane, WA

PUBLISHING STAFFEDITORKrista Sierra

CONTRIBUTING EDITORSally Farrand

PROGRAM MANAGERFay Nham

ART DIRECTORJeff Gherman

BUSM PROGRAM DEVELOPMENT STAFFLara Zisblatt, MA, Assistant Director

Julie White, MS, Administrative Director

Elizabeth Gifford, Program Manager

TABLE OF CONTENTS

4 Primary Care Management of Type 2 Diabetes:Data From a Performance Improvement Program

7 Update on the Optimal Management of PatientsWith Type 2 Diabetes

17 Case Study: Long-Term Management of a Middle-Aged Woman With Type 2 Diabetes

19 CME/CE Post-Test

FACULTY


4 FEBRUARY 2009



NATIONAL PERFORMANCE GAPS IN DIABETES CARENumerous reports in the medical literature support the needfor practice improvements in identifying and caring for patients with type 2 diabetes. According to the PhysicianConsortium for Performance Improvement (a physician-ledinitiative that includes methodologic experts, clinical expertsrepresenting more than 50 national medical specialty soci-eties, state medical societies, the Agency for Healthcare Research and Quality, and the Centers for Medicare andMedicaid Services), in contrast to American Diabetes Associ-ation (ADA) recommendations, up to 35% of Medicare patients with diabetes do not receive at least one A1C test peryear. As many as 41% do not receive a lipid profile at leastevery 2 years; and approximately 43% do not receive yearlyeye examinations.1 In addition, 2 in 5 persons with diabeteshave poor LDL cholesterol control; only 27% achieve HDLcholesterol targets;1 and 1 in 3 has poor blood pressure con-trol.1 Only 28% of non-disabled adults with diabetes reportgetting the recommended levels of physical activity.1

A number of trials have shown that aggressive efforts toachieve and maintain A1C target levels significantly decreasethe risk for adverse cardiovascular events in patients with type 2diabetes. On average, each 1% reduction in A1C is associatedwith a 37% decrease in the risk of microvascular end points anda 21% decrease in the risk of any diabetes-related end point.2

Yet, only 50% of adult patients with type 2 diabetes meet therecommended ADA goal of A1C <7%, and 20% have poorglycemic control as defined by A1C >9%.3

Poor glycemic control often reflects the reluctance of healthcare providers to intensify diabetes therapy when indicated andthe reluctance or inability of patients to follow the treatmentplan. A study by Shah and colleagues found that only 50% oftype 2 diabetes patients with high A1C levels had their medica-tion regimens intensified.4

Patient barriers also contribute to failure to meet A1C goal

levels: cost and inadequate access to health care services cannegatively impact treatment adherence.5 Individuals withtype 2 diabetes may be reluctant to add new medications totheir treatment regimens, especially insulin, which they mayview as a sign of their “failure”to control their condition,or asan additional burden in an already complex regimen.

No matter the cause, failure to achieve target A1C levels im-poses a significant burden on the patient. Brown and col-leagues found that clinicians did not initiate drug (metformin)treatment until patients with type 2 diabetes had an A1C above9% on average; by the time therapy was started,patients had ac-cumulated up to 5 years of exposure to elevated glucose levels,6

subjecting them to a significantly higher risk of microvascularand macrovascular complications.

Clinicians can certainly improve their performance in themanagement of type 2 diabetes.Many of the practice gaps canbe overcome through systems improvements at these practicesthat support both clinician and patient.Even small practice im-provements, such as adding a flow sheet to patient charts or instituting an electronic reminder system, can help clinicians to fulfill standards of care with little or no extra burden on their practices.

DATA FROM A PERFORMANCE IMPROVEMENTINITIATIVE FOR MANAGING PATIENTS WITHTYPE 2 DIABETES In an effort to bridge the gaps between knowledge and prac-tice in the management of type 2 diabetes,Boston UniversitySchool of Medicine, in collaboration with Haymarket Medical Education, has launched a year-long, Mentor QITM

initiative, “Getting Patients to Goal in Glycemic Control:A Type 2 Diabetes Performance Improvement Program.” Theoverall goals of this initiative are to improve primary care clini-cians’ compliance with evidence-based, nationally acceptedguidelines for diagnosing and managing type 2 diabetes, and to promote practical, sustainable changes in participants’

Primary Care Management of Type 2 Diabetes:Data From a Performance Improvement Program

practices. Toward this end, the program will facilitate im-provements in the care and management of patients with type2 diabetes, including the aggressive control of A1C levelsthrough regular reassessment and treatment adjustment.

Registrants will participate in the 3 program steps:• Current practice assessment through chart review• Creation and implementation of an individualized action

plan to improve practice• Completion of a second chart review to determine the

effectiveness of improvements made in clinical diabetes practice

The program has already recruited nearly 300 primary care cli-nicians from across the country. The organizers of this initia-tive surveyed participants upon registration to assess theircurrent practices regarding the management of patients withtype 2 diabetes.A number of their findings confirm previouslypublished practice gaps.

PROGRAM PARTICIPANTSAmong the primary care registrants,112 are nurse practitioners(NPs), 59 are physician assistants (PAs), and 30 are physicians.The remaining registrants represent nurses,care managers,dia-betes educators, and pharmacists. Nearly 43% practice in agroup setting,while 31% are hospital- or clinic-based;16% aresolo practitioners.Approximately one half of participants havebeen in practice for 10 years or fewer.

PRACTICE PATTERNSFifty-two percent of practices employ an electronic healthrecord, but just 30% maintain a registry of their patients withdiabetes; only 38% have implemented a quality improvementprogram around diabetes management. Even fewer practices(27%) report use of pay-for-performance measures.

The ADA recommends that to enhance diabetes manage-ment, a health care team support structure, a system for pa-tient reminders, and education on the need to adhere to theprescribed regimen are needed.7 The current survey data in-dicate that improvements in these domains are also warrant-ed: Only 54% of practices offer or encourage patienteducation, and 18% of practices do not have access to a dia-betes educator. Approximately 11% (n=26) of patients did

not have a self-management goal set and/or reviewed at theirlast visit.

CARE MANAGEMENT Among the average 237 patients seen per month by these care-givers, approximately 36% have diabetes.The average patientage is 59 years.

The survey data reveal a number of indicators that improve-ments in diabetes care are needed. In terms of identifying patientsat risk as well as assessing the efficacy of treatment interventions,asmany as 21% of surveyed clinicians did not measure A1C levels as often as is indicated in the ADA guidelines. Nearly half of pa-tients (47%) did not have their home self-monitoring fasting glu-cose collected at the last visit, and 70% did not haveself-monitoring postprandial glucose levels collected.

Among patients whose blood glucose was measured at the lastoffice visit, 75% had elevated fasting glucose (>110 mg/dL),while 71% of patients had elevated postprandial glucose levels(>140 mg/dL). Moreover, 47% (n=114) of patients had A1Cvalues greater than 7% at the last visit.

Therapeutic lifestyle interventions have been shown to havea positive effect on glucose levels and the prevention of cardio-vascular morbidity/mortality associated with diabetes. How-ever, a significant percentage (30%) of patients did not receivenutritional counseling. In addition, an exercise plan had notbeen discussed with the majority of patients.

Given the progressive nature of type 2 diabetes, the majorityof patients will require pharmacologic therapy to control glu-cose levels.Approximately 57% of patients being managed bysurvey participants receive a combination therapeutic regimen(oral drugs in addition to non-insulin injectables or insulin).This is in keeping with a host of published data suggesting thatthe majority of patients with type 2 diabetes are unable toachieve sustained glycemic control with one agent.

In terms of individualizing patient care, only 48% of clini-cians organize their appointments with patients so that spe-cific topics important to their care can be discussed. Nearly40% of providers do not distribute medication reconciliationlists,and nearly 40% do not maintain health logs.

Further, clinicians often do not intensify therapy for patientswho do not achieve glycemic targets. As many as 47% (n=48)of patients with A1C greater than 7% did not have their thera-py intensified at the last visit,while 33% (n=11) of patients with


FEBRUARY 2009 5

A1C greater than 9% are not currently taking more than 2 oralmedications or insulin.Though barriers to meeting A1C goalsinclude lack of patient participation in self-care, through thischart review process, many clinicians were able to identify atleast some areas where they could improve their performanceand better manage patients.

CONCLUSIONSDespite advances in the understanding of type 2 diabetes andthe ever-increasing number of effective treatment options,rates of the disease continue to soar.As most of these patientsare diagnosed and treated in primary care, it is important thattheir providers remain up-to-date with the latest treatmentguidelines, monitor patients regularly, and know when andhow to intensify therapy.

Type 2 diabetes is too complex a disease for clinicians to treatalone. Organizational structures can support clinicians in themanagement of their patients and can help make compliancewith guidelines a part of the system, not just the individualclinician’s responsibility. The more automatic systems in place,the less time clinicians need to think about standards of care,such as A1C testing or foot exams,and the more time they canspend on patient care.

Performance-based educational programs have the potentialto increase the primary care clinician’s confidence and ability

in improving glycemic control in their patients,thereby reduc-ing risk for morbidity and mortality,and fostering the positiveresults that can be obtained through timely and sustained in-terventions.Clinicians who participate have the opportunityto assess their current clinical practice; determine prioritiesfor changes in practice; develop strategies to implementthese changes; take action;and evaluate their results.

REFERENCES1. Physician Consortium for Performance Improvement:Adult DiabetesMeasures.Available at: http://www.amaassn.org/ama1/pub/upload/mm/370/diabetesset.pdf.Accessed October 7, 2008.

2.The Diabetes Control and Complications Trial/Epidemiology ofDiabetes Interventions and Complications (DCCT/EDIC) Study ResearchGroup. Intensive diabetes treatment and cardiovascular disease in patientswith type 1 diabetes. N Engl J Med. 2005;353:2643-2653.

3. Putzer GJ, Ramirez AM, Sneed K, et al. Prevalence of patients with type 2diabetes mellitus reaching the American Diabetes Association’s target guide-lines in a university primary care setting. South Med J. 2004;97:145-148.

4. Shah BR, Hux JE, Laupacis A, et al. Clinical inertia in response to inade-quate glycemic control: do specialists differ from primary care physicians?Diabetes Care. 2005;28:600–606.

5. Odegard PS, Gray SL. Barriers to medication adherence in poorly con-trolled diabetes mellitus.Diabetes Educ. 2008;34:692-697.

6. Brown JB, Nichols GA, Perry AP. The burden of treatment failure intype 2 diabetes. Diabetes Care. 2004;27:1535-1540.

7.American Diabetes Association.ADA program improves diabetes care.Available at: http://www.medscape.com/viewarticle/411895.AccessedOctober 7, 2008.


6 FEBRUARY 2009



Primary care NPs, PAs, and MDs are invited to join the complimentary Mentor QI TM activity, “Getting Patients to Goal in Glycemic Control: A Type 2 Diabetes Performance Improvement Program,” to improve their practice and obtain up to 26AMA Category 1 CreditsTM.

Would You Like to Participate in a Type 2 Diabetes Performance Improvement Program?

This is an American Board of Family Medicine (ABFM)-approved program that can be appliedtoward ABFM Maintenance of Certification for Family Physicians (MC-FP) requirements. To register online, please go to: http://www.mentorqi.com. For more information, please call Boston University School of Medicine at (617) 638-4605 or (800) 688-2475.

A SUPPLEMENT TO THE CLINICAL ADVISORGETTING TO GOAL IN GLYCEMIC CONTROL:


There is a worldwide epidemic of diabetes mellitus, affectingup to 170 million individuals; the incidence is expected todouble in the next 20 years.1,2 Diabetes is the 7th leadingcause of death in the United States. Currently, more than 24 million Americans have diabetes, and 1.5 million newcases are diagnosed per year (Figure 1). A startling 6 millionare unaware they have the disease.3,4 In addition, 1 in 5 olderAmericans (>60 years of age) have diabetes.3

It is estimated that up to 50% of patients with diabetes al-ready have a disease-related complication at the time of diag-nosis.5 According to the Centers for Disease Control andPrevention (CDC), patients with diabetes are 2 to 4 timesmore likely to develop heart disease and/or stroke.3 Beckmanand colleagues noted that the rate of myocardial infarction(MI) was 20% in patients with diabetes compared with only3.5% for patients without the disease.6 Similarly, the rate of re-current MI was more than twice that for non-diabetic pa-tients. For patients with acute coronary syndrome, thepresence of diabetes worsens both early and late outcomes.The prevalence of diabetes among patients who suffer stroke is3 times greater than among matched controls.7

Patients with diabetes commonly develop the symptomaticforms of peripheral arterial disease (PAD). The majority ofpeople with diabetes aged >40 years have impaired sensation intheir feet.3 Severe forms of peripheral neuropathy are a con-tributing factor for amputation and, as a result of this alongwith concomitant vascular problems, more than 60% of non-traumatic lower-limb amputations occur in people with dia-betes.3 Diabetes is the leading cause of new cases of kidneyfailure and adult blindness.3

Beyond the medical and social impact of this epidemic, theeconomic burden of diabetes is substantial.According to theAmerican Diabetes Association (ADA), the total cost of dia-betes is $174 billion per year, encompassing $116 billion indirect costs and $58 billion in indirect costs.3 Approximately $1of every $5 spent on health care in this country results fromcaring for an individual with diabetes.3 Most cases of thedisease are managed in primary care.

An important consideration in appreciating the impact ofdiabetes is the fact that as many as 57 million Americans haveprediabetes,defined as impaired fasting glucose (IFG) and/orimpaired glucose tolerance (IGT). According to the CDC,nearly 26% of US adults aged 20 years and older have IFG,defined as FG of 100 to 125 mg/dL; this figure rises to 35%among adults aged 60 and older. In addition, IGT is a pre-diabetes state defined as a 2-hour postprandial blood glucose of140 to 199 mg/dL. It is important to recognize that patientswith IFG and/or IGT are not only at risk of progressing to diabetes, but also are at increased risk for cardiovascular complications.

Failure to achieve target A1C levels of <7% imposes a signifi-cant burden on patients,subjecting them to a higher risk of mi-crovascular and macrovascular complications.9 Despite thisknowledge, the availability of clinical guidelines to enhancecare of patients with diabetes mellitus, the array of pharmaco-logic and nonpharmacologic options for treating the disease(See Table 1),and the body of medical literature demonstratingthe efficacy of these interventions,the management of patientswith diabetes in general is less than adequate.8-10

Update on the Optimal Management ofPatients With Type 2 Diabetes

FIGURE 1. Overview of Diagnosed and UndiagnosedDiabetes in the United States – 2008

• Incidence: 1.5 million new cases diagnosed yearly• Number of adult patients predicted to double by 2025• Vast majority (>90%) of cases are type 2 diabetes

Adapted from American Diabetes Association. Available at: http://www.diabetes.org.Accessed December 10, 2008.

People With Diabetes: 24 million (8.0% of the population)

Diagnosed:18 million

Undiagnosed:6 million

People WithoutDiabetes

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The optimal management of type 2 diabetes involves acomplex process of identifying patients at risk,following nation-al guidelines including appropriately screening patients forglycemic abnormalities,selecting drug regimens that meet indi-vidual patient needs,and aggressively adjusting therapeutic inter-ventions to achieve glycemic targets.This monograph will focuson the pathogenesis and treatment of type 2 diabetes mellitus,with particular attention on developing strategies that addressglycemic abnormalities, and the importance of maximizingtherapeutic efficacy in those patients who are not achievingglycemic control. In addition, strategies for practice improve-ments in the overall management of patients with type 2 dia-betes will be discussed.After participating in this educationalactivity, primary care clinicians will be better able to developand implement effective treatment regimens and to apply evi-dence-based improvement strategies to their clinical practice.

PATHOGENESIS OF TYPE 2 DIABETESIt is important for clinicians to understand the pathogenesis oftype 2 diabetes so that specific therapeutic agents can be target-ed to the underlying physiologic changes. In addition, it is im-portant to more quickly recognize patients at risk of developingthe disease so that preventive strategies may be employed. Incontrast to Type 1 diabetes mellitus in which there is β-cell destruction that causes absolute insulin deficiency, type 2 diabetes—accounting for 90% to 95% of diabetes cases—is achronic disease characterized by resistance to the action of

insulin in peripheral tissues in muscle,fat,and liver; defective in-sulin secretion, particularly in response to a glucose stimulus;and increased glucose production by the liver.5 Patients withnewly diagnosed or short-duration type 2 diabetes are often hy-perinsulinemic but the degree of hyperinsulinemia is sufficientto overcome the insulin resistance and maintain euglycemia.

The transition from IFG and IGT to diabetes may takemany years, but as many as 70% of patients with pre-diabeteswill progress to diabetes. While some patients may have suffi-cient β-cell reserve to maintain a euglycemic state by dietrestriction, weight control, and exercise, the majority of pa-tients with IFG or IGT will ultimately require treatment withanti-diabetes agents.

Importantly,patients with insulin resistance and impaired in-sulin secretion are not only at risk for developing diabetes,butare at increased risk for a number of significant cardiovasculardisease (CVD) risk factors including hypertension and dyslipi-demia, and ultimately CVD itself.3,4 Patients with IGT exhibitdefects in insulin secretion that can be detected before the on-set of overt hyperglycemia.5

At the center of this triad of insulin resistance,defective insulinsecretion, and increased hepatic glucose production is a dys-functional β-cell.The β-cell defect is marked by an absent first-phase insulin and C-peptide response to an intravenous glucoseload and a reduced second-phase response. In type 2 diabetes,excess glucagon and diminished insulin secretion drive hepaticglucose output and contribute to hyperglycemia.5

Two important gastrointestinal hormones play a key role inregulating glucose levels: glucagon-like peptide-1 (GLP-1)and glucose-dependent insulinotropic hormone (GIP).Thesehormones are secreted in response to a meal or ingested oral glu-cose. They stimulate insulin secretion from the β-cell. In addi-tion, GLP-1 also suppresses glucagon secretion by affecting α−cells in the pancreas, and is expressed in the brain during ameal with actions on the stomach and appetite.Thus,GLP-1 de-creases the β-cell workload by returning the rate of gastric emp-tying to normal and increasing the sensation of satiety inaddition to decreasing prandial hepatic glucose output.10

These actions are known as the incretin effect and the size ofthis effect depends on the amount of glucose. In patients withtype 2 diabetes, the incretin effect is usually diminished. GIPand GLP-1 are inactivated by the enzyme dipeptidyl peptidase 4(DPP-IV).10 A complex interaction between these hormones,


MedicationRoute ofAdministration

Efficacy asMonotherapy*

Insulin (various) Parenteral >2.5

GLP analogs Parenteral 0.6

Amylin analog Parenteral 0.6

Sulfonylureas Oral 1.5

Biguanides (metformin) Oral 1.5

α-glucosidase inhibitors Oral 0.5–0.8

Thiazolidinediones Oral 0.8–1.0

Glinides Oral 1.0–1.5

DPP-IV inhibitors Oral 0.5-0.9* Measured as a reduction in A1C (%)

TABLE 1. Diabetes Agents and Efficacy as Monotherapy

neural signals, and food triggers the normal β-cellresponse, while in patients with IFG, IGT, or type 2 diabetes,glycemic regulation is impaired.

It is important to remember that both fasting plasma glucose(FPG) and postprandial plasma glucose (PPG) contribute tooverall glycemic control. Basal insulin addresses FPG, but PPGalso contributes to elevated A1C, so strategies to control bothmay be needed.11-14

In addition to exogenous basal and prandial insulin, ongoingresearch has enabled scientists to develop drugs such as incretinmimetics like exenatide and endogenous incretin enhancers likesitagliptin that target these specific physiologic defects and haveproven to be effective in addressing postprandial hyperglycemia.

DIAGNOSIS OF TYPE 2 DIABETES: RECOGNITION OF RISK FACTORS, SCREENING,AND FOLLOW-UPIn light of the large number of individuals who have the diseaseand/or insulin resistance, appropriately screening patients atrisk and carefully monitoring glycemic control among patientswith type 2 diabetes is of paramount importance.

In its latest Standards of Care, the ADA provides guidanceon the frequency of screening and indicators that should beused as well as the values at which diabetes should be diag-nosed.8 FPG and/or 2-hour oral glucose tolerance test(OGTT) is the preferred test in non-pregnant adults andchildren.Testing should be conducted in patients who:8

• Are overweight or obese (BMI >25 kg/m2) • Have one or more additional risk factors (Table 2)• Are 45 years of age or older

DIAGNOSIS OF PRE-DIABETES AND DIABETESThe criteria for diagnosing diabetes include:8

• FPG: ≥126 mg/dL (7.0 mmol/L) or• Symptoms of hyperglycemia plus a casusal plasma glucose

≥200 mg/dL or• 2-hr plasma glucose ≥200 mg/dL (11.1 mmol/L) during anOGTT

A1C levels should be measured at least twice a year in pa-tients with diabetes who are achieving target glycemic levels;A1C should be measured quarterly in patients whose medica-tion regimen has changed or who have not achieved treat-ment goals.

Screening for other risk factors such as elevation in bloodpressure and lipid abnormalities is important to identify treat-able conditions that often co-exist with diabetes and increaserisk for adverse events.8 Blood pressure should be <130/80 mm Hg and LDL cholesterol should be <100 mg/dL(2.6 mmol/L).Patients whose values exceed these levels shouldbe treated with appropriate anti-hypertensive agents and statintherapy (HMG-CoA reductase inhibitors).Regardless of lipidlevel, the ADA also recommends statin therapy for patientswith diabetes who have overt CVD or who are over 40 andhave one or more CVD risk factors.Patients with overt CVDshould strive to achieve LDL levels <70 mg/dL.8 Blood pres-sure should be measured at every office visit.Fasting lipid levelsshould be assessed at least annually in patients with diabetes.

TREATMENT INTERVENTIONS The main goal of type 2 diabetes therapy is to achieveglycemic levels that are as close to normal as possible withoutproducing significant hypoglycemia.8,15 However, theachievement of normal levels may not be possible on a sus-tained basis. Based on data from numerous clinical trials, theADA has set forth the following goals for nonpregnant adults:

• A1C:< 7.0%• Preprandial capillary plasma glucose:70-130 mg/dL• Peak postprandial capillary plasma glucose:<180 mg/dL(<10.0 mmol/L)

While several groups have recommended striving for A1C


TABLE 2. Major Risk Factors for Type 2 Diabetes

Overweight (BMI >25 kg/m2)

Habitual physical inactivity

Race/ethnicity (eg, Native American, Pacific Islander, LatinAmerican, African-American, Asian American)

Previously identified IFG or IGT

Hypertension (>140/90 mm Hg in adults)

HDL cholesterol <35 mg/dL (0.90 mmol/L) and/or triglyceride>250 mg/dL (2.82 mmol/L)

History of gestational diabetes mellitus or delivery of a babyweighing >9 lb (4.1 kg)

Polycystic ovary syndrome

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levels closer to 6.5% or even 6.0%, the benefits of reachingthese levels have not yet been proven. The Action in DiabetesandVascular Disease (ADVANCE) collaborative group recent-ly reported a 10% decrease in micro- and macrovascular eventswith intensive glucose control reflected in A1C levels of 6.5%.16

In contrast and at the same time,the Action to Control Cardio-vascular Risk in Diabetes (ACCORD) study group reportedincreased mortality without a reduction in cardiovascular eventsin patients striving to achieve A1C levels of 6.0% and below.17

Investigators for both trials recommended further study to de-termine whether these results were a reflection of the at-riskpatient populations involved (and their older ages),or whetherthe findings uncovered a previously unrecognized harm inachieving such low A1C levels. In the 2009 revision to the Clinical Practice Recommendations, the ADA states that,“until more evidence becomes available, the general goal ofA1C <7% appears reasonable for many adults for macrovas-cular risk reduction.”18 Further, the ADA states that the A1C goal may be slightly higher or lower based on patient charac-teristics (eg, presence/history of hypoglycemia, duration ofdiabetes, life expectancy);18 goals should be individualized foreach patient.

To achieve the ADA-recommended measures of glycemiccontrol,therapy for type 2 diabetes must be multifaceted.Treat-ment interventions should not only address hyperglycemia but

also lifestyle and self-care,and should include ongoing follow-upto ensure the sustainability of the desired glucose levels.Comorbid conditions that may be present at the time of diag-nosis or may be significant risk factors in complex patient casesmust also be controlled for.

In addition to glycemic measures,the ADA and other organi-zations also recommend management of comorbid conditionssuch as hypertension and dyslipidemia,which are present at thetime of diagnosis in many patients.8 These additional factorscontribute substantially to the significant risk of cardiovascularevents in patients with diabetes or insulin resistance.

In recognition of the complexity of diabetes as a disease,the ADA and other professional organizations focus on theimportance of a team approach to management.8 To achieveglycemic goals, engagement of the patient is of utmost importance.The ADA has established 10 national standardsfor diabetes self-management education (DSME) to improve clinical outcomes and patient quality of life.19 Achief component of patient engagement is frequent self-monitoring of blood glucose (SMBG) levels and periodicmeasurement of A1C levels by health care providers.8 SMBGis particularly important for patients taking insulin to ensureglycemic control and to prevent hypoglycemia and give patients the opportunity to make treatment adjustments on a daily basis.


TABLE 3. Mechanisms of Action (MOA) of Diabetes Agents10,20

Drug (Class/Examples) MOA

Insulin secretagoguessulfonylurea, repaglinide,nateglinide

Potentiate glucose-triggered insulin secretion or provoke insulin secretion independent of current glucose levels by binding to elements of the ATP-dependent potassium channel complex in membranes of β-cells

Metformin Potentiates the suppressive effects of insulin on hepatic glucose production

α-glucosidase inhibitors Blunt postprandial increments of glucose by acting within the intestinal lumen to impair theaction of enzymes that digest complex carbohydrates, disaccharides and delay proximal absorptionof glucose and stimulate gut incretins such as GLP-1 and GIP by distal carbohydrate delivery

Thiazolidinedione (TZD) Improve insulin sensitivity by binding to peroxisome-proliferative-activated receptor-γ, suppressingrelease of free fatty acids, and increasing secretion of hormones such as adiponectin, improvinginsulin sensitivity

Pramlintide (synthetic amylin) Central neuroendocrine inhibition of gastric emptying and glucagon secretion, increases satietyand blunts postprandial hyperglycemia

Incretin mimetics (exenatide) Correct GLP-1 deficiency, suppress glucagon secretion and slow gastric emptying (reduce appetite),and potentiate glucose-dependent insulin secretion

DPP-IV inhibitors (incretin enhancers)

Prevent enzymatic degradation and inactivation of GIP and GLP-1


LIFESTYLE MODIFICATIONSFor patients with type 2 diabetes,therapeutic lifestyle interven-tions are the first step.The ADA has set out guidelines for nutri-tional therapy to achieve weight loss (5% to 10% of bodyweight) and regular physical activity (150 min/week) thatshould,if possible,include resistance training 3 times per week.8

These measures have been shown to help prevent the progres-sion to diabetes among individuals with insulin resistance.20

Smoking cessation should also be an important part of the rec-ommended lifestyle modifications.

Unfortunately, benefits of therapeutic lifestyle interventionsas the sole approach to either insulin resistance or diabetes areshort-lived, and glycemic control deteriorates in the majorityof cases over time.15 Providers must then select a pharmacolog-ic treatment regimen to meet the needs of the patient and tomaximize the potential for adherence.

SELECTION OF INITIAL PHARMACOTHERAPYGiven the more than 90 diabetes drugs currently available, it iseasy to understand the challenge the clinician faces in choosing anappropriate agent as monotherapy, and in developing combina-tion regimens if the target A1C levels are not achieved. Initialtherapy targets fasting and preprandial glucose levels. Neweragents such as incretin mimetics and DPP-IV inhibitors targetpostprandial glucose levels. (For specific information aboutmechanisms of action of these agents,see Table 3.)

National and international guidelines are fairly consistent inrecommending monotherapy with an oral antidiabetic drug(OAD) as an appropriate next step after initiation of lifestyle in-terventions in patients with type 2 diabetes. The ADA/European Association for the Study of Diabetes (EASD) recentlyupdated its algorithm for selecting therapy (Figure 2) that empha-sizes the need for rapid addition (2 to 3 months) of medicationand transition to new regimens when target glycemic goals arenot achieved or sustained.15 In particular,the revised ADA/EASDalgorithm recommends that metformin be initiated along withlifestyle modifications at the time of type 2 diabetes diagnosis.Amylin agonists, α-glucosidase inhibitors, glinides, and DPP-IVagents are not included because of their lower or equivalent over-all glucose-lowering effectiveness.However,these may be appro-priate choices for some patients. Exenatide and pioglitazone canbe used as second-tier drugs when avoidance of hypoglycemia isa leading concern.Rosiglitazone is not recommended.

The key is to lower glucose levels without producing hypoglycemia and avoiding adverse effects such as weightgain, nausea, and diarrhea that accompany many agents.Four classes of drugs are broadly viewed as acceptable first-line monotherapy: sulfonylureas, metformin, insulin, and incretins.

MONOTHERAPYIf the patient’s A1C is modestly elevated (7%-8%), metformin

FIGURE 2. Updated ADA/EASD Algorithm For the Management of Type 2 Diabetes15

At diagnosis:

Lifestyle+

Metformin

Lifestyle + Metformin+

Basal Insulin


Intensive Insulin

Tier 1: Well-validated core therapies


Sulfonylureaa


PioglitazoneLifestyle + Metformin

+Pioglitazone

+ Sulfonylureaa

STEP 2STEP 1 STEP 3

Tier 2: Less well-validated therapies

No hypoglycemiaEdema/CHFBone loss


GLP-1 agonistb

No hypoglycemia Weight lossNausea/vomiting


Basal Insulin

aSulfonylureas other than glybenclamide (glyburide) or chlorpropamide. bInsufficient clinical use to be confident regarding safety.

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12 FEBRUARY 2009



would be an appropriate choice because it is less likely to pro-duce hypoglycemia.20 Alternatively, a glinide or a thiazolidine-dione (TZD) may also be considered as the first step inantidiabetes therapy for individuals with modest A1C eleva-tions. For patients whose A1C is 9% or greater, initial therapywith a sulfonylurea or insulin is recommended to achieve rapidreduction (1.5%-2.0%) in A1C.Patients with high A1C valuesat diagnosis will be less likely to respond to monotherapy, andthe clinician may need to add additional agents.21

The dosage of metformin should be titrated upward over 1 to 2 months until a maximum level of 1000 mg bid isachieved. Gastrointestinal (GI) side effects may occur as thedosage is increased;escalation can be halted and reinstituted at alater time, or it may be an indication to change or add agents.Metformin is contraindicated in patients with increased creati-nine clearance.Sulfonylurea agents may be uncommonly asso-ciated with allergic or GI side effects. TZDs have beenassociated with weight gain, edema, and anemia. Moreover,there is controversy about their role in producing cardiovascu-lar events (heart failure,MI).22

Other agents, such as α-glucosidase inhibitors (which targetpostprandial hyperglycemia) and glinides (which are short-acting insulin secretagogues), have been shown to be more effective in trials than placebo,but have not been widely stud-ied for efficacy compared with the 3 agents mentioned above.α-Glucosidase inhibitors or glinides may be useful in the eventthat adverse effects make metformin, sulfonylureas, or TZDsunacceptable choices.23

Typically in type 2 diabetes, β-cell deterioration over timeresults in reduced efficacy of a single oral agent.As reported bythe United Kingdom Prospective Diabetes Study (UKPDS),monotherapy compared with diet increased the number ofpatients achieving A1C targets.24 However, by the third year,only 50% of patients achieved A1C levels of 7%,and by year 9,only 25% achieved recommended A1C levels. Thus, the authors concluded that the majority of patients will requiremultiple therapies.

COMBINATION THERAPYGreater therapeutic efficacy can be expected when 2 drugswith different mechanisms of action are combined.25 More-over, less than maximal doses of both drugs may diminish thelikelihood of adverse effects from maximal doses of either

agent when used alone.Normally, increases in plasma glucosestimulate endogenous insulin secretion, so that when the glu-cose level decreases,so too does insulin secretion.This balanceis disturbed when insulin secretion is impaired as occurs in di-abetes or insulin resistance.Thus,oral agents that augment theremaining insulin secretory capacity or reduce demand, re-duce insulin resistance, or reduce hepatic glucose output areused in combination.

As suggested by the ADA/EASD algorithm,after dosage in-creases for the selected agents with persistent hyperglycemia,one can rationally combine oral antidiabetic drugs (OADs).15

There is no consensus regarding the addition of the seconddrug. 15 Drugs that can be added to metformin include insulin,sulfonylureas,orTZDs (Figure 3).15

If the addition of a second OAD does not achieve the de-sired A1C levels, there are other options prior to initiating in-sulin therapy. Newer therapies that augment the incretineffect (GLP-1 mimetic or DPP-IV inhibitor) have providedalternatives to lower glucose with reduced risk of hypo-glycemia and GI disturbances. Exenatide can be added tometformin and/or sulfonylurea and achieve a reduction inpostprandial glucose. An additional advantage of this agent isthe lack of weight gain that is associated with insulin andOADs.10

Sitagliptin addresses primarily PPG elevations and achievesmodest A1C improvement in patients with type 2 diabetes.26,27

Studies of pramlintide, an amylin mimetic, have shown that it reduces A1C significantly.It is indicated in combination with


FIGURE 3. Combination Therapy for Type 2 Diabetes

Approach to Combination TherapyIntensifying Therapy

metformin or glitazone+

sulfonylurea/glinideor glucosidase inh

FPG >130 mg/dL A1C >7%FPG <130 mg/dL A1C <7%

Continue AGI, DPP-IV inhib, exenatide, pramlintide,

insulin

sulfonylurea/glinide+

metformin or glitazone

prandial insulin,with or without OADs,and permits the use ofreduced insulin dose while not contributing to weight gain.10,20

If these measures are not sufficient to lower FPG, PPG, orA1C,then initiating insulin therapy is the next rational option.

INITIATING INSULIN THERAPYBasal, rapid-acting, and premixed insulin analogs are less likelyto be associated with hypoglycemia compared with human in-sulins.28 Keeping in mind that both preprandial and postpran-dial glycemic control is necessary,there are multiple approachesto initiating insulin that depend on the patient’s glycemic re-sponse to oral medication and what hyperglycemic manifesta-tions should be targeted.

In general, the first step is to address fasting glucose levelswith basal insulin therapy with an effort toward the simplestregimen.11 An individual with both preprandial and postpran-dial hyperglycemia would benefit from basal insulin therapy,beginning with NPH or detemir at bedtime,or glargine at anytime. A patient with fasting hyperglycemia and normal day-time glycemic levels would also benefit from basal insulin de-temir, or intermediate-acting NPH at bedtime. Preferencemight be given to NPH as a means of reducing the cost ofmore expensive insulin analogs,but the 3 agents are equally ef-fective in reducing A1C.However, there is less nocturnal hy-poglycemia with bedtime administration of basal analogsglargine and detemir versus NPH.29

These suggested strategies would require further intensifica-tion if initial efforts to treat hyperglycemia did not achieve A1Ctargets.Once basal insulin is optimized,prandial rapid or short-acting insulin is started,usually before the largest meal and thenadded to other meals. If using bedtime NPH, one could con-sider morning NPH, followed by the addition of rapid orshort-acting insulin before meals.

An alternate option for basal/bolus therapy might be to initiatetherapy with 1 administration of human or insulin analog premixed (biphasic) insulin at dinner, twice-daily (breakfast anddinner), or even 3 times daily with each meal, depending on the patient’s response.Premixed insulin should not be given at bedtime.

The premixed analogs, while more expensive than regularhuman premixed insulin,offer advantages including:30

• Equivalent or improved control compared with basal insulinin patients with poorly controlled diabetes (A1C levels >8.5%)

• Lower risk of hypoglycemia

However,they also come with some disadvantages,including:30

• Difficult to target A1C to <7% without increased hypoglycemia• Basal and prandial components cannot be individually titrated• Limited mealtime flexibility• Greater weight gain compared with basal insulin• Difficult to administer correction doses• Separate lunchtime prandial dose may be required• Requires more frequent SMBG compared with basal insulin• Transition to basal bolus regimen more complex than withbasal insulin

BARRIERS TO INSULIN INITIATIONA number of barriers to insulin initiation exist and must beidentified and overcome before any insulin program can besuccessful. These include both patient resistance and clinicianresistance. Patient barriers may include: needles/injections areequated with pain; presence of complications/comorbidities;inconvenience; and feeling like he or she has “failed”therapy.31

Barriers on the part of the clinician may include: the time-consuming nature of insulin regimens; inadequate support/resources; lack of updated information; and the belief that insulin is a “last resort.” Concerns shared by both patients andproviders include worries about the potential for hypo-glycemia and weight gain as well as the costs (financial and oth-erwise) of treatment.31

To overcome barr iers on the part of the clinician,health care providers could consider system changessuch as creating an insulin initiation protocol thatwould guide their choice of medication. Clinicianscould also consider developing a relationship with adiabetes expert in their area, to consult with whennecessary. To overcome patient barriers, clinicians couldlook for resources in their area to refer patients for self-man-agement education and meal-planning; be able to work to-ward providing ongoing self-management support; andaddress any emotional issues that may be affecting self-careability. To help patients comply with treatment options, clinicians should first determine the patient’s viewof therapy,what problems he or she thinks might be encoun-tered, and how these concerns can be relieved. By assessingthe patient’s view of therapy first, clinicians can work withthem to eventually acheive glycemic control through appro-priate therapeutic goals.


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PATIENT EDUCATIONControlling blood glucose levels within acceptable limits is cru-cial to the long-term health of patients with type 2 diabetes,andpatient involvement is a vital element in achieving this goal. Thepositive effects of patient education on the quality of type 2 dia-betes care have been well-documented.In addition to increasingpatient self-care,programs that emphasize self-monitoring,mealplanning,and coaching result in significant weight loss,improvedmetabolic control, and lower required doses of hypoglycemicagents.32 A recent study that examined the effects of a structureddiabetes education intervention at diagnosis on glycemic control,weight loss,and smoking cessation during a 12-month follow-upperiod found that patients in the intervention group lost moreweight and were more likely to have stopped smoking by the endof the follow-up period than were those in the control group.33

While it is clear that patient education is an essential compo-nent of the clinical management of type 2 diabetes, the bestway to implement education protocols in practice is less so.Thefollowing tips may be helpful for clinicians:

• Assess each patient’s diabetes self-care knowledge and skills• Ask patients about meal planning,physical activity,medica-tion,blood glucose monitoring

• Address patient barriers to self-care (fear of treatment;compli-

cations;denial;unrelated life stressors;lack of family/social sup-port;high cost of care;comorbidities;complexity of treatmentregimen;emotional disorders such as anxiety and depression)

• Set short-term,realistic goals (distribute no more than 3 healthmessages per visit;provide written instructions and resources)

• Use materials to promote self-management • Provide appropriate materials for reinforcement,work withpatient preferences for learning (written materials, classes,DVDs)

To ensure clear communication,clinicians should first assess eachpatient’s level of health literacy.Various methods can be imple-mented to be sure that patients understand what is being taught:

• Reassure (“I want to be sure that I explained things to youclearly”)

• Teach back (“In your own words, can you tell me what wediscussed?”)

• Showme (Self-care skills require demonstration and practice;www.askme3.org)

IMPLEMENTING SUCCESSFUL STRATEGIESIN INDIVIDUAL PRACTICE SETTINGSImproving care of patients with type 2 diabetes has become amajor goal for many practice settings. Performance improve-ment strategies have shown positive effects on glycemic con-trol; in particular, team changes and case management haveshown robust improvements.34

Clinicians do not need to handle all aspects of patient manage-ment by themselves. The “learn more and work harder”attitude toward improving practice will not sustain improvementsin care as will long-term,system-wide changes that enlist the helpof support staff and other clinicians.To begin development ofstrategies for practice improvement in their management of pa-tients with type 2 diabetes,clinicians should ask themselves whatgaps they see between care as it is and as it should be for patients;identify goals that they would like to accomplish over a set periodof time; and understand and implement techniques that canchange the nature of care delivery in their practices.

One tool that might be helpful for clinicians trying to imple-ment a change in their practice is the Model for Improvement,which introduces change on a small scale with the Plan-Do-Study-Act (PDSA) model (Figure 4).PDSA cycles allow clini-cians to test and implement change in real work settings,measuring to determine if a specific change is an improve-


FIGURE 4. The PDSA Cycle for Learning and Improvement

Act

• What changes are to be made?

• Next cycle?

Study

• Complete the analysis of the data

• Compare data to predictions

• Summarize what was learned

Plan

• Objective• Questions and

predictions (why)• Plan to carry out the

cycle (who, what,where, when)

• Plan for data collection

Do

• Carry out the plan• Document problems

and unexpected observations

• Begin analysis of the data

Once a team has set an aim, established its membership, and developed measures to determine whethera change leads to an improvement, the next step is to test the change in the real work setting. The Plan-Do-Study-Act (PDSA) cycle is shorthand for testing a change — by planning it, trying it, observing theresults, and acting on what is learned. This is the scientific method, used for action-oriented learning.

Institute for Healthcare Improvement. Available at: http://www.ihi.org/IHI/Topics/Improvement/ImprovementMethods/HowToImprove/testingchanges.htm. Accessed December 17, 2008.

ment.35 After testing a change on a small scale, learning fromeach test,and refining the change through several PDSA cycles,the health care team can implement the change on a broaderscale,and then spread the change to other parts of the organiza-tion or in other organizations.

When implementing any practice change, clinicians shouldstart small,making one concrete change in their practice and thenintroducing it to other clinicians.Any changes should be studiedto be sure they are true improvements (eg, utilizing the PDSAmodel).Resources to achieve glycemic control in patients withtype 2 diabetes are readily available;to optimize outcomes in theirpatients,providers must be aware of these resources,and be will-ing and able to utilize them in their clinical practice.

INTERVENTIONSA number of practice interventions have been shown to havepositive effects on the management of patients with type 2 dia-betes.These include:

Flow Sheets. Use of flow sheets has been shown to improve pa-tient care and adherence to evidence-based diabetes guidelines.36

An example chart flow sheet for type 2 diabetes can be found onthe Web site of the American Medical Association PhysiciansConsortium for Improvement: http://www.ama-assn.org/ama/pub/category/17750.html. Chart flow sheets for over 30other disease states are also available on the site.

Medication Reconciliation. To prevent errors and adversedrug events resulting from oversights, duplication, and otherdiscrepancies in a patient’s medication record, the Institute forHealthcare Improvement has made medication reconciliationa key strategy in its 100,000 Lives Campaign.Medication rec-

onciliation was also one of the 2006 National Patient SafetyGoals set by the Joint Commission on Accreditation ofHealthcare Organizations.The process consists of 3 steps:ver-ification (collecting the patient’s medication history); clarifi-cation (ensuring that medications and dosages are appropriate);and reconciliation (resolving any discrepancies and document-ing changes in orders).

Integration of Follow-Up Care With Phone Calls. Callingpatients can be a useful way to provide reminders (eg, for up-coming visits, to refill medications) and for coaching (eg, toimprove self-care,enforce lifestyle interventions).37

Algorithmic Care.Data support the fact that practice changes,such as the adoption of treatment algorithms, can lead to improved patient outcomes. In the Treat-to-Target trial, the systematic self-titration of bedtime basal insulin added to oraltherapy allowed the majority of patients with type 2 diabeteswith A1C levels between 7.5% and 10% who were on oralagents alone to achieve A1C <7%.29 This was likely a result of theimplementation of a simple regimen that facilitated earlier andmore effective insulin use in routine medical practice.Likewise,the GOAL A1C trial examined the use of algorithmic care inprimary care management of patients with type 2 diabetes.38

With minimal instruction,patients were able to follow an insulindose-titration algorithm and achieve significant A1C reductions,regardless of intensity of titration monitoring. This study sup-ported the facts that use of a less aggressive insulin algorithm stillresulted in better glycemic control, and that primary-care clini-cal practices can adopt algorithmic care when instituting insulin.

Optimization of Resources. Use of resources in the practicesuch as a dietitian,diabetes educator,and/or nurse can help im-prove outcomes when used to incorporate a self-managementprogram for the patient (see sidebar, Additional Resources forDiabetes Practice Improvement).

CONCLUSIONSThe timely identification of patients with type 2 diabetes is essential if the progression and complications of this worldwideepidemic are to be reduced.Appropriate screening of high-risk patients and frequent monitoring of glycemic indicatorsare crucial to the timely initiation and adjustment of therapy.Understanding the complex pathophysiology of diabetes will enable health care providers to choose therapy rationally,correctly targeting individualized abnormalities of glycemic


ADDITIONAL RESOURCES FOR DIABETESPRACTICE IMPROVEMENTAlgorithmic CareGOAL Trial. Kennedy L, et al. Diabetes Care. 2006;29:1-8.

Group Classes/Conversation Mappinghttp://www.healthyi.com/hcp/diabetes/Default.aspx

Nurse Case Management in the UnderinsuredPhilis-Tsimikas A, et al. Diabetes Care. 2004;27:110-115.

Point-of-Care TestingRust G, et al. Int J Health Care Qual Assur. 2008;21:325-335.

Self-Management EducationSone H, et al. Diabetes Care. 2002;25:2115-2116.

Nurse-Directed Diabetes CareFunnell MM, et al. Diabetes Care. 2007;30:1630-1637.

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16 FEBRUARY 2009


control.The effective treatment of the hyperglycemia associatedwith diabetes mellitus, involving OADs, insulin, incretins, andnewer therapies, is critical not only to reducing symptoms ofhyperglycemia and improving the quality of life for patientswith type 2 diabetes,but also to preventing morbidity and mor-tality from associated micro- and macrovascular disease. Thecareful selection of pharmacologic therapeutic interventionsalong with lifestyle counseling can help achieve the goals setforth by the ADA and other professional organizations.

Patient education and self-management and the involvementof the entire health care team will provide the support to achieveoptimal management. In addition, effective, evidence-based in-terventions exist that can be readily applied to individual primarycare practice,with the goal of improving patient care.

Type 2 diabetes is a complex disease that requires a complexapproach in order to maximize patient health outcomes. Anideal strategy is one that integrates the 3 critical points of dia-betes care:a prepared practice team,an integrated organization,and an informed patient.

REFERENCES1. Moore AF, Florez JC. Genetic susceptibility to type 2 diabetes and impli-cations for antidiabetic therapy. Annu Rev Med. 2008;59:95-111.2. Rosenstock J. Reflecting on type 2 diabetes prevention: more questionsthan answers! Diabetes Obes Metab. 2007;9(suppl 1):3-11.3. National Diabetes Fact Sheet. Centers for Disease Control andPrevention.Available at: http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2007.pdf.Accessed: September 29, 2008.4. Nathan DM, Davidson MB, DeFronzo RA, et al. Impaired fasting glucose and impaired glucose tolerance: implications for care. Diabetes Care.2007;30:753-759.5. Buse JB, Polonsky KS, Burant CF.Type 2 Diabetes Mellitus. In: WilliamsTextbook of Endocrinology, 11th ed. Kronenberg HM, Melmed S, PolonskyKS, Larsen PR (eds). Philadelphia, Saunders Elsevier, 2008.6. Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis: epidemi-ology, pathophysiology, and management. JAMA. 2002; 287:2570-2581.7. Himmelmann A, Hansson L, Svensson A, et al. Predictors of stroke in the elderly. Acta Med Scand. 1988;224:439-443.8.American Diabetes Association. Standards of Medical Care in Diabetes—2008. Diabetes Care. 2008;31(suppl 1):S12-S54.9. Brown JB, Nicholes GA, Perry AP.The burden of treatment failure in type 2 diabetes. Diabetes Care. 2004;27:1535-1540.10. Riddle MC, Drucker DJ. Emerging therapies mimicking the effects of amylin and glucagon-like peptide-1. Diabetes Care 2006;29:435-449.11. Ilag LL, Kerr L, Mallone JK,Tan MH. Prandial premixed insulin analogueregimens versus basal insulin analogue regimens in the managment of type 2diabetes: an evidence-based comparison. Clin Ther. 2007;29:1254-1270.12. Halimi S, Raskin P, Lievl A, et al. Efficacy of biphasic insulin aspart inpatients with type 2 diabetes. Clin Ther. 2005; 27(suppl B):S57-S74.13. Holman RR,Thorne KI, Farmer AJ, et al.Addition of biphasic, pran-dial, or basal insulin to oral therapy in type 2 diabetes. N Engl J Med.2007;57:1716-1730.14. Raccah D, Bretzel RG, Owens D, Riddle M.When basal insulin therapy

in type 2 diabetes mellitus is not enough—what next? Diabet Metab Res Rev.2007;23:257- 264.

15. Nathan DM, Buse JB, Davidson Mayer B, et al. Medical management ofhyperglycemia in type 2 diabetes: a consensus algorithm for the initiationand adjustment of therapy. Diabetes Care. 2009;32:193-203.16.ADVANCE Collaborative group. Intensive blood glucose control andvascular outcomes in patients with type 2 diabetes. N Engl J Med.2008;358: 2560-2572.17.ACCORD study group. Effects of intensive glucose lowering in typediabetes. N Engl J Med. 2008;358:2545-2559.18. American Diabetes Association. Summary of revisions for the 2009clinical practice recommendations. Diabetes Care. 2009;32(suppl 1):S3-S5.19. Funnell MM, Brown TL, Childs BP, et al. National standards for diabetesself-management education. Diabetes Care. 2007;30:1630-1637.20. Diabetes Prevention Program Research Group. Reduction in theIncidence of Type 2 diabetes with lifestyle intervention or metformin. NEngl J Med. 2002;346:393-403.21. Riddle MC. Glycemic management of type 2 diabetes: an emergingstrategy with oral agents, insulins, and combinations. Endocrinol Metab Clin North Am. 2005;34:77–98.22. Krentz AJ, Patel MB, Bailey CJ. New drugs for type 2 diabetes mellitus:what is their place in therapy? Drugs. 2008;68:2131-2162,23.Van de Laar FA, Lucassen PL,Akkermans RP, et al.Alpha-glucosidaseinhibitors for patients with type 2 diabetes: results from a Cochrane system-atic review and meta-analysis. Diabetes Care. 2005;28:154-163.24.Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet,sulfonylurea, metformin or insulin in paients with type 2 diabetes mellitus;progressive requirement for multiple therapies (UKPDS 49). JAMA. 1999;281:2005-2012.25. Riddle MC. Combined therapy with insulin plus oral agents: is there any advantage? Diabetes Care. 2008;31:S125-S130.26.Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type2 diabetes: systematic review and meta-analysis. JAMA. 2007;298:194-206.27. Goldstein BJ, Feinglos MN, Lunceford JK, et al. Effect of initial combi-nation therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and met-formin on glycemic control in patients with type 2 diabetes. Diabetes Care.2007;30:1979–1987.28. Riddle MC.Timely addition of insulin to oral therapy for type 2 dia-betes. Diabetes Care. 2002;25:395-396.29. Riddle MC, Rosenstock J, Gerich J.The Treat-to-Target Trial: random-ized addition of glargine or human NPH insulin to oral therapy of type 2diabetic patients. Diabetes Care. 2003;26:3080–3086.30. Mooradian AD, Bernbaum M,Albert SG. Narrative review: a rationalapproach to starting insulin therapy. Ann Intern Med. 2006;145:125-134.31. Polonsky W. Psychological insulin resistance: the patient perspective.Diabetes Educ. 2007;33(suppl 7):241S-244S.32. Gruesser M, Bott U, Ellermann P, et al. Evaluation of a structured treat-ment and teaching program for non-insulin-treated type II diabetic outpa-tients in Germany after the nationwide introduction of reimbursement poli-cy for physicians. Diabetes Care. 1993;16:1268-1275.33.Weinger K. Diabetes education at diagnosis: sooner rather than later? NatClin Pract Endocrinol Metab. 2008;4:482-483.34. Shojania KG, Ranji SR, McDonald KM, et al. Effects of qualityimprovement strategies for type 2 diabetes on glycemic control: a meta-regression analysis. JAMA. 2006;296:427-440.35. Institute for Healthcare Improvement. Improvement methods.Availableat: http://www.ihi.org/IHI/Topics/Improvement/ImprovementMethods/HowToImprove/.Accessed October 24, 2008.36. Hahn KA, Ferrante JM, Crosson JC, et al. Diabetes flow sheet use associ-ated with guideline adherence. Ann Fam Med. 2008;6:235-238.37. Piette JD,Weinberger M, Kraemer FB, McPhee SJ. Impact of automatedcalls with nurse follow-up on diabetes outcomes in a Department ofVeterans Affairs Health Care System: a randomized controlled trial. DiabetesCare. 2001; 24:202-208.38. Kennedy L, Herman WH, Strange P, Harris A; GOAL A1C Team. Impactof active versus usual algorithmic titration of basal insulin and point-of-careversus laboratory measurement of HbA1c on glycemic control in patientswith type 2 diabetes: the Glycemic Optimization with Algorithms and Labsat Point of Care (GOAL A1C) trial. Diabetes Care. 2006;29:1-8.

Follow-up: 1 Year LaterThe following year, she returns having lost 5 lb.Her blood pressure is now 135/88 mm Hg. Her FPG is now 145 mg/dL, her A1C is 8.2%, and her lipid values are now: TC: 229 mg/dL; LDL-C: 140 mg/dL;HDL-C: 49 mg/dL; TG: 220 mg/dL.

Question 1Your next treatment decision would be to add:1. A lipid-lowering agent2. Metformin3. Sulfonylurea4. α-glucosidase inhibitorYou prescribe simvastatin, 20 mg/d, and metformin,500 mg once a day. You ask her to return in a monthto evaluate the effectiveness of these measures. In 2 months, she returns to your office; there is nochange in her weight, while the other measures showsome improvement: FPG is 135 mg/dL, A1C is 7.9%,and her lipid values are now: TC: 200 mg/dL; LDL-C:110 mg/dL; HDL-C: 49 mg/dL; TG: 210 mg/dL.

Encouraged by her progress, you tell her that anadjustment in her medication doses may bring hercloser to American Diabetes Association (ADA) goals.

You increase her simvastatin dose to 40 mg/day andtitrate her metformin dose until it is 850 mg bid.Again, you ask her to return in 1 month to evaluatethe progress. Unfortunately, Edna fails to return forthis visit, despite calls from your office to reschedule.

Next Follow-up: 1 Year LaterAfter a 1-year absence, Edna returns to your office,complaining of fatigue and waking up several times at night to urinate. She tells you that she has tried to continue taking her medications as directed but confesses to missing some doses and is having trou-ble filling prescriptions due to the cost.


FEBRUARY 2009 17

CASE STUDYLong-Term Management of a Middle-Aged Woman With Type 2 DiabetesEdna is a 55-year-old substitute teacher. She first came to see you 4 years ago. At that time, at 5’6”, she weighed180 lb and had a body mass index (BMI) of 29. Her fasting plasma glucose (FPG) was 100 mg/dL, and her A1Clevel was 6.5%. Her blood pressure was 140/90 mm Hg, and her lipid values were: total cholesterol: 198 mg/dL;LDL-C: 130 mg/dL; HDL-C: 49 mg/dL; and TG: 202 mg/dL. She is a former smoker (20 pack-years) who quit 3 yearsprior to this visit. Her cousin has type 1 diabetes and her uncle has type 2 diabetes. At that visit, you diagnosed herwith pre-diabetes after a 2-hour glucose challenge. You recommended that she lose weight, reduce her intake ofsaturated fats and increase her intake of fruits and vegetables, and begin a moderate exercise program (eg, walking).

The following year, she returned for an annual physical examination. She had lost 10 lb and her BMI was 27.4. Her blood pressure was 150/90 mm Hg, and her laboratory report showed the following: FPG: 110 mg/dL(impaired) and A1C: 7.6%, and her lipids were unchanged (TC: 198 mg/dL; LDL-C: 130 mg/dL; HDL-C: 49 mg/dL;TG: 202 mg/dL). You reinforced the importance of her continuing her exercise program and losing weight, and pre-scribed lisinopril, 10 mg/day. An oral glucose challenge test was done to confirm the diagnosis of type 2 diabetes.The patient was distressed.

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Physical examination reveals that she has gainedweight—she is currently 170 lb and her BMI is backto 27.4. Her blood pressure is again 140/90 mm Hg.Her FPG is now 165 mg/dL, her A1C is 9.5%, and her lipid values are now TC: 230 mg/dL; LDL-C:170 mg/dL; HDL-C: 45 mg/dL; TG: 250 mg/dL.

Question 2 Would you add another oral drug, switch to adifferent agent, or increase the metformin dose?It is clear from the patient’s values that monotherapywill not be sufficient to manage her progressive dis-ease. Fifty percent of patients with type 2 diabetesrequire additional medications after 3 years to achievetarget glycosylated hemoglobin (A1C) <7%.1,2

Increasing the dose of metformin again is possible, butthe risk of side effects increases as the dosage increas-es. Moreover, combining drugs with complementarymechanisms of action might be more effective.

Sulfonylureas are associated with weight gain butcan be added to metformin in a fixed combination;the weight loss potential of metformin might work tooffset weight gain. Combining metformin with a thia-zolidinedione (TZD) such as pioglitazone would havethe additional benefit of reducing lipids and is anotherpossibility. A third alternative might be to add anincretin mimetic or enhancer.3

You decide to add a sulfonylurea (glipizide) to met-formin (2.5 mg/500 mg) twice a day, 10 to 15 minutesbefore a meal. You have increased the dose of herlisinopril to 20 mg/d and have switched her to atorva-statin, 10 mg. You ask the patient to return in 12 weeks to check the efficacy of this regimen. Youalso ask that she see the diabetes educator at thelocal hospital to reinforce the information you havebeen providing to her about her disease; your officemakes an appointment for the following day. Ednakeeps that appointment. The diabetes educator reports

to you that she is continuing to have contact with thepatient because of persistently elevated fasting glu-cose. You increase her glipizide/metformin medicationto 5 mg/1000 mg twice daily.

Next VisitIn 12 weeks, Edna returns. She has lost approximately4 lb, and her blood pressure is now 130/85 mm Hg.Her laboratory values have improved. FPG is now 135 mg/dL, her A1C is 8.2%, and her lipid values arenow TC: 190 mg/dL; LDL-C: 110 mg/dL; HDL-C: 45mg/dL; TG: 155 mg/dL.

Question 3Will you switch this patient to insulin or add athird oral agent?You decide that Edna requires a third oral antidiabeticagent or that insulin should be added. The patientexpresses great reluctance to use an injectable drug;thus, you postpone use of insulin or exenatide. You prescribe sitagliptin, 100 mg, and ask that the patientcome back in 3 weeks or sooner to assess her renalfunction. Clinical trials involving DPP-IV inhibitors have been shown to have sustained effect for at least 2 years, but ultimately this patient may end up oninsulin. After 8 weeks, her FPG is 110 mg/dL, her lipidsremain stable, and A1C is closer to goal, 7.5%. Sheagrees to return in 3 months to ensure the currentregimen continues to be effective.

References1. Grossman E, Goldbourt U. Hypertension Optimal Treatment(HOT) trial. Lancet. 1998;352:572.2. The Heart Outcomes Prevention Evaluation (HOPE) study investi-gators. Effects of an angiotensin-converting-enzyme inhibitor,ramipril, on cardiovascular events in high-risk patients. N Engl JMed. 2000;342:145-153.3. Uwaifo GI, Ratner RE. Novel pharmacologic agents for type 2diabetes. Endocrinol Metab Clin North Am. 2005;34:155-197.

CME/CE POST-TEST

GETTING TO GOAL IN GLYCEMIC CONTROL:Practical Strategies for Improved Outcomes in Type 2 Diabetes

1. An overall goal of the MENTOR QI™ Type 2 Diabetes Performance Improvement Program is to:a. Promote practical, sustainable changes in

participants’ practicesb. Provide direct-to-patient education to improve

compliance with type 2 diabetes treatmentc. Research experimental options for the treatment

of patients with type 2 diabetesd. Facilitate live, group classes for patients with

type 2 diabetes

2. Type 2 diabetes is a chronic disease characterized by:a. Resistance to the action of insulin in peripheral

tissues in muscle, fat, and liverb.Defective insulin secretion, particularly in

response to a glucose stimulusc. Increased glucose production by the liverd.All of the above

3. Regardless of lipid level, the American DiabetesAssociation (ADA) recommends that patients with diabetes who have overt cardiovascular disease receive therapy with a:a. Statinb.Bile acid sequestrantc. Fibrated.Niacin

4. The ADA guidelines recommend that patients with type 2 diabetes should have regular physicalactivities for how many minutes per week?a. 90b.120c. 150d.180

5. Which diabetic agent class works by suppressingglucagon secretion and slowing gastric emptying?a. Thiazolidinedione b. Insulin secretagoguec. α-glucosidase inhibitord. Incretin mimetic

6. For patients whose A1C is 9% or greater, the recommended initial therapy to achieve rapidreduction in A1C is: a. Metforminb.Thiazolidinedione c. Sulfonylurea d.Glitazone

7. Which of the following anti-diabetes agents posethe greastest risk for gastrointestinal upset?a. Thiazolidinedioneb.Metforminc. Sulfonylureasd.DPP-IV inhibitor

8. An individual with both preprandial and postprandial hyperglycemia would best benefit from which basal insulin preparation at bedtime?a. NPH insulin b. Insulin glargine c. Insulin lisprod.Analog premixed insulin

9. A significant advantage of the premixed insulins is that they have:a. Prandial components that can be

individually titratedb. Increased mealtime flexibilityc. Easily administered correction dosesd.A lower risk of hypoglycemia versus human

premixed insulins

10.The Institute for Healthcare Improvement hasmade ________ a key strategy in its 100,000 livescampaign.a. Patient flow sheets b.Algorithmic care c. Medication reconciliationd.Plan-Do-Study-Act Cycles

FEBRUARY 2009 19

To participate and receive credit for this activity, please read the monograph and take the test. Fill in the answer sheet andevaluation and submit before February 28, 2010. CME/CE credit will be awarded if a score of 70% or better is achieved. Forquestions please contact Boston University School of Medicine at 617.638.4605.

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CME/CE QuestionsPractical Strategies for Improved Outcomes in Type 2 Diabetes

To receive AAMMAA PPRRAA CCaatteeggoorryy 11 ccrreeddiitt™or American Academy of Nurse Practitioners continuing education credit:Via Mail or Fax: Please submit the answer sheet to Boston University School of Medicine, Continuing Medical Education,E.DIABHAYM08, 72 East Concord St., A305, Boston, MA 02118, FAX: 617-638-4905.Your certificate will be mailed to you within 4-6 weeks.

Online: Receive your certificate instantly at www.bucmetest.com. After registering, enter “E.DIABHAYM08” in the Test Code Search field.Please do not mail the original if you submit online.

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