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Synopsis of the 2017 U.S. Department of Veterans Affairs/ U.S. Department of Defense Clinical Practice Guideline: Management of Type 2 Diabetes Mellitus Paul R. Conlin, MD; Jeffrey Colburn, MD; David Aron, MD, MS; Rose Mary Pries, DrPH; Mark P. Tschanz, DO; and Leonard Pogach, MD, MBA

Description: In April 2017, the U.S. Department of Veterans Af- fairs (VA) and the U.S. Department of Defense (DoD) approved a joint clinical practice guideline for the management of type 2 diabetes mellitus.

Methods: The VA/DoD Evidence-Based Practice Work Group convened a joint VA/DoD guideline development effort that in- cluded a multidisciplinary panel of practicing clinician stakehold- ers and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel de- veloped key questions in collaboration with the ECRI Institute, which systematically searched and evaluated the literature through June 2016, developed an algorithm, and rated recom-

mendations by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.

Recommendations: This synopsis summarizes key features of the guideline in 7 areas: patient-centered care and shared decision making, glycemic biomarkers, hemoglobin A1c target ranges, individualized treatment plans, outpatient pharmaco- logic treatment, glucose targets for critically ill patients, and treatment of hospitalized patients.

Ann Intern Med. 2017;167:655-663. doi:10.7326/M17-1362 Annals.org For author affiliations, see end of text. This article was published at Annals.org on 24 October 2017.

Diabetes is the leading cause of major complica-tions, such as end-stage renal disease and lower extremity amputations, and is a significant contributor to ischemic heart disease, stroke, peripheral vascular disease, and vision loss (1). There has been increasing acceptance of the importance of individualizing glyce- mic management and assessment of risk for adverse events, especially hypoglycemia (2– 6). This is of great importance for all patients, especially older adults (aged ≥65 years) with comorbid conditions. In 2013, 12.0 million older adults in the United States had diabe- tes, comprising 40% of the 30.2 million persons with the disease (7). Older adults account for an estimated 60% to 70% of the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) diabetic population (largely retirees) (VA/DoD. Unpublished data). These considerations make safe and effective diabetes manage- ment a policy priority for health care providers (physi- cians, nurses, dietitians, and pharmacists) and policymak- ers in both the VA and the DoD.

The 2017 VA/DoD Clinical Practice Guideline (CPG) for the Management of Type 2 Diabetes Mellitus in Primary Care offers health care providers an evidence-based framework to evaluate, treat, and man- age persons with type 2 diabetes mellitus in the context of their individual needs and preferences (8). The current article is a summary of key CPG recommendations, which was developed with multiple stakeholders to ensure rep- resentation by a broad spectrum of clinicians. It provides practice recommendations for the care of patients with diabetes, with an emphasis on shared decision making.

GUIDELINE DEVELOPMENT AND REVIEW PROCESS

These recommendations were developed using methods established by the VA/DoD Evidence-Based Practice Work Group (EBPWG) (9), which are aligned

with standards for trustworthy guidelines (10). The EBPWG and the U.S. Army Medical Command selected guideline panel cochairs (1 each from the VA and the DoD). The cochairs then selected a multidisciplinary panel of practicing clinician stakeholders, including pri- mary care physicians (family and internal medicine), en- docrinologists, medical nutritionists, pharmacists, dia- betes educators, and nurse practitioners. At the start of the CPG development process and at other key points throughout, all members were required to submit dis- closure statements for potential conflicts of interest in the previous 24 months. Verbal affirmations of no con- flicts were used during meetings throughout the devel- opment process. The project team was also subject to random Web-based surveillance (for example, ProPublica).

The VA/DoD contracted with The Lewin Group, a third party with expertise in clinical practice guideline development, to facilitate meetings. The guideline panel, in collaboration with the ECRI Institute, devel- oped 9 key questions using the PICOTS (population, intervention, comparator, outcomes, timing of out- comes measurement, and setting) format. A systematic search of the peer-reviewed literature from January 2009 through March 2016 was conducted to find evidence relevant to the key questions that focused on randomized trials, systematic reviews, and meta- analyses of fair or better quality. One key question was

See also:

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updated through 14 June 2016. The search methods and results are detailed in the full guideline (8). The guideline panel rated recommendations by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method (11).

The guideline panel focused on developing new and updated recommendations using the evidence re- view for the key questions. The panel also considered, without a complete review of the relevant evidence, the current applicability of recommendations that were in- cluded in the 2010 CPG.

As part of the development process, a patient fo- cus group was also convened to better understand the perspectives of patients receiving diabetes treatment in the VA and the DoD. Five patients were included, con- sistent with the requirements of the federal Paperwork Reduction Act. All patients had type 2 diabetes and were veterans receiving care in the VA. The focus group explored knowledge of treatment options, views on the delivery of care, patients' needs and prefer- ences, and the effect of diabetes on their lives. Impor- tant concepts that emerged from the focus group were shared with the panel and informed guideline develop- ment. It was acknowledged that this convenience sam- ple may not be representative of all VA and DoD pa- tients receiving treatment for type 2 diabetes.

The draft guideline was sent to more than 15 ex- pert reviewers inside and outside the federal sector. Comments were reviewed and, where appropriate, were incorporated into the final guideline based on panel consensus. The VA/DoD EBPWG approved the final document on 3 April 2017 and released it on 17 April 2017. Recommendations are presented in the Ta- ble, and an algorithm for establishing a personalized glycemic goal and treatment plan is presented in the Figure. Key recommendations are reviewed in this article.

RECOMMENDATIONS Provide Patient-Centered Care and Incorporate Shared Decision Making

The CPG strongly encourages clinicians to incorpo- rate shared decision making and partner with their pa- tients. Shared decision making is the process by which the patient and family, in conjunction with the care pro- vider, reach an agreement about a plan of care and

Table. Summary of Recommendations From the 2017 VA/DoD CPG on the Management of Type 2 Diabetes Mellitus

General approach to type 2 diabetes care Shared decision making to enhance patient knowledge and

satisfaction is recommended. All patients with diabetes should be offered ongoing, individualized

diabetes self-management education via various methods tailored to their preferences, learning needs, and abilities and based on available resources.

Offer ≥1 type of bidirectional telehealth intervention (typically health communication via computer, telephone, or other electronic means) involving licensed independent practitioners to patients selected by their primary care provider as an adjunct to usual patient care.

Glycemic control targets and monitoring Set an HbA1c target range based on absolute reduction of risk for

significant microvascular complications, life expectancy, patient preferences, and social determinants of health using shared decision making.

Develop an individualized glycemic management plan based on the provider's appraisal of the risk–benefit ratio and patient preferences.

Assess patient characteristics, such as race, ethnicity, chronic kidney disease, and nonglycemic factors (e.g., laboratory methods and assay variability), when interpreting results of HbA1c, fructosamine, and other glycemic biomarker testing.

Individualize the target range for HbA1c, taking into account individual preferences, presence or absence of microvascular complications, and presence or severity of comorbid conditions.

A target HbA1c range of 6.0%–7.0% (if it can be safely achieved) is recommended for patients with a life expectancy greater than 10–15 y and no or mild microvascular complications.

In patients with type 2 diabetes, an HbA1c target range of 7.0%–8.5% is appropriate (if it can be safely achieved) for most persons with established microvascular or macrovascular disease, comorbid conditions, or life expectancy of 5–10 y.

A target HbA1c range of 8.0%–9.0% is recommended for patients with type 2 diabetes with a life expectancy <5 y; significant comorbid conditions; advanced complications; or difficulties with self-management attributable to mental status, disability, or other factors (such as food insecurity or insufficient social support).

Providers should be aware that HbA1c variability is a risk factor for microvascular and macrovascular outcomes.

Nonpharmacologic treatments Offer therapeutic lifestyle counseling that includes nutrition, physical

activity, cessation of smoking and excessive use of alcohol, and weight control to patients with diabetes (see VA/DoD CPGs for obesity, substance use disorders, and tobacco use cessation).

A Mediterranean diet is recommended if it aligns with patients' values and preferences.

A nutrition intervention strategy to reduce the percentage of energy from carbohydrates to 14%–45% per day and/or foods with a lower glycemic index are recommended in patients with type 2 diabetes who do not choose a Mediterranean diet.

Inpatient care Targeting blood glucose levels to <6.1 mmol/L (<110 mg/dL) for all

hospitalized patients with type 2 diabetes receiving insulin is not recommended.

Adjust insulin to maintain a blood glucose level between 6.1 and 10.0 mmol/L (110 and 180 mg/dL) only for patients with type 2 diabetes who are critically ill or have acute myocardial infarction in ICU settings.

Use of a split-mixed insulin regimen for all hospitalized patients with type 2 diabetes is not recommended.

A regimen that includes basal insulin and short-acting mealtime or basal insulin and correction insulin is recommended for non–critically ill hospitalized patients with type 2 diabetes.

Provide medication education and diabetes survival skills to patients before hospital discharge.

Table 1—Continued

Consideration for combination pharmacologic therapy Metformin should be given as the first-line agent unless it is

contraindicated. When initial therapy no longer provides adequate glycemic control,

addition of a second-line agent from another class rather than substitution (which should be reserved for intolerance of or adverse effects from a drug) is usually necessary.

When selecting an agent, consider efficacy, contraindications, drug inter- actions, comorbidities, and potential adverse effects. Discuss with patients the various treatment options, and arrive at a shared treatment plan.

CPG = clinical practice guideline; DoD = U.S. Department of Defense; HbA1c = hemoglobin A1c; ICU = intensive care unit; VA = U.S. Depart- ment of Veterans Affairs.

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Figure. Algorithmic approach to evaluating glycemic control risk factors, setting a personalized glycemic control target range, providing self-management (including lifestyle and nutrition) education, and initiating or reevaluating medication therapy.

Patient with type 2 diabetes mellitus Comorbidities and Other Considerations

lschemic vascular disease Advanced diabetic complications Diminished life expectancy Cognitive impairment or dementia Cardiovascular disease Mental health/substance use conditions Substance use disorders Any chronic kidney disease Motor disorders Acute episodes of care Cancer and transplant Transitions of care, especially initiation of insulin or change in insulin requirements, e.g., new insulin regimen at discharge

Does the patient have severe or sustained hyperglycemia or hypoglycemia needing urgent/ emergency care?

Assess patient's social determinants of health (e.g., loss of partner, food sufficiency, economic status change)

Provide all patients with understandable health information/education

Does the patient understand and feel confident about ability to self-manage? Consider teach- back method

Is the patient receiving medication?

Discusss diet and exercise

Initiate medication therapy with metformin or other agents if indicated, considering adverse effects, contraindications, and patient preferences

Are there adverse effects or other barriers/concerns with medication?

Are there problems with patient medication adherence?

Is the patient within glycemic target range?

Adjust medication therapy as indicated; consider adverse effects, contraindications and patient preferences; discuss setting new targets

Adjust and/or change medication

Reassess status and goals at next scheduled visit

Provide appropriate intervention (e.g., motivational interviewing) to address patient medication adherence; discuss with patient and family as appropriate

Refer patient to diabetes self- management education and/or medical nutrition therapy and ensure appropriate intervention to address patient adherence to lifestyle changes. Consider teach-back method

Using shared decision making, determine a personalized glycemic control target and behavioral goals by: Determining recommended glycemic control target using risk stratification criteria Discussing or evaluating the glycemic control target according to patient factors Setting a glycemic control target range after discussion with patient Setting behavioral goals Coordinating care between primary care and specialty care as needed

Consider referral to the emergency department or an endocrinologist as appropriate

Assess patient and glycemic control, taking into consideration the patient's: Age Reproductive status Comorbidities (see sidebar) Stability Medication adverse effects and contraindications

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treatment. Key principles include readiness of the pa- tient and family, tools with understandable information about the benefits and harms of all options, and strat- egies to identify and incorporate patient preferences. Patients cannot effectively participate in care and shared decision making unless they understand diabe- tes and how they can be involved in planning and car- rying out the jointly developed care plan.

Shared decision making reinforces a trusted thera- peutic relationship and increases patient satisfaction and treatment “buy-in” with regard to the methods used to reach a particular goal or treatment plan (12– 14). It should be used not only for patients with stable glycemic control but also to assist those who are not able or willing to make lifestyle changes and decisions that affect their diabetes at any time during the course of treatment. At a minimum, shared decision making should be included at the time of diagnosis, during dif- ficulties with management, and at times of transition or development of complications (14).

Benefits include greater knowledge of medications (13) and understanding of risks (14). In addition, patient-centered care and shared decision making to- gether may decrease patient anxiety, increase trust in clinicians (15), and improve treatment adherence (16). Family involvement should be considered if appropri- ate, especially in older adults (17). Patient information should be culturally appropriate; understandable and actionable by people with limited literacy skills; and ac- cessible to those with physical, sensory, or learning needs (18).

As part of the patient-centered care approach to diabetes management, clinicians should explore with the patient the outcomes of previous opportunities for shared decision making, their ability to self-manage, prior efforts to change health behaviors, past treatment experiences (including reasons for discontinuing treat- ment), and relevant clinical outcomes. In actively shar- ing decisions, they should involve the patient in priori- tizing problems to be addressed and setting specific goals regardless of the setting or level of care.

Assess Patient Characteristics and Nonglycemic Factors When Interpreting Results of Hemoglobin A1c, Fructosamine, and Other Glycemic Biomarker Testing

Many factors affect measurement of hemoglobin A1c (HbA1c) besides the level of glycemia (19). Because HbA1c level depends on the duration of erythrocyte ex- posure to glucose, conditions that alter erythrocyte life span affect the measured level of HbA1c (20, 21). Iron deficiency anemia, which prolongs erythrocyte life span and exposes the cell to glucose for a longer period, is associated with falsely elevated HbA1c levels (22). In contrast, conditions that shorten erythrocyte life span (such as hemolytic anemia) may result in falsely low HbA1c levels. Various other conditions, such as chronic kidney disease, may alter HbA1c measurement. Hemo- globin variants can result in falsely elevated or falsely lowered HbA1c levels, depending on the assay used (23–25). In addition, oral hypoglycemic agents (met-

formin or sulfonylureas) may alter the relationship be- tween blood glucose and HbA1c levels, although the clinical significance is unclear (26).

There are also racial/ethnic differences in HbA1c levels for a given level of glycemia. A previous study found that African Americans with prediabetes (27) had HbA1c values that were 0.4% higher than among white persons; those who were within 3 years of diagnosis (28) also had higher HbA1c values than white persons for any measure of glycemia. This difference cannot be explained by measured differences in glycemia, clinical factors known to affect HbA1c measurement, or so- ciodemographic factors (27, 28). Therefore, it is recom- mended that a new diagnosis of diabetes be based on a confirmatory fasting blood glucose level of at least 7.0 mmol/L (≥126 mg/dL) if the initial HbA1c value is 6.5% to 6.9%.

How and where the HbA1c level is measured can also affect results because of intralaboratory variation (variation in test accuracy and precision) and interlabo- ratory variation (variation related to use of different test methods). A single HbA1c measurement, even from a high-quality laboratory, has a margin of error such that the true value is within a range defined by the coeffi- cient of variation. Sequential HbA1c values that are within 0.5% do not statistically differ from one another unless the assay coefficient of variation is less than 3%, and ideally less than 2% (29). Treatment decisions based solely on a single HbA1c measurement without consideration of other clinical data, such as glucose monitoring results, may lead to unnecessary initiation or intensification of therapy. Comparing HbA1c tests performed in different clinical laboratories introduces another source of error, as does use of point-of-care HbA1c testing, which is not subject to systematic quality oversight. Assessing the effect of these patient charac- teristics and nonglycemic factors that affect HbA1c lev- els allows for better individualization of management. For these reasons, the VA/DoD does not recommend the use of estimated average glucose level, which is derived from HbA1c values using a formula.

Set HbA1c Target Ranges Based on Absolute Reduction in Risk for Significant Microvascular Complications, Life Expectancy, and Patient Preferences

An individualized approach to treatment goals is recommended, based on the patient's absolute risk for microvascular complications balanced against comorbidities, estimated life expectancy, presence or absence of existing complications, the risk and incon- venience associated with polypharmacy, risk for hypo- glycemia and other adverse events, effects on concom- itant conditions (such as weight), and overall treatment burden.

The shared decision-making process might be af- fected by the framing of trial results. Clinicians should therefore consider a patient's values and preferences when discussing the magnitude of clinically important outcomes and harms from trials (11). The VA/DoD CPG recommends that clinicians discuss absolute risk reduc-

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tion rather than relative risk reduction when conveying to patients their estimated likelihood of achieving a reduction in clinically significant complications or po- tential risks of therapy. The VA/DoD CPG summarizes the available evidence from major clinical trials as well as meta-analyses to inform strength of recommenda- tions (30 – 44) that apply to patients with both recent- onset and longer-duration diabetes with established complications.

Develop Individualized Treatment Plans Based on Complications, Comorbidities, Life Expectancy, and Patient Preferences

The CPG proposes HbA1c target ranges (rather than an all-or-nothing target value) based on the pres- ence or absence of microvascular complications, co- morbidities, and life expectancy. This is rooted in the substantial body of evidence showing a direct relation- ship between glucose control and microvascular com- plications (for example, retinopathy, neuropathy, and nephropathy). The overarching goal of these recom- mendations is to develop individualized treatment plans and HbA1c target ranges that are tailored to a patient's unique characteristics and goals of care.

Higher HbA1c levels carry greater risk for complica- tions, and decreasing levels prospectively reduces risk (30, 31, 33, 34). The relationship between HbA1c and risk for microvascular complications is continuous and accelerates when levels exceed 9% (35). There is no apparent HbA1c threshold above which benefits are not accrued by decreasing levels, but the absolute risk re- duction is less at lower levels (31). Thus, a decrease in HbA1c level may have minimal clinical impact on com- plications in patients with limited life expectancy. Con- versely, there are no data on the appropriate lower limit for achieved HbA1c level, although strong data ex- ist on the risks for hypoglycemia as HbA1c is targeted to near-normal levels for patients receiving insulin (36). Lower levels of HbA1c (closer to 6%) may be reasonable in younger patients treated with metformin alone.

Microvascular complications develop over an ex- tended period. Thus, persons with long life expectancy and no or mild microvascular complications (such as early background retinopathy, microalbuminuria, or mild neuropathy) may benefit from a lower HbA1c level (6.0% to 7.0%) (Supplement, available at Annals.org).

For patients with comorbidities or complications that shorten life expectancy (<10 years), higher HbA1c target ranges are appropriate. Systematic reviews com- paring intensive and conventional glucose control showed no statistically significant differences in all- cause mortality or death from cardiovascular disease but did show statistically significant risk reduction for microvascular complications, such as nephropathy, ret- inopathy, and lower extremity amputation (36 –38). These trials provided no firm evidence that decreasing HbA1c levels to less than 8.5% reduces risk for death from cardiovascular disease (39). Depending on the presence and degree of microvascular complications, HbA1c target ranges of 7.0% to 8.0% or 7.5% to 8.5% are appropriate for most patients (Supplement).

The presence of major comorbidities that decrease life expectancy (<5 years) or advanced microvascular complications (such as severe nonproliferative or pro- liferative retinopathy, renal insufficiency [stage 3b or greater chronic kidney disease], insensate extremities, or autonomic neuropathy) may justify a higher HbA1c target range. Such patients are less likely to benefit from intensive glucose control and more likely to have risks from treatment.

Intensive glucose control may cause frank harms, such as increased risk for death from cardiovascular events (40) and severe hypoglycemia (that is, hypogly- cemia requiring help from another person). Risk factors for hypoglycemia include use of specific drugs (insulin and sulfonylureas), advanced age (>75 years), cognitive impairment, and chronic kidney disease (including causes unrelated to diabetic nephropathy) (41– 43). Ad- ditional risk factors include lack of appropriate glucose monitoring, inadequate diabetes education, lack of family and social support systems, and food insuffi- ciency. There are racial differences between estimated average glucose level and HbA1c values in patients with established type 2 diabetes based on 7-point glucose testing (44). Thus, self-monitoring results and HbA1c test results may be discordant. The presence of any of these factors should prompt a discussion about higher HbA1c target ranges.

Assessing the effect of these patient characteristics and nonglycemic factors that affect HbA1c levels allows for better individualization of management. Thus, we recommend that treatment goals involve target ranges for HbA1c rather than levels above or below a specific value for most persons with diabetes. This approach is consistent with clinical and laboratory science and avoids unnecessary intensification of therapy due to fluctuations within the range. This recommendation al- lows for individualized treatment plans and is consis- tent with patient values.

Pharmaceutical Agents Should Be Selected on the Basis of Efficacy, Contraindications, Drug Interactions, Comorbidities, and Potential Adverse Effects and Patients Should Be Engaged With the Various Treatment Options and Should Arrive at a Shared Treatment Plan With Their Clinician

When individualized glycemic goals are not achieved with nonpharmacologic therapy, such as diet and increased physical activity, adjunctive therapy with medications is indicated. The magnitude of the reduc- tion in HbA1c level necessary to achieve goals should be considered when choosing medications, along with hypoglycemia risk, weight gain, administrative burden, and cost.

Although evidence for pharmacologic treatment options was not systematically reviewed as part of this guideline update, the VA/DoD CPG made the following recommendations based on a review of a recent sys- tematic review conducted by the Agency for Healthcare Research and Quality (45). First, when selecting a med- ication, efficacy, contraindications, drug interactions,

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comorbidities, and potential adverse effects must be considered. Clinicians should discuss the various treat- ment options with patients and arrive at a shared treat- ment plan. Second, metformin should be given as the first-line agent unless it is contraindicated. Third, when initial therapy no longer provides adequate glycemic control, addition of a second-line agent from another class rather than substitution is usually necessary. Sub- stitution should be reserved for intolerance of or ad- verse effects from a drug. Finally, a combination of 2 antihyperglycemic drugs has the benefit of reducing hyperglycemia by working on different mechanisms that cause it. Combination therapy needs to be guided by clinical considerations in addition to antihyperglyce- mic efficacy.

Three medications (metformin, empagliflozin, and liraglutide) have shown a specific benefit for cardiovas- cular outcomes in patients with type 2 diabetes who are at high risk for cardiovascular events. However, al- though each of these medications decreases average blood glucose level, the mechanism for improved car- diovascular outcomes cannot be ascribed solely to in- tensive glycemic control.

A limitation of studies is that many patients seen in practice, especially older patients with significant risks for potential complications from newer therapies, are often excluded from clinical trials. Clinicians should therefore be aware of drug alerts from the U.S. Food and Drug Administration because harms of therapy will continue to evolve based on postmarketing surveil- lance. Both the VA (46) and the DoD (47) maintain cri- teria for use, which are updated frequently.

Aggressive Glucose Control Is Not Recommended in Hospitalized Patients

Hyperglycemia during hospitalization is associated with adverse outcomes, and glucose-lowering interven- tions reduce morbidity and mortality in critically ill pa- tients. However, there is uncertainty about the appro- priate glucose target for hospitalized patients and about which patients benefit from glucose-lowering in- terventions. Randomized trials examining inpatient gly- cemic control and/or insulin therapy are often limited to hospitalized patients with severe illness (for example, illness requiring admission to the intensive care unit, acute myocardial infarction, or acute stroke). A large multicenter trial among critically ill patients with diabe- tes showed that a blood glucose target less than 10.0 mmol/L (<180 mg/dL) resulted in lower mortality than a target of 4.4 to 6.1 mmol/L (80 to 110 mg/dL), and the lower range was associated with increased hypoglyce- mia (odds ratio, 14.7) (48). These data should not be extrapolated to inpatients who are not in the intensive care unit because the evidence on glycemic control tar- gets in non– critically ill hospitalized patients is of low quality (49).

Achieving near-normal glucose levels in hospital- ized patients without risk for hypoglycemia can be chal- lenging. Hypoglycemic episodes are associated with in- creased risk for death in patients in the intensive care unit (50). Fingerstick blood glucose monitoring is often

performed in hospitalized patients with diagnosed dia- betes, hyperglycemia, or both to identify potentially harmful hyperglycemia and hypoglycemia. There is no evidence to support a given frequency of such monitor- ing. Therefore, the frequency of glucose monitoring should take into account the diabetes treatment method used (such as insulin or oral agents), the effect of hyperglycemia on the clinical condition requiring hospitalization, and the patient's overall stability.

Use Basal Insulin and Short-Acting Mealtime Insulin or Basal Insulin and Correction Insulin for Hospitalized Patients Who Are Not in the Intensive Care Unit

Although much attention has focused on the ap- propriate glucose target in hospitalized patients, the literature examining treatment methods for diabetes in hospitalized patients is growing (51–54). Key factors to consider in devising a glucose control strategy are pre- hospital diabetes treatment, in-hospital dietary intake, and factors that can either increase (for example, corti- costeroids) or decrease (for example, renal or liver fail- ure) insulin resistance. In patients with insulin deficiency (for example, type 1 diabetes or long-standing type 2 diabetes), providing basal insulin along with short- acting preprandial doses to cover food intake and cor- rection doses for glucose elevations tends to work well. This is referred to as a basal– bolus-plus-correction reg- imen. Such treatment schemes are often underused in the hospital, possibly due to complexity, fear of hypo- glycemia, and challenges in transferring home-based insulin regimens to the hospital setting. Many patients are instead prescribed correction insulin alone (for ex- ample, sliding-scale insulin), based on doses assigned to treat a prespecified glucose range on a scale or ta- ble. Sliding-scale insulin regimens are viewed as easy to implement but should be discouraged. Unlike regi- mens that use basal and preprandial insulin, sliding- scale insulin does not have favorable in-hospital out- comes. Basal insulin with preprandial correction doses used in general medical and surgical patients with type 2 diabetes produced similar glycemic control and rates of hypoglycemic events compared with a more com- plex regimen of basal– bolus and correction doses. Both regimens resulted in better glycemic control and fewer treatment failures than use of sliding-scale insulin alone (54). Use of basal– bolus insulin also reduced risk for postsurgical complications (51).

DISCUSSION OF DIFFERENCES BETWEEN GUIDELINES

There are similarities and differences between the recommendations from the VA/DoD CPG and those from the Standards of Medical Care in Diabetes, issued by the American Diabetes Association (ADA) (55–57); Diabetes in Older Adults: A Consensus Report, a joint report of the ADA and the American Geriatrics Society (ADA/AGS) (17); and the American Association of Clin- ical Endocrinologists (AACE) CPG (58).

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Although the ADA notes that such factors as age, race/ethnicity, and certain clinical conditions may result in differences between HbA1c level and measures of glycemic control, use of HbA1c level alone for diagnosis of diabetes is acceptable (55). In contrast, the VA/DoD CPG concluded that evidence showing racial differ- ences between HbA1c level and glycemic control for diagnosis and treatment is strong (7). Therefore, the CPG recommends that to establish a new diabetes di- agnosis, an HbA1c value of 6.5% to 6.9% should be con- firmed with an elevated fasting blood glucose level (>7.0 mmol/L [>126 mg/dL]). The guideline panel agreed that requiring a fasting blood glucose level in this setting did not pose an undue burden compared with the potential effect of an incorrect diagnosis of diabetes on life or disability insurance premiums or mil- itary career trajectory.

The VA/DoD (8), the ADA (56), and the ADA/AGS (17) recommend individualized approaches based on patient preferences. The VA/DoD CPG also recom- mends target ranges rather than thresholds. An empha- sis on dichotomous HbA1c thresholds may result in cli- nicians and patients viewing values marginally above the threshold as being clinically significant, which could result in inappropriate intensification of therapy without consideration for absolute benefits and risks. A range can accommodate known laboratory and clinical fac- tors that affect interpretation of HbA1c test results. In addition, the VA/DoD CPG is the only one to state that the evidence is strong that race affects the relationship between HbA1c level and glycemic control. The ADA states that it is prudent to establish HbA1c goals with consideration of both individualized self-monitoring blood glucose results and HbA1c results in ethnic pop- ulations (56). In addition, the VA/DoD CPG recom- mends against the use of estimated average glucose level. Thus, the VA/DoD CPG was the most explicit in stating that a target glycemic range can best balance these competing priorities and avoid intensification of therapy to a marginally higher HbA1c test result.

The VA/DoD CPG differs not only in the nature of the target but in what the target should be. For exam- ple, the ADA and the ADA/AGS recommend an HbA1c level less than 8% for patients with advanced disease, limited life expectancy, or other mitigating factors but as high as 8.5% for frail adults. The AACE recommends that the goal of therapy should be an HbA1c level of 6.5% or lower for most nonpregnant adults, if it can be achieved safely. A range of 7% to 8% is recommended in patients with a history of severe hypoglycemia, lim- ited life expectancy, advanced renal disease, or macro- vascular complications (58).

In contrast, the VA/DoD CPG concluded that, on average, the potential absolute benefit of decreasing HbA1c level from 8.5% to 8.0% in high-risk patients was less than the potential risk for harms from increasing medication therapy. The VA/DoD CPG recommends a range of 7.5% to 8.5% for most patients with life expec- tancy less than 10 years and significant comorbid con- ditions and a range of 8% to 9% for those with limited life expectancy (<5 years).

Insulin management recommendations in the in- tensive care unit are similar between the VA/DoD and ADA guidelines. The ADA recommends that insulin therapy should be initiated for treatment of persistent hyperglycemia starting at a glucose threshold of 10.0 mmol/L (180 mg/dL), with a target range of 7.8 to 10.0 mmol/L (140 to 180 mg/dL) for most critically ill pa- tients. The VA/DoD CPG recommends that insulin doses be adjusted to maintain a blood glucose level of 6.1 to 10.0 mmol/L (110 to 180 mg/dL) for critically ill patients or those with acute myocardial infarction. These recommendations should not be extrapolated to other hospital settings in the absence of randomized controlled trials.

In summary, the VA/DoD CPG attempts to convey to clinicians, policymakers, and patients the rationale for personalizing treatment on the basis of results from major trials, limitations of the HbA1c test, and evalua- tion of patient risk for adverse drug events. Conveying complex information in an understandable manner to individual patients and families through a formal pro- cess of shared decision making is thus foundational to setting and revising goals that are meaningful, safe, and achievable in everyday clinical practice (59).

From VA Boston Healthcare System, West Roxbury, Massachu- setts; San Antonio Military Medical Center, Fort Sam Houston, Texas; Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio; VHA National Center for Health Promotion and Disease Prevention, Durham, North Carolina; San Diego Internal Med- icine, San Diego, California; and Veterans Affairs Central Of- fice, Office of Specialty Care Services, Washington, DC.

Disclaimer: The views expressed in this article are not to be construed as those of the U.S. Department of Veterans Affairs or the U.S. Department of Defense.

Acknowledgment: The authors thank the participants of the VA/DoD working group for their commitment to advancing evidence-based care for diabetes (see Appendix G of the CPG [8]) and the patient focus group for their valuable in- sights into the care we provide them.

Financial Support: Development of the VA/DoD CPG was sup- ported by the Office of Quality, Safety and Value of the U.S. Department of Veterans Affairs.

Disclosures: Dr. Aron reports a grant from the U.S. Depart- ment of Veterans Affairs Health Services Research and Devel- opment Service during the conduct of the study and is a member of the quality measures committee of the Endocrine Society. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline .org/authors/icmje/ConflictOfInterestForms.do?msNum=M17 -1362.

Requests for Single Reprints: Leonard Pogach, MD, MBA, Vet- erans Affairs Central Office, Office of Specialty Care (P11), 810 Vermont Avenue, Washington, DC 20420; e-mail, leonard [email protected].

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Current author addresses and author contributions are avail- able at Annals.org.

References 1. Rewers A, Barrett-Connor E, Wingard D, Wong N, Goldberg R, Pikula A, et al. Complications of diabetes and related conditions. In: Cowie CC, Casagrande SS, Menke A, Cissell MA, Eberhardt MS, Meigs JB, et al. Diabetes in America. 3rd ed. NIH publication no. 17-1468. Bethesda: National Institutes of Health; 2017:17-36. Ac- cessed at www.niddk.nih.gov/about-niddk/strategic-plans-reports /Pages/diabetes-america-3rd-edition.aspx on 10 August 2017. 2. Pogach LM, Brietzke SA, Cowan CL Jr, Conlin P, Walder DJ, Sawin CT; VA/DoD Diabetes Guideline Development Group. Develop- ment of evidence-based clinical practice guidelines for diabetes: the Department of Veterans Affairs/Department of Defense guidelines initiative. Diabetes Care. 2004;27 Suppl 2:B82-9. [PMID: 15113788] 3. Qaseem A, Vijan S, Snow V, Cross JT, Weiss KB, Owens DK; Clin- ical Efficacy Assessment Subcommittee of the American College of Physicians. Glycemic control and type 2 diabetes mellitus: the opti- mal hemoglobin A1c targets. A guidance statement from the Amer- ican College of Physicians. Ann Intern Med. 2007;147:417-22. [PMID: 17876024] 4. Introduction: the American Diabetes Association's (ADA) evidence-based practice guidelines, standards, and related recom- mendations and documents for diabetes care. Diabetes Care. 2012;35 Suppl 1:S1-2. [PMID: 22187466] doi:10.2337/dc12-s001 5. AGS Choosing Wisely Workgroup. American Geriatrics Society identifies five things that healthcare providers and patients should question. J Am Geriatr Soc. 2013;61:622-31. [PMID: 23469880] doi: 10.1111/jgs.12226 6. Diabetes agents. In: U.S. Department of Health and Human Ser- vices. National Action Plan for Adverse Drug Event Prevention. Washington, DC: U.S. Department of Health and Human Services; 2014:99-130. Accessed at www.health.gov/hcq/pdfs/ADE-Action -Plan-Diabetes-Agents.pdf on 10 August 2017. 7. Centers for Disease Control and Prevention. National Diabetes Statistics Report 2017: Estimates of Diabetes and Its Burden in the United States. 2017. Accessed at www.cdc.gov/diabetes/pdfs/data /statistics/national-diabetes-statistics-report.pdf on 10 August 2017. 8. U.S. Department of Veterans Affairs/U.S. Department of Defense. VA/DoD Clinical Practice Guidelines for the Management of Diabe- tes Mellitus in Primary Care. 2017. Accessed at www.healthquality. va.gov/guidelines/CD/diabetes on 10 August 2017. 9. U.S. Department of Veterans Affairs/U.S. Department of Defense. VA/DoD CPG Policy Guidance. Updated 10 April 2013. Accessed at www.healthquality.va.gov/policy/index.asp on 10 August 2017. 10. Laine C, Taichman DB, Mulrow C. Trustworthy clinical guidelines [Editorial]. Ann Intern Med. 2011;154:774-5. [PMID: 21646561] doi: 10.7326/0003-4819-154-11-201106070-00011 11. Schünemann H, Brozek J, Guyatt G, Oxman A, eds. Handbook for grading the quality of evidence and the strength of recommen- dations using the GRADE approach. Updated October 2013. Ac- cessed at http://gdt.guidelinedevelopment.org on 10 August 2017. 12. Hsu WC, Lau KH, Huang R, Ghiloni S, Le H, Gilroy S, et al. Utili- zation of a cloud-based diabetes management program for insulin initiation and titration enables collaborative decision making be- tween healthcare providers and patients. Diabetes Technol Ther. 2016;18:59-67. [PMID: 26645932] doi:10.1089/dia.2015.0160 13. Branda ME, LeBlanc A, Shah ND, Tiedje K, Ruud K, Van Houten H, et al. Shared decision making for patients with type 2 diabetes: a randomized trial in primary care. BMC Health Serv Res. 2013;13:301. [PMID: 23927490] doi:10.1186/1472-6963-13-301 14. Buhse S, Mühlhauser I, Heller T, Kuniss N, Müller UA, Kasper J, et al. Informed shared decision-making programme on the preven- tion of myocardial infarction in type 2 diabetes: a randomised con- trolled trial. BMJ Open. 2015;5:e009116. [PMID: 26567256] doi:10 .1136/bmjopen-2015-009116

15. Bertakis KD, Azari R. Patient-centered care is associated with de- creased health care utilization. J Am Board Fam Med. 2011;24:229- 39. [PMID: 21551394] doi:10.3122/jabfm.2011.03.100170 16. Robinson JH, Callister LC, Berry JA, Dearing KA. Patient- centered care and adherence: definitions and applications to im- prove outcomes. J Am Acad Nurse Pract. 2008;20:600-7. [PMID: 19120591] doi:10.1111/j.1745-7599.2008.00360.x 17. Kirkman MS, Briscoe VJ, Clark N, Florez H, Haas LB, Halter JB, et al; Consensus Development Conference on Diabetes and Older Adults. Diabetes in older adults: a consensus report. J Am Geriatr Soc. 2012;60:2342-56. [PMID: 23106132] doi:10.1111/jgs.12035 18. Agency for Healthcare Research and Quality. Use the Teach- Back Method: Tool 5. Health Literacy Universal Precautions Toolkit. 2nd ed. February 2015. Accessed at www.ahrq.gov/professionals /quality-patient-safety/quality-resources/tools/literacy-toolkit/health littoolkit2-tool5.html on 9 August 2017. 19. Radin MS. Pitfalls in hemoglobin A1c measurement: when results may be misleading. J Gen Intern Med. 2014;29:388-94. [PMID: 24002631] doi:10.1007/s11606-013-2595-x 20. Cohen RM, Franco RS, Khera PK, Smith EP, Lindsell CJ, Ciraolo PJ, et al. Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c. Blood. 2008;112:4284-91. [PMID: 18694998] doi:10.1182/blood-2008-04-154112 21. Smith EP, Cohen RM. Physiologic concepts that may revise the interpretation and implications of HbA1c in clinical medicine: an American perspective. J Diabetes Sci Technol. 2015;9:696-700. [PMID: 25691656] doi:10.1177/1932296815572255 22. English E, Idris I, Smith G, Dhatariya K, Kilpatrick ES, John WG. The effect of anaemia and abnormalities of erythrocyte indices on HbA1c analysis: a systematic review. Diabetologia. 2015;58:1409-21. [PMID: 25994072] doi:10.1007/s00125-015-3599-3 23. Goldstein DE, Little RR, Lorenz RA, Malone JI, Nathan D, Peter- son CM. Tests of glycemia in diabetes. Diabetes Care. 1995;18:896- 909. [PMID: 7555528] 24. Little RR, Rohlfing CL, Hanson S, Connolly S, Higgins T, Weykamp CW, et al. Effects of hemoglobin (Hb) E and HbD traits on measurements of glycated Hb (HbA1c) by 23 methods. Clin Chem. 2008;54:1277-82. [PMID: 18556332] doi:10.1373/clinchem.2008 .103580 25. Little RR, Rohlfing CL, Hanson SE, Schmidt RL, Lin CN, Madsen RW, et al. The effect of increased fetal hemoglobin on 7 common Hb A1c assay methods [Letter]. Clin Chem. 2012;58:945-7. [PMID: 22357875] doi:10.1373/clinchem.2012.181933 26. Kim IY, Kim MJ, Lee DW, Lee SB, Rhee H, Song SH, et al. Gly- cated albumin is a more accurate glycemic indicator than hemoglo- bin A1c in diabetic patients with pre-dialysis chronic kidney disease. Nephrology (Carlton). 2015. [PMID: 25974106] doi:10.1111/nep .12508 27. Herman WH, Ma Y, Uwaifo G, Haffner S, Kahn SE, Horton ES, et al; Diabetes Prevention Program Research Group. Differences in A1c by race and ethnicity among patients with impaired glucose tol- erance in the Diabetes Prevention Program. Diabetes Care. 2007;30: 2453-7. [PMID: 17536077] 28. Viberti G, Lachin J, Holman R, Zinman B, Haffner S, Kravitz B, et al; ADOPT Study Group. A Diabetes Outcome Progression Trial (ADOPT): baseline characteristics of type 2 diabetic patients in North America and Europe. Diabet Med. 2006;23:1289-94. [PMID: 17116177] 29. Sacks DB, Arnold M, Bakris GL, Bruns DE, Horvath AR, Kirkman MS, et al. Executive summary: guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem. 2011;57:793-8. [PMID: 21617153] doi:10.1373 /clinchem.2011.163634 30. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood- glucose control with sulphonylureas or insulin compared with con- ventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837-53. [PMID: 9742976] 31. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, et al. Association of glycaemia with macrovascular and microvascular

CLINICAL GUIDELINE Synopsis of the VA/DoD Guideline on Management of Type 2 Diabetes Mellitus

662 Annals of Internal Medicine • Vol. 167 No. 9 • 7 November 2017 Annals.org

complications of type 2 diabetes (UKPDS 35): prospective observa- tional study. BMJ. 2000;321:405-12. [PMID: 10938048] 32. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359:1577-89. [PMID: 18784090] doi:10.1056 /NEJMoa0806470 33. UK Prospective Diabetes Study (UKPDS) Group. Effect of inten- sive blood-glucose control with metformin on complications in over- weight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352: 854-65. [PMID: 9742977] 34. Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, Davis M, et al; Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabe- tes mellitus. N Engl J Med. 1993;329:977-86. [PMID: 8366922] 35. The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the Diabetes Con- trol and Complications Trial. Diabetes. 1995;44:968-83. [PMID: 7622004] 36. Hemmingsen B, Lund SS, Gluud C, Vaag A, Almdal T, Hemming- sen C, et al. Targeting intensive glycaemic control versus targeting conventional glycaemic control for type 2 diabetes mellitus. Co- chrane Database Syst Rev. 2011:CD008143. [PMID: 21678374] doi: 10.1002/14651858.CD008143.pub2 37. Hasan R, Firwana B, Elraiyah T, Domecq JP, Prutsky G, Nabhan M, et al. A systematic review and meta-analysis of glycemic control for the prevention of diabetic foot syndrome. J Vasc Surg. 2016;63: 22S-28S. [PMID: 26804364] doi:10.1016/j.jvs.2015.10.005 38. Callaghan BC, Little AA, Feldman EL, Hughes RA. Enhanced glu- cose control for preventing and treating diabetic neuropathy. Co- chrane Database Syst Rev. 2012:CD007543. [PMID: 22696371] doi: 10.1002/14651858.CD007543.pub2 39. Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, et al; VADT Investigators. Glucose control and vascular compli- cations in veterans with type 2 diabetes. N Engl J Med. 2009;360: 129-39. [PMID: 19092145] doi:10.1056/NEJMoa0808431 40. Gerstein HC, Miller ME, Ismail-Beigi F, Largay J, McDonald C, Lochnan HA, et al; ACCORD Study Group. Effects of intensive gly- caemic control on ischaemic heart disease: analysis of data from the randomised, controlled ACCORD trial. Lancet. 2014;384:1936-41. [PMID: 25088437] doi:10.1016/S0140-6736(14)60611-5 41. Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, Fish L, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care. 2013;36:1384-95. [PMID: 23589542] doi:10.2337/dc12-2480 42. ORIGIN Trial Investigators. Predictors of nonsevere and severe hypoglycemia during glucose-lowering treatment with insulin glargine or standard drugs in the ORIGIN trial. Diabetes Care. 2015; 38:22-8. [PMID: 25352653] doi:10.2337/dc14-1329 43. Bruderer SG, Bodmer M, Jick SS, Bader G, Schlienger RG, Meier CR. Incidence of and risk factors for severe hypoglycaemia in treated type 2 diabetes mellitus patients in the UK—a nested case-control analysis. Diabetes Obes Metab. 2014;16:801-11. [PMID: 24612200] doi:10.1111/dom.12282 44. Wolffenbuttel BH, Herman WH, Gross JL, Dharmalingam M, Ji- ang HH, Hardin DS. Ethnic differences in glycemic markers in pa- tients with type 2 diabetes. Diabetes Care. 2013;36:2931-6. [PMID: 23757434] doi:10.2337/dc12-2711 45. Maruthur NM, Tseng E, Hutfless S, Wilson LM, Suarez-Cuervo C, Berger Z, et al. Diabetes medications as monotherapy or metformin-

based combination therapy for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2016;164:740-51. [PMID: 27088241] doi:10.7326/M15-2650 46. U.S. Department of Veterans Affairs. Pharmacy Benefits Manage- ment Services. 2017. Accessed at www.pbm.va.gov on 10 August 2017. 47. Military Health System; Defense Health Agency. DoD Pharmacy & Therapeutics Committee. 2017. Accessed at www.health.mil /PandT on 10 August 2017. 48. Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, et al; NICE-SUGAR Study Investigators. Intensive versus conventional glu- cose control in critically ill patients. N Engl J Med. 2009;360:1283-97. [PMID: 19318384] doi:10.1056/NEJMoa0810625 49. Murad MH, Coburn JA, Coto-Yglesias F, Dzyubak S, Hazem A, Lane MA, et al. Glycemic control in non-critically ill hospitalized pa- tients: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2012;97:49-58. [PMID: 22090269] doi:10.1210/jc.2011-2100 50. Kalfon P, Le Manach Y, Ichai C, Bréchot N, Cinotti R, Dequin PF, et al; CGAO-REA Study Group. Severe and multiple hypoglycemic episodes are associated with increased risk of death in ICU patients. Crit Care. 2015;19:153. [PMID: 25888011] doi:10.1186/s13054-015- 0851-7 51. Umpierrez GE, Smiley D, Jacobs S, Peng L, Temponi A, Mulligan P, et al. Randomized study of basal-bolus insulin therapy in the inpa- tient management of patients with type 2 diabetes undergoing gen- eral surgery (RABBIT 2 surgery). Diabetes Care. 2011;34:256-61. [PMID: 21228246] doi:10.2337/dc10-1407 52. Farrokhi F, Klindukhova O, Chandra P, Peng L, Smiley D, Newton C, 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;6:1022-9. [PMID: 23063027] 53. Smiley D, Umpierrez GE, Hermayer K, Newton C, Jacobs S, Ol- son DE, et al. Differences in inpatient glycemic control and response to subcutaneous insulin therapy between medicine and surgery pa- tients with type 2 diabetes. J Diabetes Complications. 2013;27:637- 41. [PMID: 23911535] doi:10.1016/j.jdiacomp.2013.05.007 54. Umpierrez GE, Smiley D, Hermayer K, Khan A, Olson DE, New- ton C, et al. Randomized study comparing a basal-bolus with a basal plus correction insulin regimen for the hospital management of medical and surgical patients with type 2 diabetes: Basal Plus Trial. Diabetes Care. 2013;36:2169-74. [PMID: 23435159] doi:10.2337 /dc12-1988 55. American Diabetes Association. 2. Classification and diagnosis of diabetes. Diabetes Care. 2017;40:S11-24. [PMID: 27979889] 56. American Diabetes Association. 6. Glycemic targets. Diabetes Care. 2017;40:S48-56. [PMID: 27979893] 57. American Diabetes Association. 11. Older adults. Diabetes Care. 2017;40:S99-104. [PMID: 27979898] 58. Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, et al. Consensus statement by the American Associa- tion of Clinical Endocrinologists and American College of Endocri- nology on the comprehensive type 2 diabetes management algorithm—2017 executive summary. Endocr Pract. 2017;23:207-38. [PMID: 28095040] doi:10.4158/EP161682.CS 59. Agency for Healthcare Research and Quality. The SHARE Ap- proach. 2017. Accessed at www.ahrq.gov/professionals/education /curriculum-tools/shareddecisionmaking/index.html on 10 August 2017.

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Current Author Addresses: Dr. Conlin: Chief, Medical Service, VA Boston Healthcare System, 1400 VFW Parkway, West Rox- bury, MA 02132. Dr. Colburn: Staff Endocrinologist, San Antonio Military Med- ical Center, 3551 Roger Brooke Drive, JBSA Fort Sam Hous- ton, TX 78234-4504. Dr. Aron: Director, Clinical Program Research and Evaluation, Louis Stokes Cleveland VA Medical Center, Administrative Building EUL 5M677, 10701 East Boulevard, Cleveland, OH 44106. Dr. Pries: National Program Manager, Veterans Health Educa- tion Program, VHA National Center for Health Promotion and Disease Prevention (10P4N), Office of Patient Care Services, 3022 Croasdaile, Suite 200, Durham, NC 27705. Dr. Tschanz: Associate Program Director, Naval Medical Cen- ter San Diego, Internal Medicine, Building 3/3, 34800 Bob Wilson Drive, San Diego, CA 92134. Dr. Pogach: National Director, Medicine, Veterans Affairs Cen- tral Office, Office of Specialty Care Services (P11), 810 Ver- mont Avenue, Washington, DC 20420.

Author Contributions: Conception and design: P.R. Conlin, J. Colburn, D. Aron, R.M. Pries, M.P. Tschanz, L. Pogach. Analysis and interpretation of the data: P.R. Conlin, J. Col- burn, D. Aron, R.M. Pries, M.P. Tschanz, L. Pogach. Drafting of the article: P.R. Conlin, J. Colburn, D. Aron, R.M. Pries, M.P. Tschanz, L. Pogach. Critical revision of the article for important intellectual con- tent: P.R. Conlin, J. Colburn, D. Aron, R.M. Pries, M.P. Tschanz, L. Pogach. Final approval of the article: P.R. Conlin, J. Colburn, D. Aron, R.M. Pries, M.P. Tschanz, L. Pogach. Provision of study materials or patients: J. Colburn.

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