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At this year's annual meeting of the American Association of ClinicalEndocrinologists (AACE), it was reported that only 33% of U.S. patients withdiabetes achieved AACE's recommended glycated hemoglobin (A1C) goal of
6.5%. The American Diabetes Association (ADA) recommends an A1C goal of<7%. A recurring question was raised yet again: Why do AACE and ADA havedifferent A1C targets?
It is important to be clear about exactly what each group maintains in itspublished guidelines. AACE states simply that its goal is6.5%.1 ADA notonly states that its goal is <7%, but also notes that it is critical toinclude the following "key concepts in setting glycemicgoals":
ADA suggests that one should strive for the lowest A1C appropriate for thepatient based on these concepts.
ADA uses several key considerations in setting a guideline. Each guidelinemust be evidence-based and indicate the level of evidence. A guideline shouldhave a favorable risk-benefit or cost-benefit relationship. Guidelines shouldbe clearly written, with the realization that they may be interpreted quiteliterally by providers, health care systems, governmental agencies,pharmaceutical companies, and the courts.
Ideally, ADA guidelines should be consistent with guidelines issued byother organizations. In this regard, it is important to note that ADA haspublished its A1C goal as <7% since1995,3 and AACEpublished its guideline of 6.5% in2002.1
SHARED EVIDENCE BASE
The evidence base used by AACE and ADA is exactly the same. To myknowledge, there are no studies considered by one organization that are notconsidered by the other. The major database for both guidelines consists ofresults from the Diabetes Control and Complications Trial(DCCT)4,5and the U.K. Prospective Diabetes Study(UKPDS).6,7Both studies demonstrated that with declining A1C levels comes a significantdecline in the risk and progression of the microvascular complications ofdiabetes. Neither study demonstrated a level of A1C below which furtherbenefit was not obtained. Significantly, the mean A1Cs attained by the"intensively treated group" in these two studies were 7.1% (DCCT)and 7% (UKPDS). In addition, both studies reported a significantly increasedrisk of hypoglycemia in the intensive groups.
FAVORABLE RISK-BENEFIT OR COST-BENEFIT RELATIONSHIP
In view of the patient with type 1 diabetes, ADA has considered carefullythe risk-benefit relationship, noting that as A1C falls below 7%, the benefitdecreases markedly while the risk of hypoglycemia grows. This suggests thepossibility that for some patients, lowering A1C into that range will beassociated with greater harms than benefits. Thus a target of <7% balancesthe risk of hypoglycemia with the benefit of this level of glycemiccontrol.
In type 2 diabetes, where hypoglycemia is far less frequent, therisk-benefit assessment suggests that lower goals may be desirable.
However, we must consider the cost-benefit relationship. Placing thepatient on another oral medication or starting the patient on insulin needs tobe weighed against the potential benefit of further A1C reduction. If thequestion is, "What should be done to decrease my patient's A1C from 6.9%(meeting the ADA target) to 6.5% (meeting the AACE target)?" it must berealized that within that range of A1C reduction the potential benefit issmall indeed, based on current data.
Finally, it is clear from virtually every short- and long-terminterventional study that it is very difficult (and expensive) to achieve A1Clevels on average <7%—making the cost-benefit ratio prohibitive forat least some patients.
GUIDELINE CONSISTENCY
Many argue that the difference between the ADA and AACE A1C recommendationsdistracts patients and providers from the reality that most patients are notnear either goal. It also creates the impression that "even the expertscannot agree."
Although there are not good data to tell us the mean A1C in the U.S.,diabetes experts often estimate that it is 8.5–9%. This suggests that weshould spend less time discussing what the goal should be and moretime discussing how to improve glycemic control, and thereby get moreof our patients to either goal. This point is particularly true when onerealizes that, based on available data, we would accomplish far more bytargeting those with high A1Cs and decreasing their A1Cs significantly than byarguing about how to further improve the A1Cs of those who, most would agree,are doing well by either standard. 
Footnotes
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References
2. American Diabetes Association: Standards of medical care indiabetes (Position Statement). Diabetes Care 28 (Suppl. 1): S4–S36, 2005.
3. American Diabetes Association: Standards of medical care forpatients with diabetes mellitus (Position Statement). DiabetesCare 18 (Suppl. 1):S8–S19, 1995.
4. The Diabetes Control and Complications Trial Research Group: Theeffect of intensive treatment of diabetes on the development and progressionof long-term complications in insulin-dependent diabetes mellitus.N Engl J Med 329:977–986, 1993.
5. American Diabetes Association: The relationship of glycemicexposure (HbA1c) to the risk of development and progression ofretinopathy in the Diabetes Control and Complications Trial.Diabetes 44:968–983, 1995.[Abstract]
6. U.K. Prospective Diabetes Study (UKPDS) Group: Intensiveblood-glucose control with sulfonylureas or insulin compared with conventionaltreatment and risk of complications in patients with type 2 diabetes (UKPDS33). Lancet 352:837–853, 1998.[Medline]
7. Stratton IM, Adler AI, Neil HA, et al.: Association of glycaemiawith macrovascular and microvascular complications of type 2 diabetes (UKPDS35): Prospective observational study. BMJ 321: 405–412, 2000.
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