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Individualizing Glycemic Targets in Type 2 Diabetes Mellitus: Implications of Recent Clinical Trials

Faramarz Ismail-Beigi, MD, PhD; Etie Moghissi, MD; Margaret Tiktin, NP; Irl B. Hirsch, MD; Silvio E. Inzucchi, MD; and Saul Genuth, MD
[+] Article and Author Information

From Case Western Reserve University, Cleveland, Ohio; University of California, Los Angeles, Los Angeles, California; University of Washington, Seattle, Washington; and Yale University, New Haven, Connecticut.


Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M10-2380.

Requests for Single Reprints: Faramarz Ismail-Beigi, MD, PhD, Department of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44122-4951; e-mail, fxi2@case.edu.

Current Author Addresses: Drs. Ismail-Beigi and Genuth and Ms. Tiktin: Department of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44122-4951.

Dr. Moghissi: 4644 Lincoln Boulevard, Suite 409, Marina Del Rey, CA 90292.

Dr. Hirsch: University of Washington Medical Center, 1959 Northeast Pacific Street, Seattle, WA 98915-6176.

Dr. Inzucchi: Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520.

Author Contributions: Conception and design: F. Ismail-Beigi, E. Moghissi, M. Tiktin, S.E. Inzucchi.

Analysis and interpretation of the data: F. Ismail-Beigi, E. Moghissi, I.B. Hirsch, S.E. Inzucchi, S. Genuth.

Drafting of the article: F. Ismail-Beigi, E. Moghissi, M. Tiktin, I.B. Hirsch, S. Genuth.

Critical revision of the article for important intellectual content: F. Ismail-Beigi, E. Moghissi, M. Tiktin, I.B. Hirsch, S.E. Inzucchi, S. Genuth.

Final approval of the article: F. Ismail-Beigi, E. Moghissi, M. Tiktin, I.B. Hirsch, S.E. Inzucchi, S. Genuth.

Collection and assembly of data: F. Ismail-Beigi, E. Moghissi.


Ann Intern Med. 2011;154(8):554-559. doi:10.7326/0003-4819-154-8-201104190-00007
Text Size: A A A

One of the first steps in the management of patients with type 2 diabetes mellitus is setting glycemic goals. Professional organizations advise setting specific hemoglobin A1c (HbA1c) targets for patients, and individualization of these goals has more recently been emphasized. However, the operational meaning of glycemic goals, and specific methods for individualizing them, have not been well-described. Choosing a specific HbA1c target range for a given patient requires taking several factors into consideration, including an assessment of the patient's risk for hyperglycemia-related complications versus the risks of therapy, all in the context of the overall clinical setting. Comorbid conditions, psychological status, capacity for self-care, economic considerations, and family and social support systems also play a key role in the intensity of therapy. The individualization of HbA1c targets has gained more traction after recent clinical trials in older patients with established type 2 diabetes mellitus failed to show a benefit from intensive glucose-lowering therapy on cardiovascular disease (CVD) outcomes. The limited available evidence suggests that near-normal glycemic targets should be the standard for younger patients with relatively recent onset of type 2 diabetes mellitus and little or no micro- or macrovascular complications, with the aim of preventing complications over the many years of life. However, somewhat higher targets should be considered for older patients with long-standing type 2 diabetes mellitus and evidence of CVD (or multiple CVD risk factors). This review explores these issues further and proposes a framework for considering an appropriate and safe HbA1c target range for each patient.

Figures

Grahic Jump Location
Figure.
Framework to assist in determining glycemic treatment targets in patients with type 2 diabetes.

Glycemic goals and treatment intensities are shown in terms of increasing severity or magnitude of clinical variables, as well as with limitations set by the psychosocioeconomic context. Greater height of a triangle indicates increased clinical concern about the considered variable. If a patient's position on the various triangles is widely disparate, the treatment target should be determined by the farthest-right position. As always, sound clinical judgment should prevail in these circumstances. The location of the triangles in the figure is not meant to represent their relative importance in setting glycemic targets. The depicted targets assume stable outpatient treatment protocols. Depending on the set glycemic target range for any given patient, the target range may have to be decreased (for example, for a patient in the intensive care unit with an acute infection) or increased (for example, for a patient admitted for acute renal injury) for various periods. Note that although hemoglobin A1c and mean blood glucose levels have a strong positive correlation in populations, this relationship varies substantially at an individual level and across certain populations (for various medical, nonmedical, and unknown reasons) among both glucose levels at a given hemoglobin A1c value and hemoglobin A1c values at a given average blood glucose level (30). A hemoglobin A1c value represents the mean effect of glycation reaction on hemoglobin over 2 to 3 months, whereas blood glucose levels obtained by fingersticks give a more accurate picture of glycemic control on a day-to-day basis.

Grahic Jump Location

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Response to Ismail-Beigi
Posted on April 25, 2011
David C. Aron
Cleveland VA Medical Center
Conflict of Interest: None Declared
To the Editor: The recent article by Ismail-Beigi et al.(1) emphasizes that one size does not fit all when it comes to A1c goals for patients with diabetes "“ an important and increasingly recognized conclusion in light of recent large randomized controlled trials. However, assertion that "Each organization discusses the importance of individualizing glycemic goals but provides little guideline on how this should be done" is not correct. The VA/DoD Clinical Practice Guidelines for Diabetes have for more than 10 years included stratified targets based on life expectancy and co-comorbidities.(2,3, 4) Moreover, all of the trials referred to in their article were utilized in updating the guidelines which were released in August, 2010. The glycemic targets recommended by Ismail-Beigi et al. range from A1c of 6% to ~8%. In contrast, The VA/DoD Diabetes Practice Guidelines Working Group recommends target ranges rather than single targets "”from <7%, 7-8%, and 8-9%. See Table. Using ranges permits the flexibility necessary for patient safety that may be discouraged in our age of pay-for performance. In addition, we used ranges not only to because it better reflects life expectancy but also because of the limitations of A1c testing accuracy particularly in some currently approved or CLIA-waived testing methods (Point of Care tests) which cannot confidently detect changes in A1c of less than .05% (5). This may result in overestimation of A1c with consequent unwarranted intensification of therapy resulting in an increased likelihood of hypoglycemia.

Major comorbiditya

or

physiologic age

Microvascular complications

Absent or mildb

Moderatec

Advancedd

Absent

> 10 years of life expectancy

< 7

< 8

8-9e

Presentf

5-10 years of life expectancy

< 8

< 8

8-9e

Markedg

< 5 years of life

expectancy

8-9e

8-9e

8-9e

 

Major comorbidity includes, but is not limited to, any or several of the following active conditions: significant cardiovascular disease, severe chronic kidney disease, severe chronic obstructive pulmonary disease, severe chronic liver disease, recent stroke, and life-threatening malignancy. bMild microvascular disease is defined by early background retinopathy, and/or microalbuminuria, and/or mild neuropathy. cModerate microvascular disease is defined by preproliferative (without severe hemorrhage, intraretinal microvascular anomalies [IRMA], or venous bleeding) retinopathy, or persistent, fixed proteinuria (macroalbuminuria), and/or demonstrable peripheral neuropathy (sensory loss). dAdvanced microvascular disease is defined by severe nonproliferative (with severe hemorrhage, IRMA, or venous bleeding) or proliferative retinopathy, and/or renal insufficiency (serum creatinine level, > 2.0 mg/dL), and/or insensate extremities or autonomic neuropathy (for example, gastroparesis, impaired sweating, or orthostatic hypotension). Further reductions may be appropriate, balancing safety and tolerability of therapy. Major comorbidity is present, but is not end-stage and management is achievable. Major comorbidity is present and either is end-stage or management is significantly challenging

David Aron, MD, MS, Associate Chief of Staff/Education, Cleveland VA Medical Center Cleveland, OH david.aron@va.gov;

Paul R. Conlin, MD Chief, Medical Service Boston VA Medical Center Boston, MA PCONLIN@PARTNERS.ORG

Curtis Hobbs, MD Director, Diabetes Care Center Madigan Healthcare System Tacoma WA 98431 curtis.hobbs@us.army.mil

Robert A. Vigersky, MD Director, Diabetes Institute Walter Reed Health Care System ROBERT.VIGERSKY@US.ARMY.MIL

Leonard Pogach, MD, MBA VA National Program Director for Diabetes New Jersey VA Healthcare System Leonard.pogach@va.gov

The authors are members of the VA-DoD Diabetes Guideline Working Group. The authors report no actual or potential conflicts of interest with regard to this letter. The opinions expressed herein are those of the authors and do not necessarilyreflect those of the U.S. Government, or any of its agencies.

References

1. Ismail-Beigi F, Moghissi E, Tiktin M, Hirsch IB, Inzucchi SE, Genuth S. Individualizing Glycemic Targets in Type 2 Diabetes Mellitus: Implications of Recent Clinical Trials Ann Intern Med. 2011;154:554-559.

2. Pogach LM, Brietzke SA, Cowan CL Jr., Walder DJ, Sawin CT; VA/DoD Diabetes Guideline Development Group. Development of evidence-based guidelines for diabetes: The Department of Veterans Affairs/Department of Defense guide¬lines initiative. Diabetes Care. 2004;27(suppl 2):B82-B89.

3. US Department of Veterans Affairs Office of Quality and Performance; US Army Medical Command Quality Management Division. VA/DoD clinical practice guideline for the management of diabetes mellitus. http://www.healthquality.va.gov/diabetes /DM2010_SUM-v4.pdf [DoD: https://www.QMO. amedd.army.mil]. Updated August 2010. Accessed March 8, 2011.

4. Pogach L, Conlin PR, Hobbs C, Vigersky RA, Aron D for the VA-DoD Diabetes Guideline Working GroupVA-DoD Update of Diabetes Guidelines: What Clinicians Need to Know About Absolute Risk of Benefits and Harms and A1c Laboratory Accuracy. Federal Practitioner 2011; April: 39-44

5. Little RR, Rohlfing CL, Sacks DB; National Glycohemoglobin Standardization Program (NGSP) Steering Committee. Status of hemoglo¬bin A1c measurement and goals for improvement: From chaos to order for improving diabetes care. Clin Chem. 2011;57(2):205-214.

Conflict of Interest:

None declared

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