Glycated hemoglobin—also known as hemoglobin A1C, HbA1c, or A1C—reflects the glycemic exposure of a patient’s red blood cells over a 60- to 90-day period and has become the standard indicator in the United States of glycemic control in diabetes. Although it is readily agreed that an A1C level of ~4.0%-6.0% is considered “normal” for people who do not have diabetes, there is no consensus as to a target A1C level for patients with diabetes.
Multiple, large scale clinical trials, including the Diabetes Complications and Control Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS), provide evidence that the risk for macrovascular and microvascular complications begins to increase at an A1C level of 6.5%—with patients having A1C levels >8% experiencing significantly greater complication rates—and lowering the A1C level of patients with diabetes below 7% reduces the risk of microvascular complications.
Although this information has formed the basis for the A1C recommendations of the leading diabetes professional organizations in the U.S., precise targets for glycemic control in patients with diabetes have not yet been firmly established—which can lead to confusion. Both to reduce the potential for confusion and acknowledge that every patient is different, in 2002 CADRE released its A1C recommendations:
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The CADRE Recommended A1C
Normal A1C (nondiabetes): 4.0% - 6.0%
Target A1C in diabetes: Lowest A1C possible without unacceptable hypoglycemia*
Action recommended: A1C >7.0%
*Caution recommended in children, the elderly, and higher risk populations
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As shown above, CADRE believes that an A1C value >7% requires further intervention and that whenever action is prescribed, the goal should be to achieve an A1C as close as possible to the nondiabetes range (i.e., the DCCT criteria of 4.0% to 6%) without unacceptable side effects (to either the patient or healthcare provider), most notably hypoglycemia.
It is equally important to note, however, that exceptions may need to be made. A1C goals may need to be modified by the practitioner when working with higher-risk populations or when patients continue to experience frequent or severe hypoglycemic reactions. The validity of this position was recently highlighted by the decision to stop one arm of a major diabetes trial. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial compared the benefits of intensive treatment (an A1C target of <6.0%) with standard glycemic treatment (A1C target 7.0%-7.9%) in middle-aged or older patients with type 2 diabetes and a high risk of a cardiovascular disease event. The intensive treatment arm of the study was stopped after an average treatment period of 4 years due to a higher degree of mortality in that group when compared with the standard treatment group. Although the reasons for this increased mortality have not yet been determined, intensive glycemic control was clearly not of benefit to these high-risk patients. However other recent studies, such as the ADVANCE study, failed to confirm the findings of ACCORD.
Recommendations of other leading United States diabetes organizations follow:
ADA
For many years, the ADA recommended an A1C treatment goal of <7% with action recommended at A1C levels >8%, while acknowledging that more stringent goals (i.e., a normal A1C, <6%) could be considered in individual patients. In 2006, the goals were changed to recommend an A1C goal of <7% for patients in general, with an A1C goal as close to normal (<6%) for the individual patient, without significant hypoglycemia, and less stringent goals for patients with a history of severe hypoglycemia, the very young or old, and patients with comorbid conditions and/or limited life expectancies.
The 2008 recommendations are:
· A1C goal for nonpregnant adults in general of <7%
· A1C goal for selected individuals of as close to normal as possible (<6%) without significant hypoglycemia
· Less stringent A1C goals for children, and patients with a history of severe hypoglycemia, limited life expectancies, comorbid conditions, or longstanding diabetes and minimal or stable microvascular complications.
More information on the ADA recommendations can be found at:
http://care.diabetesjournals.org/cgi/reprint/31/Supplement_1/S12
ACE/AACE
The American College of Endocrinology (ACE) and the American Association of Clinical Endocrinologists (AACE) adopted a target A1C of <6.5% at their diabetes treatment consensus conference in 2001. The organizations have created a series of detailed “Roadmaps to Achieve Glycemic Control in Type 2 Diabetes Mellitus” for use by health care providers; these Roadmaps recommend action at A1C levels >6.5% with detailed individualized treatment regimens and advancement of therapy every 3 months until the target A1C is achieved.
More information on the AACE recommendations can be found at:
http://www.aace.com/meetings/consensus/dcc/pdf/dccwhitepaper.pdf
The “Roadmaps” can be found at:
http://www.aace.com
