The American Diabetes Association has officially endorsed the use of hemoglobin A_1c as an option for diagnosing diabetes.

In its Standards of Medical Care in Diabetes, updated annually, the ADA for the first time in 2010 is officially endorsing the use of HbA_1c as one of four options for diagnosing diabetes, with a cut-point of 6.5% or greater. Recommendations for use of the three previous diagnostic criteria remain unchanged, including a fasting plasma glucose (FPG) of 126 mg/dL or above, a 2-hour plasma glucose of 200 mg/dL or greater following a 75-g oral glucose tolerance test, or a random plasma glucose of 200 mg/dL or greater in an individual with classic symptoms of hyperglycemia (Diabetes Care 2010[suppl 1]:S11-S61 [doi: 10.2337/dc10-S011]).

In June 2009, the use of HbA_1c for diabetes diagnosis was endorsed in a consensus statement by an expert panel comprising members of the American Diabetes Association, the European Association for the Study of Diabetes, and the International Diabetes Federation. However, that statement was not the official position of the respective organizations (Diabetes Care 2009;32:1327-34).

The new ADA endorsement is based in part on the fact that HbA_1c assays are now highly standardized, and “their results can be uniformly applied both temporally and across populations.” In addition, epidemiologic data show a relation between HbA_1c and the risk of retinopathy similar to that shown for corresponding FPG and 2-hour postprandial glucose thresholds. The HbA_1c is also more convenient since fasting is not required, and is likely to be more stable than glucose measurements, the statement said.

The ADA acknowledged that these advantages must be balanced by greater cost, limited availability of HbA_1c in some parts of the developing world, and incomplete correlation between HbA_1c and the average glucose in certain individuals. Also, the HbA_1c can be misleading in patients with certain forms of anemia and hemoglobinopathies. Indeed, unpublished data suggest that use of the HbA_1c with a cutoff of 6.5% or higher identifies one-third fewer cases of undiagnosed diabetes than does a FPG of 126 mg/dL or greater.

However, the ADA said, “in practice, a large portion of the diabetic population remains unaware of their condition. Thus, the lower sensitivity of A_1c at the designated cut-point may well be offset by the test’s greater practicality, and wider application of a more convenient test (A_1c) may actually increase the number of diagnoses made.” (See diagnostic criteria below.)

Not everyone agrees. Dr. Zachary T. Bloomgarden of Mount Sinai School of Medicine, New York, said in an interview that while it may be appropriate to use HbA_1c as a screening tool to determine who would then be asked to return for an oral glucose tolerance test, he believes that using it for diagnosis is not appropriate because it could lead to overdiagnosis among people with high hemoglobin glycation, or “high glycators,” and underdiagnosis of “low glycators.”

For example, Dr. Bloomgarden said, older individuals have higher HbA_1c levels than do younger people, and blacks have higher HbA_1c levels than do whites for a given level of glucose tolerance, so these individuals might be systematically overdiagnosed. On the other hand, many ill persons seeing a physician for chronic kidney disease or other conditions associated with anemia might be low glycators, leading to underdiagnosis. “These are rather common, each certainly affecting 10% of the population to a clinically relevant extent,” said Dr. Bloomgarden, editor of the Journal of Diabetes.

The ADA’s decision to endorse the HbA_1c as a diagnostic tool is “overall, not to my mind satisfactory,” he commented.

But Dr. Mayer Davidson, who was part of the expert panel that endorsed HbA_1c for diagnosing diabetes last summer, is on the opposite end of the spectrum. He said the recommendation to use HbA_1c for diabetes diagnosis is long overdue, and that the ADA erred in not removing glucose criteria as diagnostic options. The International Expert Committee had recommended use of the glucose criteria only if a standardized HbA_1c assay was not available, he noted in an interview.

“Unfortunately, the ADA kept the glucose criteria, which will lead to the confusing situation of people who have diabetes by one criterion but not by the other when both are measured, which is likely to occur frequently,” said Dr. Davidson, professor of medicine, Charles Drew University and David Geffen School of Medicine at the University of California, Los Angeles.

Based on the expert committee’s deliberations, it’s likely that the ADA and the other organizations will ultimately transition to use of HbA_1c alone for diagnosis, but it may take time. Until then, he advised that physicians who want to use repeat testing for diagnosis stick to the same test both times to avoid confusion. Bottom line: “One should not intermingle the glucose and A_1c criteria.”

The ADA document says that using the same test is “preferred” but provides specific guidance for both testing scenarios.

Along with the 6.5% cutoff for diabetes diagnosis, the ADA now categorizes patients with HbA_1c levels of 5.7%-6.4% under the new heading “Categories of Increased Risk for Diabetes,” replacing “Diagnosis of Pre-Diabetes.” The 5.7% threshold was derived from unpublished data suggesting that it has the best combination of sensitivity (39%) and specificity (91%) to identify cases of impaired fasting glucose. Other analyses suggest that an HbA_1c of 5.7% is associated with a diabetes risk similar to that of the high-risk participants in the landmark Diabetes Prevention Program trial.

Other significant changes from the ADA’s 2009 Standards of Medical Care include the following:

– The section “Antiplatelet agents” has been extensively revised to reflect recent trial data that call into question the benefit of aspirin for primary cardiovascular disease prevention in moderate- or low-risk patients. The new recommendation is to consider aspirin therapy as a primary prevention strategy in those with diabetes at increased cardiovascular risk (10-year risk greater than 10%). This includes men over 50 years of age or women at least 60 years of age with at least one additional major risk factor.

– The section “Retinopathy screening and treatment” has been updated to include a recommendation on use of fundus photography as a screening strategy.

– The section “Diabetes care in the hospital” has been extensively revised to reflect new evidence calling into question very tight glycemic control goals in critically ill patients.

– A new section on cystic fibrosis–related diabetes has been added.

Both Dr. Bloomgarden and Dr. Davidson stated that they have no financial disclosures.

Criteria for the Diagnosis of Diabetes

1. Hemoglobin A_1c 6.5% or greater.*

OR

2. FPG 126 mg/dL (7.0 mmol/L) or greater. Fasting is defined as no caloric intake for at least 8 h.*

OR

3. Two-hour plasma glucose of 200 mg/dL (11.1 mmol/L) or greater during an oral glucose tolerance test.*

OR

4. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose of 200 mg/dL (11.1 mmol/L) or greater.

*In the absence of unequivocal hyperglycemia, criteria 1–3 should be confirmed by repeat testing.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

美国糖尿病学会(ADA)已正式批准血红蛋白A1c(HbA1c)可作为糖尿病的一种诊断方法。 

在其每年更新的《糖尿病诊疗标准》中，ADA于2010年首次正式批准HbA1c作为糖尿病4种诊断方法中的一种，其诊断界值为≥6.5%。对于之前3种诊断标准的建议未变，包括空腹血糖(FPG)为≥126 mg/dl，75 g口服糖耐量试验2h血糖为≥200 mg/dl，或有典型高血糖症状的个体随机血糖为≥200 mg/dl(Diabetes Care 2010[suppl 1]:S11-S61 [doi: 10.2337/dc10-S011])。 

在2009年6月，一个由ADA、欧洲糖尿病研究协会和国际糖尿病联合会成员组成的专家小组发布的共识声明中支持将HbA1c用于糖尿病的诊断。但该声明并不代表各组织的官方立场(Diabetes Care 2009;32:1327-34)。 

ADA的这一最新批准部分源于HbA1c检测如今已高度标准化，并且“其结果既可暂时应用，亦可应用于大众”。另外，流行病学资料显示，HbA1c与视网膜病风险相关，这与在FPG和2h餐后血糖阈值的发现相似。该声明称，由于不需要禁食，HbA1c检测也更为方便，并可能较血糖检测更为稳定。 

ADA承认，HbA1c的上述众多优势必须权衡以下问题：费用更高、HbA1c检测在发展中地区的某些地方应用受限和HbA1c与某些个体的平均血糖水平不完全相关等。另外，对于某些类型的贫血和血红蛋白病患者，HbA1c可能造成误诊。实际上，有尚未发表的资料显示，与FPG≥126 mg/dl相比，应用HbA1c≥6.5%标准确诊的糖尿病患者人数要多1/3。 

然而，ADA说：“临床上，大部分糖尿病患者对其病情并不知情。因此，A1c在指定界值时的较低灵敏度可被其更大的实用性抵消，而更方便的检测方法(A1c)的更广泛应用事实上可能发现更多的患者”(见下文诊断标准)。 

并非所有人均支持这一观点。来自纽约西奈山医学院的Zachary T. Bloomgarden博士在一次受访时称，将HbA1c检测作为一种筛查工具来确定哪些人需要进一步进行口服糖耐量试验可能更为合适。他认为，将HbA1c检测用于糖尿病的诊断并不合适，这是因为对于糖化血红蛋白水平较高的患者，它可能会导致糖尿病的过度诊断，而那些糖化血红蛋白水平较低的患者却可能被漏诊。 

Bloomgarden博士说，例如老年人的HbA1c水平较年轻人高，在特定糖耐量时，黑种人的HbA1c水平较白种人高，那么这些人可能会被系统地过度诊断。另一方面，许多因慢性肾病或其他与贫血相关的疾病而就诊的患者，其糖化血红蛋白可能较低，从而可能被漏诊。《糖尿病杂志》(Journal of Diabetes)的编辑Bloomgarden博士说：“这些都非常常见，在临床相关程度上均可影响10%的人群。” 

他评论道，ADA批准将HbA1c作为一种糖尿病诊断工具的决定，“总的来讲，在我看来并不令人满意”。 

但Mayer Davidson博士持相反观点，他是于2009年夏天支持HbA1c用于糖尿病诊断的专家小组成员之一。他说，将HbA1c用于糖尿病诊断的建议已被延误很久，ADA仍未将血糖标准从糖尿病诊断选项中剔除是一个错误。他在一次受访时指出，国际专家委员会已建议仅在无法行标准化HbA1c检测时应用血糖标准进行糖尿病诊断。 

洛杉矶加州大学David Geffen医学院和Charles Drew大学的医学教授Davidson博士说：“不幸的是，ADA仍保留了血糖标准，它将导致一种标准诊断某人患上糖尿病而另外一种标准却认为无病的混乱局面，这种事情可能会经常发生。” 

该专家委员会审议认为，ADA和其他组织可能最终将过渡到仅应用HbA1c检测进行糖尿病的诊断，但这需要时间。他建议，在此之前，为作出诊断而欲进行重复检查的医生仍应坚持每次均用同一种检测方法，以免造成混乱。底线是：“杜绝将血糖标准与A1c标准相混合”。 

ADA文件说，应“优先”应用同一检测方法，但对两种检测方法均提出了具体指导。 

除将HbA1c的6.5%水平作为糖尿病的诊断界值外，ADA现在还将HbA1c水平为5.7%~6.4%的患者归类为“糖尿病高危人群”，用以取代“糖尿病前期诊断”。此5.7%的界值来自于尚未发表的资料，该资料显示，此界值对于发现空腹血糖水平紊乱患者的灵敏度(39%)和特异性(91%)均佳。其他研究表明，HbA1c水平为5.7%者发生糖尿病的风险与里程碑式临床研究“糖尿病预防计划”中高危受试者相当。 

ADA 2009糖尿病诊疗标准中的其他重大改变包括如下： 

根据最近有关质疑阿司匹林在中低危患者作为心血管疾病初级预防的益处的临床研究资料，对“抗血小板制剂”部分进行了全面修订。新的建议是，对于心血管疾病风险升高(10年风险大于10%)的糖尿病患者，可考虑应用阿司匹林治疗作为一种初级预防措施。这包括具有至少1种主要危险因素、年龄>50岁的男性或年龄≥60岁的女性。

• 更新“视网膜病筛查和治疗”部分，建议将眼底照相术作为一种筛查措施。 
• 根据对危重症患者严格血糖控制目标提出质疑的新证据，对“院内糖尿病诊治”部分进行了全面修订。 
• 新增了有关糖尿病相关囊性纤维化的内容。 

Bloomgarden博士和Davidson博士均表示无利益冲突声明。 

糖尿病诊断标准 

1. 血红蛋白A1c水平≥6.5%*。或 
2. FPG≥126 mg/dl (7.0 mmol/l)。空腹定义为至少8h内无热量摄入*。或 
3. 口服糖耐量试验时2h血糖≥200 mg/dl (11.1 mmol/l)*。或 
4. 在伴有典型的高血糖或高血糖危象症状的患者，随机血糖≥200 mg/dl (11.1 mmol/l)。 

*在无明确高血糖时，应通过重复检测来证实标准1~3。 

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