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Clinical Guidelines |

Glycemic Control and Type 2 Diabetes Mellitus: The Optimal Hemoglobin A1c Targets. A Guidance Statement from the American College of Physicians FREE

Amir Qaseem, MD, PhD, MHA; Sandeep Vijan, MD, MS; Vincenza Snow, MD; J. Thomas Cross, MD, MPH; Kevin B. Weiss, MD, MPH; Douglas K. Owens, MD, MS, Clinical Efficacy Assessment Subcommittee of the American College of Physicians*
[+] Article and Author Information

From the American College of Physicians, Philadelphia, Pennsylvania; Veterans Affairs Health Services Research and the University of Michigan, Ann Arbor, Michigan; Medstudy, Colorado Springs, Colorado; Hines Veterans Affairs Hospital, Hines, Illinois; Northwestern University, Chicago, Illinois; Veterans Affairs Palo Alto Health Care System, Palo Alto, California; and Stanford University, Stanford, California


Note: Guidance statements are guides only and may not apply to all patients and all clinical situations. Thus, they are not intended to override clinicians' judgment. All ACP guidance statements are considered automatically withdrawn or invalid 5 years after publication or once an update has been issued.

Grant Support: Financial support for the development of this guideline comes exclusively from the ACP operating budget.

Potential Financial Conflicts of Interest: Grants received: V. Snow (Agency for Healthcare Research and Quality, Centers for Disease Control and Prevention, Novo Nordisk, Bristol-Myers Squibb, Pfizer Inc., Merck Pharmaceuticals). Receipt of payment for manuscript preparation: S. Vijan (American College of Physicians).

Requests for Single Reprints: Amir Qaseem, MD, PhD, MHA, American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106; e-mail, aqaseem@acponline.org.

Current Author Addresses: Drs. Qaseem and Snow: American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106.

Dr. Vijan: Veterans Affairs Health Services Research, 2215 Fuller Road, Mailstop 11H, Ann Arbor, MI 48105.

Dr. Cross: Medstudy, 1761 South 8th Street, Suite H, Colorado Springs, CO 80906.

Dr. Weiss: Hines Veterans Affairs Hospital, PO Box 5000, Hines, IL 60141.

Dr. Owens: Veterans Affairs Palo Alto Health Care System, 117 Encina Commons, Stanford, CA 94305.


Ann Intern Med. 2007;147(6):417-422. doi:10.7326/0003-4819-147-6-200709180-00012
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This guidance statement is derived from other organizations' guidelines and is based on an evaluation of the strengths and weaknesses of the available guidelines. We used the Appraisal of Guidelines, Research and Evaluation in Europe (AGREE) appraisal instrument to evaluate the guidelines from various organizations. On the basis of the review of the available guidelines, we recommend:Statement 1: To prevent microvascular complications of diabetes, the goal for glycemic control should be as low as is feasible without undue risk for adverse events or an unacceptable burden on patients. Treatment goals should be based on a discussion of the benefits and harms of specific levels of glycemic control with the patient. A hemoglobin A1c level less than 7% based on individualized assessment is a reasonable goal for many but not all patients.Statement 2: The goal for hemoglobin A1c level should be based on individualized assessment of risk for complications from diabetes, comorbidity, life expectancy, and patient preferences.Statement 3: We recommend further research to assess the optimal level of glycemic control, particularly in the presence of comorbid conditions.

*This paper, written by Amir Qaseem, MD, PhD, MHA; Sandeep Vijan, MD, MS; Vincenza Snow, MD; J. Thomas Cross, MD, MPH; Kevin B. Weiss, MD, MPH; and Douglas K. Owens, MD, MS, was developed for the American College of Physicians' Clinical Efficacy Assessment Subcommittee: Douglas K. Owens, MD, MS (Chair); Donald E. Casey Jr., MD, MPH, MBA; J. Thomas Cross Jr., MD, MPH; Paul Dallas, MD; Nancy C. Dolan, MD; Mary Ann Forciea, MD; Lakshmi Halasyamani, MD; Robert H. Hopkins Jr., MD; and Paul Shekelle, MD, PhD. Approved by the ACP Board of Regents on 28 October 2006.

Diabetes mellitus is a leading cause of morbidity and mortality in the United States. Approximately 20.8 million people in the United States (7% of the population) have diabetes, and approximately 90% to 95% of people with diabetes have type 2 diabetes. The incidence rate of diabetes in the United States for 2005 is 1.5 million cases in people age 20 years or older. Various trials have validated the need for tight glycemic control (13). Various important indices used to measure blood glucose levels include fasting or preprandial glucose, 2-hour postprandial glucose, bedtime glucose, and hemoglobin A1c levels. The terms glycosylated hemoglobin or glycated hemoglobin are also used in the literature in lieu of hemoglobin A1c.

The purpose of this paper is to present the available guidelines from various organizations to help internists and other primary care physicians with effective management for glycemic control in type 2 diabetes mellitus and target level for hemoglobin A1c. The target population for this guideline is all patients with type 2 diabetes. This evidence is based on the review of the guidelines presented in this paper. This guidance statement is derived from other organizations' guidelines and is based on an evaluation of strengths and weaknesses of the available guidelines.

The American College of Physicians (ACP) Clinical Efficacy Assessment Subcommittee (CEAS) made a policy decision to address the clinical topic areas designated by the Institute of Medicine (IOM) as priorities for improvement in their quality chasm report (4) and their priorities report (5). In the case of an IOM priority area where multiple guidelines are available from many reputable organizations, the CEAS decided to use a different methodological approach rather then develop another guideline on the topic. The CEAS felt that it would be more useful to provide clinicians with a rigorous review of the currently available guidelines so that they could make evidence-based care decisions. Glycemic control in diabetes mellitus was a priority area cited in the IOM report, and it is currently also a high-priority target of many pay-for-performance and pay-for-reporting programs throughout the United States. Thus, the CEAS developed this guidance statement for our members to address the evidence base for needed improvements of glycemic control in diabetes mellitus and how implementation of evidence-based guidelines can help improve the care they deliver.

We followed the Appraisal of Guidelines, Research and Evaluation in Europe (AGREE) collaboration method to produce this report (6). The AGREE appraisal instrument asks 23 questions in 6 domains: scope and purpose, stakeholder involvement, rigor of development, clarity and presentation, applicability, and editorial independence. The AGREE criteria do not consider information about the guideline development process that lies outside of the guideline document and is not specifically mentioned in the guideline document. Each guideline is scored by using a simple additive metric. Before conducting the evaluation, members of the guiding team from the ACP and the authors agreed on a method of stratifying the ratings into 3 main categories; these criteria are outlined in Table 1. We did not weigh scores according to these 3 categories but note our findings in our overall qualitative assessment of the guidelines as discussed here. Specifically, we viewed a lack of an explicit link between evidence and recommendations as a major flaw. A second tier of criteria included whether the authors performed a systematic search, used explicit criteria for selecting evidence, and described methods for formulating recommendations. The remaining AGREE criteria were considered as part of the overall score.

Table Jump PlaceholderTable 1.  Guideline Evaluation Criteria

We began by searching MEDLINE in February 2005 using the keyword diabetes, limited to guideline. This produced 416 articles. We then supplemented this by searching the National Guideline Clearinghouse for guidelines on diabetes. We reviewed the titles and abstracts of each document. Most of these articles did not address glycemic control (many were on such topics as screening, diagnosis of diabetes, or management of hypertension). We also excluded primary research studies, duplicate references, and outdated references (for example, the American Diabetes Association's standards of care are updated annually, so we used only the most recent guideline). We excluded articles that were not in English because of the extensive resources needed for the translation (another 8 to 12 references; the number varied because there were duplicate publications of some guidelines). We also excluded the University of Michigan guidelines because an author of our manuscript was the team leader for those guidelines. Finally, several guidelines (typically those produced by individual U.S. states) were excluded because they were explicit adoptions of other guidelines, most often those of the American Diabetes Association. We updated the search in May 2006, discovering 12 new citations, but other than an update to 1 guideline, we did not identify any new relevant guidelines.

We then obtained copies of the identified guidelines if they were available to the general public, either electronically or through publication in medical journals. These guidelines were reviewed independently by 2 reviewers using the AGREE method, with a focus on the 3 major categories that were viewed as important by the CEAS. Each guideline was scored; scores were tabulated across the domains of interest and were compared (Table 2). Although total quantitative scores varied somewhat, the qualitative assessment of guideline quality was highly consistent between the 2 reviewers; indeed, the overall rankings of the quality of the guidelines were nearly identical.

Table Jump PlaceholderTable 2.  Mean Guideline Scores across Domains of the Appraisal of Guidelines, Research and Evaluation in Europe Instrument

Guidelines were then parsed for specific recommendations relating to glycemic control (most of the guidelines encompassed a broad range of diabetes management recommendations, rather than focusing on glycemic control alone). Specific comments relating to decisions about glycemic management goals were recorded to generate an assessment of how these goals varied across guidelines. Recommendations were based on the level of evidence supporting the recommendations along with the overall quality of the guideline.

Guidelines from Other Organizations

American Association of Clinical Endocrinologists (2002)

The guideline states that normalization of blood glucose levels should be the goal. The suggested target hemoglobin A1c level is 6.5% or less (8).

Comments: This guideline is based on consensus review with no systematic literature review.

American Academy of Family Physicians (1999–2005)

The guideline states that because of differences in patients' life expectancies and comorbid conditions, it is inappropriate to set a uniform target hemoglobin A1c level for all patients with type 2 diabetes (7).

Comments: This guideline is very comprehensive. It clearly discusses the literature search, and the recommendations follow the evidence. This guideline has not been updated since 1999. Because the guideline does not state a specific target hemoglobin A1c level, assessing guideline-concordant care will be difficult.

American Diabetes Association (2006)

The guideline states that lowering hemoglobin A1c values has been associated with a reduction of microvascular and neuropathic complications of diabetes (9). The hemoglobin A1c goal for patients in general is less than 7%. The American Diabetes Association also recommends that more stringent goals, such as a normal hemoglobin A1c value of less than 6%, be considered in individual patients if they are achievable without significant hypoglycemia. Less stringent goals may be appropriate for patients with limited life expectancies, very young or older adults, and individuals with comorbid conditions. Aggressive glycemic management with insulin may reduce morbidity in patients with severe acute illness, perioperatively, after myocardial infarction, and in pregnancy.

Comments: These are the most commonly cited and adopted guidelines. However, there is no reference to a systematic review used as the basis for these recommendations.

American Geriatrics Society (2003)

The guideline states that, for older persons, target hemoglobin A1c levels should be individualized. A reasonable goal for hemoglobin A1c in relatively healthy adults with good functional status is 7% or lower. For frail older adults, persons with a life expectancy of less than 5 years, and others in whom the risks of intensive glycemic control outweigh the benefits, a less stringent target, such as 8%, is appropriate (10).

Comments: These recommendations are based on a comprehensive literature review but are limited to geriatric populations and such conditions as depression, urinary incontinence, falls, and cognitive impairment.

Canadian Diabetes Association (2003)

The guideline states that glycemic targets must be individualized; however, therapy in most patients with type 1 or type 2 diabetes should be targeted to achieve a hemoglobin A1c level of 7.0% or lower in order to reduce the risk for microvascular and macrovascular complications (11). If it can be safely achieved, lowering postprandial plasma glucose targets toward the normal range (hemoglobin A1c value ≤6.0%) should be considered.

Comments: These recommendations may place a higher weight on evidence from observational studies than do other guidelines. In addition, the recommendation to achieve the target level of 6% or lower is based on consensus.

Institute for Clinical Systems Improvement (2004)

The guideline states that the goal for glycemic control is a hemoglobin A1c level less than 7.0% (12). The hemoglobin A1c target should be individualized; higher levels may be appropriate in patients with advanced age, at high risk for hypoglycemia, and with limited life expectancy (12).

Comments: There was no information about stakeholders involved in the development of this guideline. Recommendations were based on comprehensive review, but description of the process was limited.

National Institute for Health and Clinical Excellence (2002)

The guideline states that for each individual, a target hemoglobin A1c (aligned with the Diabetes Control and Complications Trial) between 6.5% and 7.5% should be set on the basis of the risk for macrovascular and microvascular complications (13).

Comments: This guideline is based on a very comprehensive evidence review. However, the guideline is long because of the breadth of topics covered.

Scottish Intercollegiate Guidelines Network (2001)

This guideline suggests that good glycemic control should be maintained to reduce risk, noting that the target should be “around 7.0%” (14).

Comments: This guideline is based on a very comprehensive evidence review and focused on prevention and management of complications of diabetes. However, it does not have a section focusing just on glycemic control.

Veterans Health Administration (2003)

The guideline states that for patients with very mild or no microvascular complications of diabetes, and those without major concurrent illnesses and with a reasonable life expectancy, the hemoglobin A1c target should be 7% (15).

Comments: This guideline has a comprehensive discussion of risks and benefits of glycemic control.

Guidelines differed in whether they recommended a specific hemoglobin A1c target, and for those that did, the choice of target hemoglobin A1c varied. All guidelines except those from the American Academy of Family Physicians set hemoglobin A1c targets. Most guidelines used a target hemoglobin A1c level of approximately 7%, but several recommended tailoring the target hemoglobin A1c according to such factors as risk for microvascular and macrovascular complications, patient life expectancy, and comorbid conditions. All guidelines agree on setting individualized target hemoglobin A1c levels.

On the basis of the review of the available guidelines, we recommend the following:

Statement 1: To prevent microvascular complications of diabetes, the goal for glycemic control should be as low as is feasible without undue risk for adverse events or an unacceptable burden on patients. Treatment goals should be based on a discussion of the benefits and harms of specific levels of glycemic control with the patient. A hemoglobin A1c level less than 7% based on individualized assessment is a reasonable goal for many but not all patients.

The goals for glycemic control should be as low as is feasible without undue risk for adverse events, such as hypoglycemia. Clinicians should counsel patients and emphasize the importance of good glycemic control. Clinicians should discuss treatment goals with each patient and agree jointly on goals that are feasible, given the patient's comorbid conditions, preferences, and ability to manage the treatment regimen. Therapy in many patients should be targeted to achieve a hemoglobin A1c value less than 7% to reduce the risk for complications from diabetes. However, this goal will not be appropriate for all patients. In patients who are older or frail, at increased risk for adverse complications from tight control, or have substantially reduced life expectancy from comorbid conditions, hemoglobin A1c goals higher than 7% may be appropriate. In patients who are at increased risk for microvascular complications, stringent targets may be appropriate.

Statement 2: The goal for hemoglobin A1c level should be based on individualized assessment of risk for complications from diabetes, comorbidity, life expectancy, and patient preferences.

With consideration of the importance of glycemic control, the goals for glycemic control should be individualized on the basis of the life expectancy of the patient, presence or absence of microvascular and macrovascular complications, risk for adverse events related to glucose control, and patient preferences. Less stringent targets may be appropriate in patients who have short life expectancy or are at higher risk for adverse complications of therapy.

Statement 3: We recommend further research to assess the optimal level of glycemic control, particularly in the presence of comorbid conditions.

Understanding the benefits and harms of various levels of glycemic control remains challenging, particularly in complex patients with other comorbid conditions. In addition to the importance of glycemic control, management of blood pressure and lipid levels is also essential to prevent complications of diabetes. Further research that elucidates optimal level of glycemic control in patients of different ages, in patients with comorbid conditions, and in patient populations representative of those seen in practice would provide important additional guidance for management of diabetes.

UK Prospective Diabetes Study (UKPDS) Group.  Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998; 352:837-53. PubMed
CrossRef
 
The 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 diabetes mellitus. N Engl J Med. 1993; 329:977-86. PubMed
 
Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group.  Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005; 353:2643-53. PubMed
 
Committee on Quality of Health Care in America.  Crossing the quality chasm: a new health system for the 21st century. Washington, DC: Institute of Medicine; 2001.
 
Committee on Identifying Priority Areas for Quality Improvement.  Priority areas for national action: transforming health care quality. Washington, DC: Institute of Medicine; 2003.
 
AGREE Collaboration.  Development and validation of an international appraisal instrument for assessing the quality of clinical practice guidelines: the AGREE project. Qual Saf Health Care. 2003; 12:18-23. PubMed
 
Woolf SH, Davidson MB, Greenfield S, Bell HS, Ganiats TG, Hagen MD. et al.  The benefits and risks of controlling blood glucose levels in patients with type 2 diabetes mellitus. Leawood, KS: American Academy of Family Physicians; 1999.
 
American Association of Clinical Endocrinologists.  The American Association of Clinical Endocrinologists Medical Guidelines for the Management of Diabetes Mellitus: the AACE System of Intensive Diabetes Self-Management—2002 Update. Endocr Pract. 2002; 8:40-82.
 
American Diabetes Association.  Standards of medical care in diabetes—2006. Diabetes Care. 2006; 29:Suppl 1S4-42. PubMed
 
California Healthcare Foundation/American Geriatrics Society Panel on Improving Care for Elders with Diabetes.  Guidelines for improving the care of the older person with diabetes mellitus. J Am Geriatr Soc. 2003; 51:S265-80. PubMed
 
Canadian Diabetes Association Clinical Practice Guidelines Expert Committee.  Canadian Diabetes Association 2003 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. Can J Diabetes. 2003; 27:suppl 2S1-S152.
 
Institute for Clinical Systems Improvement.  Management of type 2 diabetes mellitus. Bloomington, MN: Institute for Clinical Systems Improvement; 2004.
 
McIntosh A, Hutchinson A, Home P. et al.  Clinical guidelines and evidence review for type 2 diabetes: management of blood glucose. Sheffield, United Kingdom: ScHARR, University of Sheffield; 2002.
 
.  Management of diabetes: a national clinical guideline. Edinburgh, United Kingdom: Scottish Intercollegiate Guidelines Network; 2001.
 
Management of Diabetes Mellitus. Washington, DC: Clinical Practice Guideline Working Group, Veterans Health Administration, Department of Veterans Affairs and Health Affairs, Department of Defense; December 1999 (Update 2003). Office of Quality and Performance publication no. 10Q-CPG/DM-03.
 

Figures

Tables

Table Jump PlaceholderTable 1.  Guideline Evaluation Criteria
Table Jump PlaceholderTable 2.  Mean Guideline Scores across Domains of the Appraisal of Guidelines, Research and Evaluation in Europe Instrument

Audio

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References

UK Prospective Diabetes Study (UKPDS) Group.  Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998; 352:837-53. PubMed
CrossRef
 
The 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 diabetes mellitus. N Engl J Med. 1993; 329:977-86. PubMed
 
Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group.  Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005; 353:2643-53. PubMed
 
Committee on Quality of Health Care in America.  Crossing the quality chasm: a new health system for the 21st century. Washington, DC: Institute of Medicine; 2001.
 
Committee on Identifying Priority Areas for Quality Improvement.  Priority areas for national action: transforming health care quality. Washington, DC: Institute of Medicine; 2003.
 
AGREE Collaboration.  Development and validation of an international appraisal instrument for assessing the quality of clinical practice guidelines: the AGREE project. Qual Saf Health Care. 2003; 12:18-23. PubMed
 
Woolf SH, Davidson MB, Greenfield S, Bell HS, Ganiats TG, Hagen MD. et al.  The benefits and risks of controlling blood glucose levels in patients with type 2 diabetes mellitus. Leawood, KS: American Academy of Family Physicians; 1999.
 
American Association of Clinical Endocrinologists.  The American Association of Clinical Endocrinologists Medical Guidelines for the Management of Diabetes Mellitus: the AACE System of Intensive Diabetes Self-Management—2002 Update. Endocr Pract. 2002; 8:40-82.
 
American Diabetes Association.  Standards of medical care in diabetes—2006. Diabetes Care. 2006; 29:Suppl 1S4-42. PubMed
 
California Healthcare Foundation/American Geriatrics Society Panel on Improving Care for Elders with Diabetes.  Guidelines for improving the care of the older person with diabetes mellitus. J Am Geriatr Soc. 2003; 51:S265-80. PubMed
 
Canadian Diabetes Association Clinical Practice Guidelines Expert Committee.  Canadian Diabetes Association 2003 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. Can J Diabetes. 2003; 27:suppl 2S1-S152.
 
Institute for Clinical Systems Improvement.  Management of type 2 diabetes mellitus. Bloomington, MN: Institute for Clinical Systems Improvement; 2004.
 
McIntosh A, Hutchinson A, Home P. et al.  Clinical guidelines and evidence review for type 2 diabetes: management of blood glucose. Sheffield, United Kingdom: ScHARR, University of Sheffield; 2002.
 
.  Management of diabetes: a national clinical guideline. Edinburgh, United Kingdom: Scottish Intercollegiate Guidelines Network; 2001.
 
Management of Diabetes Mellitus. Washington, DC: Clinical Practice Guideline Working Group, Veterans Health Administration, Department of Veterans Affairs and Health Affairs, Department of Defense; December 1999 (Update 2003). Office of Quality and Performance publication no. 10Q-CPG/DM-03.
 

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Hemoglobin A1c in Dialysis Patients
Posted on September 25, 2007
Anthony J Bleyer
Section on Nephrology, Wake Forest University School of Medicine, Winston-Salem, NC 27157
Conflict of Interest: None Declared

The publication, "Clinical Guidelines: Glycemic Control and Type 2 Diabetes Mellitus: The Optimal Hemoglobin A1c Targets. A Guidance Statement from the American College of Physicians"(1) discussed the importance of achieving hemoglobin A1c (HbA1c) targets in patients with diabetes. Although they mention the lack of existing evidence supporting targets in those with co-morbid conditions, they failed to mention inherent inaccuracies of the HbA1c assay in those with severe kidney failure on hemodialysis. This group is at extremely high risk for cardiovascular complications(2). Approximately 200,000 Americans on dialysis have diabetes mellitus(3). Glycohemoglobin levels are lower than expected in this population, compared with ambient blood glucose measurements and relative to the glycated albumin assay. This effect appears related, in part, to uremia- associated reductions in erythrocyte lifespan (2). Indeed, an association between glycohemoglobin levels and survival in United States hemodialysis patients only becomes evident after controlling for hemoglobin levels(4).

Managing diabetes in the dialysis population is exceedingly difficult. These patients are at high risk for diabetic complications, in the face of increased risk for hypoglycemia(5). They also cannot utilize all pharmacologic therapies (e.g., metformin). Physicians need to be cognizant of the inaccuracy of glycosylated hemoglobin in this population. Glycosylated hemoglobin values below 7% in the hemodialysis population do not necessarily indicate optimal control, and may provide clinicians and patients a false sense of security.

Reference List

(1) Qaseem A, Vijan S, Snow V, Cross T, Weiss KB, Owens DK. Glycemic control and Type 2 diabetes mellitus: The Optimal Hemoglobin A1c targets. A guidance statement from the American College of Physicians. Ann Int Med. 2007;147:417-22.

(2) Inaba M, Okuno S, Kumeda Y, Yamda S, Imanishi Y, Tabata T et al. Glycated albumin is a better glycemic indicator than glycated hemoglobin values in hemodialysis patients with diabetes: effect of anemia and erythropoietin injection. J Am Soc Nephrol. 2007;18:896-903.

(3) National Institutes of Health: National Institute of Diabetes, Digestive, and Kidney Disease. USRDS 2007 Annual Data Report: Atlas of Chronic Kidney Disease and End Stage Renal Disease in the U.S. Bethesda,MD: 2007.

(4) Kalantar-Zadeh K, Arnovitz J, Kopple JD, McAllister CJ, Regidor DL, Whellan D et al. Hemoglobin A1C and survival in maintenance hemodialysis patients. Diabetes Care. 2007;30:1049-55.

(5) Fischer KF, Lees JA, Newman JH. Hypoglycemia in hospitalized patients. N Engl J Med. 1986;315:1245-50.

Conflict of Interest:

The authors have conducted a study sponsored by Asahi Kasei Pharma Corporation evaluating an assay of glycated albumin.

Using the AGREE to compare multiple guidelines
Posted on September 29, 2007
Valerie A. Palda
Guidelines Advisory Committee and University of Toronto
Conflict of Interest: None Declared

We read with interest the ACP guidelines on glycemic control in Type 2 diabetes mellitus (1). The use of the AGREE instrument to compare the methodologic rigour of various guidelines is a meaningful step forward, to our knowledge used regularly only by a few groups such as the Guidelines Advisory Committee in Ontario (http://www.gacguidelines.ca) and more widely in Europe by the Belgian Centre for Evidence-Based Medicine (http://www.cebam.be) and others (http://www.agreetrust.org/links.htm). Using well-developed guidelines as a basis for forming recommendations is an important strategy to improve quality of care and may also lead to efficiencies in the development process.

Nevertheless, we have two concerns with the methodology used to assess the guidelines. First, using a total AGREE score as the authors do in Table 2 (1), averaging the scores of all six domains, assumes each domain is of similar importance. However the developers of the AGREE Instrument specifically state that the domain scores should not be aggregated into a composite score because they are independent (2). Each domain score is calculated by standardising the summed up scores of individual items. Moreover, the relative importance of the domains is not static and depends on the values of the raters. In other words, total scores provide no data on performance within each domain and currently, we do not know in which of these domains bias is more likely to influence recommendations or practice (3).

Our second concern regarding the methodology of the ACP guideline is the use of only two raters. It is considered the standard for systematic reviews to have two abstractors for data, but the inter-rater agreement is optimized when at least four trained raters are used to apply the AGREE score. While current efforts with the AGREE Next Steps Project (Phase 1 and Phase 2) (4) are aimed to address this human resource demand, the current standard to achieve acceptable reliability is four (3).

The methodology of guideline development is evolving rapidly, with groups such as the Guidelines International Network (http://www.g-i-n.net) and the ADAPTE project (http://www.adapte.org) providing collaborative guidance to interested developers (5). We hope that the American College of Physicians will consider participating in these activities, providing wisdom acquired over many years of evidence-based guideline development.

References:

1. Qaseem A, Vijan S, Snow V, Cross T, Weiss KB, Owens DK. Glycemic control and Type 2 diabetes mellitus: The Optimal Hemoglobin A1c targets. A guidance statement from the American College of Physicians. Ann Int Med. 2007;147:417-22.

2.The AGREE Collaboration. The Appraisal of Guidelines for Research & Evaluation (AGREE) Instrument, 2001. London: The AGREE Research Trust. (http://www.agreetrust.org)

3. The AGREE Collaboration. Development and validation of an international appraisal instrument for assessing the quality of clinical practice guidelines: the AGREE project. Quality and Safety in Health Care 2003; 12(1): 18-23.

4. see http://www.agreetrust.org/projects.htm Accessed September 29 2007

5. Fervers B, Burgers JS, Haugh M, Latreille J, Mlika-Cabanne N, Paquet L, Coulombe M, Poirier M, Burnand B, for the ADAPTE working group. Adaptation of clinical guidelines: a review of methods and experiences. Int J Qual Health Care 2006; 18: 167-176.

Conflict of Interest:

None declared

The hegemony of "tight control"
Posted on October 2, 2007
Thomas E. Finucane
Johns Hopkins Bayview Medical Center
Conflict of Interest: None Declared

The ACP guidelines on glycemic control and type 2 diabetes present the familiar chestnut that, "Various trials have validated the need for tight glycemic control." The authors provide three references for this remark. Two of these are from the Diabetes Control and Complications Trial, which studied type 1 diabetes, and thus are not directly relevant. The third is UKPDS 33, a trial of tight control which found no significant difference in two aggregate endpoints; all-cause mortality and any diabetes-related death. The third aggregate endpoint showed a difference in a composite of diabetes-related events and found significant reduction.. The benefit was limited to microvascular events and was due largely to a reduction in the need for retinal photocoagulation.

The burdens of "tight glycemic control" can be considerable, and the "need" for tight control hasn't actually been validated. This is particularly true for the frail and elderly.

Conflict of Interest:

None declared

Guideline adaptation: an appealing alternative to de novo guideline development
Posted on October 12, 2007
Beatrice Fervers
SOR and Centre Leon Berard, Lyon, France
Conflict of Interest: None Declared

The Adapte Collaboration (www.adapte.org), an international group aiming to enhance the use of evidence through more efficient development and implementation of guidelines by guideline adaptation read with great interest the process used by the ACP to develop their statement for glycemic control (1). The development and maintenance of high quality guidelines require substantial time, expertise and resources and the ACP has used an attractive alternative to de novo guideline development. Yet, guideline adaptation also presents challenges. While guideline developers often consider existing guidelines as a source of evidence, few are using a formal process for reviewing and selecting high quality guidelines among the heterogeneous, ever-expanding volume of sometimes differing or even contradictory recommendations.

The ACP performed a comprehensive search to identify existing guidelines and used the AGREE instrument to assess their quality. This instrument has become a widely accepted standard for assessing guideline methodological quality, but does not assess guideline content. We think it is important to explicitly assess how up-to-date source guidelines are, whether recommendations are consistent with the underlying evidence, clinically useful and applicable within the targeted context of use (2, 3). Evidence supporting recommendations may be outdated within three years (4). Not all guidelines assessed by the ACP provide an explicit link between the recommendations and the underlying evidence and seven of the 9 guidelines are older than three years. Furthermore, organisational and cultural differences between countries can lead to legitimate variations in recommendations, even if the evidence based is the same (5). Thus, guidelines produced in one setting may not be appropriate for another, without modification.

The Adapte Collaboration has developed a systematic approach for the adaptation of guidelines and produced a manual and a resource toolkit. The process is designed to help customize existing guidelines to a different setting while preserving evidence-based principles as well as to encourage confidence in, acceptance, and use of adapted guidelines by targeted users.

1. Qaseem A, Vijan S, Snow V, Cross T, Weiss KB, Owens DK. Glycemic control and type 2 Diabetes Mellitus: The optimal Hemoglobin A1C targets. A guidance statement for the American College of Physicians. Ann Intern Med 2007; 147:417-422

2. Graham ID, Harrison MB, Brouwers M, Davies BL, Dunn S. Facilitating the use of evidence in practice: evaluating and adapting clinical practice guidelines for local use by health care organizations. J Obstet Gynecol Neonatal Nurs 2002;31:599-611.

3. Fervers B, Burgers JS, Haugh M, Latreille J, Mlika-Cabanne N, Paquet L, et al. Adaptation of clinical guidelines: literature review and proposition for a framework and procedure. Int J Qual Health Care 2006;18:167-76.

4. Shekelle P, Eccles MP, Grimshaw JM, Woolf SH. When should guidelines be updated? BMJ 2001; 323:155-7.

5. Eisinger F, Geller G, Burke W, Holtzman NA. Cultural basis for differences between US and French clinical recommendations for women at increased risk of breast and ovarian cancer. Lancet 1999;353:919-20.

Conflict of Interest:

None declared

In Response
Posted on December 21, 2007
Amir Qaseem
American College of Physicians
Conflict of Interest: None Declared

We would like to thank the authors of the letters for their comments on ACP's guidance statement on "Glycemic Control and Type 2 Diabetes: The Optimal Hemoglobin A1c Targets". We concur that the AGREE instrument is not comprehensive enough to capture issues such as those raised by the Adapte Collaboration. In the paper, we acknowledged the limitations of the AGREE instrument such as the inability to capture guideline development process that lies outside the guideline document. Due to these limitations, ACP developed additional criteria that are listed in table 1 of the guidance statement document that addresses concerns such as translation of evidence into recommendations. However, we agree with the authors that our criteria did not account for organizational and cultural difference between different countries and hope for a new and improved evaluation instrument that can account for shortcomings such as the ones raised in the letter.

The concern related to the use of aggregate scores vs. individual domain scores is valid and that is why we included a table in the paper showing scores for each individual question to give the reader an idea how guidelines faired against each other. In addition, we individually evaluated each guideline and summarized their strengths and weaknesses that were not necessarily based on the AGREE instrument.

We also considered the issue of using two raters. In addition to the two raters, other members of the committee also reviewed selected parts of the guidelines. We agree that more reviewers are helpful, however, and are investigating ways to increase the number of reviewers for the assessments with the AGREE instrument.

Conflict of Interest:

None declared

In Response
Posted on February 12, 2008
Robert E. Hoyt
Naval Hospital Pensacola
Conflict of Interest: None Declared
TO THE EDITOR: After admitting a 66 year old compliant type 2 diabetic with severe hypoglycemia due to oral hypoglycemic agents, I read the ACP guidance statement on glycemic control with great interest (1). Clinicians recognize the importance of decreasing practice variability by following evidence based guidelines. On the other hand, clinical guidelines may be a harder sell if the supporting evidence is lacking or there is risk related to the treatment. Unfortunately, much of what is written about the association of hyperglycemia and outcomes is based on observational studies and not on clinical trials. Importantly, the widely reported clinical trial, the United Kingdom Prospective Diabetes Study (UKPDS) failed to show a reduction in macrovascular disease with tighter glucose control. Although the UKPDS showed improvement in microvascular disease with tighter control, there was not a difference in visual acuity or blindness in spite of the reduced need for photocoagulation and there was no reduction in renal failure, in spite of reduced microalbumin levels. Not surprisingly, patients in the intensive treatment group had more episodes of hypoglycemia (2).

As pointed out in the editorial by Pogach in the same issue of the Annals, the 2007 diabetic guidelines by the American Diabetes Association (ADA) state "there are no clinical trial data available for the effects of glycemic control in patients with advanced complications, the elderly (>65 years of age) or young children"(3)(4). How many busy clinicians will make the effort to read this 37 page guideline to find this caveat and how many local guidelines warn clinicians about the need to be less stringent with the elderly or with patients with co-morbidities? How many physicians spend the majority of their visit with diabetic patients trying to improve glycemic control with little time left for intensified blood pressure and hyperlipidemia control and smoking cessation?

Two important clinical trials were reported this month. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) stopped its intensive glycemic control arm (HbA1c <6.0%) due to an unexplained 20% relative risk increase in all cause mortality (5). The follow-up STENO-2 trial studied type 2 diabetic patients with microalbuminuria, treating multiple risk factors in accordance with ADA guidelines, compared to conventional therapy. They were able to show that at 13.3 years of follow-up there was a 20% absolute risk reduction in all cause mortality (6).

Until we better understand the true risk of intensive glycemic control we should exercise caution and focus on multiple risk factor reduction and individualization of glycemic control, as recommended by the ACP guidelines.

Robert E. Hoyt MD, FACP Pensacola, Fl 32508

Potential Financial Conflicts of Interest: None disclosed

References

1. Qaseem A, Vihan S, Snow V, Cross JT, Weiss KB, Owens DK. Glycemic Control and Type 2 Diabetes Mellitus: The Optimal Hemoglobin A1C Targets. A Guidance Statement from the American College of Physicians. Ann Intern Med. 2007;147:417-422 [PMID: 17876024]

2. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837-53 [PMID: 9742976]

3. Pogash LM. "Doctor, How CERTain Are We That This Diabetes Medication Is Best For Me?" Ann Intern Med. 2007;147:428-9 [PMID: 17652707]

4. American Diabetes Association. Standards of medical care in diabetes"”2007. Diabetes Care. 2007;30 Suppl 1:S4-S41. [PMID: 17192377]

5. Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. NHLBI. www.nhlbi.nih.gov . February 6 2008 (Accessed February 7 2008)

6. Gaede, P, Lund-Andersen, H, Parving HH, Pedersen O. Effect of a Multifactorial Intervention on Mortality in Type 2 Diabetes. N Engl J Med 2008;358:580-91

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Summary for Patients

Control of Blood Sugar in Type 2 Diabetes: A Guidance Statement from the American College of Physicians

The summary below is from the full report titled “Glycemic Control and Type 2 Diabetes Mellitus: The Optimal Hemoglobin A1c Targets. A Guidance Statement from the American College of Physicians.” It is in the 18 September 2007 issue of Annals of Internal Medicine (volume 147, pages 417-422). The authors are A. Qaseem, S. Vijan, V. Snow, J.T. Cross, K.B. Weiss, and D.K. Owens, for the Clinical Efficacy Assessment Subcommittee of the American College of Physicians.

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